234 



DESCRIPTIONS OF ANTIBIOTICS 



2. Hiiiman, J. W. and Hoeksema, H. Abstr. 



129th Meeting Am. Chem. Soc. 17M-18AI, 

 1956. 



3. British Patent 768,971, February 27, 1957. 



Cellocidin 



Produced by: Slreptomyces chibaensis (1). 



Method of extraction: Broth-filtrate stirred with 

 activated carbon at pH 6.4 to 6.8. Elation with 80 

 per cent aqueous methanol. Concentration of elu- 

 ate in vacuo precipitates the antibiotic. Recrystal- 

 lization from hot aqueous methanol (1). 



Chemical and physical properties: Acetylenedi- 

 carboxamide (2). Formula given in Chapter 6. 

 Melts at 216-218°C (decomposition). Slightly solu- 

 ble in water, methanol, ethanol, and acetone. In- 

 soluble in other organic solvents. Relatively stable 

 at acid pH and neutrality. Unstable at alkaline 

 pH, decomposing with evolution of ammonia 

 when boiled. Ultraviolet absorption spectrum 

 maximum at 299 m^ (£''1™ 290) in 0.1 N NaOH) 

 (1). Infrared spectrum given in reference 1. Cata- 

 lytic reduction product is succinamide. Major 

 acid hydrolysis product is C4H3O4CI (chlorofumaric 

 acid) (2). 



Biological activity: Active on Micrococcus flavus 

 and E. coli at 10 ^g per ml, B. subtilis at 20 ^g per 

 ml, and Staph, aureus at 200 ng per ml. Active on 

 M. tuberculosis BCG at 3 /xg per ml. Active in vitro 

 on N.F. mouse sarcoma but not in vivo on Ehrlich 

 ascites carcinoma (1). 



Toxicity: LD50 (mice) 11 mg per kg intrave- 

 nously (1). 



References: 



1. Suzuki, S. et al. J. Antibiotics (Japan) 



llA: 81-83, 1958. 



2. Suzuki, S. and Okuma, K. J. Antibiotics 



(Japan) 11 A: 84-86, 1958. 



Cellostalin 



Produced by: Streptomyces cellostalicus (1). 



Synonym: Similar to l)lasticidin S. 



Method of extraction: Broth-filtrate passed 

 through an IRC-50 column (11+) and eluted with 

 80 per cent aqueous acetone (I), followed by 80 

 per cent acetone containing 0.2 N HCl (II). Frac- 

 tion I contains an unrelated unti-Sarcina anti- 

 biotic. Fraction II is adjusted to pH 6.0, concen- 

 trated in vacuo, and dried. Residue extracted with 

 anhydrous methanol, filtered, and dried in vacuo. 

 Final precipitation from acidic methanol with 

 acetone. Purified by chromatography on alumina 

 and Darco G-60 (1). 



Chemical and physical properties: Basic sub- 

 stance. Very soluble in water; slightly soluble in 



methanol; insoluble in ethanol, butaiiol, acetone, 

 ether, and other organic solvents. Forms a pic- 

 rate, reineckate, and phosphotungstate. Stable at 

 acid and neutral pH. Ultraviolet absorption spec- 

 trum maximum at 265 niyu (E\cm 115) (distilled 

 water). Infrared spectrum given in reference 1. 

 Positive ninhydrin, Sakaguchi, and Molisch tests. 

 Negative biuret, Millon, Fehling, maltol, FeCls , 

 and Elson-Morgan tests. C = 22.10% (sic; proba- 

 bly 52.10%) ; H = 4.52%; N = 13.15%; O = 27.77%. 

 Sulfate: Colorless platelets. Reineckate: Crystal- 

 line substance; m.p. 156-166 °C (1). 



Biological activity: Very slightly active (50 to 

 100 fig per ml) on certain gram-positive and gram- 

 negative bacteria, including Micrococcus citreus, 

 B. anthracis, Sarcina lutea, Salmonella, Ps. aerugi- 

 nosa, Pr. vulgaris, and Clostridium botulinum, but 

 not Staph, aureus, E. coli, or B. subtilis. Slightly 

 more active (6.3 to 100 fxg per ml) on yeasts and 

 fungi. Static action on Trichomonas vaginalis at 

 100 fig per ml (1). Active on Ehrlich ascites carci- 

 noma (1, 2). 



Toxicity: LD50 (mice) about 15 mg per kg intra- 

 peritoneally (1). 



References: 



1. Hamada, S. Tohoku J. Ivxptl. Med. 67: 



173-179, 1958. 



2. Hamada, S. and Sato, S. Tohoku J. Ivxptl, 



Med. 67: 181-186, 1958. 



Cepliaioiiiyciii 



Produced by: Streptomyces tanashiensis var. 

 cephalomyceticus . 



Method of extraction: Adsorption on IRC-50 or 

 XE-64 resins (H"*"). Resins washed with water. 

 Elution with aciueous ammonia at pH 9.0. Pre- 

 cipitation of eluate at pH 3.6. Precipitate washed 

 with cold 2 per cent aqueous acetic acid, redis- 

 solved in water at pH 9.0, and centrifuged. The 

 supernatant adjusted to pH 5.1. The resulting 

 precipitate is purified further ]\v re])eating the 

 last series of operations. 



Chemical and physical properties: Protein-like, 

 brownish, amorphous substance. Does not pass 

 through semipermeable membranes. Soluble in 

 water at pH values of less than 1 or more than 6. 

 Insoluble in organic solvents. Salted out of aciue- 

 ous solutions at three-fourths saturation with 

 (NH4)2S04 . It is precipitated by alum, picric 

 acid, and trichloroacetic acid. Positive Sakaguchi, 

 biuret, ninhydrin, diazo, and Folin tests. Negative 

 Fehling, Molisch, and xanthoproteic reactions. No 

 decoloration of bromine and permanganate solu- 

 tions. C = 55.39%; H = 6.66%; N = 9,93%. S, P, 

 and halogens not detected. Acid hydrolysates 



