318 



DESCRIPTIONS OF ANTIBIOTICS 



Free acid: CssHf^Ou : C = 65.42%; H = 9.90%. 

 Nasalt:i)—CB.z = 3.99%. 



Biological activity: Active on gram-po.sitive bac- 

 teria (0.12 to 0.5 ng per ml), mycobacteria (0.5 to 

 4.0 Mg per ml), C. albicans (2 yug per ml). Tricho- 

 phyton mentagrophytes (16 yug per ml). Gram-nega- 

 tive bacteria are resistant to 64 /xg per ml. 

 Biological activity inhibited by K+. Inhibits 

 respiration and phosphate uptake in the presence 

 of several substrates; also inhibits mitochondrial 

 adenosinetriphosphatase. This inhiliition is de- 

 pendent in part on the str\ictural integrity of the 

 mitochondria (3). 



Toxicity: LD50 (mice) 2.5 mg per kg intraperi- 

 toneally. 



References: 



1. Harned, R. L. et al. Antibiotics & Chemo- 



therapy 1: 594-596, 1951. 



2. Benedict, R. G. and Lindenfelser, L. A. 



Given in Benedict, R. G. Botan. Rev. 

 19: 229-320, 1953. 



3. Lardy, H. A. et al. Biochim. et Biophys. 



Acta 78: 587-597, 1958. 



Nironiycins 



Produced by: Streptoniyces albus. 



Synonyms: Closely related to cycloheximide and 

 fermicidin. 



Method of extraction: Extraction of broth at pH 

 7.4 with butanol. Evaporation of butanol under 

 reduced pressure to syrup; washed with petroleum 

 ether. Resulting crude residue dissolved in water 

 and extracted with ethyl acetate; concentrated in 

 vacuo to syiup. Syrup washed with petroleum ether 

 and dried. Residue dissolved in butyl alcohol and 

 passed through an alumina column to remove im- 

 purities. Active effluent evaporated. Upon addi- 

 tion of benzene, white crystals appear and are re- 

 moved. Benzene solution evaporated. Residue 

 washed with petroleum ether and dried. Crude 

 powder dissolved in 20 per cent aqueous acetone 

 and chromatographed on carbon. Elution with 

 progressively drier acetone. Fractions active 

 against Saccii. sake combined and the acetone 

 evaporated. Active powder purihed by counter- 

 current distribution (benzene-water, 1:1, 30 trans- 

 fers). One active substance shows a peak at Tube 

 6 (niromycin A) and another at Tube 9 (niromy- 

 cin B). Niromycin A is further purified by repeat- 

 ing distribution, but is unstable and does not 

 crystallize. Niromycin B crystallized from ethyl 

 acetate (1). 



Chemical and phi/sical properties: Xiro)nycin A: 

 Hygroscopic, white, amorphous, neutral sub- 

 stance; m.p. 98-105°C. Soluble in water, methanol, 



ethanol, butanol, ethyl acetate, butyl acetate, ace- 

 tone, and chloroform. Slightly solul)Ie in benzene 

 and ether. Insoluble in petroleum ether. No spe- 

 cific ultraviolet light absorption. No optical rota- 

 tion (c = 1 per cent in ethanol). Positive Tollen 

 and 2,4-dinitrophenylhydrazine reactions. Nega- 

 tive ninhydrin, FeCls , Fehling, Benedict, Molisch, 

 biuret, and permanganate reactions (1). Niromy- 

 cin B: Neutral substance. White hygroscopic crys- 

 tals; m.p. 47-67°C. Same solubility properties, 

 color reactions, light absorption, and optical rota- 

 tion as niromycin A. C = 62.57%; H = 7.54%; 

 N = 5.3%. Infrared spectrum given in reference 1. 

 Semicarbazone: m.p. 175-1 76°C. C = 42.06%; H = 

 7.33%; N = 35.90%. 24-Dinitrophenylhydrazone: 

 m.p. 199-200°C (decomposition). C = 56.29%; 

 H = 5.53%; N = 15.16%. Suggested formula for 

 niromycin B: C14H21NO4 (1). 



Biological activity: Both niromycins are active 

 against fungi and viruses, but not against bac- 

 teria. Examples of minimal inhiVntory concentra- 

 tions in ^g per ml: Hansenula anomala: A = 1.5, 

 B = 0.7; Sacch. cerevisiae: A = 0.35, B = 0.17; 

 Sacch. sake: A = 0.7, B = 0.35; A. niger: A = B = 

 >1000. In tissue cultures, niromycin A inhil)its 

 Newcastle disease virus at 0.01 ^g per ml ; nontoxic 

 to chick embryo cells at 6.25 jug per ml. Niromycin 

 B inhibits Newcastle disease virus at 0.036 /ug per 

 ml and shows no toxicity at 0.75 Mg per ml. Both 

 substances inhil)it multiplication of influenza 

 virus in chick embryos (2). 



Toxicity: Niromycin A: LD50 (mice) 40 to GO mg 

 per kg intravenously. Niromycin B: LDsn (mice) 

 48 mg per kg, (rats) 1.8 mg per kg intravenously. 



References: 



1. Osato, T. ('/ a/. J. Antibiotics (Japan) 13A: 



110-113, 1960. 



2. Osato, T. e/ o/. J. Antibiotics (Japan) 13A: 

 97-109, 1960. 



INitrosporin 



Produced ly: Streptomyces nitrosporeus (1). 



Method of extraction: I. Adsorption on charcoal 

 or cation exchange resin and elution with acidic 

 acetone or dilute HCl. II. Broth extraction by 

 ethyl ether, butyl or ethyl acetate at pH 7.0. Re- 

 extracted into water at pH 2.0. Back-extracted 

 into ethyl acetate at pH 7.0 and extract concen- 

 trated in vacuo. Chromatographed on alumina, 

 developed with ethyl acetate. Fractions pooled 

 and lyophilized. Solid taken up in water, warmed, 

 filtered, then cooled to precipitate crystals (1). 



Chemical and physical properties: Basic white 

 crystalline substance. Browns at 115-120°C; m.p. 

 130-140°C. Soluble in ethanol and ethyl acetate. 



