DESCRIPTIONS OF AXTIlilOTICS 



195 



l)iotic" differs from echinoinyciii, !)ut is similar to 

 the echinomycin-like antibiotic of Berger. It may 

 also be related to actinoleukin (1). 



Method of extraction: Isolated from mycelium 

 by extraction with acetone. Extract evaporated 

 off and residue extracted with chloroform. Chloro- 

 form concentrated. Precipitated from concentrate 

 by addition of petroleum ether. Chromatographed 

 on alumina from benzene. Crystallized from aceto- 

 nitrile (1 ). 



Cheiuical and physical properties: Crystalline; 

 m.p. 210-215°C. Ultraviolet absorption spectrum 

 maximum at 320 mix, minimum at 285 m/x. C-^ii- 

 H37O6-7N6S; C = 65.19% {sic, probably 5(i.l9'f); 

 H = 6.47%; N = 13.66%; S = 5.56% Acid 

 hydrolysis products include serine, alanine, and 

 dimethylleucine, the first two in cqui molar 

 quantities, not exceeding 33 per cent. Boiling 

 with 3 per cent XaOH for 2 hours yields 1.3 

 moles of NH, (1). 



Biological activity: Active at maximal tolerated 

 levels on Crocker sarcoma and lymplnjsarcoma and 

 Ehrlich's carcinoma in mice, and on sarcoma 45 

 (rats) (2). 



Toxicity: At low do.ses, causes l)lood abnormali- 

 ties and changes in the size of the spleen (2). 



References: 



1. Brazhnikova, M. G. Abstr. Communs. Sym- 



posium on Antilnotics. Prague, 1959, j)p. 

 140-141. 



2. Shorin, V. A. Aljstr. Communs. Symposivmi 



on Antibiotics. Prague, 1959, pp. 1(S5-186. 



3. Rossolemo, (). K. et at. Antibiotiki K 6): 



54-59, 1959. 



Antibiotic T,(»«(» H.I'. 



Produced by: Strcptomyces sp. resemliling S. 

 kitasaloensis. 



Method of extraction: Broth-filtrate extracted 

 with butanol at acid pH. Solvent back-extracted 

 with water at pH 7 to 8. Aqueous extract adjusted 

 to acid pH and extracted with eth\'l acetate. 



Chemical and physical properties: Acidic sub- 

 stance; m.p. 200-205°C (decomposition). Soluble 

 in alcohols, ethyl acetate, and pyridine. Salts solu- 

 ble in water. "(CeHsOsX,)^: C = 38.3%; H = 

 4.45%; O = 42.4%; N = 14.7%. pK„ = 6. Ultra- 

 violet absorption spectrum maxima at 227 mju 

 (£lL 532), 271 niM (^'IL 650), and 304 m/x <£'u'm 

 663). Optically inactive. 



Biological activity: Very slightly active on gram- 

 positive and gram-negative bacteria. Not active 

 on mycobacteria. Active in vitro and in vivo (mice, 

 rats) on Trichomonas vaginalis. Active on Enda- 

 moeha histolytica. 



Toxicity: Ll).iii (mice) 50 mg per kg subcutane- 

 ously, about 500 mg per kg orally. 



Reference: 1. Despois, R. et al. Ciorn. micro- 

 biol. 2: 76-90, 1956. 



Antibiotic AYF 



Produced by: Strcptomyces aureofaciens. Culture 

 also produces tetracycline. 



Synonynis: Probably synonymous with aureo- 

 facin and ayfactin. 



Method of extraction: Mycelium slurried in n- 

 butanol, adjusted to pH 9.0 to 10.0, and filtered. 

 Extract washed with aciueous sochiun ethylene- 

 diaminetetraacetate at pH 9.5. Concentration of 

 butanol-extract precipitates antibiotic. May also 

 be extracted from the washed concentrated buta- 

 nol with water at pH 11.5 to 12.0. Acidification of 

 aqueous phase to pH 5.0 precipitates the anti- 

 biotic. Purified by washing with methyl isobutj'l 

 ketone-chloroform-acetone (9:9:2) and water at 

 ])H 1.5. Separated into two substances by extrac- 

 tion with methanolic CaCU . Fraction B goes into 

 the CaCl> solution and precipitates out on addi- 

 tion of water. It is reprecipitated from the same 

 solution, then partitioned between butanol and a 

 2 i)er cent a([ue<)iis Na ethylenediaminetetraace- 

 tate solution, adjusted to pH 9.5 with NH4OH; 

 concentration of the butanol phase yields Frac- 

 tion B. Fraction A is crystallized from chmethyl- 

 formamide or dimethylacetamide by dilution with 

 water. 



Chemical and phy^ictil properties: Weakly acidic 

 heptaenes. Proctiim A: Dark lirown crystalline 

 substance. Insolul)le in water and common or- 

 ganic solvents. Moderately soluble in dimethyl- 

 formamide (becoming more solulale in presence of 

 CaClj) and dimethylacetamide (solubility also 

 enhanced by CaCla). Soluble in pyridine and di- 

 methyl sulfo.xide. Ultraviolet absorption spectrum 

 maxima at 344, 363, 383 (E'lL 526) and 409 mn 

 (dimethylacetamide). C = 62.6%; H = 7.86%,; 

 X = 2.8% (Dumas) and 2.5' c (Kjeldahl). Fraction 

 B: Dark yellow crystalline substance. Soluble to 

 700 Mg ppi" nil in water at pH 3 to 10, to >2 per 

 cent in methanolic CaCl-2 , dimethylformamide, 

 pyridine, and dimethyl sulfoxide, and insoluble 

 in common organic solvents. Ultraviolet absorp- 

 tion spectrum the same as Fraction A except 

 -fi'icm 556 at 383 m/.i. Infrared spectrum given in 

 reference 1. C = (i2.4% ; H = 7.62%:; N = 2.8% 

 (Kjeldahl). 



Biological activity: Active on yeasts and fungi. 

 Active in vivo (mice) against C. albicans infections. 

 Toxicity: Complex: LD.50 (mice) 3.82 mg per kg 

 intraperitoneally, >1000 mg per kg orally. 



