KR101435638B1 - A novel hispidin-type compound having enoyl-ACP reductase inhibition and antibacterial activity - Google Patents

Abstract

The present invention relates to an antimicrobial composition comprising a novel hydropinic compound represented by the formula (1), a compound represented by the formula (1) or (2) as an active ingredient, a composition for inhibiting the enylidialdehyde activity, And a method for producing the compound. The compounds of the present invention strongly inhibit the activity of Fab I and Fab K enzymes and thus have strong antimicrobial activity against pathogenic microorganisms and antibiotic resistant bacteria. Especially, they are useful for the treatment of infectious diseases caused by super bacteria by exhibiting antimicrobial activity against MRSA There is an effect that can be used.

Description

[0001] The present invention relates to a novel heptidine-based compound having an antioxidative activity and an antimicrobial activity, and a novel herpidine-type compound having an enol-ACP reductase inhibitory and antibacterial activity.

The present invention relates to an antimicrobial composition comprising a novel hydropinic compound represented by the formula (1), a compound represented by the formula (1) or (2) as an active ingredient, a composition for inhibiting the enylidialdehyde activity, To a process for preparing said compound.

In general, direct or indirect damages caused by pathogenic microorganisms cause economic, environmental and medical problems. There are many problems in the whole society, such as the loss due to corruption during the process of food distribution in the food industry, the harmfulness and environmental pollution caused by the use of excessive chemical insecticide in agricultural industry and the appearance of antibiotic resistant strains due to misuse of antibiotics. I have to. Although reasonable antibiotic therapy in the treatment of infectious diseases is an important factor in determining the prognosis of patients, the selection of effective antibiotics is becoming more difficult due to the emergence of the above-mentioned antibiotic resistant strains.

For example, since methicillin-resistant S. aureus (MRSA), which is only treated by vancomycin, the last known treatment for Staphylococcus aureus, the most common cause of human infection, has been in question since the 1970s, Vancomycin resistant Enterococcus (VRE) was first found in Europe in 1988 and vancomycin intermediate-resistant S. pneumoniae in Japan, USA, France, and Korea in the late 1990s. aureus, and VISA). Furthermore, vancomycin-resistant Staphylococcus aureus (VRSA), which is highly resistant to vancomycin, has been reported for the first time in the world by the Centers for Disease Control in 2002, and the spread of so-called "superbacteria" This is getting very high. As a result, the problem of antibiotic resistance emerges as a global crisis, and the development of a new concept of antibiotics is urgently required.

On the other hand, as a result of the microbiological genome research of the hospital, which was started in the mid 1990s, a new antibiotic target has been discovered and the possibility of developing a new concept of antibiotic has been opened. Enoyl-ACP reductase, one of the new antibiotic targets identified and validated using microbial genomic information, has been shown to be responsible for the growth of microorganisms, which is responsible for the end of the elongation phase of the fatty acid synthesis cycle As an essential enzyme, it is present in both Gram-positive and negative bacteria and has attracted attention as a new antibiotic target because it has a very low homology with humans. In particular, it has been reaffirmed as an action point of antibiotics development as it has been revealed as an action target of a bactericide triclosan and an isoniazid treatment of tuberculosis, the mechanism of which is unknown.

Enoyl reductase enzymes include three isoforms such as Fab I, Fab K, and Fab L, and include Staphylococcus aureus, E. coli, and the like. Fab I is commonly present in most major pathogenic bacteria and only Fab K is present in S. pneumoniae.

Therefore, the new Fab I inhibitor is promising as a novel therapeutic agent that can treat existing antibiotic resistant bacteria. In addition, new Fab K inhibitors are promising as a treatment for S. pneumoniae.

Accordingly, the present inventors have made intensive efforts to develop Fab I and Fab K inhibitors from natural products such as microorganisms and plants. As a result, it has been found that a novel felinstin compound isolated from Phellinus linteus strain 08090-29 strongly inhibits Fab I and Fab K And has antimicrobial activity against resistant microorganisms. Thus, the present invention has been completed. Further, the present inventors confirmed that the histidine compound strongly inhibits Fab I and Fab K and exhibits antimicrobial activity against resistant bacteria, thus completing the present invention.

An object of the present invention is to provide an antimicrobial composition comprising a compound represented by the general formula (1) or (2), an isomer thereof, a derivative thereof or a pharmaceutically acceptable salt thereof.

Another object of the present invention is to provide a composition for inhibiting the activity of the compound of formula (I) or (II).

Another object of the present invention is to provide a quasi-drug composition for antimicrobial use comprising the compound represented by the general formula (1) or (2) as an active ingredient.

It is a further object of the present invention to provide a process for the preparation of said compounds.

Another object of the present invention is to provide a compound represented by the general formula (1).

In order to achieve the above object, in one aspect, the present invention provides an antimicrobial composition comprising a compound represented by the following general formula (1) or (2), an isomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof.

[Formula 1: pelin statin]

[Chemical Formula 2: Hispidine]

The compounds of the present invention include pelmistatin or histidine, as well as isomers, derivatives or pharmaceutically acceptable salts thereof. The above pelvistatin was newly developed by the present inventors as a histidine compound.

In the present invention, an 'isomer' means a compound having the same chemical formula but not the same. Examples of such an isomer include structural isomers, geometric isomers, optical isomers and geometric isomers. Stereoisomers are compounds having the same chemical structure but different in terms of the arrangement of atoms or groups in space, and optical isomers (enantiomers) means two stereoisomers of a compound having mutually non-overlapping enantiomers, An isomer means a stereoisomer having two or more asymmetric centers and whose molecules are not mirror images of each other.

In the present invention, "derivative" means a compound obtained by substituting part of the structure of a pelustactin or a histidine compound with another atom or atomic group, and "pharmaceutically acceptable salt" means a compound that is relatively non- Means salt.

The compounds of the present invention have excellent Fab I or Fab K inhibitory activity. The term "Fab I" or "Fab K" in the present invention means the isosteric structure of the enoyleiductase, which is an enzyme currently attracting attention as an antibiotic target. The compound of the present invention effectively inhibits the Fab I or Fab K It can be used as an antibacterial substance.

In one embodiment of the present invention, the enzyme inhibitory activity of pelustactin against Fab I of Staphylococcus aureus, which is a major pathogen, was measured. As a result, the IC ₅₀ of pelustactin was 6 μM and the Fab I activity was strongly Respectively. In addition, it was confirmed that the IC ₅₀ of pelustactin against Fab K of Streptococcus pneumoniae, a causative organism of pneumonia, was 5.8 μM, which strongly inhibited Fab K activity (Example 3 and Table 2).

In addition, in one embodiment of the present invention, the inhibitory effect of histidine on Fab I of Staphylococcus aureus, which is a major pathogen, was measured. As a result, the IC ₅₀ of the histidine was 12.6 μM and the Fab I activity Which is a strong inhibitor. In addition, it was confirmed that the IC ₅₀ of the histidine against Fab K of Streptococcus pneumoniae causing pneumonia was 6.4 μM, which strongly inhibited Fab K activity (Example 3 and Table 2). These results support that the compound of the present invention can be used as an antimicrobial composition.

The compound of the present invention can be synthesized according to a method commonly used in the art, and can also be obtained as a natural compound produced from a strain. The compound of the present invention can be preferably produced from Phellinus linteus strain, more preferably from Phellinus linteus strain 08090-29. In the present invention, the term "phenyllus linteus" means a mushroom strain, and the inventors of the present invention have firstly isolated the pelvistatin of the formula (1) from the mushroom strain and found that the First.

In another aspect, the present invention provides a method for treating an infectious disease caused by a pathogenic microorganism or resistant bacterium, comprising the step of administering the antimicrobial composition of the present invention to a subject suffering from an infectious disease caused by a pathogenic microorganism or resistant bacteria.

In the present invention, the term "treatment" means any action that improves or alleviates a symptom caused by an infectious disease caused by a pathogenic microorganism or resistant microorganism by administering a pharmaceutical composition. In the present invention, the term " Refers to all animals including humans who have developed or are capable of developing an infectious disease caused by resistant microorganisms. By administering the antimicrobial composition of the present invention to an individual, the disease can be effectively treated.

In the present invention, the pathogenic microorganisms are all microorganisms that invade the living body of a plant or animal to cause parasitic disease or cause harm, and include bacteria, yeasts and fungi of gram-positive and gram-negative bacteria, Rutaceae, Staphylococcus epidermis, Bacillus subtilis, Streptococcus pneumoniae, or Candida albicans.

In the present invention, the resistant microorganism means that the bacterium exhibits resistance to antibiotics as a result of continuous use of the drug to treat or prevent any disease and its complications, or any bacterial disorder and its complications. Examples of such antibiotics include cephalosporins, quinolones and fluoroquinolones, penicillins, beta lactamase inhibitors, carbepenem, monobactam, macrolide and lincomamine, glycopeptides, rifampin, oxazolidinone, tetracycline, aminoglyco And antibiotics resistant to the above-mentioned antibiotics are also resistant to persistent disease, preferably MRSA (methicillin-resistant Staphylococcus aureus) or QRSA (Staphylococcus aureus) Quinolone-resistant Staphylococcus aureus).

In one embodiment of the present invention, the antimicrobial activity of pelustactin against Staphylococcus aureus, MRSA, and Streptococcus pneumoniae was measured, and as a result, the MIC of each strain of pelustactin was 128 쨉 g / Ml, indicating strong antibacterial activity (Example 4 and Table 3).

In addition, in one embodiment of the present invention, the antimicrobial activity of histidine against Staphylococcus aureus, MRSA and Streptococcus pneumoniae was measured, and as a result, the MIC for each strain of the histidine was all 64 / / ml, indicating strong antibacterial activity (Example 4 and Table 3). Therefore, the antimicrobial composition of the present invention can be effectively used for the prevention or treatment of infectious diseases caused by pathogenic microorganisms or resistant bacteria.

The antimicrobial composition of the present invention may contain not only the compound of the present invention, but also at least one known active ingredient having antimicrobial activity against pathogenic bacteria.

In addition, the antimicrobial composition of the present invention may further comprise a pharmaceutically acceptable carrier.

The term "pharmaceutically acceptable carrier " in the present invention means a liquid or solid filler that is involved in carrying or transporting any subject composition or ingredient from one organ or part of the body to another organ, Refers to a pharmaceutically acceptable material, composition or vehicle, such as a diluent, excipient, solvent or encapsulating material, wherein the composition of the present invention further comprises a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredient described above for administration . Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

The antimicrobial composition of the present invention may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like oral preparation, external preparation, suppository or sterilized injection solution according to a conventional method Can be used. In detail, when formulating, it can be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like. Such a solid preparation can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc., with the compound of formula (I). In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of liquid formulations for oral use include suspensions, solutions, emulsions, syrups and the like, but are not limited thereto. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, Preservatives, and the like. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

In addition, the composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may be determined depending on the condition and weight of the patient, The type of administration, the route of administration, and the period of time, but can be appropriately selected by those skilled in the art. If necessary, it may be administered once or several times a day, and may be used alone or in combination with methods using surgery, hormone therapy, drug therapy and biological response modifiers for the prevention or treatment of pathogenic bacteria and resistant bacteria .

In another aspect, the present invention provides a composition for inhibiting the activity of an enoyleoidase activity, which comprises a compound represented by the above formula (1) or (2).

In the present invention, the enoyl-ACP reductase is converted to an enoyl-acyl carrier protein (ACP) reductase at the final stage of four reactions involved in each cycle of fatty acid biosynthesis of the bacteria Means a bacterial enzyme that is believed to function as an enzyme.

The enzyme is widely distributed in bacteria and plants, and is a protein enzyme necessary for synthesizing lipid constituting a bacterial biomembrane. There are three isoforms of Fab I, Fab K and Fab L, Fab I is commonly found in pathogenic bacteria such as Staphylococcus aureus, methicillin-resistant staphylococci and quinolone-resistant staphylococci, and Fab K is known to exist mainly in pneumococcal strains.

Preferably, the enyliductase may be Fab I or Fab K, and in one embodiment of the present invention, the compound represented by Formula 1 or Formula 2 has an inhibitory activity against Fab I and Fab K (Example 3 and Table 2).

In another aspect, the present invention provides a quasi-drug composition for antimicrobial use comprising the compound represented by the above formula (1) or (2) as an active ingredient. That is, the present invention provides a quasi-drug composition for the purpose of preventing or improving an infectious disease caused by pathogenic microorganisms or resistant bacteria.

The quasi-drug composition of the present invention can be used in combination with other quasi-drugs or quasi-drugs, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).

The quasi-drug composition may be disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.

In another embodiment, there is provided a method for producing a recombinant vector comprising the steps of: 1) culturing a strain of phenyllus linteus or a mutant thereof; 2) extracting the culture broth and the mycelium of the strain obtained in the step 1) with an organic solvent and extracting with ethyl acetate; And 3) performing chromatography on the ethyl acetate extract obtained in the step 2) to produce the compound of the present invention.

The above step 1) may include a mutant strain (natural mutant or artificial mutant strain) derived from the strain as well as a strain newly produced by the genetic engineering method, as well as the Pseudomonas lentus strain.

In addition, the Phenyllus linteus strain may preferably be a Phenyllus lentheus strain 08090-29.

The cultivation of the Pseudomonas sp. Strain or its mutant strain is carried out in a culture medium containing a nutrient source to which conventional microorganisms can be used. As a nutrient source, a known nutrient source which is conventionally used for the cultivation of fungi is used. For example, the carbon source may be glucose, starch syrup, dextrin, starch, molasses, animal oil, vegetable oil, etc. The nitrogen sources may include wheat bran, soybean meal, wheat, malt, cottonseed oil, Extract, ammonium sulfate, sodium nitrate, urea, and the like. If necessary, it is very effective to add sodium chloride, potassium, magnesium, cobalt, chlorine, phosphoric acid, sulfuric acid and other inorganic salts promoting ion production. As the culture method, it is possible to cultivate shaking or stationary culture under aerobic conditions.

The incubation temperature may be slightly different depending on the conditions when culturing under the above conditions, but it is usually suitable to cultivate at 20 to 37 ° C, and in most cases, cultivation is carried out at 26 to 30 ° C. In addition, the culturing period was the most when the pelvistatin compound of the present invention was produced when cultured for 7 days to 10 days in both the shaking culture and the stationary culture.

The step 2) is a step of extracting the culture broth and mycelia of the Phenyllus lentheus strain or its mutant strain, and the pelvistatin compound is present in the mycelium as well as the culture broth of the strain. Therefore, an organic solvent such as acetone was added to the culture broth and the mycelium of the strain, and the active ingredient was extracted from the culture broth and mycelium. The acetone was evaporated under reduced pressure, and the solvent was extracted with ethyl acetate. The ethyl acetate solvent layer was concentrated under reduced pressure to remove ethyl acetate do.

The step 3) is a step of separating the compound of the present invention. Purification and separation of the compound can be carried out without any limitation in the methods commonly used in the art. If necessary, the kind of the medium, the culture conditions, It is obvious that the yield and the yield can be controlled. In one embodiment of the present invention, the compound of the present invention is prepared by chromatographing an ethyl acetate extract in the following manner illustratively.

The ethyl acetate concentrate obtained in the above step 2 was subjected to silica gel column chromatography using chloroform: methanol 20: 1 to 1: 1, and the obtained active fraction was concentrated under reduced pressure to obtain an oily crude active ingredient. And purified by Sephadex ODS column chromatography. Finally, ODS TLC was performed on the active fraction under a solvent condition of methanol: water = 60: 40, ODS TLC was conducted again under acetonitrile: water = 30: 70 containing 0.1% TFA to obtain two pure compounds, Pelustatin and histidine were obtained (Example 2).

In another embodiment, the present invention provides a pelvistatin compound represented by the general formula (1).

Phellinstatin is a novel compound obtained by culturing Phenyllus lentheus strain 08090-29, obtained as a yellow powder, having a molecular formula of C ₃₉ H ₂₇ O ₁₅ , and having a molecular weight of 734.

The compounds of the present invention strongly inhibit the activity of Fab I and Fab K enzymes and thus have strong antimicrobial activity against pathogenic microorganisms and antibiotic resistant bacteria. Especially, they exhibit strong antimicrobial activity against MRSA, . ≪ / RTI >

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagram showing the chemical structure of pelustatin according to the present invention. FIG.
2 is a view showing the chemical structure of the histidine according to the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the following examples are illustrative of the present invention and are not intended to limit the scope of the present invention.

< Example  1> Phellinus linteus  Culture of 08090-29 strain

Phellinus linteus 08090-29, purchased from the National Institute of Agricultural Science and Technology (RDA), was cultivated in a medium containing 2% glucose, 0.5% polypeptone, 0.2% yeast extract, 0.1% KH ₂ PO ₄ , 0.05% MgSO ₄ .7H ₂ O was used after adjusting the pH to 5.6 to 5.8 before sterilization. 100 ml of the Erlenmeyer flask containing 20 ml of the seed medium was sterilized at 121 ° C for 20 minutes and then plated at a slope of the Phellinus linteus strain 08090-29 at a temperature of 28 ° C for 3 days. And was used as a tea seed culture. The cells were then transferred to a 500 ml Erlenmeyer flask 48 μl containing sterile medium containing 2% glucose, 0.5% polypeptone, 0.2% yeast extract, 0.1% KH ₂ PO ₄ , 0.05% MgSO ₄ .7H ₂ O ) Were inoculated with the seed culture and cultured at 28 DEG C for 7 to 10 days with shaking.

< Example  2> Isolation and purification of the compound of the present invention

The culture solution and the acetone extract of the mycelium cultured in Example 1 were subjected to solvent extraction three times with ethyl acetate. The thus-obtained ethyl acetate solvent layer containing the active ingredient was concentrated under reduced pressure to remove ethyl acetate, and then subjected to silica gel column chromatography using chloroform: methanol in a solvent of 20: 1 - 1: 1. The active fraction thus obtained was concentrated under reduced pressure to obtain an oily crude active ingredient, which was purified by Sephadex ODS column chromatography using methanol as a solvent. Finally, the active fraction was subjected to ODS TLC under a solvent condition of methanol: water = 60: 40, ODS TLC was performed again under the conditions of acetonitrile: water = 30: 70 containing 0.1% TFA, &Lt; / RTI &gt;

The physicochemical properties of pelustin and histidine isolated from the Phellinus linteus strain 08090-29 were as follows.

Compound 1: Pelin statin

1) Appearance of substance: yellow powder;

2) Molecular weight: 734;

3) High resolution ESI-MS:

Experimental value m / z 733.1196 (MH) ^- (C ₁₈ H ₁₇ O ₉ ), calculated 733.1199;

4) Molecular formula: C ₃₉ H ₂₇ O ₁₅ ;

5) Ultraviolet absorption spectrum [UV (MeOH)? Max (log?)]: 202 (4.37), 284 (3.62), 372 (3.73) nm;

6) IR spectrum: 3432, 2924, 1635, 1500, 1251 cm ^-1 ;

7) Polarizability: [a] D = 5.7 [deg.] (C0.14, MeOH);

8) Nuclear magnetic resonance (NMR) data: ¹ H and ¹³ C NMR data using methanol (CD ₃ OD-d ₄ ) as a solvent are shown in Table 1 below.

9) Chemical formula

Compound: Hispidine

1) Appearance of substance: yellow powder;

2) Molecular weight: 246;

3) Molecular formula: C ₁₃ H ₁₀ O _5;

4) Nuclear magnetic resonance (NMR) absorption spectrum: ¹ H data using methanol (CD ₃ OD-d ₄ ) as a solvent is as follows.

D, 2.19, H-10), 6.78 (1H, s, H-5), 6.58 (1H, d, 8.1, H-14), 6.94

5) The chemical structural formula

< Example  3> Pelin statin and Hispidine  Compound Fab  I and Fab  K inhibiting activity

In order to confirm the Fab I inhibitory activity of the compound according to the present invention, an enzyme activity measurement experiment as described below was performed.

For the enzymatic activity measurement, the method of Ward et al. (See Biochemistry 38, 12514 (1999)) was modified and used. Fab I derived from Staphylococcus aureus produced by recombinant technology was used. The activity measurements were performed in 50 mM sodium phosphate buffer (pH 7.5) and 400 [mu] M trans-2-octenoyl N-acetylcysteamine thioester, NADPH nicotinamide adenine dinucleotide) 200 μM and 150 nM Fab I were used. After incubation at room temperature for 60 minutes, the absorbance of NADPH was measured at 340 nm using a UV-spectrometer. The pelvistatin and the histidine prepared in Example 2 were dissolved in a dimethylsulfoxide (DMSO) solvent to be added within 2% of the total reaction solution to evaluate the enzyme inhibition ability. The enzyme inhibitory activity is expressed as a percentage of the disappearance of NADH in the presence of the test compound relative to the degree of disappearance of NADH in the absence of the test compound, and the concentration of each test compound inhibiting 50% of the enzyme activity was determined by IC ₅₀ . The results are shown in Table 2.

Also, the method of Zheng et al. (J. Antibiotics 59 (12): 808-812, 2006) was used for measuring the Fab K activity. Fab K enzyme derived from Pseudomonas aeruginosa produced by recombinant technology was used. The activity measurements were performed in 50 mM sodium phosphate buffer (pH 6.5), using 50 μM trans-2-octenoyl N-acetylcysteamine thioester and 200 μM NADH as substrate and 150 nM Fab K Respectively. After incubation at room temperature for 60 minutes, the absorbance of NADH was measured at 340 nm using a UV-spectrometer. The results are shown in Table 2.

compound IC ₅₀ (μM) S. aureus Fab  I S. pneumoniae Fab  K Pelin statin 6 5.8 Hispidine 12.6 6.4

As shown in Table 2, IC ₅₀ for Fab I of pelustatin and the histidine compound showed excellent Fab I inhibitory activity as 6 μM and 12.6 μM, respectively. In addition, the IC _{50 values} of pelustatin and the histidine compound for Fab K were 5.8 μM and 6.4 μM, respectively, indicating excellent Fab K inhibitory activity.

< Example  4> Pelin statin and Hispidine  Antibacterial activity of compounds

In order to confirm the antimicrobial activity of the pelustatin and the histidine compound according to the present invention, the following experiment was conducted.

The test strains were cultured in MHB (Mueller Hinton broth) and antimicrobial activity was measured by broth microdilution. The test bacteria that had been cultured overnight were diluted to 2 x 100,000 / ml, and then 100 μl / well was dispensed into each well of a 96-well plate. The compound was gradually diluted 2-fold from a concentration of up to 128 μg / ml Respectively. The compound was diluted in DMSO (dimethylsulphoside) and the concentration was adjusted to 1/100. After culturing for 20 hours, the OD value was measured at 650 nm to investigate the growth of bacteria. The minimum concentration of the compound completely inhibiting the growth of the bacteria was determined by MIC. The results are shown in Table 3 below.

compound MIC  (占 퐂 / ml) S. aureus MRSA S. pneumoniae Pelin statin 128 128 128 Hispidine 64 64 64

As shown in Table 3, the pelvistatin compound of the present invention is effective against Staphylococcus aureus, a major pathogen, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (128 [mu] g / ml MIC). In addition, the histidine compound of the present invention also showed excellent antimicrobial activity against Staphylococcus aureus, MRSA and Streptococcus pneumoniae resistant to antibiotics (64 μg / ml MIC).

Claims (11)

A composition for antimicrobial use comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.
[Chemical Formula 1]

The composition of claim 1, wherein the compound is produced from Phellinus linteus strain 08090-29.
The composition of claim 1, wherein the composition is selected from the group consisting of Staphylococus aureus, Bacillus subtilis, Staphylococcus epidermis, methicillin-resistant Staphylococcus aureus, Wherein the composition exhibits an antimicrobial activity against at least one bacterium selected from the group consisting of Staphylococcus aureus (MRSA), Quinolone-resistant Staphylococcus aureus (QRSA), and Streptococcus pneumoniae. .
The composition of claim 1, wherein said compound has Fab I or Fab K inhibitory activity.
2. The composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier.
delete delete delete A quasi-drug composition for antimicrobial use comprising a compound represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]

1) culturing a Phellinus linteus strain or a mutant thereof;
2) extracting the culture broth and the mycelium of the strain obtained in the step 1) with an organic solvent and extracting with ethyl acetate; And
3) The method of producing a compound of Chemical Formula 1, comprising the step of performing chromatography on the ethyl acetate extract obtained in the step 2) to obtain a compound of Chemical Formula 1.
[Chemical Formula 1]

A compound represented by the following formula (1).
[Chemical Formula 1]

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