ES368198A1 - Antibiotic complex - Google Patents

Abstract

The novel antibiotic axenomycine, also named F.I. 2604, is produced by cultivating Streptomyces lisandri n. sp., I.P.V 1951, I.M.R.U. 3935, I.M.I. 137178, or an axenomycine-producing strain thereof, under aerobic conditions in an aqueous medium containing assimilable sources of carbon and nitrogen and mineral salts, and isolating the axenomycine from the cultivated medium. The cultivation is preferably carried out at 23-37 C. and pH 6-9 for 60-160 hours. Axenomycine is a complex of two components, axenomycines A and B. The complex and its components are amorphous yellowish-white substances, soluble in methyl, ethyl and propyl alcohol, sparingly soluble in water, ethyl acetate, acetone and chloroform, and insoluble in benzene and petroleum ether. They reduce Fehling's solution and ammoniacal silver nitrate, give a positive reaction with tetrazole blue and a weakly positive Molisch reaction. They give negative reactions with ferric chloride, the aniline phthalate test for aldoses and the naphthoresorcinol test for ketoses. Axenomycine A has the following characteristics: elementary analysis, 61.74% C, 8.52% H, 28.87% O molecular weight 1451.3 melting point 127-142 C. to give a transparent reddish gel [[alpha]]23 D = + 10À5 (C = 0.9 in MeOH) Rf = 0.49 on silica gel at pH 7.0 using n. butanol: acetic acid: water = 4: 0.5: 1 U.V. spectrum in MeOH has absorption peaks at 249, 254 and 330 mÁ and a shoulder at 265-268 mÁ I.R. spectrum in a KBr disc has peaks at 2.94, 3À44, 5.78, 6.00, 6.16, 6.24, 6.88, 7.25, 7.41, 8.61, 8.85, 9.35, 10.00, 10.40, 10.95, 11.8 and 12À5 Á. Axenomycine B has the characteristics: elementary analysis, 62.8% C., 8.58% H, 27.8% O molecular weight 1330.2 melting point 122- 140 C. [[alpha]]23 D = + 5 (C = 0.9 in MeOH) Rf = 0À61 on silica gel at pH 7À0 using n. butanol: acetic acid: water = 4À0 : 0À5: 1 U.V. spectrum in MeOH has absorption peaks at 249, 254 and 330 mÁ and a shoulder at 265- 268 mÁ I.R. spectrum in a KBr disc has peaks at 2.94, 3À40, 5.82, 6.00, 6.16, 6.24, 6.86, 7.25, 7.41, 8.60, 8.85, 9.35, 10.00, 10.40, 10.98, 11.8, and 12À5 Á. The antibiotic complex may be extracted from the separated mycelium with e.g. methanol, or from the whole broth with a water-immiscible solvent, and purified by precipitation with a non-solvent followed by counter-current distribution. The two components may be separated by chromatography on a silica gel column at pH 7.0, developing with BuOH: HAc: H 2 O, 4: 0À5: 1 by volume. The antibiotics have anthelmintic, antiprotozoal and antifungal activity. Pharmaceutical compositions comprise axenomycine complex or one of its components A or B together with a pharmaceutically acceptable vehicle.