MXPA02002422A - Compositions and therapeutic methods involving isoflavones and analogues thereof - Google Patents

Abstract

Isoflavone compounds are described and recommended as therapeutic agents. Exemplified and preferred compounds are (a). Indications show compounds have good competitive binding to estrogen receptors. This is exemplified.

Description

, Ris and íe so:? independently hydrogen, hydroxy, 0R9, OC (0) R? o, OS (C) R? o, CHO, C (0) R? o, COOH, CO2R10, CONR3R4, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamiro, dialkylamino, nitro or halo, provided that when Ri is hydroxy, or OC (0) RA, where RA is alkyl or an amino acid, and R2 is hydrogen, hydroxy, ORB where RB is an amino acid or C (0) RA where R? is as previously defined, and is hydrogen, then Y is not 4-hydroxyphenyl or 4-alkylphenyl; when Ri is hydroxy, or OC (0) RA where RA is alkyl or an amino acid, and R2 is hydrogen, hydroxy, ORB where RB is an amino acid or C (0) RA where RA is as previously defined, and Y is 4 -hydroxyphenyl or 4-alkylphenyl, then W is not hydrogen; when Ri is hydroxy, or FC (0) R4 where R4 is alkyl or an amino acid, and Y is 4-hydroxyphenyl or 4-alkylphenyl, and W is hydrogen, then hypertension; benign prosthetic hypertrophy; all forms of cancer, including breast cancer; uterine cancer; ovarian cancer; Testicular cancer; cancer of the large intestine; dometrial cancer; prosthetic cancer; uterine cancer; atheroescle: osis; Alzheimer disease; inflammatory diseases including inflammatory bowel disease, ulcerative colitis, Crohn's disease; rheumatic diseases, including rheumatoid arthritis; acne; baldness including male palsy baldness (hereditary alopecia); psoriasis; diseases associated with oxidative stress, including cancer; myocardial infarction; attacks; art :: itis; damage to the skin induced by sunlight or cataracts. Therefore, according to another aspect of the present invention, there is provided a method for the treatment, prophylaxis, relief, defense against, and / or prevention of the opioid syndrome including: hot flashes, anxiety, depression, mood swings, non-sweating, pain in the head, and urinary incontinence; osteoporosis; premenstrual syndrome, including fluid retention, cyclic mastalgia, and dysmenorrhea; Reynaud's syndrome; Reynaud's phenomenon; Buerger's disease; coronary artery spasms; migraine headaches; hypertension; Benign Drosthetic hypertrophy; all forms of cancer, including breast cancer; Cancer uterine; ovarian cancer; Testicular cancer; cancer of the large intestine; endometrial cancer; prosthetic cancer; uterine cancer; atherosclerosis; Alzheimer disease; inflammatory diseases including inflammatory bowel disease, ulcerative colitis, Crohn's disease; rheumatic diseases, including rheumatoid arthritis; acne; baldness, including male palsy baldness (alopecia heredit.aria); psoriasis; diseases associated with oxidative stress, including cancer; myocardial infarction; attacks; arthritis; Skin damage induced by sunlight or cataracts (hereinafter referred to by convenience as "therapeutic indications") which comprises, administering to a subject, a therapeutically effective amount of one or more compounds of formulas I and II as defined above. Yet another aspect of the present invention is the use of the compounds of formulas I and II for the manufacture of a medicament for the treatment, alleviation, defense against, prophylaxis and / or prevention of one or more of the therapeutic indications. Yet another aspect of the present invention is the use of one or more compounds of the formulas I and II in the treatment. relief, defense against, prophylaxis and / or prevention of one or more of the therapeutic indications.

And another aspect of the present invention comprises an agent for the treatment, prophylaxis, treatment, defense against and / or treatment of the therapeutic indications, which comprises one or more compounds of the formulas I and II either alone or in association with one or more carriers or excipients A further aspect of the invention is a therapeutic composition, which comprises one or more compounds of the formulas E and II, in association with one or more carriers and / or pharmaceutical excipients. Yet another aspect of the present invention is a beverage or food product, which contains one or more compounds of the formulas I and II. Another aspect of the present invention is a microbial culture, or a food product that contains one or more microbial strains, whose microorganisms produce one or more compounds of the formulas I and II. Another aspect of the present invention is a microbial culture or a food product that contains one or more microbial strains, whose microorganisms produce one or more compounds of the formulas I and II. Yet another aspect of the present invention relates to one or more microorganisms, which produce one or more compounds eg formulas I and II. Preferably, the microorganism is a culture. purified, which can be mixed and / or administered with or more than other cultures which produce the compounds of formula I and II. Through this specification the following claims, unless otherwise required by the text, the word "comprises", and variations such as "understood" or "comprising" shall be understood to imply the inclusion of an integer or set step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The term "alkyl or" is taken to refer to both linear and branched alkyl groups, such as methyl, ethyl, propyl isopropyl, butyl, isobutyl, secbutyl, tertiary butyl, and the like. The alkyl group has 1 to 10 carbon atoms, preferably from 1 to 6 carbons, more preferably methyl, ethyl or isopropyl. The alkyl group may be optionally substituted by PPr one or more of fluorine, chlorine, bromine, iodine, carboxyl, C 1 -C alkoxycarbonyl, C 1 -C 4 alkylaminocarbonyl, di (C 1 -C 4 alkyl) amino carbonyl, hydroxyl, alkoxy: from C? -C, fomyloxy, C? -C4 -carbonyloxy alkyl, C? ~ C alkylthio, C3-C6 cycloalkyl or phenyl.

The term "aryl" is taken to include phenyl and naphthyl and may be optionally substituted by one or more of C? ~C alkyl, hydrolyzo, C?-C4 alkoxy, carbonyl, C alco alkoxycarbonyl. -C4, C 1 -C 4 alkylcarbonyloxy or halo The term "halo" is taken to include fluorine, chlorine, bromine and iodine, preferably fluorine and chlorine, more preferably fluorine Reference to, for example, "haloalkyl", will include alkyl monohalogenated, dihalogenated and even perhalogenated. Preferred haloalkyl groups are trifluoromethyl and pentafluoroethyl. The particularly preferred compounds of the present invention are selected from: The compounds of the present invention have particular application in the treatment of diseases associated with or resulting from estrogenic effects, androgenic effects, vasodilatory and spasmodic effects, inflammatory effects and oxidative effects. The amount of one or more compounds of the formulas I and II, which is required in a therapeutic treatment according to the invention, will depend on a number of factors, which include the specific application, the nature of the particular compound used, the condition to be treated, the mode of administration and the condition of the patient. The compounds of the formulas I and II can be administered in a manner and amount as practiced in a conventional manner. See for example, Goodman Gilman, Thej Phramacological Basis of Therapeutics, 1299 (7th edition 1985). The specific dose used will depend on the condition being treated, the condition of the subject, the route of administration and other well-known factors as indicated above. In general, a daily dose per patient can be in the range of 0.1 mg to 2 mg; tipieamenté from 0.5 mg to 1 g; preferably from 50 mg to 200 mg. The production of the pharmaceutical compositions for the treatment of the therapeutic indications described herein, are typically prepared by the of the condition to be tethered and of the nature of the particular active compound, which is used. The formulation suitable for oral administration can be prepared in discrete units, such as capsules, sachets, pills or tablets, each containing a predetermined amount of the active compound; as a powder or granule: s; as a solution or suspension in a liquid or non-aqueous liquid; or as an oil in water or water in oil emulsion. Such formulations may be prepared by any method or pharmacy, which includes the step of bringing into association in active compound and a suitable carrier (which may contain one or more accessory ingredients as noted above). In general, the formulations of the invention are prepared by uniformly and intimately mixing the active compound with a liquid carrier or finely divided solid., or both, and then, if necessary, molding the resulting mixture, such as to form a unit dose. For example, a tablet can be prepared by compressing or molding a powder or granules containing the active compound, optionally, with one or more accessory ingredients. Compressed tablets can be prepared by compressing, in a suitable machine, the free-flowing compound, such as a powder or granules, optionally blended with a binder, lubricant, inert diluent, t * and / or surface active agents / dispersants. The 3 molded tablets can be made by molding, in a suitable machine, the pulverized compound moistened with inert liquid binder. Formulations suitable for buccal administration, include pellets comprising the active compound in a flavored bas, usually sucrose and acacia or tragacanth.; and the tablets comprising the compound in an inert base such as gelatin and glycerin or sucrose and acacia. The compositions of the present invention, suitable for parenteral administration, conveniently comprise the sterile aqueous preparations of the active compounds, which preparations are preferably isotonic. with the blood of the future recipient. These preparations are preferably administered intravenously, although administration can also be effected by means of subcutaneous, intramuscular, or intradermal injection. Such preparations can be conveniently prepared by mixing the compound with water or a glycine buffer and rendering the resulting solution sterile and isotonic with the blood. Injectable formulations according to the invention, generally contain from 0.1% to 60% w / v of the effective compound and are administered at a rate of 0.1 mL / minute / kg. Formulations suitable for rectal administration are preferably presented as unit dosage suppositories. These can be prepared by mixing the active compound with one or more conventional solid carriers, for example, cocoa butter, and then molding the resulting mixture. Formulations suitable for topical administration to the skin, preferably take the form of an ointment, cream, lotion, paste, gel, spray, aerosol, or oil. The carriers, which may be used, include Vaseline, lanolin, polyethylene glycols, alcohols, and a combion]) of two or more thereof. The active compound is generally present at a concentration of from 0.1% to 0.5% w / w, for example, from 0. 5% to 2% p / p. Examples of such compositions include cosmetic creams for the skin. Formulations suitable for transdermal administration can be presented as discrete patches adapted to remain in intimate contact with the epidermis of the recipient for a prolonged period of time. Such patches suitably contain the active compound optionally as an aqueous solution damped of, for example, the concentration of 0.1 M to 0.2 M with respect to said < active asset. Formulations suitable for transdermal administration can also be administered by ionophoresis see, for example, Pharmaceutical Research 3 (6), 318)) and then take the form of an optionally buffered aqueous solution of the active compound. Suitable formulations comprise bis / tris citrate or buffer (pH 6) or ethanol / water and contain from 0.1 M to 0.2 M of the active ing edient. The active compounds may be administered in the form of foodstuffs, such as added to, mixed in, coated, combined or otherwise added to the foodstuff. The term "food product" is used in the broadest possible sense and includes liquid formulations such as beverages, including dairy products 3 and other foods, such as healthy bars, post, etc. The food formulations containing the compounds of the invention can be prepared easily according to standard practices. The compounds of the present invention have potent antioxidant activity and therefore find wide application in pharmaceutical and vetery uses, in cosmetics such as skin creams, to prevent the aging of the skin, in sunscreens, in food, healthy drinks, shampoo, and the like. It has surprisingly been found that the compounds of the formulas I and II, interact synergistically with vitamin E to protect lipids, proteins and other biological structures from oxidation. Accordingly, a further aspect of the invention provides a composition comprising one or more compounds of the formulas I or II, vitamin E, and optionally, the carriers and / or excipients pharmaceutically, veterinarily or cosmetically acceptable. Therapeutic methods, uses and compositions may be for the administration to humans or animals, such as companion or domestic animals (such as dogs and cats), birds (such as chickens, turkeys, ducks), livestock (such ss) such as cattle, sheep, pigs and goats) and the like. The compounds of formulas I and II can be prepared by the standard methods known to those skilled in the art. Suitable methods may be entered, for example, in International Patent Application WO 98/08503, which it is incorporated herein in its entirety as a reference. The methods, which can be employed by those skilled in the art of chemical synthesis to elaborate the general ring structures represented in formulas I and II, are depicted in schemes 1-8 below. Chemical protection, deprotection, syntheses, and other techniques known to those skilled in the art may be used in the synthesis of compounds where appropriate. In the formulas represented in the diagrams below, the portions Ri, R2, R6, Rs, Ru, Ris, Rie, W and X are as defined: riba. The portion T is either Z or ZA as defined in: I or II. The reduction of the isoflavone derivatives can be effected by methods well known to those skilled in the art, including reduction by sodium borohydride, and hydration over metal catalyst, such as Pd / C, Pd / CaCO3 and oxide of Platinum (IV) (Adam's catalyst) in protic or aprotic solvents. The final products and the isomeric relationships can be varied, depending on the catalyst / solvent system chosen. The diagrams shown are not considered to be limiting on the scope of the invention described herein. substituted isoflavones. For example, starting with 5- methyl resorcinol da ', 7-dihydroxy-5-methylisoflavone, while the use of 3-hydroxy phenyl acetic acid in the general synthesis method gives 3'-hydroxy derivatives isoflavone Isoflavan-4-ones EXAMPLE 2 Synthesis of 6-chloro-4'-7-diacetoxyisoflavone A mixture of 6-chloro-4 ', 7-dihydroxyisoflavone (1.25 g, 4.3 mmol), acetic anhydride (7.5 mL) and pyridine (1.4 mL) was heated in an oil bath at 105-110 ° C for 1 h.

After cooling the mixture to room temperature, it was stirred for another 30 minutes, during which time, the diacetate crystallized from the solution. The product was filtered, washed thoroughly with aqueous methane (50%) and dried to give the β-chloro-4 ', 7-diacetoxyisoflavone (1.2 g, 75%) as colorless prisms. H NMR (CDC13): d 2.32 (s, 3H, OCOCH3) 2. 41 (s, 3H, OCOCH3), 7.16 id, 2H, J 8.6 Hz, ArH), 7.36 (s, ÍH, H8), 7.57 (d, 2H, J Hz, ArH), 8.00 (s, ÍH, H5), 8.37 (s, 1H, H2; EXAMPLE 3 Synthesis of 6-chlorp-4 ', 7-diacetoxyisoflavan-4-one The Adam catalyst (0.045 g) was added to a solution of 6-chloro-4 ', 7-di acetoxyisoflavone (0.25 g, 0.7 mmol) in ethyl acetate (30 mL) and the mixture was stirred to the ambient temperature under a hydrogen atmosphere for 24 h. The catalyst was removed by filtration through Celite and the resulting filtrate was evaporated in vacuo. The residue was recrystallized from ethanol to give 6-chloro-4 ', 7-diacetoxyisoflavone-4-one (0.15 g, 60%) as colorless plates. l NMR (CDC13): d 2.29 (s, 3H, OCOCH3), 2. 37 (s, 3H, OCOCH3), 3.98! Dd, ÍH, J 6.0 Hz, 7.5 Hz H3! 4.68 (m, 2H, H2), 6.87 (s, 0.H, H8), 7.07 (d, 2H, J 8.6 Hz, ArH), 7.27 (d, 2H, J 8.6 Hz, ArH) 01 (s, ÍH , H5; EXAMPLE 4 Synthesis of 6-chloro-4 ', 7-dihydroxyisoflavan-4-one Imidazole (0.60 g) was added to a suspension of 6-chloro-4,7'-diacetoxyisoflavan-4-one (0.24 g, 0.06 mmol) in absolute ethanol (5.0 mL) and the mixture was refluxed for 45 min under argon. . The solution was concentrated under reduced pressure and distilled water (10 mL) was added to the residue. The mixture was left overnight in the refrigerator and the precipitate or resultant was filtered, washed with water and dried to give 6-chloro-4 ', 7-dihydroxyisoflavan-4-one (0 14g, 75%) like white powder. 1 HOUR NMR (d6-acetone): d3.87 (t, Q.H, J 7.2 Hz, H3), 4.64 (d, 2H, J 6.2 Hz, H2), 6.59 (s, 1H, H8), 6.78 (d, 2H, J 8.7 Hz, ArH), 7.10 (d, 2H, J 8.7 Hz, ArH), 7.70 (bs, ÍH, OH) 7.77 (s, 1H, H5).

EXAMPLE 5 Synthesis of 4 ', 7-diacetoxy-5-methylisoflavone A mixture of 4', 7-dihydroxy-5-methylisoflavone (1.51 g, 5.6 mmol), acetic anhydride 9 mL) and pyridine (1.7 mL) was heated in an oil bath at 105-110 ° C for 1 h. After cooling the mixture to room temperature, was stirred for another 30 minutes, during which time, the diacetate crystallized from the solution. The product was filtered, washed thoroughly with water and recrystallized from methanol to give 4 ', 7-diacetoxy-1-methylisoflavone as colorless prisms (1.8g, 91%), p. F. 195-97 ° C. X H NMR (CDC13): d 2.32 (s, 3 H, OCOCH 3), 2.35 (s, 3 H, OCOCH 3), 2.87 (s, 3 H, Me), 6.92 (bs, ÍH, H8), 7. 2 (bs, ÍH , H5), 7.16 (d, 2H, J 7 Hz, ArH), 7.55 (d, 2H, J 8.7 Hz, ArH), 7.89 (s, ÍH, H2). EXAMPLE 6 Synthesis of 4 ', 7-diacetoxy-5-methylisoflavan-4-one Palladium on tie sulfate (5%, 0.06 g), was added to a solution of 4', 7-diacetoxy-5-methylisislavone (0.30 g) , 0.8 mmol) in ethyl acetate (50 mL) and the mixture was stirred at room temperature under a hydrogen atmosphere for 24 h. The catalyst was removed by filtration through Celite and the resulting filtrate was evaporated in vacuo. The residue was recrystallized from ethanol to give 4 ', 7-diacetoxy-5-methylisophyl | van-4-one 80.20g, 67%) as colorless plates, m.p. 143-45 ° C, X H NMR (CDCl 3): d 2.29 (s, 3 H, OCOCH 3), 2.30 (s, 3 H, X OCH 3), 2.62 (s, 3 H, Me), 3.95 (t, 1 H, J 7.2 Hz, H3), 4.62 (d, 2H, J6.8 Hz, H2), 6.59 (d, IH, J 2.2 Hz, H8), 6.66 (d, IH, J 2.2 Hz, H5), 7.07 (d, 2H, J 8.3 Hz, ArH), 7.28 (d, 2H, J 8.3 Hz, ArH). EXAMPLE 7 Synthesis of 4 ', 7-c; ihydroxy-5-methylisoflavone Imidazole (0.63 g) was added to a suspension of 4,7-diacetoxy-5-methylisoflavan-4 -one (0.50 g, 1.4 mmol) in absolute ethanol (20.0 mL) and the mixture was refluxed for 45 min under argon. The solution was concentrated under reduced pressure and distilled water (10 mL) was added to the residue. The mixture was left overnight in the refrigerator and the resulting precipitate was filtered, washed with water and dried to give 7'-dihydroxy-5-methylisoflavan-4-one (0.25g, 66%) as a powder. White. 1 HOUR NMR (d6-acetone): d 2.51 (s, 3H, Me), 3.76 (t, ÍH, J 5.7 Hz, H3), 4.57 (d, 2H, J 7.1 Hz H2 '6.26 (d, ÍH, J 2.2 Hz, H8), • 6.35 (d, ÍH, J 2.2 Hz, H5), 6.78 (d, 2H, J 8.7 Hz, ArH), 7.11 (d, 2H, J 8.7 Hz, ArH). Isoflavan-4-ols and Isoflav-3-enos EXAMPLE 8 Synthesis of 4 ', 7-diacetoxy-5-methylisoflavan-4-ol The 4' 7-diacetoxy-5-me: ilisoflavan-4-ol was prepared by reduction of the 4 ', 7-diacetoxy-5- methylisoflavone (0.25 g) with Adam's catalyst in ethyl acetate (30 mL) under a hydrogen atmosphere for 72 hours. The solution was filtered through a pad of Celite to give predominantly cis-4 ', 7-diacetoxy-5-methylisoflavan-4-ol. XH NMR CDC13): d 2.26 (s, 3H, OCOCH3), 2. 30 (s, 3H, OCOCH3), 2.62 3, 3H, Me), 3.24 (dt, ÍH, J 3.4 Hz, J 11.8, Hz, H3), 4.31 (ddd, ÍH, J 1.4 Hz, 3.6 Hz, 10.5 Hz , H2); 4.57 (dd, ÍH, J 1 D.5 Hz, 11.8 Hz, H2), 4.82 (bs, ÍH, H4), 6.51 (d, ÍH, J 2.1 Hz, H8), 6.59 (d, ÍH, J 2.1 Hz , H6), 7.06 (d, 2H, J 8.6 H:, ArH), 7.29 (d, 2H, J 8.6 Hz ArH) EXAMPLE 9 Synthesis of 4 ', 7-cyclohetoxy-5-methylisoflav-3-ene 4', 7-diacetoxy-5-methylisoflav-3-ene was prepared by dehydration of cis- and trans-4'-7 -diacetoxy-5-metilisoflavan-4-ol (0.2 c) with phosphorus pentoxide (2.0 in dry dichloromethane 20 mL). The crude product was subjected to silica column chromatography using dichloromethane as the eluent. 1 H NMR (CDC13): d 2.28 (s, 3 H, OCOCH 3), 2.31 (s, 3 H, () COCH 3), 2.36 (s, 3 H, Me), 5. O, s, 2 H, H 2), 6.49 (d , ÍH, J 2.0 Hz, H8), 6.52 (d, ÍH, J 2.2 Hz, H5), 6.89 (s, ÍH, H4), 7.14 (d, 2H, J 8.6 Hz, ArH), 7.44 (d, 2H , J 8.6 Hz, ArH) EXAMPLE 10 Synthesis of 4 ', 7-d! Ihydroxy-5-methylisoflav-3-ene EXAMPLE 13 Synthesis of isoflivan-5,7-diol Isoflavan-5,7-diol was prepared by reducing a suspension of 5,7-dihydroxyisoflaylium chloride (0.5 g) with palladium on charcoal (5%, 0.1 g) in acetic acid (15 ml) containing thiol acetate (2.5 ml) under a hydrogen atmosphere. The crude product was recrystallized from 1,2-dichloromethane to give isoflavane as colorless needles, m.p. 76-78 ° C (p.f. lit 77-79 ° C). EXAMPLE 14 Synthesis of 4 ', 5, -triacetoisoflaño 4', 5, 7-triacetoxiispflano was prepared by reducing a suspension of 4 ', 5, 7-trihydroxyisoflavilio chloride (0.31 g) with platinum oxide 80.04 g) in a mixture of anhydride or acetic acid (2.0 mL) and ethyl acetate (10 mL) under a hydrogen atmosphere. After removal of the catalyst, the crude product was refluxed with pyridine (0.5 ml) and the resulting triacetate was isolated by evaporation of the solvent and recrystallization of the residue, P.f. 126-28 ° C. EXAMPLE 15 Synthesis of Isofla an-4 ', 5, 7-triol Isoflavan-4 ', 5, 7-t: iol was prepared from 4', 5, 7-triacetoxyisoflavan by removal of the acetyl groups by hydrolysis. P.f. 206-8 ° C EXAMPLE 16 The binding affinity of several compounds of the invention for both estrogen receptor subtypes was determined with the "Equip • HTS of the Competitor's Alpha or Beta Estrogen Receptor Assay Nucleus", distributed by Panvera Corporation (Product No. P2614 / 2615). The 6-cldro-4 ', 7-dihydroxyisoflavan-4-one showed good competitive binding to the estrogen receptor with the following results: ER receptor alpha = 37.82 uM ER receptor beta = 32.14 uM The results show that the compounds of the present invention have particular application in the treatment of diseases associated with or resulting from estrogenic effects, androgenic effects, vasodilatory and spasmodic effects, inflammatory effects and oxidative effects. Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It should be understood that the invention includes all variations and modifications. The invention it also includes all the steps, features, compositions and compounds mentioned or indicated in the specification, individually, collectively or collectively, and any and all combinations of any of two or more of said steps and characteristics.

Claims (1)

1. CONR3R4, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, provided that, when Ri is hydroxy, or OC (0) RA, where RA is alkyl or an amino acid, and R2 is hydrogen hydroxy, ORB where RB is an amino acid or C (0) RA where R is as previously defined, and W is hydrogen, then Y is not 4-hydroxyphenyl or 4-alkylphenyl; when Ri is hydroxy, or OC (0) RA where RA is alkyl or an amino acid, and R is hydrogen, hydroxy, ORB where RB is an amino acid or C (0) RA where R is as previously defined, And it is 4-hydroxiferyl or 4-alkylphenyl, then W is not hydrogen; when Ri is hydroxy, u pC (0) R4 where R4 is alkyl or an amino acid, and Y is 4-hydroxyphenyl or 4-alkylphenyl, and is hydrogen, then effective of one or more compounds selected from formulas I and II 5. The use of one or more compounds selected from formulas I and II for the manufacture of a medicament for the treatment, alleviation, defense against, prophylaxis and / or prevention of one or more of the therapeutic indications, according to claim 4. 6. The use of one or more compounds selected from formulas I and II in the treatment, alleviation, defense against, prophylaxis and / or prevention of one or more indications. Therapeutics according to claim 4. 7. An agent for the treatment, prophylaxis, alleviation, defense against and / or treatment of therapeutic indications according to claim 4, characterized in that it comprises one or more compounds selected from the Formulas I and II, either alone or in association with one or more carriers or excipients. 8. A therapeutic composition, characterized in that it comprises one or more compounds selected from formulas I and II in association with one or more carriers and / or pharmaceutical excipients. 9. A beverage or food product, characterized in that it contains one or more compounds selected from formulas I and II 10. A microbial culture or a food product, characterized in that it contains one or more microbial strains whose microorganisms produce one or more compounds selected from the formulas I and II. 11. One or more microorganisms, characterized in that they produce one or more: selected compounds of formulas I and II.