232 



DESCRIPTIONS OF ANTIBIOTICS 



Carziiiophilin A 



Produced by: Streptomyces sahachiroi (1, 7). 



Synonytn: Carziiiophilin (3). 



Method of extraction: Extraction of culture- 

 filtrate with organic solvents such as butyl ace- 

 tate, benzene, or chloroform at pH 6.0 to 7.0. 

 Back-extraction in water at pH 9.0 to 10.0. Aque- 

 ous extract either (a) freeze dried; (1)) precipitated 

 by addition of (NH4)2S04 , and precipitate purified 

 by extraction into acetone or butanol; or (c) 

 chromatographed on alumina at pH 5 to 8 and 

 eluted with alkaline aqueous acetone, pH 7 to 10 

 (1, 7). Broth-filtrate stirred with diatomaceous 

 earth or similar adsorbent at pH 6.5, and eluted 

 with methanol at pH 7 to 10. Eluate concentrated 

 in vacuo at about pH 7.0. Concentrate extracted 

 with organic solvents at pH 5 to 8, then back- 

 extracted into water at pH 7 to 10 and freeze 

 dried (7). 



Chemical and physical properties: Acidic sub- 

 stance. Colorless needles. Darkens above 205°C; 

 m.p. 217-222°C (decomposition). Soluble in ace- 

 tone, chloroform, ethjd and butyl acetate, ben- 

 zene, dioxane, and aqueous alkali. Slightly soluble 

 or insoluble in water, methanol, ethanol, ether, 

 carbon tetrachloride, and petroleum ether 

 kin = +57.8° (chloroform). Ultraviolet absorp- 

 tion spectrum maxima: 218, 250, and 283 m/i (2 

 per cent NaHCO,, or methanol) ; 230 m/x {£{7^1 940) 

 and 283 m^ (^!cm 460) (0.1 N NaOH); 219 and 252 

 mp (ether); 210 and 330 ni/x (acetone); 270 niyu 

 (CHCI3); 242 and 378 m^ (CS.). Infrared data 

 given in reference 2. Positive l^romine, xantho- 

 proteic, diphenylamine, 2,4-dinitrophenylhydra- 

 zine, and sodium nitroprusside tests. Gives the 

 following reactions: Bayers test (KMn04 in 

 NaOH, green); ninhydrin (yellow), and anthrone 

 (yellow). Negative Molisch, Sakaguchi, Fehling, 

 Benedict, FeClj , and Tollen reactions. Forms 

 salts with alkalies. Biological activity destroyed 

 by thiourea, cysteine, methionine, hydroquinone, 

 vitamin B12 , H2O2 , and ultraviolet light. Thermo- 

 stable in dry state; unstable in aqueous solutions. 

 C = 59.78%; H = 5.17%; N = 6.93%. Molecular 

 weight 800 to 1200. Alkaline decomposition pro- 

 ducts include two crystalline substances: I. 

 m. p. 78-79°C; colorless needles; CuHis-uOj . II. 

 m. p. 177-180°C; colorless granular crystals; 

 C12-13H12-13O3 (1, 3, 4, 7). 



Biological activity: Active in vitro against gram- 

 positive bacteria {Sarcina lutea) and mycobac- 

 teria. Limited activity against gram-negative 

 bacteria, except members of the genus Brucella 

 and K. pneumoniae (1). Active on Nocardia aster- 

 aides at 10 Mg per ml but not on protozoa (7). Not 



active on fungi (1). Pure substance has about 20 

 times more activity on Yoshida sarcoma than 

 crude material (8). Active on ascitic forms of 

 Ehrlich carcinoma, hepatoma 7974, sarcoma 180, 

 and Krebs 2 carcinoma (1, 6). Certain concentra- 

 tions stimulate root tip growth of Allium cepa. 

 A very slight reduction in the number of mitotic 

 figures was noted at the highest concentration 

 used (8). Kills HeLa cells at 0.031 ng per ml (5). 



Toxicity: LD50 (mice) 150 fxg per kg intraven- 

 ously (4). Subcutaneous or intramuscular adminis- 

 tration causes induration, necrosis, and ulceration 

 at site of injection. Leukopenia and urobilin in 

 urine also noted (2). 



Utilization: Some effects on neoplastic disease 

 (2,7). 



References: 



1. Hata, T. et al. J. Antibiotics (Japan) 7A: 



107-112, 1954. 



2. Shimada, N. et al. J. Antibiotics (Japan) 



8A: 67-76, 1955. 



3. Kamada, H. et al. J. Antibiotics (Japan) 



8A: 187-188, 1955. 



4. Kamada, H. et al. Chemotherapy 4: 8, 



1956. 



5. Umezawa, H. Ciiorn. microbiol. 2: 160-193, 



1956. 



6. Sugiura, K. and Creech, H. J. Ann. N. Y. 



Acad. Sci. 63: 962-976, 1956. 



7. British Patent 777,287, June 19, 1957. 



8. Ammann, C. A. and Safferman, R. S. Anti- 



biotics & Chemotherapy 8: 1, 1958. 



Catenuliii 



Produced by: Streptomyces sp. 



Synonyms: Closely related to hydroxymycin and 

 paromomycin. 



Method of extraction: Adsorption on carbon or 

 precipitation as the salt (I) of eriochrome violet. 

 A methanolic solution of I treated with triethyl- 

 amine sulfate gives crude catenulin sulfate. Can 

 be crystallized as the helianthate or the p{p'- 

 hydroxyphenylazobenzene) sulfonate salt from 

 hot water. 



Chemical and physical properties: Sulfate: In- 

 soluble in methanol. End-absorption of ultraviolet 

 light. Infrared spectrum said to be ch;iracteristic 

 of a polypeptide, [afj' = -|-51.9° (c = 1 per cent 

 in water). C = 31.45%; H = 6.15%; N = 7.92%; 

 SO4 = 28.12%. All the nitrogen is basic. Prolonged 

 acid hydrolysis yields a product tentatively identi- 

 fied as neamine by paper chromatography. Differ- 

 entiated from neomycins A and B and the strepto- 

 mycins by paper chromatography. Stable in 

 aciueous solution from pH 1.5 to 10.0. 



