DESCRIPTIONS OF ANTIBIOTICS 



231 



ously, intraperitoneally, intramuscularly, and 

 subcutaneously. 

 References: 



1. Hosoya, S. Ann. Meeting Japan. Chemo- 



therapy Soc. 3: 128-131, 1955. 



2. Harada, Y. and Kiibo, S. J. Antit)iotics 



(Japan) 9B: 160-167, 1956. 



3. Harada, Y. and Tanaka, S. J. Antibiotics 



(Japan) 9A: 113-117, 1956. 



4. Umezawa, H. Giorn. micro])iol. 2: 160-193, 



1956. 



Cardiciii 



Produced by: Xocardia sp. 



Method of extraction: Mycelium extracted with 

 hot methanol; or acidified broth extracted with 

 butanol. Methanol concentrated /// vacuo, and 

 cardicin precipitated on addition of ether. I. 

 Dissolved in dilute NH4OH and reprecipitated on 

 acidification. II. Purification by extraction of an 

 acidified aqueous solution with butanol. Butanol 

 washed with NaHCO.'i and water, and step II re- 

 peated. 



Chemical and physical properties: Stable. Acidic 

 form insoluble in water, saline solution, ether, and 

 acetone; soluble in methanol, ethanol, and hy- 

 drous butanol. Sodium salt insoluble in ether and 

 V)utanol; soluble in water, methanol, ethanol, and 

 large volumes of hydrous butanol. 



Biological activity: Active in vitro against gram- 

 positive bacteria, fungi, and the following phages: 

 staphylo])hage, streptophage. Bacillus cereus 

 phage, B. megaterium phages, coliphage, and en- 

 terococcus phage. Active in eggs on PR 8, Lee, 

 and FM-1 strains of influenza virus. 



Toxicity: 93 ^g injected intraperitoneally or 

 subcutaneously kills mice in 2 days. 



Reference: 1. Machlowitz, R. A. et al. Anti- 

 biotics & Chemotherapy 3: 966-970, 1953. 



C 



arvoni^ cm 



Produced by: Streptomyces filamentosus (1, 2). 



Method of extraction: Extracted from broth- 

 filtrate with butyl or ethyl acetate. Extracted 

 from mycelium with alcohols, benzene, or petro- 

 leum ether (2). 



Biological activity: Active on gram-positive bac- 

 teria, including mycobacteria. Less active on 

 gram-negative bacteria. Active on Yoshida sar- 

 coma (rats), increasing survival time and produc- 

 ing some cures (1, 2). 



References : 



1. Okami, Y. et id. J. Antibiotics (Japan) 

 6A: 153-157, 1953. 



2. Yamamoto, T. and Umezawa, H. Japanese 

 Patent 396, January 26, 1955. 



Carzinocidin 



Produced by: Streptomyces kitasawaensis (2). 

 This culture also produces actinomycin A (3). 



Method of extraction: I. Formation of a pre- 

 cipitate by adjusting the broth-filtrate to pH 5.0 

 and adding 5 per cent by volume of a 20 per cent 

 ZnClo solution. Precipitate extracted with 1 per 

 cent Na2lIP04 solution. To this solution at pH 

 7.0, 80 per cent saturated ammonium sulfate is 

 addetl. A precipitate forms, which is dissolved in 

 water and purified by dialysis. Addition of acetone 

 forms a precipitate of crude brown-black carzino- 

 cidin powder (1). II. Broth-filtrate adsorbed on 

 carbon at pH 2.4, and eluted with water at pH 

 8.0. Eluate concentrated at pH 4.4 and freeze 

 dried. Purified by extracting an aqueous solution 

 with butanol at pH 6.5; extract evaporated in 

 vacuo (3). 



Chemical and physical properties: Polypeptide 

 containing cj'stine, lysine, glycine, and glutamic 

 acid. No crystals form; no definite melting point. 

 Soluble in alkaline water. Slightly soluble in 20 

 per cent acetone (pH 8.0), 20 per cent methanol, 

 20 per cent ethanol, 20 per cent pyridine, and bu- 

 tanol-saturated alkaline water. Insoluble in acidic 

 water. No specific ultraviolet absorption. Positive 

 xanthoproteic and Pauly reactions. "Pseudoposi- 

 tive" Millon reaction. Negative biuret, Adam- 

 kiewicz, Liebermann, H2SO4 , ninhydrin, diphen- 

 ylamine, cysteine, nitroprusside, Folin, anthrone, 

 Sakaguchi, and FeCla reactions. Unstable to heat, 

 especially at alkaline pH. C = 37.2%; H = 6.1%; 

 N = 12.2%; S = 3.5%. Molecular weight >6000 

 (3). 



Biological activity: Slight activity against C. 

 albicans, Torula utilis, and Sacch. cerevisiae. Ac- 

 tive in mice against Ehrlich carcinoma, mainly 

 against the subcutaneous solid tvmior form. Slight 

 activity against Yoshida sarcoma (1, 3). 



Toxicity: LD50 (mice) 4.7 mg per kg intraven- 

 ously, 43.5 mg per kg intraperitoneally, 20 mg per 

 kg subcutaneously. Cystine and methionine do 

 not decrease the toxicity of this substance in mice 

 (1,3). 



References: 



1. Harada, Y. et al. J. Antibiotics (Japan) 



9A: 6-15, 1956. 



2. Harada, Y. and Tanaka, S. J. Antibiotics 



(Japan) 9A: 113-117, 1956. 



3. Harada, Y. et al. Japanese Patents 789, 790, 



and 791, February 18, 1959; and 898, Feb- 

 ruary 21, 1959. 



