MXPA06008029A - Bis-indole pyrroles useful as antimicrobials agents - Google Patents

Abstract

Compounds of Formula (I), commonly referred to as bis-indole pyrroles, including isolated naturally-occurring compounds, synthetic and semi-synthetic derivatives thereof having antimicrobial properties and to antimicrobial compositions that include one or more of bis-indole pyrroles and their derivatives or analogs having antimicrobial properties are disclosed. Pharmaceutical compositions comprising such compounds and methods of treating bacterial infections with the disclosed compounds or the disclosed pharmaceutical compositions are also disclosed.

Description

BIS-INDOLIR PIRROLS USEFUL AS ANTIMICROBIAL AGENTS Related Requests This application claims priority for United States Provisional Application Number 60 / 539,053, filed on January 23, 2004 and United States Provisional Application Number 60 / 627,235, filed at November 12, 2004 incorporated herein by reference in its entirety. Background of the Invention Field of the Invention The present invention relates to certain compounds and methods for the preparation and use of certain compounds in the fields of chemistry and medicine. More specifically, the present invention relates to compounds and methods for making and using compounds useful as antimicrobial agents, and refers to pharmaceutical dosage forms comprising such compounds. Description of the Related Art Antimicrobials are generally used to destroy or suppress the growth or reproduction of microbes such as bacteria. Antimicrobial compounds can act on target microbes in a variety of ways. For example, the antimicrobial compound can prevent the synthesis of DNA or protein, - - it can alter the cell wall of a microbe either by altering the permeability of the cell wall or by altering the synthesis and repair of the cell wall. Although there are numerous known antimicrobial compounds, and numerous known mechanisms by which antimicrobial compounds can function, problems have recently increased in the availability of antibiotic treatment options, for both early and late stage infections, by bacteria. There are many reasons for the increase in the problems, but a main reason refers to the biological weapons design potential of resistant isolates and the evolutionary development of resistance to existing antibiotics. Therefore, new antimicrobials and new sources of antimicrobials are desirable and of great value. There are many characteristics that may be relevant when trying to decide whether or not a particular compound is useful as an antimicrobial. Relevant factors include, but are not limited to, the relative potency of the compound against a specific microbe or against a spectrum of microbes, and the relative selectivity of the antimicrobial activity of the compound to direct the invading pathogen against the host organism. There are also long-term problems, including the likelihood that the microbe may develop resistance to one or more compounds - antimicrobials. There are also practical problems, such as the cost and commercial availability of the antimicrobial compound. A possible source of antimicrobial compounds are natural marine derived products. The oceans are massively complex and host a diverse assembly of microbes that occurs in environments of extreme pressure, salinity, and temperature variations. Marine microorganisms have developed unique metabolic and physiological capacities that not only ensure survival in extreme habitats, but also offer the potential to produce metabolites that would not be observed from terrestrial microorganisms. (Okami, Y. 1993 J. Mar Biotechnol, 1:59). Representative structural classes of such metabolites include terpenes, peptides, polyketides, and compounds with mixed biosynthetic origins. Many of these molecules exhibit anti-tumor, anti-bacterial, anti-fungal, anti-inflammatory or immunosuppressive activities (Bull, AT et al., 2000 Microbiol.Mol. Biol.Rev., 64: 573; Cragg, GM & DJ Newman 2002, Trends Pharmacol Sci. 23: 404, Kerr, RG &SS Kerr 1999 Exp. Opin. Ther. Patents 9: 1207; Moore, BS 1999 Nat. Prod. Rep. 16: 653; Faulkner, DJ 2001, Nat. Prod. Rep. 18: 1; Mayer, AM &VK Lehman 2001 Anticancer Res. 21: 2489), validating the usefulness of this source of therapeutic isolation agents. further, the isolation of new antibiotics that represent alternative mechanical classes for those currently commercial, will probably lead to resistance based on the mechanism that they have been manufactured as pathogens for purposes of biological terrorism. One such class of compounds, studied in other unrelated fields of research, is bis-indole pyrrole and in particular, chromopyrrolic acid. A subset of this class of molecules is described by Hoshino et al., (Biosci, Biotech, Biochem 57, 775-781 (1993)). Hashimoto et al., Tetrahedron letters. 35: 2559-2560 (1994) suggests that a particular derivative, a double substituted pyrrole with two methoxy carbonyls symmetrically bound to prrol, has moderate anti-HSV-1 virus activity in vitro. The functionality of this compound and its analogues is not well understood. Other references have examined similar derivatives for these compounds (Frode et al., Tetrahedron Lett., 35: 1689-1690 (1994)). More recently, Sodeoka et al., (US Pat. No. 6,589,977, issued July 8, 2003), which is incorporated herein by reference, has suggested a role for bis-indole pyrrole derivatives as inhibitors of cell death Sodeoka et al., Examined various pyrrole derivatives of bis-indole for their inhibitory activity of cell death.

- SUMMARY OF THE INVENTION In some aspects, a compound having a structure of Formula I, and its pharmaceutically acceptable salts and prodrug esters is provided: Formula I a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; each Rx, R2 and R5 is selected separately from the group consisting of hydrogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C2 alkyl, unsaturated C2-C2 alkenyl, or alkynyl C2-C2, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, halogenated alkyl including alkyl-polyhalogenated, and some combination thereof; every five R3 and every five R4 represent substituent (s) in an indole ring at position (s) 2-, 4-, 5-, 6-, or 7- and each of the five R3 and each one of the five R4 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C24 alkyl, unsaturated C2-C24 alkenyl , or C2-C24 alkynyl, acyl, acyloxy, ester, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio , arylthio, oxysulfonyl, carboxy, cyano, halogenated alkyl including polyhalogenated alkyl, and some combination thereof; R6 represents substituent (s) on a pyrrole ring at (2-) or 5- position, and each of the two R6 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C2 alkyl, unsaturated C2-C2 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy , aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, halogenated alkyl including polyhalogenated alkyl, and some combination thereof. In some embodiments, there is the proviso that if all R3 and R4 are either hydrogen or hydroxyl, Rs at the 5-position and R6 at the 2- position are not identical esters or carboxylic acids. In some embodiments, there is the additional proviso that when the substituents on R3 are identical to the substituents on R4, the substituents on R6 in the 5- position and the 2- position are not the same. In another aspect, a compound having a structure of Formula I, and its pharmaceutically acceptable prodrug salts and esters are provided: Formula I a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; each Rx, R2 and R5 is selected separately from the group consisting of hydrogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated L-C24 alkyl, unsaturated C2-C24 alkenyl, or alkynyl C -C4, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, sugar, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl , carboxy, cyano, CO-0-R7, carbonyl-CCO-R7, - (CH2) n-COOR7, -CO- (CH2) n-COOR7, aminoalkyl (- (CH2) n-NR8R9), and halogenated alkyl including polyhalogenated alkyl, where n is an integer from 1 to 6; each R7, R8 and Rg is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C24 alkyl, C2-C2 alkenyl unsaturated, or C2-C2 alkynyl, acyl, acyloxy, ester, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof; every five R3 and every five R4 represents substituent (s) in an indole ring at position (s) 2-, 4-, 5-, 6- or 7- and each of the five R3 and each of the five R4 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C2 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl; each Rs represents substituent (s) on a pyrrole ring at position (s) 2- or 5-, and each of the two Rs is selected separately from the group consisting of hydrogen atom, mono variants -substituted, poly-substituted or unsubstituted of the following residues: saturated C? -C2 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, amide (-CO-NR8R9), alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl , cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, ester, alkyloxycarbonyl, aryloxycarbonyl, CO-0-R7, carbonyl-CCO-R7, - (CH2) n-C00R7, -CO- (CH2) n-C00R7, alkylthio, arylthio, oxysulfonyl, carboxy, cyano and halogenated alkyl including polyhalogenated alkyl. In some embodiments, there is the additional caveat that R6 in the 5- position and R6 in the 2- position are not identical if all the R3 and R are either hydrogen or hydroxyl. In some embodiments there is the additional caveat that if 1) an alkyl group exists in R5 and if 2) R6 in the 2-position and in the 5- position is either hydrogen or oxygen, then R3 and R are not symmetrical. In some embodiments, there is the additional caveat that if there is an alkylamine in Ri or R2, then there is at least one non-hydrogen substitution in R6, or there are at least 3 halogens in R3 and R4. In another aspect, a compound having a structure of Formula I, and its pharmaceutically acceptable prodrug salts and esters are provided: Formula I a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen, and may include a non-nitrogen hetero atom, such as sulfur or oxygen, instead of nitrogen (s) in Formula I; each Rl7 R2 and R5 is selected separately from the group consisting of - hydrogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C2 alkyl, unsaturated C2-C24 alkenyl, or C2-C2 alkynyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, acyl, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, carbohydrate, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, CO-0-R7, carbonyl-CCO- R7, - (CH2) n-COOR7, -CO- (CH2) n-COOR7, - (CH2) n-NR8R9), and halogenated alkyl including polyhalogenated alkyl, wherein n is an integer between 1 and 6; each R7, R8 and R9 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C24 alkyl, C2-C24 alkenyl unsaturated, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof; the five R3 and the five R represent substituent (s) on an indole ring at position (s) 2-, 4-, 5-, 6- or 7-, where each of the five R3 and each of the five R's is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Ci-C24 alkyl, unsaturated C2-C24 alkenyl or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio , oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl; every two R6 represents substituent (s) on a pyrrole ring at (2-) or 5- position, and each of the two R6 is selected separately from the group consisting of hydrogen atom, mono variants -substituted, poly-substituted or unsubstituted of the following residues: saturated Ci-C24 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, (-CO-NR8R9), C0-0-R7, carbonyl -CCO-R7, (CH2) n-COOR7, -CO- (CH2) n-COOR7, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, ester, - (CH2) n-NR8Rs, alkoxycarbonyl, -aryloxycarbonyl, and halogenated alkyl including polyhalogenated alkyl. In some embodiments, there is the additional caveat that R6 in the 5- position and R6 in the 2-position are not identical. In some embodiments there is the additional caveat that if there is an alkylamine in Ri or R2, then there is at least one non-hydrogen substitution in Re, or there are at least 3 halogens in the combination of R3 and R4. In some additional embodiments the ring atoms of these compounds are not modified. In some embodiments, the above compounds have at least two of the five R3 which are hydrogen atoms and at least two of the R4 which are hydrogen atoms. In some embodiments, the above compounds have at least one of the five R3 which is a halogen atom and the indole rings do not include additional hetero atoms, but include indole nitrogen. In some embodiments, the above compounds have at least one of the five R3 which is a halogen atom and at least one of the five R4 which is a halogen atom. In some embodiments, the above compounds have at least two of the five R3 which is a halogen atom. In some embodiments, the above compounds have at least one of the five R3 which is a chloride atom. In some embodiments, the above compounds have one of two R6 which is an alkoxy carbonyl, one of the Rg is a hydrogen atom, at least one of the five R3 is a chloride atom, and R1 (R and R5 are each one hydrogen atom In some embodiments, the above compounds have one of two positions in R6 which is an alkoxy carbonyl In some embodiments, the above compounds have R6 as a methoxy carbonyl In some embodiments, the above compounds have the structure selected from the group consisting of the structures of Formulas II, III, IV, V, VI, VII, VIII, XI, XII, XIII, XIV, XV, XV, XVI, XVII, XVIII, XIX, XIX ', XX, XXI ', XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVII-A, XXVII-C, XXVIII, XXVIII-A, XXIX, XXIX-A, XXX, XXXI, XXXI-A, and XXXI-B and its pharmaceutically acceptable salts and drug prodrugs In some embodiments, the above compounds have the structure of Formula II, and their pro-drug salts and esters pharmaceutically acceptable gases: Formula II In some embodiments, the above compounds have at least two of the ten R3 and R4 which are halogen atoms. In some embodiments, the above compounds have at least three of the ten R3 and R4 which are halogen atoms. In some embodiments, the above compounds have at least two of the ten R3 and R4 which are chlorine atoms. In some embodiments, the above compounds have at least two of the ten R3 and R4 which are bromine atoms. In some embodiments, the above compounds have at least three of the ten R3 and R4 which are bromine atoms. In some aspects, the above compounds are part of a pharmaceutical composition. In some embodiments, the above compounds have an antimicrobial agent. In some embodiments, the above compounds are in a solid unit dose form. In some aspects, a method for treating a microbial infection is provided. The method comprises administering a compound having a structure of Formula I, and its pharmaceutically acceptable prodrug salts and esters: Formula I a ring may include one or more additional hetero-ates, such as nitrogen, sulfur or oxygen; and can - - include a non-nitrogen hetero atom, such as sulfur or oxygen, instead of nitrogen (s) in Formula I; each Rx, R2 five R3, five R, R5 and two R6 is independently selected from the group consisting of a hydrogen atom, a halogen, a sugar, an aminoalkyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues : saturated C? -C2 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, -CO-O-R7, carbonyl-CCO-R7, CO-NR8R9, - (CH2) n- C00R7, -CO- (CH2) n-COOR7, - (CH2) n-NR8R9), ester, alkoxycarbonyl, aryloxycarbonyl, and n is an integer from 1 to 6; each R7, R8 and R9 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C24 alkyl, C2-C24 alkenyl unsaturated, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof. In some embodiments, at least one of the substitutions Ri, R2, five R3, five R4, R5 and two Rg are asymmetric. In some embodiments, the two substitutions Rs are asymmetric. In some embodiments, the five substitutions R4 and the five R3 are asymmetric. In some embodiments, at least five R3 are a halogen atom, and at least one R is a halogen atom, and the indole rings do not include additional hetero-atoms, but include indole nitrogen. In some embodiments, R8 is - (CH2) 2- and R9 is - (CH2) 2-, and R8 and R9 are directly connected together in order to form a five-membered ring. In some embodiments, R8 is - (CH2) 2- and R9 is - (CH2) 2-, and R8 and R are connected to each other through R10 so as to form a six-membered ring, and Rio is selected from group consisting of CH2, NH, O, and S. In some embodiments, one of the two Rs is an alkoxycarbonyl, one of the R6 is a hydrogen atom, at least one of the five R3 is a chloride atom, and R1 (R2 and R5 are each hydrogen atoms) In some embodiments, alkoxycarbonyl is a methoxycarbonyl., the above methods further comprise the steps of identifying a subject that would benefit from the administration of an antimicrobial agent, and carrying out the method on the subject. In some embodiments, the microbial infection is an infection of at least one gram-positive bacterium. In some embodiments, the microbial infection is an infection of at least E. faecalis-Vans. In some embodiments, the microbial infection is an infection of at least H. influenzae. In some embodiments, any of the above compounds or the compounds described herein may be used to treat a microbial infection. In one aspect, a method for treating a microbial infection is provided. The method comprises administering a compound having a structure selected from the group consisting of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XV, XVI, XVI, XVII, XVIII, XIX, XIX ', XX, XXI', XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVII-A, XXVII-B, XXVII-C, XXVIII, XXVIII-A, XXIX, XXIX-A, XXX, XXXI, XXXI-A, and XXXI-B and 1) a pharmaceutically acceptable salt or 2) pro-drug ester thereof. In some embodiments, the compound has a structure selected from the group consisting of Formula II, III, IV, VI, V, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XV, XVI, XVII , XVIII, XVIII, XIX, XIX ', XX, XXI', XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVII-A, XXVII-B, XXVII-C, XXVIII, XXVIII-A, XXIX, XXIX -A, XXX, XXXI, XXXI-A, and XXXI-B.

In some aspects, a method for making a compound described above is provided. The method comprises culturing strain NPS012745 in a culture, and recovering the compound of formula I from the culture. In some embodiments, the method further comprises the step of isolating a single pyrrole analogue of bis-indole. In some embodiments, the single compound is a compound described above. As will be appreciated by the person skilled in the art, in some embodiments, any of the above compounds can be used for any of the treatment methods. Similarly, in some embodiments, any of the compounds of the described methods can also be used in and of themselves. The methods described may also include the steps of obtaining and purifying the above compound as described in greater detail herein. Synthetic and synthetic methods are also described. In some aspects, the use of a compound having the structure of Formula I in the manufacture of a medicament for treating a microbial infection is provided.

Formula I a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; each Rl t R2 five R3, five R, Rs and two R6 is independently selected from the group consisting of hydrogen atom, a sugar, an aminoalguile, mono-substituted, poly-substituted or unsubstituted variants of the following residues: CX alkyl Saturated C24, unsaturated C2-C4 alkenyl, or C2-C2 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, -CO-O-R7, carbonyl-CCO-R7, CO-NR8R9, - (CH2) n-C00R7, -CO - (CH2) n-COOR7, - (CH2) n-NR8R9), ester, alkoxycarbonyl, aryloxycarbonyl, and n is an integer from 1 to 6; each R7, R8 and R9 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C24 alkyl, C2-C24 alkenyl unsaturated, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof. In some embodiments, at least one of the substitutions Ri, R2, five R3, five R4, R5 and two R6 are asymmetric. In some embodiments, the two substitutions R6 are asymmetric. In some embodiments, R8 is - (CH2) 2- and R9 is - (CH2) 2-, and R8 and Rg are directly connected together in order to form a five-membered ring. In some embodiments, R8 is - (CH2) 2- and R9 is - (CH2) 2-, and R8 and R are connected to each other via R10 so as to form a six-membered ring, and R10 is selected from group consisting of CH2, NH, 0, and S. In some aspects, a compound having the structure of Formula I is provided as a medicament.

- Formula I a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; each Rl r R2 five R3, five R4, Rs and two R6 is independently selected from the group consisting of hydrogen atom, a sugar, an aminoalkyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues: Ci aligyl -C24 saturatedunsaturated C2-C2 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl , hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, -CO-O-R7, carbony1-CCO-R7, CO-NR8R9, - (CH2) n-COOR7, -CO- (CH2 ) n-COOR7, - (CH2) n-NR8Rg), ester, alkoxycarbonyl, aryloxycarbonyl, and n is an integer from 1 to 6; each R7, R8 and Rg is independently selected from the group consisting of hydrogen atom, halogen atom, variants mono-substituted, poly-substituted or unsubstituted of the following radicals: alkyl Cx-C2 saturated C2-C24 unsaturated or C2-C24, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonilacilo, amino, aminocarbonyl, aminocarboiloxi, nitro, azido, phenyl, hydroxy, alkylthio, arylthio , oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof. Other embodiments refer to methods for treating an individual using certain compounds described herein and compositions comprising the compounds described herein. Brief Description of the Drawings The accompanying drawings, which are incorporated and form part of the specification, merely illustrate certain preferred embodiments of the present invention. Together with the rest of the specification, they are intended to serve to explain the preferred modes for making certain compounds of the invention to those skilled in the art. In the drawings: Figure 1 illustrates an HPLC chromatograph of a - composite of the invention, showing the various points of the various structures. Figure 2A-E illustrates the UV spectra of certain compounds of the invention. The spectra were obtained in acetonitrile / H20. Figure 3A illustrates the spectrum ^? NMR of the compound of Formula XI. Figure 3B illustrates the XH NMR spectrum of the compound of Formula XIII. Figure 3C illustrates the NMR spectrum of the compound of Formula XIV Figure 3D illustrates the 1H NMR spectrum of the compound of Formula XV Figure 3E illustrates the XH NMR spectrum of the compound of Formula XVI Figure 3F illustrates the 1H NMR spectrum of the compound of Formula XVII Figure 3G illustrates the 1H NMR spectrum of the compound of Formula XVIII Figure 3H illustrates the XH NMR spectrum of the compound of Formula XX Figure 31 illustrates the spectrum ^? NMR of the compound of Formula XXII Figure 3J illustrates the XH NMR spectrum of the compound of Formula XXIII.

Figure 3K illustrates the aH NMR spectrum of the compound of Formula XXIV. Figure 3L illustrates the R NMR spectrum of the compound of Formula XXV. Figure 3M illustrates the spectrum ^? NMR of the compound of Formula XXVI. Figure 4 illustrates scheme I involving Negishi coupling reactions. Detailed Description of the Preferred Modalities Numerous references are cited herein. The references cited herein, including US patents. cited herein, are considered incorporated by reference in their entirety in this specification. The definitions provided herein control any conflicting definition of the references incorporated by the reference. The embodiments of the invention include, but are not limited to, providing a method for the preparation of compounds including novel compounds, including bis-indole pyrroles and their analogs, and for providing a method for producing pharmaceutically acceptable antimicrobial compositions, for example . The methods may include compositions in a relatively high yield, wherein the compounds and / or their derivatives are among the active ingredients in these compositions. Other embodiments refer to providing new compounds that are not obtained by the methods currently available. In addition, the embodiments relate to methods for treating infectious diseases, particularly human infectious diseases, particularly those caused by microbes, which comprise the step of administering an effective amount of a member of a class of new compounds. Preferred embodiments refer to the compounds and methods for making and using such compounds described herein, but these objectives are not necessarily met in all embodiments of the present invention. The embodiments provide compounds and methods for producing a class of compounds, wherein the compounds are represented by Formula I: Formula I The compounds described have the structure of Formula I above. In certain embodiments, the ring (s) contain (s) one or more additional hetero atoms and may include another hetero atom in place of the nitrogen (s). The ring structure can be freely substituted according to the person skilled in the art. In a more preferred embodiment, only sections explicitly identified as Ri-Rg are replaced, although multiple substitutions are allowed. In certain embodiments, the substitution (s) to Rx-R6 may include the substitution of a hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: CX-C2 alkyl saturated, unsaturated C2-C24 alkenyl, or C-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacylamino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, and may also include ester, alkoxycarbonyl, aryloxycarbonyl carbonyl-CCO-R7, - (CH2 ) n-COOR7, -CO- (CH2) n-C00R7, amide, alkylamine, sugar, -C0-0-R7 and carbonyl -CC0-R7, wherein R7 is selected from a hydrogen atom, halogen atom, and saturated Cx-C24 alkenyl, unsaturated Cx-C24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, -zido, substituted nitro, phenyl, substituted phenyl groups, and the similar. In certain preferred embodiments, Rg at the -5 position and R6 at the -2 position are not identical esters or identical carboxylic acid groups, if all R3 and R are either hydrogen or hydroxy, or alternatively R6 at the 5- position and Rs in the 2- position are not identical if all R3 and R4 are either hydrogen or hydroxy, or alternatively, R6 in the 5- position and Rs in the 2-position are not identical. In some embodiments, amides (-CO- NR8R9) are included as possible substitution (s) to Rx-R6. In some embodiments, the amide is only a substituent on R6. In some embodiments, when there is an amide, there are at least three halides in the combination of R3 and R4. R8 and R9 can be independently selected from a hydrogen, saturated Cx-C24 alkyl, unsaturated Cx-C24 alkenyl, cycloalkyl, cycloalkenyl, hydroxy, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, phenyl, and substituted phenyl groups. In some embodiments, R8 and R9 may be selected from a list of possible substituents for R7. In some embodiments, NR8R9 comprises a ring. That is, when taken together, R8 and R9 can form a ring, for example, - (CH2) 4- or - (CH2) 2 -R? O- (CH2) 2-RX0- (CH2) 2 to form a 5 or 6 membered ring together with the N atom wherein RXo is selected from CH2, NH, O and S. In certain embodiments, the substituents on Rx-Rg include sugars, such as mono-, di-, or poly-saccharides substituted or unsubstituted, or amino sugars. In some embodiments, when there is a sugar, the substituents R3 and R will include at least three halogens. In some embodiments, Rx, R2 and R5 are the only substituents in Formula I that can include sugars or substituted alkyl groups such as - (CH2) n-COOR7, -CO- (CH2) n-COOR7, aminoalkyl (- (CH2 ) n-NR8R9) or its salts. In these examples, n is an integer from 1 to 6 and R7 is selected from the possible substituents of R7 described above. In one embodiment, the antimicrobial comprises any bis-indole pyrrole. In preferred embodiments, any of the above substitutions to Formula I, in any of the positions Rx-Rs are contemplated. In preferred embodiments, although it is allowed to substitute R1-R5 with any of the above-mentioned possible substitutions, each R6 is selected separately from the group consisting of an alkoxycarbonyl and a carbonyl group. In preferred embodiments, the two R6 are two methoxy carbonyl. In other preferred embodiments, R6 is a single methoxy carbonyl. In another embodiment, R6 is two carboxyls. In preferred embodiments, R6 is a single carboxyl group. In one embodiment, the general class of bis-indole pyrroles and bis-indole pyrrole analogs includes substitution (s) in Rx, R2, R3, R4 and R5 which can independently be any of the above-mentioned substitutions. , including multiple substitutions as permissible, with the proviso that the substitution (s) in R6 is limited to asymmetric substitutions. In other words, the substitution at position 2 and position 5 of the pyrrole can not be the same. In a more preferred embodiment, the asymmetric substitution comprises an alkoxy carbonyl. In an even more preferred embodiment, the alkoxycarbonyl is located at the 2-position of the prrol ring. Even in a more preferred mode, the alkoxycarbonyl is a methoxycarbonyl. In an alternative mode, although the substitutions in R6 are limited only to asymmetric substitutions, there can not be a link between position 2 of the two indols. In an even more preferred embodiment, the base structure shown in Formula I can not be different, except as explicitly noted by the symbols Rx-Rs. In another modality, the substitution (s) in Rx, R, R5 and R6 may (independently) be any of the above-mentioned substitutions, including multiple substitutions as permissible, although the substitution (s) in R3 and R4 comprise (n) at least one halogen. In another embodiment, the only non-hydrogen substitutions in R3 and R4 are Cl atoms. In another embodiment, R3 represents substitutions of two chlorine atoms at positions 5 and 6 of indolyl, although the 2-position of pyrrole is an alkoxycarbonyl. In one embodiment, the substitutions at R3 and R4 are asymmetric substitutions comprising at least one halogen atom. In another embodiment, the substitutions in R3 and R4 are symmetrical, but the substitution (s) is selected from the halogen group, including Cl, F, Br, and I. In another embodiment, although the substitution is symmetric, the identity of the substitution in each indolyl is different. For example, in such embodiment, R3 may be a Cl atom at the 5-position of the indolyl ring, although R4 may be an F atom at the 5-position of the indolyl ring. In addition, R3 and R can be symmetric or asymmetric substitutions in the indole. In another embodiment, at least one of the substituents on R3 and / or R comprises a halogen atom and R6 is an asymmetric substitution. In a preferred embodiment, although at least one of R3 and / or R comprises a halogen atom, R6 comprises an asymmetric acyl group with optional additional substitutions therein. In another preferred embodiment, although at least one of R3 and / or R4 comprises a halogen, Re comprises a carboxyl group. In another preferred embodiment, although at least one of R3 and / or R comprises a halogen, R6 comprises an alkoxycarbonyl. In - a modality, in the previous compounds, Rx, R2 and R? they are preferably hydrogen atoms. The numbering conventions for each of the rings is as follows. For substitutions to prrol, nitrogen is position 1, while the first carbon in clockwise rotation (as shown by the molecule in Formula I) is position 2; therefore the carbon to the left of the nitrogen, as shown in Formula I, is the 5-position. For indole substitutions on the right side of the structure deployed in Formula I, the nitrogen is the 1 'position, while the first carbon in the clockwise direction, with the indole as the center, is the 2 'position. The 3 'position forms a bond with the prrol, the next carbon is 3a', while the next 4 carbons are numbered 4 '-7', leaving the last carbon 7a ', which forms a bond with 3a'. the numbering for the indole on the left side is similar, except that the numbering runs in the counterclockwise direction, as shown by the molecule in Formula I, from nitrogen, 1"to carbon 7a". When reference is made to a particular pyrrole, the symbol '' may be excluded, since it is not required as a reference. In another embodiment, the compound has the structure of Formula II: - - Formula II For the compound of Formula II, and other compounds in which one or more indole rings have a substituent of one or more halogen atoms, (e.g., the compounds of Formulas II, IV, VI, VII, VIII, XI, XII, XIV, XV, XV, XVI and XVII), the position (s) of the halogen atom (s) (especially if that halogen atom is a chloride or bromine atom), can be modified, unless the molecular formula is preserved. The compound of Formula II has a molecular formula of C22HX4C13N302, and a molecular weight of 458.73478. In another embodiment, the compound has the structure of Formula III: Formula III The compound of Formula III has a molecular formula of C 22 HX 5 Cl 2 N 3, 2, and a molecular weight of 424.28975. In another embodiment, the compound has the structure of Formula IV: Formula IV The compound of Formula IV has a molecular formula of C20HXXC14N3, and a molecular weight of 435.14277. In another embodiment, the compound has the structure of Formula VI: Formula VI The compound of Formula VI has a molecular formula of C 24 HX 7 C 12 N 302, and a molecular weight of 482.32679. In another embodiment, the compound has the structure of Formula VII: Formula VII The compound of Formula VII has a molecular formula of C2HX3C12N302, and a molecular weight of 410.26266. In another embodiment, the compound has the structure of Formula VIII: Formula VIII The compound of Formula VIII has a molecular formula of C22HX3C12N304, and a molecular weight of 454.27261. In another embodiment, the compound has the structure of Formula IX: Formula IX - The compound of Formula IX has a molecular formula of C2HX9N304, and a molecular weight of 413.43673. In another embodiment, the compound has the structure of Formula X: Formula X The compound of Formula X has a molecular formula of C2oHX5N3, and a molecular weight of 297.36265. In another embodiment, the compound has the structure of Formula XI: Formula XI The compound of Formula XI has a molecular formula of C 24 HX 8 C 1 N 30, and a molecular weight of 447.88176. In another embodiment, the compound has the structure of Formula XII: Formula XII The compound of Formula XII has a molecular formula of C2XHX2C13N302, and a molecular weight of 444.70769. In another embodiment, the compound has the structure of Formula XIII: Formula XIII The compound of Formula XIII has a molecular formula of C23H? 7ClN404, a mass of 448.0938 and a molecular weight of 448.8583. In another embodiment, the compound has the structure of Formula XIV: Formula XIV The compound of Formula XIV has a molecular formula of C2XHX4C12N02, a mass of 424.04938 and a molecular weight of 425.26702. In another embodiment, the compound has the structure of Formula XV: Formula XV The compound of Formula XV has a molecular formula of C22H? 5BrClN302, a mass of 467.00362 and a molecular weight of 468.73022. In another embodiment, the compound has the structure of Formula XVI: Formula XVI The compound of Formula XVI has a molecular formula of C22HX5Br2N302, a mass of 510.95310 and a molecular weight of 513.18152. In another embodiment, the compound has the structure of Formula XVII: Formula XVII The compound of Formula XVII has a molecular formula of C22HX4C12FN302, a mass of 441.04471 and a molecular weight of 442.26938. In another embodiment, the compound has the structure of Formula XVIII: Formula XVIII The compound of Formula XVIII has a molecular formula of C 24 HX 7 F 2 N 304, a mass of 449.11871 and a molecular weight of 449.40641. In another embodiment, the compound has the structure of Formula XIX: Formula XIX The compound of Formula XIX has a molecular formula of C22HX5C1FN302, a mass of 407.08368 and a molecular weight of 407.82462. In another embodiment, the compound has the structure of Formula XX: Formula XX The compound of Formula XX has a molecular formula of C24HX7C1FN304, a mass of 465.08916 and a molecular weight of 465.86070. In another embodiment, the compound has the structure of Formula XXI: Formula XXI The compound of Formula XXI has a molecular formula of C22HX4C12FN302 / a mass of 441.04471 and a molecular weight of 442.26938. In another embodiment, the compound has the structure of Formula XXII: Formula XXII The compound of Formula XXII has a molecular formula of C24HX6C12FN30, and a molecular weight of 500.3055. In another embodiment, the compound has the structure of Formula XXIII: Formula XXIII The compound of Formula XXIII has a molecular formula of C2HX8FN304, and a molecular weight of 431.4159. In another embodiment, the compound has the structure of Formula XXIV: Formula XXIV - The compound of Formula XXIV has a molecular formula of C22HX4C1F2N302, and a molecular weight of 425.8151. In another embodiment, the compound has the structure of Formula XXV: Formula XXV The compound of Formula XXV has a molecular formula of C24HX8FN304, and a molecular weight of 431.4159. In another embodiment, the compound has the structure of Formula XXVI: Formula XXVI The compound of Formula XXVI has a molecular formula of C23H18N404, and a molecular weight of 414.4136. In some embodiments, the compound has the structure of Formula XXVII or a corresponding salt: ..

Formula XXVII In some embodiments, R8 and R9 of Formula XXVII are, for example, ethyl, and n = 2. For example, the compound may have the following structure of Formula XXVII-A: Formula XXVII-A In some embodiments, R8 and R9 of Formula XXVII are, for example, ethyl, and n = 3. For example, the compound may have the following structure of Formula XXVII-B: - - Formula XXVII-B In some embodiments, R8 and R9 of Formula XXVII are, for example, -C (CH2) 2-0- (CH2) 2-, can form a ring with the nitrogen amine, and n = 2. For example, the compound may have the following structure of Formula XXVII-C: Formula XXVII-C In some embodiments, the compound has the structure of Formula XXVIII or a corresponding salt: - Formula XXVIII In some embodiments, R8 and R9 of Formula XXVIII are, for example, ethyl, and n = 2. For example, the compound may have the following structure of Formula XXVIII-A: Formula XXVIII-A In some embodiments, the compound has the structure of Formula XXIX or a corresponding salt: Formula XXIX In some embodiments, R8 and R9 of Formula XXIX may be, for example, ethyl, and n = 2. For example, the compound may have the following structure of Formula XXIX-A: Formula XXIX-A In another embodiment, the compound has the structure of Formula XXX: Formula XXX In another embodiment, the compound has the structure of Formula XXXI: Formula XXXI In some embodiments, R8 and R9 of Formula XXXI are, for example, ethyl and hydrogen, respectively. For example, the compound may have the following structure of Formula XXXI-A: Formula XXXI-A In some embodiments, R8 and R9 of Formula XXXI when taken together are, for example, - (CH2) 2-0- (CH) 2-, and form a ring with the amide nitrogen. For example, the compound may have the following structure of Formula XXXI-B: Formula XXXI-B In another embodiment, the compound has the structure of Formula V: Formula V Certain embodiments also provide pharmaceutically acceptable salts and pro-drug esters of the compound of Formula I, including the compounds of Formulas II-IV, VI-XXI, Formulas XXII-XXVI, Formulas XXVII-XXXI and Formula V, and provide methods for obtaining and purifying such compounds by the methods described herein. The term "pro-drug ester", especially when referring to a pro-drug ester of the compound of Formula I synthesized by the methods described herein, refers to a chemical derivative of the compound that is rapidly transformed in vivo to produce the compound, - for example, by hydrolysis in blood or internal tissues. The term "pro-drug ester" refers to derivatives of the compounds described herein formed by the addition of any of various ester or thioester groups which are hydrolyzed under physiological conditions. Examples of pro-drug ester groups include pivoyloxymethyl, acetoxymethyl, phthalythyl, indanyl, and methoxymethyl, and thioester, as well as other groups such as are known in the art, including a group (5-R-2-oxo-1, 3- dioxolen-4-yl) methyl. Other pro-drugs can be prepared by preparing a corresponding thioester of the compound, for example, reactivating with an appropriate thiol, such as thiophenol, cysteine or derivatives thereof, or propanothiol. Other examples of pro-drug ester groups can be found, for example, T. Higuchi and V. Stella, in "Pro-Drugs as Novel Delivery Systems", Vol. 14, A.C.S. Symposium Series, American Chemical Society (1975); and "Bioreversible Carrier in Drug Design: Theory and Application", edited by E. B. Roche, Pergamon Press: New York, 14-21 (187) (which provides examples of esters useful as prodrugs for compounds containing carboxyl groups). Each of the aforementioned references is incorporated herein by reference in its entirety. The term "pro-drug ester" as used herein, also refers to a chemical derivative of the compound which is rapidly transformed in vivo to produce the compound, for example, by hydrolysis in blood. The term "pharmaceutically acceptable salt", as used herein, and particularly when referring to a pharmaceutically acceptable salt of a compound, including Formula (I) and Formula (I), synthesized by the methods described herein, refers to any pharmaceutically acceptable salt of a compound, and preferably refers to an acid addition salt of a compound. Preferred examples of pharmaceutically acceptable salt are the alkali metal salts (sodium or potassium), the alkaline earth metal salts (calcium and magnesium), or ammonium salts derived from ammonia or from pharmaceutically acceptable organic amines, for example CX alkylamine. C7, cyclohexylamine, triethanolamine, ethylenediamine or tris- (hydroxymethyl) -a -methane. With respect to compounds synthesized by the method of this embodiment which are basic amines, preferred examples of pharmaceutically acceptable salts are acid addition salts of pharmaceutically acceptable inorganic or organic acids, for example, hydrohalic, sulfuric, phosphoric or aliphatic acid or carboxylic acid or aromatic sulphonic, for example acetic, succinic, lactic, malic, tartaric, citric, ascorbic, nicotinic, methanesulfonic, p-toluenesulfonic, or naphthalenesulfonic acid.

- Preferred pharmaceutical compositions described herein include pharmaceutically acceptable prodrug salts and esters of the compound of Formula (I) obtained and purified by the methods described herein. Accordingly, if the manufacture of the pharmaceutical formulations involves an intimate mixture of the pharmaceutical excipients and the active ingredient in its salt form, then it is preferred to use pharmaceutical excipients which are non-basic, ie excipients whether acidic or neutral. It will also be appreciated that the phrase "compounds and compositions comprising the compound" or any similar phrase means encompassing compounds in any form suitable for pharmaceutical delivery, as discussed in greater detail herein. For example, in certain embodiments, the compounds or compositions comprising the same may include a pharmaceutically acceptable salt of the compound. In one embodiment, the compounds can be used to treat microbial diseases. It is understood that the disease broadly covers infectious diseases, and also autoimmune diseases, non-infectious diseases, and chronic conditions. In a preferred embodiment, the disease is caused by a microbe, such as a bacterium. The methods of use may also include the steps of administering a compound or composition comprising the compound to an individual with an infectious disease or cancer. The infectious disease can be, for example, one caused by Bacillus, such as B. anthracis and B. cereus, or one caused by gram-negative bacteria such as E. coli. It could also be caused by S. pneumoniae or S. pyogenes, H. influenzae, S. epidermidis or S. aureus, E. faecalis, E. faecium and the like. The compound or composition can be administered with a pharmaceutically acceptable carrier, diluent, excipient and the like. The term "halogen atom" as used herein, means any of the stable radio atoms in column 7 of the Periodic Table of Elements, i.e., fluorine, chlorine, bromine, or iodine, with fluorine and chlorine being preferred. The term "alkyl" as used herein, means any saturated, unbranched or branched, unsubstituted or substituted hydrocarbon, with Cx-C3 unsubstituted saturated, unsubstituted hydrocarbons being preferred, methyl, ethyl, isobutyl, and tert-butylpropyl and pentyl. Among the substituted saturated hydrocarbons, Cx-Cg saturated mono- and di- and substituted per-halogen hydrocarbons and amino-substituted hydrocarbons are preferred, perfluoromethyl, perchloromethyl, perfluoro-tert-butyl and perchloro-tert-butyl being more preferred.

- The term "substituted" has its ordinary meaning, found in numerous contemporary patents of the related art. See, for example, US Patents. Nos. 6,509,331; 6,506,787; 6,500,825; 5,922,683; 5,886,210; 5,874,443; and 6,350,759; all of which are incorporated herein by reference in their entirety. Specifically, the definition of substituted is as broad as that provided in the U.S. Patent. No. 6,509,331, which defines the term "substituted alkyl" so as to refer to an alkyl group, preferably 1 to 10 carbon atoms, having 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group which consists of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyacylamino, cyano, halogen, hydroxyl, carboxyl, carboxyalkyl, keto, thioke, thiol , thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocycloxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -S02-alkyl, -S02-substituted alkyl, -S0-aryl, and -S02-heteroaryl. The other patents listed above also provide standard definitions for the term "substituted" well understood by those skilled in the art.

- The term "cycloalkyl" refers to any non-aromatic hydrocarbon ring, preferably having five to twelve atoms comprising the ring. The term "acyl" refers to alkyl or aryl groups derived from an oxo acid, with an acetyl group being preferred. The term "alkenyl" as used herein, means any unsaturated hydrocarbon unbranched or branched, substituted or unsubstituted including polyunsaturated hydrocarbons being preferred Cx-C6 unsubstituted hydrocarbons, unbranched, ono-unsaturated and di-unsaturated, and mono-unsaturated substituted di-halogen hydrocarbons being more preferred. In the positions of Rx and R4, a z-isoprenyl residue is particularly preferred for the compound of structure (I). The term "cycloalkenyl" refers to any aromatic hydrocarbon ring, preferably having from five to twelve atoms comprising the ring. The terms "aryl", "substituted aryl", "heteroaryl" and "substituted heteroaryl" as used herein, refer to aromatic hydrocarbon rings, preferably having five, six or seven atoms, and most preferably that They have six atoms that comprise the ring. "Heteroaryl" and "substituted heteroaryl" refer to aromatic hydrocarbon rings in which at least one hetero-atom, eg, oxygen, sulfur, or nitrogen, is in the ring along with at least one carbon atom . The substituted aryl and heteroaryls can be substituted with any substituent, including those described above and those known in the art. The term "alkoxy" refers to any ether unbranched, branched, substituted or unsubstituted, saturated or unsaturated, being preferred Cx-C6 ethers unbranched, saturated, unsubstituted, preferably methoxy, they are also being preferred dimethyl ester , diethyl, methyl-isobutyl, and methyl-tert-butyl. The term "cycloalkoxy" refers to any non-aromatic hydrocarbon ring, preferably having from five to twelve atoms comprising the ring. The term "alkoxycarbonyl" refers to any linear, branched, cyclic, saturated, unsaturated, aliphatic, or aromatic alkoxy linked to a carbonyl group. Examples include methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl group, butoxycarbonyl group, s-butoxycarbonyl, t-butoxycarbonyl group, cyclopentyloxycarbonyl group, cyclohexyloxycarbonyl group, benzyloxycarbonyl group, allyloxycarbonyl group, phenyloxycarbonyl group, pyridyloxycarbonyl group and the like. The term "amide" refers to any compound with the structure "-C0NR2". The R groups (referred to individually as "R8" and "R9") may be the same or different. The R groups can include a hydrogen atom, alkyl Cx-C6 saturated, alkenyl Cx-C6 unsaturated cycloalkyl, cycloalkenyl, hydroxy, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, phenyl, and phenyl substituted. In some embodiments, the "-NR2" comprises a ring. For example, one group R can be - (CH2) - and the other group R can be - (CH2) 2- and the otherwise free ends of the two R groups can be linked together to form a five-membered ring. Similarly, instead of the two groups R being directly linked together, they can be linked through a group, for example R10, to form a 6-membered ring. Rxo can be selected from CH2, NH, O, and S. An example of this is shown in Formula XXI-B. The term, "alkyl amine" or "aminoalkyl" refers to an alkyl group that associates with an amine. Thus, the aminoalkyls can be represented by the formula (CH2) nNR8R9 wherein n can be any integer, for example, from 1 to 6. The groups R (R8 and R9) can be the same or different. The R groups can include a hydrogen atom, saturated Cx-C6 alkyl, unsaturated Cx-C6 alkenyl, cycloalkyl, cycloalkenyl, hydroxy, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, phenyl, and substituted phenyl groups. In some embodiments, as described above, "-NR8R9" comprises a ring. An example of this is shown in Formula XXVII-C. The term "carbohydrate" is known in the art and includes various sugars. Examples include: glucomannan, xanthan gum, pectin, guar, agar, glycosaminoglycans, chitin, cellulose, glucose, starch, amylase, amylopectin, maltose, lactose, sucrose, trehalose, cellobiose, amino sugars, uronic acids, glucitol, glucosamine, glucuronic acid , D-glucose, 3-D-glucoside, aD-glucose, furanose, pyranose, D-sedoheptulose, hexose, D-tagatose, D-fructose, fructose, galactose, mannose, D-allose, D-altrose, D-glucose , D-mannose, D-gulose, D-idosa, D-galactose, D-talose, pentoses, such as D-ribose, D-arabinose, D-xylose, and D-lixose, and etrose, such as, D- Erythrose and D-trerose. The term "sugars" refers to saccharides, such as mono, di or tri saccharides. Various exemplary sugars were previously listed under carbohydrates. The term "asymmetrically substituted" refers to a point of symmetry that goes through the nitrogen group of the pyrrole and through the bond formed between the carbon 3 and the carbon 4 of the prrol group. The real three-dimensional structure of the compound is not considered determinant if the compound is symmetric. Thus, for example, a substitution R6 would be asymmetric if the substitution at position 5 of the pyrrole at position 2 of the pyrrole was not the same. As another example, a compound with different substitutions R3 and R4 of both indole rings would also be asymmetric. The phrase "wherein a ring may include one or more additional hetero-atoms" or such a phrase indicates a substitution in the atoms comprising the structure of the ring itself. Therefore, these may include substitutions of the atoms that create the indole rings or the prrol ring. Unless denoted otherwise, the reference to a "ring" will denote the indole and / or prrol ring. The terms "pure", "purified", "substantially purified" and "isolated" as used herein, refer to the compound of the mode found to be free of other dissimilar compounds with which the compound, if found in its state natural, it would be associated in its natural state. In certain embodiments described as "pure", "purified", "substantially purified" or "isolated" herein, the compound may comprise at least 0.5% to 1%, i% to 5%, 5% to 10%, % to 20%, 20% to 50%, 50% to 70%, 70% to 90%, 90% to 95%, 95% to 99% and 99% to 100%. In some embodiments, the amount of the compound will be at least 50% or 75% of the mass, by weight, of a given sample. In some embodiments, a final product of bis-indole pyrrole can be considered purified if there is more of the final bis-indole pyrrole in a sample than there is of the initial bis-indole pyrrole. Therefore, if there is no initial bis-indole pyrrole present in a sample, in this embodiment, any amount of a bis-indole pyrrole will suffice. A "functional purity" is a measurement of the amount of a particular compound in a sample or product relative to other compounds in a sample, which may adversely impact the function of the compound. Therefore, other components in a sample that do not interfere with the activity of the compound (e.g., water), will not be used to determine the purity of a sample or product. In some embodiments, products created by the methods described herein are contemplated. Therefore, in some modalities, it is not the presence of a molecule with a structure of a given formula that is important, but the process described which results in the creation of a product with the desired properties. Unless explicitly noted, the phrases "compound of Formula #" and "compound #" are interchangeable. The terms "derivative", "variant", or other similar term refer to a compound that is an analogue of the other compound. Certain compounds of Formula (I) can be obtained and purified or can be obtained through semi-synthesis from purified modalities as described herein. Organism Production A microorganism that can be used for the production of bis-indole pyrroles, is a strain isolated from a marine sediment sample collected in Mission Bay, California. The culture (strain NPS012745) was deposited on January 7, 2004 with the American Type Culture Collection (ATCC) in Rockville, MD and assigned the ATCC patent deposit number PTA-5748. The ATCC deposit complies with all the requirements of the Budapest treaty. The culture is also maintained in and is available from the Nereus Pharmaceutical Culture Collection at 10480 Wateridge Circle, San Diego, CA 92121. In addition to the specific microorganism described herein, mutants, such as those produced by the use of mutagen, should be understood. chemical or physical, including X-rays, etc., and organisms whose genetic production has been modified by molecular biology techniques, can also be grown to produce bis-indole pyrrole compounds. Fermentation of strain NPS012745 The production of bis-indole pyrrole compounds of Formulas II, III, IV, VI and XI can be carried out by culturing strain NPS012745 in a suitable nutrient medium under the conditions described herein, preferably under submerged aerobic conditions, until detecting a substantial amount of compounds in the fermentation; harvesting by extraction of the active components of the fermentation broth with a suitable solvent; concentrating the solution containing the desired components; then subjecting the concentrated material to chromatographic separation to isolate the compounds of other metabolites also present in the culture medium. The production of compounds can be achieved at a temperature that leads to satisfactory growth of the organism produced, eg, from 16 degrees C to 40 degrees C, but it is preferable to conduct the fermentation at 22 degrees C to 32 degrees C. The aqueous medium can be incubated during a period of time necessary to complete the production of compounds monitored by high pressure liquid chromatography (HPLC), preferably for a period of about 2 to 10 days, on a rotary shaker operating at about 50 rpm at 300 rpm, preferably at 150 rpm at 250 rpm, for example. The growth of microorganisms can be achieved by the person skilled in the art through the use of the appropriate medium. Broadly, carbon sources include, glucose, fructose, mannose, maltose, galactose, mannitol and glycerol, other sugars and sugar alcohols, starches and other carbohydrates, or carbohydrate derivatives such as dextran, cerelosa, as well as complex nutrients such as oat flour, corn flour, millet, corn, and the like. The exact amount of the carbon source used in the medium will depend in part on the other ingredients in the medium, but an amount of carbohydrate between 0.5 to 25 percent by weight of the medium, for example, can be used satisfactorily. These carbon sources can be used individually or several such carbon sources can be combined in the same medium, for example. Certain carbon sources are preferred as described below. Sources of nitrogen include amino acids such as glycine, arginine, threonine, methionine and the like, ammonium salt, as well as complex sources such as yeast extracts, soaked corn liquors, distilled solubles, soybean meal, soybean meal. cotton, fish meal, peptone and the like. The various nitrogen sources can be used alone or in combination in amounts ranging from 0.5 to 25 percent by weight of the medium, for example. Among the inorganic nutrient salts, which may be incorporated in the culture medium, are the regular salts capable of producing sodium, potassium, magnesium, calcium, phosphate, sulfate, chloride, carbonate ions and the like. Also included are trace metals such as cobalt, manganese, iron, molybdenum, zinc, cadmium, and the like. The following is an exemplary fermentation protocol that can be used to prepare a batch of 10 1 organisms including bis-indole pyrroles of Formulas II, III, IV, VI and XI: 1. Inoculate the initial culture or the frozen culture. in 10 ml of culture medium and incubate at 28 degrees C and 250 rpm for 3 days. 2. Transfer -5 ml of the previous culture in 100 ml of culture medium into a 500 ml flask. Incubate the flasks at 28 degrees C and at 250 rpm on a rotary shaker for 2 days. 3. Inoculate 5 ml of each second culture in 10 500 ml flasks containing 100 ml of culture medium. Incubate these flasks at 28 degrees C and at 250 rpm on a rotary shaker for 2 days. 4. Inoculate 5 ml of each third culture in 100 500 ml flasks containing 100 ml of the production medium. Incubate these flasks at 28 degrees C and 250 rpm on a rotary shaker for 7 days. 5. Shake the culture broth with 500 ml of acetone for 15 minutes and then extract with 10 1 of EtOAc. The extract is dried in vacuo in preparation for isolation of bis-indole pyrroles. The pure compounds of Formulas II, III, IV, VI, and XI can be obtained by HPLC chromatography as described below: Column: ACE 5 C18-HL Dimensions: 15 cm X 21 mm ID Flow rate: 14.5 ml / min Detection : 290 nm Solvent: gradient of 60% MeOH 40% H20 at 100% MeOH (15 min). Fifty mg of the crude extract is dissolved in DMSO (900 μl) and this solution is injected into the HPLC column. This solution is injected using the HPLC chromatography conditions described above and the compounds of interest are eluted in the order shown in Figure 1. The fractions containing the bis-indole pyrroles can be further purified using a semi-preparative HPLC method described below: Column: ACE 5 C18-HL Dimensions: 10 mm X 250 mm ID Flow rate: 3 ml / min Detection: UV DAD Solvent: gradient of 60% MeOH 40% H20 a 100% MeOH (20 min), or isocratic 65% MeOH 35% H20 containing 0.1% ammonium acetate.

The partially purified bis-indole natural pyrrole products of Formulas II, III, IV, VI and XI can be obtained as pure materials using the conditions described above. Directed biosynthesis One embodiment provides new antibiotic compounds, or their pharmaceutically acceptable salts, which are de-chlorinated analogues; brominated; fluorinated; or of azatriptophan of the compounds of formula I produced by biosynthesis directed with the organism producing the compounds of Formula I or their mutants. The fermentation process is completed under aerobic conditions immersed in an aqueous medium containing carbon nutrient and nitrogen for a sufficient time to produce, for example, the new antibiotics of Formulas IX, XV, XV, XVI, XVII, XVII, XXV , XVIII, XIX, XIX ', XX, XXI, XXI', XXIII, XXIV, XIII, XIV, XXVI, and other similar compounds. Formation by base hydrolysis of semisynthetic derivatives: One embodiment provides novel antibiotic compounds, or their pharmaceutically acceptable salts, which are carboxylic acid derivatives of Formula I produced by base hydrolysis of Formula I, wherein one of the substituents is an ester. This process can produce, for example, compounds of Formulas VII, VIII and XII, their salts and other similar compounds. Structural Determination The structure of the compounds purified or otherwise derivatized can be elucidated by various methods, including NMR, MS, and UV. Figures 2A-E provide spectral data of these methods. Figure 2 illustrates the UV spectrum of the compounds in acetonitrile / H20. Figure 2A illustrates the UV spectrum of the compound of Formula III. Figure 2B illustrates the UV spectrum of the compound of Formula II. Figure 2C illustrates the UV spectrum of the compound of Formula VI. Figure 2D illustrates the UV spectrum of the compound of Formula IX. Figure 2E illustrates the UV spectrum of the compound of Formula XII. The aH NMR data for each of these compounds is illustrated in Table i. additionally, Figure 3 illustrates the XH NMR spectrum of several of the various compounds. Figure 3A illustrates the "" H NMR spectrum of the compound of Formula XI in CD2C12, Figure 3B illustrates the XH NMR spectrum of the compound of Formula XIII in DMSO-d6, Figure 3C illustrates the 1H NMR spectrum of the compound of Formula XIV in DMS0-ds Figure 3D illustrates the XH NMR spectrum of the compound of Formula XV in CD2C12 Figure 3E illustrates the "" H NMR spectrum of the compound of Formula XVI in CD2C12. Figure 3F illustrates the spectrum ^? NMR of the compound of Formula XVII in CD2C12. Figure 3G illustrates the aH NMR spectrum of the compound of Formula XVIII in CD2C12. Figure 3H illustrates the spectrum ^? NMR of the compound of formula XX in CD2C12. Figure 31 illustrates the XH NMR spectrum of the compound of Formula XXII in CD2C12 - Figure 3J illustrates the 1H NMR spectrum of the compound of Formula XXIII in CD2C12. Figure 3K illustrates the "" H NMR spectrum of the compound of Formula XXIV in CD2C12, Figure 3L illustrates the 1H NMR spectrum of the compound of Formula XXV in CD2C12, Figure 3M illustrates the x? L NMR spectrum of the compound of Formula XXVI in DMS0-d6 The 13C NMR data for each of the compounds of Formulas II, III, IV, VI, and XII are found in Table 2. Table 1 Assignment ^? NMR - 1 'NH 8.130 1H, br 8.1 1 1H, br 8.144 1H, br 2' '6.791 1H, d, 2.5 6.830 1H, d, .5 6.806 1H, d, 2 5 4 '' 7.472 1H, ddd, 1.9, 0.6, 0.6 7.510 1H, d, 0.6 7.539 1H, s 6 '' 7.077 1H, dd, 8.5, 2.5 7 '' 7.251 1H, dd, 8.5, 0.6 7.4 6 1H, d , 0.6 7. 32 1H,? * values d ^? referred to the internal solvent for CD2C12 at 5,320 ppm * d '' "H values referred to the internal solvent for CD2C12 at 5,320 ppm - Table 2 13C NMR Assignment Table * 13C values referred to the internal solvent for CD2C12 at 53,800 ppm ** The signals can be interchanged due to the lack of HMBC correlations for the assignment. further, by using UV spectrometry and mass spectrometry, the structural assignments can be elucidated for different modalities of the relevant compounds. The following section includes examples of structures of each such data and relevant data for several different bis-indole pyrrole compounds. For the compound of Formula II: Formula II UV spectrometry (acetonitrile / H20)? P 231.292 nm. Mass Spectrometry :, HRESI MS M + Na = 480.0059? Caic C22HX4N302Cl3Na (480.0049) = 1.9 ppm For the compound of Formula III: Formula III UV spectrometry (acetonitrile / H20)? P = 230.290 nm. Mass spectrometry: HRESI MS M + Na = 424.0612? Caic C22H16N302C12 (424.0620) = 0.7 ppm For the compound of Formula IV: Formula IV UV spectrometry (acetonitrile / H20)? P = 239.299 nm. Mass spectrometry: HRESI MS M + Na = 433.9771? Caic C20HX2N3C14 (433.9785) = 3.4 ppm For the compound of Formula VI: Formula VI UV spectrometry (acetonitrile / H20)? Max = 229.262 sh 300. Mass spectrometry: HRESI MS M + H = 482.0657? Caic C24HX8N304C12 (482.0674) = 3.7 ppm For the compound of Formula VII: Formula VII UV spectrometry (acetonitrile / H20)? Max 230,290. Mass spectrometry: HRESI MS M + H 410.0453? Caic C2XHX4N302C12 (410.0463) = 2.4 ppm For the compound of Formula VIII: Formula VIII UV spectrometry (acetonitrile / H20)? Max = 230.265, sh 300. Mass spectrometry: HRESI MS M + H = 454.0355? Caic C22HX4N304C12 (454.0361) = 1.5 ppm For the compound of Formula IX: Formula IX UV spectrometry (acetonitrile / H20)? P = 225.269, sh 321. Mass spectrometry: HRESI MS M + H = 414.1449? Caic C24H20N3O4 (414.1454) = 1.2 ppm For the compound of Formula XI: Formula XI UV spectrometry (acetonitrile / H20, 0.05% formic acid)? Max = 224.266 nm. HRESI MS M + H = 448.1068? Ca? C C24H19N304C1 (448.1064) = 0.7 ppm For the compound of Formula XII: Formula XII UV spectrometry (acetonitrile / H20)? Ma? 231.291. Mass spectrometry: HRESI MS M + H 444.0085? Caic C2XHX3N302C13 (444.0073) = 2.7 ppm For the compound of Formula XIII: - Formula XIII UV spectrometry (acetonitrile / H20)? Max = 230.292 sh 245. Mass spectrometry: HRESI MS M + H = 449.1018? Caic C23HX8N404C1 (449.1017) = 0.3 ppm For the compound of Formula XIV: Formula XIV pag. 46 UV spectrometry (acetonitrile / H20)? Max 229.290. Mass spectrometry: HRESI MS M + H 425.0567 Caic C2XHXSN402C12 (425.2670) = 1.2 ppm For the compound of the Formula XV: Formula XV pag. 46 UV spectrometry (acetonitrile / H20)? Max = 231.292. Mass spectrometry: HRESI MS M + Na = 468.0132? Caic C22HxsN302ClBr (468.0114) = 3.8 ppm In Formula XV, Rxo can be a single bromine or a single chlorine although Rxx will be the other either bromine or chlorine. For example, in one embodiment, Formula XV is that shown in Formula XV: Formula XV For the compound of Formula XVI Formula XVI UV spectrometry (acetonitrile / H20) max 230,290. Mass spectrometry: HRESI MS M + H 511.9616? Caic C22HXsN302Br2 (511.9609) = 1.4 ppm For the compound of Formula XVII: Formula XVII UV spectrometry (acetonitrile / H20)? Max 231.291. Mass spectrometry: HRESI MS M + H 442.0541? Caic C22HX5N302FC12 (442.0525) = 3.5 ppm For the compound of Formula XVIII: Formula XVIII UV spectrometry (acetonitrile / H20)? Max = 224.268, sh 338 Mass spectrometry: HRESI MS M + H 450.1279? Caic C24H18N304F2 (450.1265) = 3.1 ppm For the compound of Formula XIX ': Formula XIX 'UV spectrometry (acetonitrile / H20)? Max = 230.291. Mass spectrometry: HRESI MS M + H = 408.0907? Caic C22H1SN302C1F (408.0915) = 2.1 ppm In Formula XIX ', R12 can be a single fluorine, a single chlorine, both or neither, although Rx3 will be correspondingly a chlorine, a fluorine , none or both.

For example, in one embodiment, Formula XIX 'is that shown in Formula XIX: Formula XIX For the compound of Formula XX: Formula XX UV spectrometry (acetonitrile / H20)? Max = 228.268, sh 340. Mass spectrometry: HRESI MS M + H = 466.0966? Caic C24H18N304C1F (466.0970) = 0.9 ppm For the compound of Formula XXI ': Formula XXI' Spectrometry UV (acetonitrile / H20)? Ma? = 230,291. Mass spectrometry: HRESI MS M + H = 442.0510 ? caic C22HX5N302FC12 (442.0525) = 3.4 ppm In Formula XXI ', R4 can be either two chlorines, one fluorine, all three substituents, or one non-halogen substituent, with RX5 being a fluorine, two chlorines, none, or both , respectively. For example, in one embodiment, Formula XXI 'is that shown in Formula XXI: Formula XXI Additionally, the synthesis of the compound of the Formula XXI can also result in a composition comprising additional substances as well as the substance of Formula XXI '. For the compound of Formula XXII: Formula XXII UV spectrometry (acetonitrile / H20)? Max = 229.262, sh 300 HRESI MS M + H = 500.0588? Ca? C C24H17N304FC12 (500.0580) = 1.5 ppm For the compound of Formula XXIII: Formula XXIII UV spectrometry (acetonitrile / H20)? Max = 223.268, sh 321. HRESI MS M + H = 432.1350? Ca? C C24HX9N304F (432.1360) = 2. 1 ppm For the compound of Formula XXIV: Formula XXIV UV spectrometry (acetonitrile / H20)? Max = 277.290 nm. HRESI MS M + H 426.0819? Calc C22HX5N302F2C12 (426.0821) = 0.3 ppm For the compound of Formula XXV Formula XXV UV spectrometry (acetonitrile / H20)? Max = 224.270, sh 320. HRESI MS M + H = 432.1349? Calc C24Hx9N304F (432.1360) = 2.4 ppm For the compound of Formula XXVI: Formula XXVI UV spectrometry (acetonitrile weight / formic acid 0.05% / H2O weight / formic acid 0.05%)? Max = 223.272. HRESI MS M + H = 415.1402? Ca? C C23HX9N404 (415.1406) = - 1. O ppm The compounds are characterized by the above properties and have structures that can be elucidated using the data described above and in the Examples. Pharmaceutical Compositions In one embodiment, the compounds described herein are used in pharmaceutical compositions. The compounds may optionally and preferably be produced by the methods described herein. The compounds can be used, for example, in pharmaceutical compositions comprising a pharmaceutically acceptable carrier prepared for storage and subsequent administration. The embodiments also refer to a pharmaceutically effective amount of the products and compounds described above in a pharmaceutically acceptable carrier or diluent. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co.

(? .R. Gennaro, 1985), which is incorporated herein by reference in its entirety. Condoms, stabilizers, colorants and even flavoring agents can be provided in the pharmaceutical composition. For example, sodium benzoate, ascorbic acid, and p-hydroxybenzoic acid esters can be added as preservatives. In addition, antioxidants and suspending agents can be used. The bis-indole pyroles and analogous compositions can be formulated and used as tablets, capsules, or elixirs for oral administration; suppositories for rectal administration; sterile solutions, suspensions for injectable administration; patches for transdermal administration, and sub-dermal deposits and the like. The injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Suitable excipients are, for example, water, saline, dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate, cysteine hydrochloride and the like. Furthermore, if desired, the injectable pharmaceutical compositions may contain minor amounts of non-toxic auxiliary substances, such as wetting agents, pH buffering agents and the like. If desired, better absorption preparations (eg, liposomes) can be used. Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water soluble form. Additionally, suspensions of the active compounds can be prepared as appropriate oleaginous suspensions for injection. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or other organic oils such as soybean, grape or almond oils, or synthetic fatty acid esters, such as ethyl oleate or triglycerides or liposomes. Aqueous suspensions for injection may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. Optionally, the suspension may also contain stabilizers or suitable agents that increase the solubility of the compounds to allow the preparation of highly concentrated solutions. Pharmaceutical preparations for oral use can be obtained by combining the active compounds with a solid excipient, optionally by spraying the resulting mixture and processing the granule mixture after adding suitable auxiliaries, if desired, to obtain tablets or pellet cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol.; cellulose preparations such as, for example, corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the crosslinked polyvinyl pyrrolidone, agar or alginic acid or a salt thereof such as sodium alginate. The pellet cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. It can be added to the coatings of tablets or pellets dyes or pigments for identification or to characterize different combinations of active compound doses. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. It can be added to the coatings of tablets or pellets dyes or pigments for identification or to characterize different combinations of active compound doses. Such formulations can be made using methods known in the art (see, for example, US Patents Nos. 5,733,888 (injectable compositions); 5,726,181 (compounds of low solution in water); 5,707,641 (therapeutically active proteins or peptides); 5,667,809 (lipophilic agents); 5,576,012 (polymeric de-solubilization agents); 5,707,615 (anti viral formulations); 5,683,676 (medicaments in particles); 5,654,286 (topical formulations); 5,688,529 (oral suspensions); 5,445,829 (extended release formulations); 5,653,987 (liquid formulations); 5,641,515 (controlled release formulations) and 5,601,845 (spheroidal formulations); all of which are incorporated herein by reference in their entirety. In addition, various pharmaceutical compositions well known in the pharmaceutical art for uses including intraocular, intranasal and intraauricular delivery are described herein. Pharmaceutical formulations include aqueous ophthalmic solutions of the active compounds in water-soluble form, such as ophthalmic drops, or in gel gum (Shedden et al., Clin. Ther., 23 (3): 440-50 (2001)) or hydrogels (Mayer et al., Ophthalmologica, 210 (2): 101-3 (1996)); ophthalmic ointments; ophthalmic suspensions, such as micro particles, small polymer particles containing drugs suspended in a liquid vehicle medium (Joshi, A. 1994 J. Ocul. Pharmacol 10: 29-45), lipid-soluble formulations (Aim et al., Prog. Clin Biol. Res., 312: 447-58 (1989)), and microspheres (Mordenti, Toxicol, Sci. 52 (l): 101-6 (1991)); and eye inserts. All the aforementioned references are incorporated herein by reference in their entirety. Such suitable pharmaceutical formulations are formulated more frequently and preferably to be sterile, isotonic and buffered for stability and comfort. The pharmaceutical compositions may also include drops and sprays frequently prepared to stimulate nasal secretions in many aspects to ensure the maintenance of a normal ciliary action. As described in Remington's Pharmaceutical Sciences (Mack Publishing, 18th edition), which is incorporated herein by reference in its entirety, and well known to those skilled in the art, suitable formulations are more frequently and preferably isotonic, slightly buffered to maintain a pH of 5.5 to 6.5, and more frequently and preferably include appropriate antimicrobial condoms and drug stabilizers. Pharmaceutical formulations for intra-auricular delivery include suspensions and ointments for topical application in the ear. Common solvents for such otic formulations include glycerin and water. When used as an antimicrobial compound, the compound of Formula (I) or the compositions that include Formula (I) can be administered either orally or non-orally. When administered orally, it can be administered in the form of a capsule, tablet, granules, spray, syrup or other such. When administered non-orally, it may be administered as an aqueous suspension, an oil preparation or the like, or as a drip, suppository, ointment, ointment or the like, when administered by injection, subcutaneously, intraperitoneally, intravenously, intramuscularly or the similar. In one embodiment, antimicrobials can be mixed with additional substances to improve their effectiveness. In one embodiment, the antimicrobial is combined with an additional antimicrobial. In another modality, the antimicrobial is combined with a drug or medication that helps a patient taking antimicrobials. Methods of Administration In an alternative embodiment, the chemical compounds described and the pharmaceutical compositions described are administered by a particular method such as an antimicrobial. Such methods include, among others, (a) administration via oral routes, the administration of which includes administration in the form of a capsule, tablet, granules, spray, syrup, or other such; (b) administration through non-oral routes, whose administration includes administration as an aqueous suspension, an oil preparation or the like as a drip, suppository, ointment, ointment or the like; administration by injection subcutaneously, intraperitoneally, intravenously, intramuscularly, intradermally or the like; as well as (c) topical administration, (d) rectal administration, or (e) vaginal administration, as deemed appropriate by those skilled in the art to contact the compound of the present modality with living tissue; and (f) administration through controlled release formulations, depot formulations, and infusion pump delivery. As further examples of such modes of administration and as further description of the modes of administration, various methods are described herein for the administration of the chemical compounds and pharmaceutical compositions described including modes of administration through intraocular, intranasal and intraauricular routes. The pharmaceutically effective amount of the bis-indole pyrrole and analogous compositions, required as a dose, will depend on the route of administration, the type of animal, including human, being treated, and the physical characteristics of the specific animal under consideration. The dose can be designed to achieve a desired effect, but will depend on factors such as weight, diet, concurrent medication and other factors that will be recognized by those skilled in the medical art. In the practice of the modality methods, the products or compositions can be used alone or in combination with each other, or in combination with other agents - therapeutic or diagnostic. These products may be used in vivo, ordinarily in a mammal, preferably in a human, or in vitro. When used in vivo, the products or compositions can be administered to the mammal in a variety of forms, including parenterally, intravenously, subcutaneously, intramuscularly, colonicly, rectally, vaginally, nasally or intraperitoneally, using a variety of dosage forms. Such methods can also be applied to test chemical activity in vivo. As will be clearly apparent to the person skilled in the art, the useful in vivo dose to be administered and the particular mode of administration will vary depending on the age, weight and species of mammal treated, the compounds employed, and the specific use for which these compounds are used. The determination of effective dose levels, i.e., the dose levels necessary to achieve the desired result, can be achieved by one skilled in the art using routine pharmacological methods. Typically, the clinical to human applications of the products are initiated at lower dose levels, increasing the dose level until the desired effect is achieved. Alternatively, acceptable in vitro studies can also be used to establish the useful doses and routes of administration of the compositions identified by the present methods using established pharmacological methods. In studies of non-human animals, applications of potential products are initiated at higher dose levels, decreasing the dose until the desired effect is no longer achieved or until the adverse side effects disappear. The dose can vary widely, depending on the desired effects and the therapeutic indication. Typically, the doses may be between about 10 micrograms / kg and 100 mg / kg body weight, preferably about 100 micrograms / kg and 10 mg / kg body weight. Alternatively, the doses may be based and calculated according to the patient's surface area, as understood by those skilled in the art. The administration is preferably oral on a daily basis or twice daily. The exact formulation, route of administration and dosage can be selected by the individual physician in view of the patient's condition. See, for example, Fingí et al., In The Pharmacological Basis of Therapeutics, 1975, which is incorporated herein by reference in its entirety. It should be noted that the attending physician will know how and when to finalize, interrupt or adjust administration due to toxicity, or organ dysfunction. On the contrary, the attending physician will also know how to adjust the treatment to higher levels if the clinical response is not adequate (avoiding toxicity). The magnitude of a dose administered in the management of the disorder of interest will vary with the severity of the condition being treated and with the route of administration. The severity of the condition, for example, can be evaluated in part, by means of standard forecasting methods. In addition, the dose, and perhaps the frequency of the dose, will also vary according to age, body weight, and the response of the individual patient. A program comparable to the one previously treated in veterinary medicine can be used. Depending on the specific conditions to be treated, such agents can be formulated and administered systemically or locally. A variety of techniques for formulation and administration can be found in Remington's Pharmaceutical Sciences 18th ed. , Mack Publishing Co. , Easton PA (1990), which is incorporated herein by reference in its entirety. Suitable routes of administration may include oral, rectal, transdermal, vaginal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal or intraocular injections. For injection, the modality agents can be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological saline buffer. For such transmucosal administration, appropriate penetrants are used in the formulation to penetrate the barrier. Such penetrants are generally known in the art. The use of pharmaceutically acceptable vehicles for formulating the compounds described herein for the practice of the modality in doses suitable for systemic administration, is within the scope of the modality. With proper vehicle selection and proper manufacturing practice, the compositions described herein, in particular those formulated as solutions, may be administered parenterally, such as by intravenous injection. The compounds can be easily formulated using pharmaceutically acceptable carriers well known in the art in doses suitable for oral administration. Such vehicles allow formulation of the compounds of the modality such as tablets, pills, capsules, liquids, gels, syrups, mixtures, suspensions and the like for oral ingestion by the patient being treated. The agents that are intended to be administered intracellularly can be administered using techniques well known to those of ordinary skill in the art. for example, such agents can be encapsulated in liposomes, then administered as described above. All molecules present in an aqueous solution at the time of liposome formation are incorporated into the aqueous interior. The liposomal content is protected from the external micro environment, and, because the liposomes fuse with the cell membranes, they are efficiently delivered into the cell cytoplasm. Additionally, due to their hydrophobicity, small organic molecules can be administered directly intracellularly. The determination of effective amounts is within the ability of those skilled in the art, especially in light of the detailed description provided herein. In addition to the active ingredients, these pharmaceutical compositions may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries that facilitate the processing of the active compounds into preparations that can be used pharmaceutically. Preparations formulated for oral administration may be in the form of tablets, troches, capsules or solutions. The pharmaceutical compositions can be manufactured in a manner known per se, for example, by conventional mixing, dissolving, granulating, pelletizing, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes.

- The compounds described herein can be evaluated for their efficacy and toxicity using known methods. For example, the toxicology of a particular compound, or of a subset of the compounds, which share certain chemical residues, can be established by determining in vitro toxicity to a cell line, such as a mammalian, and preferably human, cell line. The results of such studies are often predictive of toxicity in animals, such as mammals, or more specifically humans. Alternatively, the toxicity of the particular compounds in an animal model, such as mice, rats, rabbits, dogs or monkeys, can be determined using known methods. The efficacy of a particular compound can be established using various recognized methods, such as in vitro methods, clinical tests in animal models, or in humans. There are in vitro models recognized in the art for almost any kind of condition, including the conditions diminished by the compounds described herein, including, cancer, cardiovascular disease, and various immune dysfunctions, and infectious diseases. Similarly, acceptable animal models can be used to establish the efficacy of chemicals to treat such conditions. By selecting a model to determine efficacy, the skilled artisan can be guided by the state of the art to select a model, dose, and route of administration and appropriate regimen. Of course, clinical trials in humans can also be used to determine the efficacy of a compound in humans. When used as an antimicrobial, the compounds described herein may be administered by both oral and non-oral routes. When administered orally, they can be administered in capsule, tablet, granule, spray or other form. When administered non-orally, they can be administered as an aqueous suspension, an oil preparation or the like or as a drip, suppository, ointment, ointment or the like, when administered by injection, subcutaneously, intraperitoneally, intravenously, intramuscularly, intradermally or the similar. Similar formulations are contemplated in the tank, and the supply in infusion pump. The compositions described herein in pharmaceutical compositions may also comprise a pharmaceutically acceptable carrier. Such compositions can be prepared for storage and for subsequent administration. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A.R. Gennaro, edition 1985). For example, such compositions can be formulated and used as tablets, capsules or solutions for oral administration; suppositories for rectal or vaginal administration; Sterile solutions or suspensions for injectable administration. The injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Suitable excipients include, but are not limited to, saline, dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate, cysteine hydrochloride, and the like. In addition, if desired, the injectable pharmaceutical compositions may contain minor amounts of non-toxic auxiliary substances, such as wetting agents, pH buffering agents, and the like. If desired, absorption enhancing preparations (e.g., liposomes) can be used. The pharmaceutically effective amount of the composition, required as a dose, will depend on the route of administration, the type of animal being treated, and the physical characteristics of the specific animal under consideration. The dose can be designed to achieve a desired effect, but it will depend on factors such as weight, diet, concurrent medication and other factors that will be recognized by experts in medical technology. The products or compositions of the embodiment, as described above, may be used alone or in combination with each other, or in combination with other therapeutic or diagnostic agents. These products can be used in vivo or in vitro. Useful doses and most useful modes of administration will vary depending on the age, weight and animal treated, and the particular compounds employed, and the specific use for which this composition or compositions are employed. The magnitude of a dose in the management or treatment of a particular disorder will vary with the severity of the condition being treated and with the route of administration, and depending on the conditions and severity of the disease, the compositions can be formulated and administered either systemically or locally. A variety of techniques for formulation and administration can be found in Remington's Pharmaceutical Sciences 18th ed., Mack Publishing Co., Easton PA (1990). To formulate the compounds of Formula (I) as an antimicrobial, known surface active agents, excipients, softening agents, suspending agents and pharmaceutically acceptable film-forming agents and coating auxiliaries and the like can be used. Preferably, alcohols, esters, sulfated aliphatic alcohols, and the like can be used as surface active agents; can be used as excipients sucrose, glucose, lactose, starch, cellulose - crystallized, mannitol, light anhydrous silicate, magnesium aluminate, magnesium metasilicate aluminate, synthetic aluminum silicate, calcium carbonate, sodium acid carbonate, calcium hydrogen phosphate, calcium carboxymethyl cellulose and the like; hardened oil softeners and the like can be used as softening agents; suspending agents or lubricants may be coconut oil, olive oil, sesame oil, peanut oil, soy; as suspending agents, cellulose acetate phthalate can be used as a derivative of a carbohydrate such as cellulose or sugar, or methylacetate-methacrylate copolymer as a polyvinyl derivative; and plasticizers such as ester phthalates and the like can be used as suspending agents. In addition to the above preferred ingredients, sweeteners, fragrances, colorants, preservatives, and the like can be added to the administered formulation of the compound produced by the method of the embodiment, particularly when the compound is to be administered orally. The compounds and compositions can be administered orally or non-orally to a human patient in the amount of from about 0.001 mg / kg / day to about 10,000 mg / kg / day of the active ingredient, and more preferably from about 0.1 mg / kg / day to about 100 mg / kg / day of the active ingredient, preferably once a day, or less preferably, about two to about ten times a day. Alternatively, and also preferably, the compound produced by the method of the embodiment may be administered preferably in the amounts determined continuously, for example, by intravenous drip. Thus, for the example of a patient weighing 70 kilograms, the preferred daily dose of the active or anti-infective ingredient would be from about 0.07 mg / day to about 700 gm / day, and more preferably, 7 mg / day to about 7 grams /day. However, as will be understood by those skilled in the art, in certain situations it may be necessary to administer the anti-infective compound (s) of the modality in amounts exceeding or even exceeding by far the dose range previously determined to be effective and effective. Aggressively particularly advanced infections. In the case of using the antimicrobial produced by the modality methods as a biochemical test reagent, the compound produced by the modality methods inhibits the progress of the disease when it is dissolved in an organic solvent or a hydrous organic solvent and applies directly to any of the various cultivated cell systems. Usable organic solvents include, for example, methanol, - methylsulfoxide and the like. For example, the formulation can be a powder, granular or other inhibitor, or a liquid inhibitor prepared using an organic solvent or a hydrous organic solvent. Although the preferred concentration of the compound produced by the method of the modality for use as an antimicrobial, anti-cancer or anti-tumor compound is generally in the range of about 1 to about 100 μg / ml, the most appropriate use amount varies depending on the type of cultured cellular system and the purpose of use, as will be appreciated by persons of ordinary skill in the art, also, in certain applications it may be necessary or preferred for those skilled in the art to use an amount outside the above range. In one embodiment, the method of using a compound of Formula I as an antimicrobial involves administering an effective amount of a bis-indole pyrrole. In a preferred embodiment, the method involves administering the compound represented by Formula II, to a patient in need of an antimicrobial, until effectively reducing the need or more preferably withdrawing it. As will be understood by the person skilled in the art, "need" is not an absolute term and merely implies that the patient can benefit from the treatment of the antimicrobial in use. By "patient" is meant an organism that can benefit from the use of an antimicrobial. For example, any organism with H. influenzae or E. coli can benefit from the application of an antimicrobial that can in turn reduce the amount of microbes present in the patient. In one modality, the health of the patient may not require the administration of an antimicrobial, however, the patient may still obtain some benefit by reducing the level of microbes present in the patient, and therefore need it. In one embodiment, the antimicrobial is effective against one type of microbe, but not against other types; therefore, allowing a high degree of selectivity in the treatment of the patient. In selecting such an antimicrobial, the methods and results described in the Examples may be useful. In an alternative embodiment, the antimicrobial is effective against a broad spectrum of microbes, preferably a broad spectrum of external and more preferably harmful bacteria, to the host organism. Even in another modality, the antimicrobial is effective against all microbes, even those natural to the host. Examples of microbes that may be targets for antimicrobials, include, but are not limited to B. anthracis, B. cereus, E. coli, S. pneumoniae, S. pyogenes, H. influenzae, S. epidermidis, S. aureus, E. faecalis, E. faecium and the like. "Therapeutically effective amount", "pharmaceutically effective amount" or a similar term means that amount of drug or pharmaceutical agent that will result in the biological or medical response sought from a cell, tissue, system, animal or human. In a preferred embodiment, the medical response is sought by an investigator, veterinarian, medical doctor or other physician. "Antimicrobial" refers to a compound that reduces the probability of survival of microbes. In one modality, the probability of survival is determined as a function of an individual microbe; therefore, the antimicrobial will increase the chance of an individual microbe dying. In one modality, the probability of survival is determined as a function of a population of microbes; therefore, the antimicrobial will increase the chances of a decrease in the microbial population. In one embodiment, antimicrobial means antibiotic or another similar term. Such antimicrobials are capable of destroying or suppressing the growth or reproduction of microorganisms, such as bacteria. For example, such antibacterials and other antimicrobials are described in Antibiotics, Chemotherapeutics and Antibacterial Agents for Disease Control (M. Grayson, editor, 1982), and Gale et al., The Molecular Basis of Antibiotic Action 2nd edition (1981) . In another modality, the antimicrobial will not change the likelihood of survival, but it will change the chances that the microbes will be harmful to the host in some way. For example, if the microbe secretes a substance harmful to the host, the antimicrobial can act on the microbe to stop the secretion. In one embodiment, an antimicrobial, while increasing the probability of the microbe dying, is minimally harmful to surrounding non-microbial cells. In an alternative embodiment, it is not important how harmful the antimicrobial is to non-microbial surrounding cells, while reducing the likelihood of survival of the microbe. In one embodiment, a bis-indole pyrrole is considered an effective antimicrobial if the bis-indole pyrrole can influence 10% of the microbes. In a more preferred embodiment, the bis-indole pyrrole is effective if it can influence 10 to 50% of the microbes. In an even more preferred embodiment, bis-indole pyrrole is effective if it can influence 50-80% of the microbes. In an even more preferred embodiment, the bis-indole pyrrole is effective if it can influence 80-95% of the microbes. In an even more preferred embodiment, the bis-indole pyrrole is effective if it can influence 95-99% of the microbes. "Influence" is defined by the mechanism of action of each compound. Therefore, for example, if a compound prevents the reproduction of microbes, then the influence is a measure of prevention of reproduction. Similarly, if a compound destroys microbes, then the influence is a measure of the death of the microbe. Not all the mechanisms of action need to be at the same percentage of effectiveness. In an alternative embodiment, a low percentage of effectiveness may be desirable if the lower degree of effectiveness is diverted by other factors, such as the specificity of the compound, for example. Therefore, a compound that is only 10% effective, for example, but deploys little in the way of harmful side effects to the host or non-harmful microbes, may still be effective. In one embodiment, the compounds described herein are administered simply to remove microbes, and do not need to be administered to a patient. For example, in situations in which microbes may present a problem, such as in food products, the compounds described herein may be administered directly to the products to reduce the risk of microbes in the products. Alternatively, the compounds can be used to reduce the level of microbes present in the surrounding environment, such as on work surfaces. After administering the compounds they can optionally be removed. This may be particularly desirable in situations where work surfaces or food products may come into contact with other surfaces or organisms that could risk being damaged by the compounds. In an alternative embodiment, the compounds can be left in the food products or on the work surfaces to allow more protection. Whether or not this is an option will depend on the relative needs of the situation and the risks associated with the compound, which may in part be determined as described in the following Examples. The following non-limiting examples are intended to describe the preferred embodiments of the methods. Variations in the details of the particular methods employed and in the precise chemical compositions obtained will undoubtedly be appreciated by those skilled in the art. EXAMPLE 1 Production of Compounds of Formulas II, III, IV, VI and XI. Fermentation. Strain NPS012745 was cultured in a 40 ml tube containing 10 ml of vegetative medium of the following per liter of seawater: starch, 10 g; yeast extract, 4 g; and peptone, 2 g. The culture was allowed to incubate for 3 days at 28 degrees C on a rotary shaker operating at 250 rpm. The vegetative culture was mixed with 2 ml of cryoprotective solution consisting of 500 g of glycerol per liter of deionized water. Portions of - - were transferred 1. 5 ml of this mixture to a sterile cryogenic tube (2 ml capacity). The vegetative cultures thus obtained were frozen and stored at -80 degrees C. The seed culture for the production of compounds NPS012745 was prepared by transferring 1.5 ml of the cryopreservative culture to a 40 ml tube containing 10 ml of sterile vegetative medium having the same composition than the previous one. The seed culture was incubated at 28 degrees C for 3 days on a rotary shaker operating at 250 rpm. Five ml of this seed culture was inoculated in a 500 ml flask containing 100 ml of the vegetative medium. The second seed cultures were incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. Five ml of each of the second seed cultures were inoculated in ten 500 ml flasks containing 100 ml of the vegetative medium. The third seed cultures were incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. Five ml of each of the three seed cultures were inoculated into the production medium having the same composition as the vegetative medium. The production culture was incubated at 28 degrees C for 7 days on a rotary shaker operating at 250 rpm. The culture broth was first stirred with 500 ml of acetone for 15 minutes and then extracted with 10 1 of EtOAc and the extract was dried in vacuo. The dried extract was then processed for the recovery of the compounds of Formulas II, IV, VI and XI. Purification. The pure compounds of Formulas II, IV, VI and XI can be obtained by HPLC chromatography as described below: Column: ACE 5 C18-HL Dimensions: 15 cm X 21 mm ID Flow rate: 14.5 ml / min Detection: 290 nm Solvent: gradient of 60% MeOH 40% H20 a 100% MeOH (15 min). Fifty mg of the crude extract is dissolved in DMSO (900 μl) and this solution is injected into the HPLC column. This solution is injected using the HPLC chromatography conditions described above and the compounds of interest are eluted in the order shown in Figure 1. The fractions containing the bis-indole pyrroles can be further purified using a semi-preparative HPLC method described below: Column: ACE 5 C18-HL Dimensions: 10 mm X 250 mm ID Flow rate: 3 ml / min Detection: UV DAD Solvent: gradient of 60% MeOH 40% H20 at 100% MeOH (20 min), or isocratic 65% MeOH 35% H20 containing 0.1% ammonium acetate. The partially purified bis-indole natural pyrrole products of Formulas II, IV, VI and XI can be obtained as pure materials using the conditions described above. The partially purified products have the following spectroscopic characteristics. Compound of Formula II: UV Spectrometry (acetonitrile / H0)? max = 231.292 nm. Mass spectrometry: HRESI MS M + Na = 480.0059? Ca? C C22HX4N302Cl3Na (480.0049) = 1.9 ppm. ^? NMR (CD2C12) see Table 1; 13C NMR (CD2C12) see Table 2. Compound of Formula UV Spectrometry (acetonitrile / H20)? max = 230.290 nm. Mass spectrometry: HRESI MS M + Na = 424.0612? Calc C22HxeN302Cl2 (424.0620) = 0.7 ppm. ^? NMR (CD2C12) see Table 1; 13C NMR (CD2C12) see Table 2. Compound of Formula IV: UV Spectrometry (acetonitrile / H20)? max ~ 239.299. Mass spectrometry: HRESI MS M + Na = 433.9771? Ca? C C20HX2N3C14 (433.9785) = 3.4 ppm. XH NMR (CD2C12) see Table 1; 13C NMR (CD2C12) see Table 2. Compound of Formula VI: UV Spectrometry (acetonitrile / H20)? max = 229.262 sh 300. Mass spectrometry: HRESI MS M + H = 482.0657? ca? c C24HX8N304C12 (482.0674) = 3.7 ppm. XH NMR (CD2C12) see Table 1; 13C NMR (CD2C12) see Table 2. Compound of Formula XI: UV Spectrometry (acetonitrile / H20 0.05% formic acid)? max = 224, 266 nm. HRESI MS M + H = 448. 1068? Ca? C C24HX9N304C1 (448.1064) = 0. 7 ppm. ^? NMR (CD2C12) see Figure 3A. Directed biosynthesis One embodiment refers to new antibiotic compounds, or their pharmaceutically acceptable salts, which are de-chlorinated analogs; brominated; fluorinated; or of azatriptophan of the compounds of formula I produced by biosynthesis directed with the organism producing the compounds of Formula I or their mutants. The fermentation process is completed under aerobic conditions submerged in an aqueous medium containing carbon and nitrogen nutrient for a sufficient time to produce the new antibiotics. EXAMPLE 2 Production of dechlorinated compound NPS012745 of Formula IX Fermentation. The seed culture of the strain NPS012745 was prepared by transferring 1.5 ml of the cryopreservative culture to a 40 ml tube containing 10 ml of sterile vegetative medium consisting of the following per liter of seawater: starch, 10 g; yeast extract, 4 g; and peptone, 2 g. The seed culture was incubated at 28 degrees C for 3 days on a rotary shaker operating at 250 rpm. Five ml of this seed culture was inoculated in a 500 ml flask containing 100 ml of the vegetative medium. The second seed culture was incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. Five ml of each of the second seed cultures were inoculated into a 500 ml flask containing 100 ml of the production medium consisting of the following per liter of deionized water; starch, 10 g; yeast extract, 4 g; and peptone, 2 g. '. The production culture was incubated at 28 degrees C for 7 days on a rotary shaker operating at 250 rpm. The culture broth was extracted with an equal volume of ethyl acetate. The extract was dried in vacuo. The dry extract, containing the dechlorinated compound NPS012745, was then processed for the recovery of the new dechlorinated analog NPS012745 of Formula IX. Purification. The compound of Formula IX was obtained by reverse phase HPLC using Gilson HPLC equipped with a fraction collector 215 using detection by UV absorbance at 214 nm. The crude extract was dissolved in 10 ml of pure DMSO. The aliquots (900 ml) of this solution were injected onto a reverse phase HPLC column (ACE 5u C18-HL, 150 mm long by 21 mm ID) using a solvent gradient of 40% ACN / 60% H20 at 100% ACN for 15 min at a flow rate of 14.5 ml / min.

- The compound of Formula IX eluted at 10.5 min and the fractions containing the pure compound of consecutive runs were drained and dried to yield 5.6 mg of compound, with a purity of > 97%. An additional purification step was used by semi-preparative reverse phase HPLC to eliminate brown discoloration of the sample. The sample (5.6 mg) was dissolved in 100% DMSO at a concentration of 1.0 mg / ml and then 250 ml was loaded onto an HPLC column of dimensions of 9.4 mm i.d. 250 mm long containing an Eclipse XDB-C18 support. The solvent gradient linearly increased from 60% MeOH / 40% H20 to 100% MeOH for 16 minutes at a flow rate of 3 ml / min. The solvent composition was then maintained at 100% MeOH for 3 minutes before returning to the initial solvent mixture. The compound of Formula IX eluted at 9.5 min as a white solid with a final purity of 98.7%. The spectroscopic characteristics of the compound of Formula IX include the following: UV spectrometry (acetonitrile / H20)? Max = 225.269 sh 321. Mass spectrometry: HRESI MS M + H = 414.1449? Ca? C24H20N3O4 (414.1454) = 1.2 ppm and XE NMR (CD2Cl2) see Table 1. EXAMPLE 3 Production of fluorinated NPS012745 compounds Fermentation. The seed culture of the strain - NPS012745 was prepared by transferring 1.5 ml of the cryopreservative culture to a 40 ml tube containing 10 ml of sterile vegetative medium consisting of the following per liter of seawater: starch, 10 g; yeast extract, 4 g; and peptone, 2 g. The seed culture was incubated at 28 degrees C for 3 days on a rotary shaker operating at 250 rpm. Five ml of this seed culture was inoculated in a 500 ml flask containing 100 ml of the vegetative medium. The second seed culture was incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. Five ml of each of the second seed cultures were inoculated into a 500 ml flask containing 100 ml of the production medium consisting of the following per liter of deionized water; starch, 10 g; yeast extract, 4 g; and peptone, 2 g and synthetic sea salt (Instant Ocean, Aquarium Systems), 30 g. The production culture was incubated at 28 degrees C for 7 days on a rotary shaker operating at 250 rpm. 5-fluorotriptophan (25 mg in 8 ml of 0.01% NaOH) or 6-fluorotriptophan (25 mg in 8 ml of 0.01% NaOH) was added to the production culture. The production culture was further incubated at 28 degrees C for 5 days on a rotary shaker operating at 250 rpm. The culture broth was extracted with an equal volume of ethyl acetate. The extract was dried in vacuo. The dry extract, containing the fluorinated NPS012745 compounds, was then processed for recovery - of new fluorinated NPS012745 analogs. Purification of 6-fluoro analogues. In order to isolate the 6-fluoro analogs from the complex crude extract (2.28 g), a reverse phase preparatory HPLC method was used for the initial purification step. The crude extract was dissolved in 36 ml of solvent mixture 5: 4 DMSO / MeOH and 900 ml of aliquots of this solution were injected onto a reverse phase HPLC column (ACE 5u C18-HL, 150 mm length by 21 mm ID ) on a Gilson HPLC system. The solvent gradient started at 50% MeOH / 50% H20 and linearly increased to 80% MeOH / 20% H20 for 15 minutes and then continued to 100% MeOH in 2 minutes at a flow rate of 14.5 ml / min. UV absorbance at 214 nm was used to detect elution of compounds and fractions were collected every 0.5 minutes using the fraction collector 215. The desired compounds were eluted between 10.5 and 17 minutes and these fractions were analyzed using conventional analytical HPLC methods to determine its composition. Further purification of the individual compounds was achieved using an isocratic method of normal phase HPLC developed in a Hitachi HPLC system with preparation pump L-7150. A fraction (91.0 mg) enriched in the compound of Formula XVII was dissolved in EtOAc to a final concentration of 10 mg / ml and 300 ml of - aliquots were loaded onto a normal phase silica column (Phemomenex Luna Si lOu, 100 A; 250 mm long by 21.2 mm id). A 45 minute HPLC method containing an isocratic solvent system of 62% Hex / 38% EtOAc at a flow ratio of 14.5 ml / min was used to separate the desired compound of Formula XVII from the other components. Chromatography was monitored by UV absorbance at 210 nm and the peaks were collected manually. The compound of Formula XVII was eluted after 25 minutes with > 90% purity. Another fraction (32.3 mg) that was enriched in the compound of the Formula XXII was processed using the same method and the parameters described above. The compound of formula XXII was eluted to 38 minutes yielding 5.3 mg of a relatively pure compound. The normal phase isocratic method was transferred to a Gilson HPLC equipped with pump heads with a maximum flow rate of 200 ml / min and a 215 Gilson fraction collector, using UV absorbance at 214 nm. A fraction (8.8 mg) obtained from the partial purification of the crude extract and containing the compound of Formula XXV was dissolved in EtOAc to a final concentration of 1 mg / ml and 350 ml of aliquots were injected onto a normal phase silica column. (Phenomenex Luna Si 10 μ, 100Á, 250 mm long by 21.2 mm id). An isocratic solvent gradient with a solvent mixture of 62% Hex / 38% EtOAc and a flow ratio of 14.5 ml / min was used to isolate the compound of Formula XXV, which was eluted as a relatively pure compound after 27 minutes The UV and NMR spectroscopic data for the products described above are presented below. Compound of Formula XVII: UV spectrometry (acetonitrile / H20)? Max = 231.291. HRESI MS M + H = 442.0541? Caic C22HX5N302FC12 (442.0525) = 3.5 ppm. XH NMR (CD2C12) see Figure 3F; 13C NMR (CD2C12), 161.36 (C6), 154.70, JCF 239 Hz (C6"), 134.52 (C7a '), 134.36 JCF 11 Hz (C7a"), 126.27 (C5'), 124.80 (C5"), 124.12 JCF 15 Hz (C5"), 124.08 (C2"), 122.23 (C6 '), 120.93, 120.93 (superimposed), 120.01, 113.67 JCF 20 Hz (C3a "), 112.48, 110.61 (C3"), 109.91 (C3') , 98.8 JCF 26 Hz (C7 ''), 51.46 (C7) Compound of Formula XXII: UV spectrometry (acetonitrile / H20)? Max = 229.262 sh 300. HRESI MS M + H = 500.0588? Ca? C C24HX7N304FC12 (500.0580 ) = 1.5 ppm XH NMR (CD2C12) see Figure 31. Compound of Formula XXV: UV spectrometry (acetonitrile / H20)? max = 224.270, sh 320. HRESI MS M + H = 432.1349? calc C24HX9N304F (432.1360) = 2.4 ppm. XH NMR (CD2Cl2) see Figure 3L. Purification of 5-fluoro analogs The initial phase of reverse phase purification - used to separate components of the crude extract containing 5-fluoro analogs was identical to that described above for the initial purification of 6-fluoro analogues. The resulting fractions eluting between 10 and 17 minutes were analyzed by HPLC-MS to determine the composition of each fraction. The fractions obtained from the partial purification of the crude extract described above were further purified to obtain pure compounds. One of the fractions contained a mixture of compounds of Formulas XVIII and XXII. An isocratic method of normal phase HPLC using 62% hexane / 38% EtOAc and a flow ratio of 14.5 ml / min was used to separate the two compounds. The fraction (24.8 mg) was dissolved in EtOAc to a final concentration of 6 mg / ml and 350 ml of aliquots were injected onto a normal phase silica column.

(Phenomenex Luna Si 10 μ, 100Á, 250 mm long by 21.2 mm id). The relatively pure compounds of the formulas XXIII and XVIII were eluted after 29 minutes and 35 minutes, respectively. Other fractions obtained from the partial purification of the crude extract were further processed to obtain analogs of Formulas XX, XXI 'and XXIV using the same isocratic method described above for the compounds of Formulas XXIII and XVIII. The compound of Formula XX - - was eluted after 35 minutes with a purity of > 98%. The compound of Formula XXI 'was eluted after 25 minutes; however, the sample appeared to contain approximately 30% of the compound of Formula II. The compound of Formula XXIV was eluted after 26 minutes; this compound was further purified by dissolving in 750 μl of 2: 1 H20 / MeOH (6.2 mg of the compound), loaded onto a C-18 Sep-pak, and eluted with 10 ml of 70% MeOH / 30% H20. The spectroscopic data relating to the above compounds of the various Formulas are presented below. Compound of Formula XVIII: UV spectrometry (acetonitrile / H20)? Max = 224.268, sh 338. HRESI MS M + H = 450.1279? Calc C24HX8N304F2 (450.1265) = 3.1 ppm. XH NMR (CD2C12) Figure 3G. Compound of Formula XX: UV spectrometry (acetonitrile / H20)? max = 228.268, sh 340. HRESI MS M + H = 466.0966? calc C24HX8N304CIF (466.0970) = 0.9 ppm. Compound of Formula XXI ': UV spectrometry (acetonitrile / H20)? Max = 230.291. HRESI MS M + H = 442.0510? Caic C22HX5N302FC12 (442. 0525) = 3. 4 ppm. Computation of Formula XXIII: UV spectrometry (acetonitrile / H20)? Max = 223.268, sh 321. HRESI MS M + H = 432.1350? Cal C24H19N304F (432.1360) = 2.1 ppm. XH NMR (CD2C12) see Figure 3J. Compound of Formula XXIV: UV spectrometry (acetonitrile / H20)? Ma? = 227.290 nm. HRESI MS M + H = 426.0819? Calc C22H? 5N302F2Cl2 (426.0821) = 0.3 ppm. XH NMR (CD2C12) see Figure 3K. EXAMPLE 4 Production of NPS012745 7-azatriptofan compounds Fermentation. The seed culture of strain NPS012745 was prepared by transferring 1.5 ml of the cryopreservative culture to a 40 ml tube containing 10 ml of sterile vegetative medium consisting of the following per liter of seawater: starch, 10 g; yeast extract, 4 g; and peptone, 2 g. The seed culture was incubated at 28 degrees C for 3 days on a rotary shaker operating at 250 rpm. Five ml of this seed culture was inoculated in a 500 ml flask containing 100 ml of the vegetative medium. The second seed culture was incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. Five ml of each of the second seed cultures were inoculated into a 500 ml flask containing 100 ml of the production medium consisting of the following per liter of deionized water; starch, 10 g; yeast extract, 4 g; and peptone, 2 g and synthetic sea salt (Instant Ocean, Aguarium Systems), 30 g. The production culture was incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. 7-azatriptophan (25 mg in 0.15 ml DMSO) was added to the production culture. The production culture was further incubated at 28 degrees C for 5 days on a rotary shaker operating at 250 rpm. The culture broth was extracted with an equal volume of ethyl acetate. The extract was dried in vacuo. The dry extract, containing the compounds of NPS012745 7-azatriptofan, was then processed for the recovery of new analogs NPS012745 7-azatriptofan of Formulas XIII, XIV and XXVI. Purification The initial purification of the crude extract containing 7-azatriptophan analogues was achieved by vacuum liquid chromatography (VLC) on silica gel. The crude extract (lg) was dissolved in dichloromethane (5 ml) and loaded onto a normal phase silica VLC column (25 mm diameter x 70 mm length). The column was dry packed and eluted in a step gradient with 100 ml volumes of the following mobile phases: 1. 30% EtOAc / 70% Hexane 2. 35% EtOAc / 65% Hexane 3. 40% EtOAc / 60 % Hexane 4. 45% EtOAc / 55% Hexane 5. 50% EtOAc / 50% Hexane 6. 55% EtOAc / 45% Hexane 7. 60% EtOAc / 40% Hexane 8. 70% EtOAc / 30% Hexane 9. 80 % EtOAc / 20% Hexane 10. 90% EtOAc / 10% Hexane 11. 100% EtOAc Most of the 7-azatriptophan analogs were eluted in the 10th step of the gradient as a mixture of XIII, XIV and XXVI (17.1 mg mass total). The mixture was further purified by reverse phase preparative semi-HPLC (Eclipse Zorbax XDB C-18, 250 mm x 10 mm id, 5 microns) using a Gilson HPLC equipped with a 215 Gilson fraction collector. The sample was dissolved in 20% DMSO / 80% methanol at a concentration of 1 mg / ml, and 100 ml of aliquots were injected onto the HPLC and eluted with the following mobile phase gradient at a flow rate of 3 ml / min: 50% MeOH / H20 with 0.1% TFA for 100% MeOH for 20 minutes. The purification was monitored by UV detection at 254 nm. The compounds of Formulas XXVI, XIII and XIV were eluted under these conditions. The spectroscopic data of these compounds are presented below. Compound of Formula XIII: UV spectrometry (acetonitrile / H20)? Max = 230.292 sh 245; mass spectrometry: HRESI MS M + H = 449.1018? caic C23H? 8N404Cl (449.1017) = 0.3 ppm. XH NMR (DMSO-d6) see Figure 3B. Compound of Formula XIV: UV spectrometry (acetonitrile / H20)? Max = 229.290; mass spectrometry: HRESI MS M + H = 425.0567? ca? c C2XHX5N402C12 (425.2670) = 1.2 ppm.

XH NMR (DMS0-d6) see Figure 3C. Compound of Formula XXVI: UV spectrometry (acetonitrile weight / formic acid 0.05% / H2O weight / formic acid 0.05%)? Max = 223.272; HRESI MS M + H = 415.1402? Ca? C C23HX9N404 (415.1406) = 1.0 ppm. XH NMR (DMS0-d6) see Figure 3M. Example 5 Production of Brominated Analogs of Formulas XV, XV and XVI Fermentation The seed culture of strain NPS012745 was prepared by transferring 1.5 ml of the cryopreservative culture to a 40 ml tube containing 10 ml of sterile vegetative medium consisting of the following per liter of sea water: starch, 10 g; yeast extract, 4 g; and peptone, 2 g. The seed culture was incubated at 28 degrees C for 3 days on a rotary shaker operating at 250 rpm. This seed culture (5 ml) was inoculated into a 500 ml flask containing 100 ml of the vegetative medium. The second seed culture was incubated at 28 degrees C for 2 days on a rotary shaker operating at 250 rpm. The second seed culture (5 ml) was inoculated into a 500 ml flask containing 100 ml of the production medium consisting of the following per liter of deionized water; glucose, 20 g; L-arginine, 2 g; KH2P04, 1 g; MgSO4-7H20, 1 g; Ammonium sulfate, 1 h; CaCO3, 2 g; and NaBr, 10 g. The production culture was incubated at 28 degrees C for 7 days on a rotary shaker operating at 250 rpm.

- The culture broth was extracted with an equal volume of ethyl acetate and the extract was dried in vacuo. Purification The brominated analogs of Formulas XV, XV and XVI were isolated from the crude extract (376 mg) through two rounds of reverse phase HPLC on a Gilson HPLC equipped with a 215 Gilson fraction collector using UV absorbance detection at 214 nm for both rounds. The crude extract was dissolved in 9 ml of pure DMSO and 500 ml of the sample was injected onto a reverse phase HPLC column (ACE 5u C18-HL, 150 mm length by 21 mm ID) per round. A linear surface gradient of 60% MeOH / 40% H20 at 100% MeOH was used for 22 minutes at a flow rate of 14.5 ml / min to separate the compounds of Formulas XV, XV or XVI almost eluting the compound of the Formula II. Separation of the compounds of Formula XV of XVI required additional reverse phase preparatory HPLC. The sample containing both compounds was dissolved in 1: 1 DMSO / MeOH at a concentration of 1.0 mg / ml and 500 ml was loaded on a reverse phase HPLC column (ACE 5u C18-HL, 150 mm length by 21 mm ID) . An isocratic solvent system consisting of 35% H20 / 65% MeOH was used for 30 minutes at a flow ratio of 14.5 ml / min and the compounds of Formulas XV and XVI were eluted at 18 and 20.5 minutes, respectively. The 2 compounds were co-eluted with the compound of Formula VI under these conditions and the presence of the mixture was detected by XH NMR. It appears that for the compound of Formula XV, the compound of Formula VI was present in 5%. A similar percentage was identified in the compound of Formula XVI. The spectroscopic properties of the products for the synthesis of each of the compounds for the above formulas are presented below. Compound of Formula XV: UV spectrometry (acetonitrile / H20)? Max = 231.292. HRESI MS M + H = 468.0120? Calc C22HX6N302ClBr (468.0114) = 1.2 ppm. XH NMR (CD2Cl2) see Figure 3D. Compound of Formula XVI: UV spectrometry (acetonitrile / H20)? Max = 230.290; HRESI MS M + H = 511.9616? Caic C22Hx6N302Br2 (511.9609) = 1.4 ppm. XH NMR (CD2Cl2) see Figure 3E. EXAMPLE 6 Formation of Semisynthetic Derivatives on the Basis of Hydrolysis Preparation of Hydrolysis Products of Esters VII, VIII, and XII A mixture of the compounds of Formulas II and VI was hydrolyzed to obtain the corresponding carboxylic acids as follows. The solid sample (24 mg) was dissolved in ACN (6 ml) and basified by the addition of a 2N solution of sodium hydroxide (5 ml). This resulted in a two-phase mixture. In order to form a mixable solution, 1 ml of methanol and 5 ml of water were added. The resulting solution was stirred at room temperature for 60 hours, after which the reaction was acidified by the addition of 20 ml of 5% HCl solution. This solution was extracted with EtOAc (40 ml x 3), the combined organic extracts were dried using MgSO 4 and dried in vacuo. A separate sample of the compound of Formula III was hydrolyzed using conditions identical to those described above. The organic extract containing the compounds of Formulas VIII and XII was purified by reverse phase HPLC using an ACE 5U 250 × 10 mm column with elution of the compounds using a gradient of MeOH / H20. Under these conditions, the compound of Formula VIII (the hydrolysis product of the compound of Formula VI) was eluted at 11.5 minutes while the compound of Formula XII was eluted at 16.5 minutes. The compound of Formula VII (the hydrolysis product of the compound of Formula III) was similarly purified and eluted at 15.5 minutes. The spectroscopic data for the above compounds of the particular formulas are described below. Compound of Formula VII: UV spectrometry (acetonitrile / H20)? Max = 230.290. ESI MS M + H = 410.1; HRESI MS M + H = 410.0453? Ca? C C2XHX4N302C12 (410.0463) = 2.4 ppm.

Compound of Formula VIII: UV spectrometry (acetonitrile / H20)? max = 230, 265 sh 300. ESI MS M + H = 453. 8; HRESI MS M + H = 454. 0355? Ca? C C22H? 4N304Cl2 (454 .0361) = 1. 5 ppm. Compound of Formula XII: UV spectrometry (acetonitrile / H20)? Max = 231, 291; HRESI MS M + H = 444. 0085? Ca? C C2XHX3N302C13 (444. 0073) = 2. 7 ppm. XH NMR see Table 1; X3C NMR, see Table 2. Biological Analysis EXAMPLE 7 Antimicrobial Analysis Minimum inhibitory concentrations are determined (MICs) according to the susceptibility test guide of the National Committee for Clinical Laboratory Standards (NCCLS) M7-A5 (Ferraro, M. 2001 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard (NCCLS), National Committee for Clinical Laboratory Standards (NCCLS), Villanova) to quantify the antimicrobial activity of the compounds of the present modality against various pathogenic bacteria. The susceptibility test is carried out by microdilution of the broth in accordance with the National guidelines Committee for Clinical Laboratory Standards (NCCLS). This procedure involves combining the test compounds with a standardized number of cells, incubating at the appropriate temperature and amount of time for each particular organism, and visually rating the concentration at which no growth was apparent in the test wells. The panel includes both drug-sensitive and drug-resistant bacteria, both gram-positive and gram-negative, including S. aureus (both MSSA and MRSA), S. pneumoniae (wild-type and penicillin-resistant), E faecalis sensitive to vancomycin, E. faecium resistant to vancomycin, E. coli, H. influenzae and P. aeruginosa. The susceptibility test was performed by microdilution of the broth according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). The antimicrobial data for the compounds of Formulas II, III, IV, VI, VII, VIII, IX, XII, XIII, XIV, XV, XV, XVI, XVII, XVIII, XXI ', XXII, XXIII, XXIV and XXV are shown in Tables 3m 4 and 5. Table 5 displays MIC values in microorganisms per ml of bis-indole pyrrole compounds against E. coli imp.

Table 3 MIC Organism (μg / ml Compound Compound Compound Compound Formula of Formula III Formula IV Formula VI S. aureus - MSSA 1.8 0.8 1.1 S. aureus - MRSA 1.5 S. epidermidis - ATCC 700578 S. epidermidis ATCC 700582 S. pneumoniae - 24 20 24 sensitive to penicillin S. pneumoniae - 24 20 20 resistant to penicillin? faecalis - Vans 1.5 2.5 E. faecium - Vanr E. coli - imp 16 > 32 coli - ATCC 25922 > 32 > 32 > 32 > 32 H. influenzae - ATCC 12 48766 H. influenzae -ATCC 16 49247 \ All data reported as averages of 2 experiments except when indicated (*) or when the two values differ by > 2 times In the latter case, both values are reported separately. * Data reported as the result of a single experiment. ** Contains approximately 30% of the compound of Formula II Many of the compounds of the above formulas were potent against Staphylococci and Enterococci both drug-sensitive and drug-resistant, with very good activity against Haemophilus influenzae and an isolate of Escherichia coli, indicating a potent broad-spectrum antibiotic. As can be seen from the above data, it appears that halogenation is beneficial for antimicrobial activity. The data also indicate that the presence of chlorine is beneficial for antimicrobial activity. Additionally, it seems that bromine substitution can be tolerated in these bis-indole pyrroles to produce still highly effective antimicrobials. EXAMPLE 8 Bactericity Bactericity is achieved using time-kill kinetics (Hoellman, DB et al., 1998 Antimicrob Agents Chemother, 42: 857) in susceptible organisms, preferably, but not limited to: B. anthracis, S. aureus, S. pneumoniae, E. faecalis, H. influenzae, E. coli. EXAMPLE 9 Synergy or Antagonism of the Drug The synergy or antagonism of the drug with current antimicrobial therapies (ciprofloxacin, doxycycline, ampicillin, chloramphenicol, norfloxacin, clindamycin, and vancomycin) is examined through the verification table (Eliopoulos, G. M. & amp;; C. B. Wennerten 2002 Antimicrob. Agents Chemother. 46: 1319) or techniques of destruction by time. EXAMPLE 10 Resistance to the innate or acquired drug Resistance to the innate or acquired drug is evaluated by determining the frequencies of spontaneous resistance - (Adrián, P. V. et al., 2000 Antimicrob Agents Chemother. 44: 3101) and the resistance acquired to the long-term serial passage of S. aureus in concentrations of the sub-MIC compound.

(Choe, C. H. et al., 2000 Antimicrob Agents Chemother, 44: 1766). The compounds of the present embodiment show little or no emergence of resistance (spontaneous resistance frequency <1 x 10-8 or 10"9 <2 dilution shift in MIC over 22 serial steps at sub-lethal drug concentrations). EXAMPLE 11 Evaluation of the maximum tolerated dose (BAT) Acute BAT studies are carried out in test mice with test concentrations ranging from 1 mg / kg to as high as can be achieved, not exceeding 50 mg / kg. The compound will be introduced according to the route of administration of the microbial model in single doses.These screening studies will start with 5-10 mice per dose group, amounting to twice the previous concentration in the surviving mice The highest concentration at which> 75% of mice survive without observable damage can be considered BAT. ics EXAMPLE 12 Formulation Administered Intravenously, by Drip, Injection or the Like To vials containing 5 g of glucose powder, aseptically add 10 mg of a compound synthesized by the method of the modality and sealed. After being charged with nitrogen, helium or other inert gas, the vials are stored in a cool place. Before use, the content is dissolved in ethanol and added to 100 ml of a 0.85% physiological salt water solution. The resulting solution is administered as a method to inhibit the growth of a cancerous tumor in a human diagnosed with such a tumor at between about 10 ml / day to about 1000 ml / day, intravenously, by drip, or through a subcutaneous injection or intraperitoneal, as deemed appropriate by those of ordinary skill in the art. EXAMPLE 13 Formulation for Oral Administration or the Like A mixture obtained by thoroughly mixing 1 g of a compound obtained and purified by the method of the embodiment, 98 g of lactose and 1 g of hydroxypropyl cellulose in granules is formed by any conventional method. The granules are dried completely and screened to obtain a granulated preparation suitable for packing in bottles or by thermal sealing. The resulting granular preparations are administered orally at between about 100 ml / day to about 1000 ml / day, depending on the symptoms, as judged appropriate by those of ordinary skill in the art to treat cancerous tumors in humans. EXAMPLE 14 Preparation of Compounds of Formulas XXVII, XXVIII and XXIX from Compound of Formula II The compound of Formula II can be derivatised with various aminoalkyl halides in the presence of a base such as K2C03, Cs2C03 or NaH to produce various compounds of the general formulas XXVII, XXVIII or XXIX. The substitution may occur in one or more of the nitrogens of Formula II. The mixtures can be separated chromatographically to obtain pure compounds.

Formula II Formulas XXVII Formula XXVIII Formula XXIX EXAMPLE 15 Preparation of Compounds of Formula XXXI from Compound of Formula II The amide derivatives of the compound of Formula II can be prepared by hydrolysis of the methyl ester to produce the carboxylic acid of Formula XII, which then it is followed by peptide coupling to form the corresponding amide of Formula XXXI.

Formula II Formula XXXI EXAMPLE 16 - - Preparation of the Compound of Formula XXX from Compound of Formula II The compound of Formula II can be derivatized with various sugars (with all hydroxyl groups protected, some protected or unprotected) at low temperatures to produce various sugar derivatives, by example, the compound of Formula XXX. Substitution may occur in one or more of the nitrogens of Formula II with or without preference. The mixtures can be separated chromatographically to obtain pure compounds.

Formula II Formula XXX EXAMPLE 17 General Synthetic Method for Preparing Compounds of the Formula II, III, VII, XII, XV, XVI, XVII, XIX, XXI, XXIV and V The Formulas II, III, VII, XII, XV, XVI, XVII, XIX, XXI, XXIV and V can be synthesized by known coupling reactions such as Stelle, Suziki and Negishi coupling reactions in bromopyrrole with several halogenated indole building blocks. Scheme I, illustrated in Figure 4, is the general method using Negishi coupling reactions. The compound of Formula V can be synthesized using 3-bromo-5,6-dichloroindole as the building block in Scheme I. NBS is N-bromosuccinimide, TIPS is triisopropylsilyl, PhLi is phenyl lithium, THF is tetrahydrofuran, PPh3 is triphenylphosphine and TBAF is tetrabutylammonium fluoride. The examples described above are only mentioned to assist in the understanding of the modalities. Therefore, those skilled in the art will appreciate that the methods can provide derivatives of compounds. The person skilled in the art will readily appreciate that the present invention is well adapted to realize the objectives and obtain the ends and advantages mentioned, as well as those inherent to it. The methods and methods described herein are presently representative of the preferred embodiments, and are exemplary and are not intended as limitations on the scope of the invention. Changes to it and other uses encompassed within the essence of the invention will be presented to those skilled in the art. It will be readily apparent to one skilled in the art that various substitutions and modifications may be made to the embodiments described herein without departing from the scope and spirit of the invention.

All patents and publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. All patents and publications are incorporated herein by reference as if it were indicated that each individual publication is specifically and individually incorporated by reference. The invention described illustratively herein may be practiced properly in the absence of any element or elements, whose limitation or limitations are not specifically described herein. The terms and expressions used are used as terms of description and not limitation, and there is no intention that in the use of such terms and expressions the exclusion of equivalents of the displayed and described characteristics of their portions is indicated. It is recognized that various modifications are possible within the scope of the invention. Therefore, it should be understood that while the present invention has been specifically described by the preferred embodiments and optional features, modifications and variations of the present concepts may be selected by those skilled in the art, and that such modifications and variations are considered to be within the scope of the embodiments of the invention.

Claims (48)

1. CLAIMS 1. A compound having a structure of Formula I, and pharmaceutically acceptable salts and prodrug esters thereof: Formula I wherein a ring may include one or more additional heteroatoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; and wherein each of Rx, R2 and R5 is selected separately from the group consisting of hydrogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, C2-C4 alkenyl unsaturated, or C2-C2 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, halogenated alkyl including polyhalogenated alkyl, and some combination thereof; wherein each five R3 and every five R4 represent substituent (s) on an indole ring at the position (s) 2-, 4-, 5-, 6-, or 7- and each of the five R3 and each of the five R's are selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, C2-C2 alkenyl unsaturated, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, halogenated alkyl including polyhalogenated alkyl, and some combination thereof; wherein R6 represents substituent (s) on a pyrrole ring at the (2-) or 5- position (s), and each of the two R6's are selected separately from the group consisting of hydrogen atom, halogen, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, unsaturated C2-C24 alkenyl, or C-C24 alkynyl, acyl, acyloxy, ester, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, halogenated alkyl including polyhalogenated alkyl, and some combination thereof; with the proviso that if all R3 and R are either hydrogen or hydroxyl, R6 in the 5- position and Rg in the 2- position are not identical esters or carboxylic acids.
2. 2. A compound having a structure of Formula I, and its pharmaceutically acceptable prodrug salts and esters: Formula I wherein a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; and wherein each of Rx, R2 and R5 is selected separately from the group consisting of hydrogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C2 alkyl, C-C24 alkenyl unsaturated, or C2-C2 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, sugar, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, CO-0-R7, carbonyl-CCO-R7, - (CH2) n-COOR7, -CO- (CH2) n-COOR7, aminoalkyl (- (CH2) n-NR8R9) , and halogenated alkyl including polyhalogenated alkyl, wherein n is an integer from 1 to 6, wherein each of R7, R8 and R9 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C-C2 alkyl, unsaturated C-C4 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl , alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a ring of 5 members, a 6-member ring or combination thereof; wherein each five R3 and every five R4 represents substituent (s) on an indole ring at position (s) 2-, 4-, 5-, 6- or 7- and each of the five R3 and each of the five R4 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C2 alkyl, unsaturated C2-C4 alkenyl or C2-C2, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonilacilo, amino, aminocarbonyl, aminocarboiloxi, nitro, azido, phenyl, hydroxy, alkylthio, arylthio , oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl; wherein each two Rs represents substituent (s) on a pyrrole ring at (2-) or 5- position, and each of the two Rs is selected separately from the group consisting of hydrogen atom, halogen atom, variants, mono-substituted poly-substituted or unsubstituted residues of the following: alkyl Cx-C24 saturated, unsaturated C2-C24, or C2-C2, acyl, acyloxy, amide (-CO-NR8Rg), alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonilacilo, amino, aminocarbonyl, aminocarboiloxi, nitro, azido, phenyl, hydroxy, ester, alkoxycarbonyl, aryloxycarbonyl, CO-0-R7, carbonyl- CCO-R7, - (CH2) n-COOR7, -CO- (CH2) n-C00R7, alkylthio, arylthio, oxysulfonyl, carboxy, cyano and halogenated alkyl including polyhalogenated alkyl; with the proviso that R6 in position 5 and g in position 2- are not identical if all R3 and R are either hydrogen or hydroxyl and with the additional proviso that if there is 1) an alkyl group in R5 and if 2) R6 in position 2- and in position 5 is either hydrogen or oxygen, then R3 and R4 are not symmetrical.
3. 3. A compound having a structure of Formula I, and its pharmaceutically acceptable prodrug salts and esters: Formula I wherein a ring may include one or more additional heteroatoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; wherein each of Rx, R2 and R5 is selected separately from the group consisting of hydrogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, unsaturated C2-C2 alkenyl , or C2-C2 alkynyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, acyl, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, carbohydrate, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio , arylthio, oxysulfonyl, carboxy, cyano, -CO-0-R ?, carbonyl-CCO-R7, - (CH2) n-COOR7, -C0- (CH2) n-COOR7, - (CH2) n-NR8R9), and halogenated alkyl including polyhalogenated alkyl, wherein n is an integer between 1 and 6; wherein each of R7, R8 and Rg is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, alkenyl C2-C24 unsaturated, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy , alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof; wherein the five R3 and the five R4 represent substituent (s) on an indole ring at position (s) 2-, 4-, 5-, 6- or 7-, where each of the five R3 and each of the five R4 is selected separately from the group consisting of hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, C2- alkenyl C24 unsaturated, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio , arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, - wherein each R6 represents substituent (s) on a pyrrole ring at (2) or 5- position, and each of the two R6 is selected separately from the group consisting of H atom hydrogen, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, -CO-NR8R9, alkyloxycarbonyloxy , aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, - CO-0- R7, carbonyl -CCO-R7, - (CH2) n-COOR7, -CO- (CH2) n-COOR7, - (CH2) n-NR8Rg, ester, alkoxycarbonyl, aryloxycarbonyl, and halogenated alkyl including polyhalogenated alkyl; with the proviso that R6 in position 5 and R6 in position 2- are not identical, except that if there is an alkylamine in Rx or R2, then there is at least one non-hydrogen substitution in R6, or there are at least 3 halogens in the combination of R3 and R; and the ring atoms are not modified.
4. 4. The compound of Claim 1, 2 or 3 wherein at least two of the five R3 are hydrogen atoms and at least two of the R4 are hydrogen atoms.
5. 5. The compound of Claim 1, 2 or 3 wherein at least one of the five R3 is a halogen atom and the indole rings do not include additional hetero atoms, but include the indole nitrogen.
6. 6. The compound of Claim 5 wherein at least one of the five R3 is a halogen atom and at least one of the five R4 is a halogen atom.
7. 7. The compound of Claim 1, 2 or 3 wherein at least two of the five R3 is a halogen atom.
8. 8. The compound of Claim 1, 2 or 3 wherein at least one of the five R3 is a chloride atom.
9. 9. The compound of Claim 8 wherein one of the two R6 is an alkoxycarbonyl, one of the Rs is a hydrogen atom, at least one of the five R3 is a chloride atom, and Rx, R2 and R5 are each one hydrogen atoms.
10. 10. The compound of Claim 1, 2 or 3 wherein one of the two positions in R6 is an alkoxycarbonyl.
11. 11. The compound of Claim 10 wherein R6 is a methoxy carbonyl.
12. The compound of Claim 2 having the structure selected from the group consisting of the structures of Formulas II, III, IV, V, VI, VII, VIII, XI, XII, XIII, XIV, XV, XV, XVI , XVII, XVIII, XIX, XIX ', XX, XXI', XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVII-A, XXVII-B, XXVII-C, XXVIII, XXVIII-A, XXIX, XXIX -A, XXX, XXXI, XXXI-A, and XXXI-B and their pharmaceutically acceptable prodrug salts and esters.
13. The compound of Claim 12 wherein the compound has the structure of Formula II, and its pharmaceutically acceptable prodrug salts and esters: Formula II
14. 14. The compound of Claim 1, 2 or 3 wherein at least two of the ten R3 and R4 are halogen atoms.
15. 15. The compound of Claim 1, 2 or 3 wherein at least three of the ten R3 and R4 are halogen atoms.
16. 16. The compound of Claim 1, 2 or 3 wherein at least two of the ten R3 and R4 are chlorine atoms.
17. 17. The compound of Claim 1, 2 or 3 wherein at least three of the ten R3 and R4 are chlorine atoms.
18. 18. The compound of Claim 1, 2 or 3 wherein at least two of the ten R3 and R4 are bromine atoms.
19. 19. The compound of Claim 1, 2 or 3 wherein at least three of the ten R3 and R4 are bromine atoms.
20. 20. A pharmaceutical composition comprising a compound of Claim 1, 2, 3 or 12.
21. The pharmaceutical composition of Claim 20, further comprising an antimicrobial agent.
22. 22. The pharmaceutical composition of the Claim 21 in a solid unit dosage form.
23. 23. The pharmaceutical composition of Claim 21, comprising the compound of Claim 13.
24. 24. A method for treating a microbial infection comprising the administration of a compound having a structure of Formula I, and its salts and esters of pharmaceutically acceptable prodrugs: - Formula I wherein a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; and wherein each of Rx, R2, R3, five R4, one R5 and two Rs is independently selected from the group consisting of a hydrogen atom, a halogen, a sugar, an aminoalkyl, mono-substituted, poly-substituted or unsubstituted of the following residues: saturated Cx-C24 alkyl, unsaturated C2-C24 alkenyl, or C2-C2 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl , amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, -CO-O-R7, carbonyl-CC0-R7, -CO-NR8R9, - (CH2) n-C00R7, -CO- (CH2) n-C00R7, - (CH2) n-NR8R9), ester, alkoxycarbonyl, aryloxycarbonyl, wherein n is an integer from 1 to 6; - - wherein each of R7, R8 and Rg is selected separately from the group consisting of a hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: CX-C24 alkyl saturated, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof.
25. 25. The method of Claim 24, wherein at least one of the Rx substitutions, R2, five R3, five R4, R5 and two R6 are asymmetric.
26. 26. The method of Claim 24, wherein the two substitutions R5 are asymmetric.
27. 27. The method of Claim 24, wherein the five substitutions R and the five R3 are asymmetric.
28. The method of Claim 24, wherein at least five R3 are a halogen atom, and at least one R is a halogen atom, and the indole rings do not include additional hetero-atoms, but include indole nitrogen .
29. 29. The method of Claim 24, wherein R8 is - (CH2) 2- and Rg is - (CH2) 2-, wherein R8 and R9 are directly connected together in order to form a five-membered ring.
30. 30. The method of Claim 29, wherein R8 is - (CH2) 2- and Rg is - (CH2) 2- where R8 and R9 are connected to each other through Rx0 so as to form a ring of six members, wherein Rx0 is selected from the group consisting of CH2, NH, 0 and S.
31. 31. The method of Claim 28, wherein one of the two R6 is an alkoxycarbonyl, one of the Rg is a hydrogen atom. , at least one of the five R3 is a chloride atom, and Rx, R2 and R5 are each hydrogen atoms.
32. 32. The method of Claim 31, wherein the alkoxycarbonyl is a methoxycarbonyl.
33. The method of Claim 24, further comprising the steps of: identifying a subject that would benefit from the administration of an antimicrobial agent, - carrying out the method on the subject.
34. 34. The method of Claim 24, wherein the microbial infection is an infection of at least one gram positive bacterium.
35. 35. The method of Claim 24, wherein the microbial infection is an infection of at least E. faecalis-Y axis.
36. 36. The method of Claim 24, wherein the microbial infection is an infection of at least H. influenzae.
37. 37. A method for treating a microbial infection comprising administering a compound having a structure selected from the group consisting of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XV, XVI, XVII, XVIII, XIX, XIX ', XX, XXI, XXI', XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVII-A, XXVII-B, XXVII-C, XXVIII, XXVIII-A, XXIX, XXIX-A, XXX, XXXI, XXXI-A, and XXXI-B and V, and 1) a pharmaceutically acceptable salt or 2) pro-drug ester thereof.
38. 38. The method of Claim 37, wherein the compound has a structure selected from the group consisting of Formula II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XV, XVI, XVII, XVIII, XIX, XIX ', XX, XXI,' XXI ', XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVII-A, XXVII-B, XXVII-C, XXVIII, XXVIII -A, XXIX, XXIX-A, XXX, XXXI, XXXI-A, and XXXI-B.
39. 39. A method for making the compound of claim 1, 2 or 3 comprising the steps of: culturing the strain NPS012745 in a culture; and recovering the compound of formula I from the culture.
40. 40. The method of Claim 39, further comprising the step of isolating a single pyrrole analogue of bis-indole.
41. 41. The method of Claim 40, wherein the single compound is the compound of claim 12.
42. 42. The method of Claim 40, wherein the single compound is the compound of claim 13.
43. 43. The use of a compound having the structure of Formula I in the manufacture of a medicament for treating a microbial infection. Formula I wherein a ring may include one or more additional heteroatoms, "such as nitrogen, sulfur or oxygen, and may include a non-nitrogen hetero atom, such as sulfur or oxygen, instead of nitrogen (s) in the Formula I; and wherein each of Rx, an R2 five R3, five R4, one R5 and two R6 is independently selected from the group consisting of a hydrogen atom, a sugar, an aminoalkyl, mono-substituted, poly-substituted variants or unsubstituted of the following residues: saturated Cx-C2 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, -C0-0-R7, carbonyl-CCO-R7, -CO-NR8R9 , - (CH2) n-C00R7, -CO- (CH2) n-COOR7, - (CH2) n- RsRg, ester, alkoxycarbonyl, aryloxycarbonyl, wherein n is an integer from 1 to 6; wherein each of R7, R8 and Rg is selected separately from the group consisting of a hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C24 alkyl, unsaturated C2-C2 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof.
44. 44. The use of Claim 43, wherein at least one of the substitutions Rx, R2, five R3, five R4, one R5 and two Rg are asymmetric.
45. 45. The use of Claim 43, wherein the two substitutions Rg are asymmetric.
46. 46. The use of Claim 43, wherein R8 is - (CH2) 2- and R9 is - (CH2) 2-, wherein R8 and R9 are directly connected together in order to form a five-membered ring.
47. 47. The use of Claim 43, wherein R8 is - (CH2) 2- and R9 is - (CH2) 2-, wherein R8 and R are connected to each other via Rxo in order to form a ring of six members, wherein R10 is selected from the group consisting of CH2, NH, O, and S.
48. 48. A compound having the structure of Formula I as a medicament. Formula I wherein a ring may include one or more additional hetero atoms, such as nitrogen, sulfur or oxygen; and may include a non-nitrogen hetero atom, such as sulfur or oxygen, in place of nitrogen (s) in Formula I; and wherein each of Rx, R2, R3, five R4, one R5 and two Rg is independently selected from the group consisting of a hydrogen atom, a sugar, an aminoalkyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated Cx-C2 alkyl, unsaturated C2-C24 alkenyl, or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino , aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, -CO-0-R7, carbonyl-CCO-R7, -C0-NR8R9, - ( CH2) n-COOR7, -CO- (CH2) n-COOR7, - (CH2) n-NR8R9, ester, alkoxycarbonyl, aryloxycarbonyl, wherein n is an integer from 1 to 6; wherein each of R7, R8 and Rg is selected separately from the group consisting of a hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C? -C2 alkyl unsaturated C2-C4 alkenyl, or C2-C24 alkynyl / acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl , hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5 membered ring, a 6 membered ring or combination thereof.