212 



DESCRIPTIOXP OF ANTIBIOTICS 



Method of extraction: Broth-filtrate evaporated 

 in vacuo at pH 5.0, dried, and extracted with an- 

 hydrous methanol. Addition of butanol to extract 

 precipitates impurities; subsequent addition of 

 acetone to the methanol i)recii)itates the anti- 

 biotic (1). 



Chemical and physical properties: Crystalline 

 helianthate; m.p. 243-247°C (Ij. 



Biological activity: Active on mycobacteria (1). 

 Not active on other bacteria (2). 



Toxicity: Doses of 10 to 20 mg in mice (intra- 

 venously and intramuscularly) are nontoxic (1). 



References: 



1. Ouchi, N. Tohoku J. Exptl. Med. 51:144, 



1951 . 



2. Kurosawa, H. J. Antibiotics (Japan) 4: 



183-193, 1951. 



Antismegmatis Antibiotic 



Produced by: Strepfomyces sp. resembling .S. 

 lavendulae. 



Method of extraction: Concentration i)y ]jrecipi- 

 tation by cold. 



Chemical and physical propeities: Heat-stable 

 at pH 7.0. 



Biological activity: Most active, at an alkaline 

 reaction, against M. suieginatis and .1/. phlei. No 

 activity against bacteria, fungi, or a pathogenic 

 strain of M. bovis. 



Reference: 1. Kelner, A. and Morton, H. E. 

 Proc. Soc. Exptl. Biol. Med. 6:i: 227-230, 1940. 



.\iititunior Antibiotic 2559 



Produced by: Streptomyces sp. (1) reseml)ling *S. 

 tanashiensis (luteomycin-producer) (3). 



Synonym: Said to resemble luteomycin (1), but 

 differs in ultraviolet absorption spectrum, ele- 

 mentary analysis, and biological activity (3). 



Method of extraction: I. Broth-filtrate extracted 

 with ethyl or butyl acetate at pH 7.0. Re-extracted 

 into water at pH 2.0. Process repeated twice using 

 less solvent each time. Adjusted to pH 5.0 and 

 freeze dried. II. Adsorption on diatomaceous 

 earth from water or butyl acetate. Eluted with 

 acetone (1). 



Chemical and physical pioperties: Basic sub- 

 stance. Orange or reddish yellow powder. HCl 

 salt: Soluble in w^ater, methanol, ethanol, and 

 acetone. Sulfate: Orange or orange-brown crystals. 

 Soluble in water. Slightly soluble in ethanol and 

 acetone. Forms a picrate, reineckate, helianthate, 

 and citrate. Positive FeCls test. Negative ninhy- 

 drin, Molisch, and Sakaguchi tests. Indicator 

 properties: Changes from orange-yellow to purple 

 from pH 7.5 to 9.0. Ultraviolet absorption spec- 



trum (at acid pH) maxima at 215, 257, and 430 

 niM (1). At alkaline pH, the peaks shift toward the 

 longer wave lengths. Sulfate: C = 48.21%; H = 

 5.40%; N = 2.21%; S = 4.97%. C26H33NOi2-H2S04 . 

 Most stable at pH 3 to 6. Less stable at alkaline 

 pH. Thermolabile (2). Acid hydrolysis product is 

 biologically active "teomycic acid," CnHssHOr , 

 which is a green-black substance with vdtraviolet 

 absorption spectrum maxima at 258 to 261 m^ 

 (£'lem485) and 355 to 356 m^ (fi'iMn 151) (methanol) 

 and no melting point up to 300°C. Other data given 

 in reference 5. 



Biological activity: Active on gram-positive 

 bacteria, but less so than luteomycin. Very little 

 or no activity on fungi and gram-negative bac- 

 teria. Active on Toxoplasma gondii in vitro (4). 

 Active in vivo (rats) against Yoshida sarcoma (1). 

 Antimitotic effect (2). Kills HeLa cells at 10 Mg 

 per ml and causes disappearance of HeLa cells 

 in mitosis at 1.25 jug per ml (6). Teomycic acid 

 (hydrolysis jjroduct) moderately active on gram- 

 positive bacteria, including mycobacteria (3 to 

 50 ng per ml). No activity on fungi or gram-nega- 

 tive bacteria. No activity on Ehrlich ascites car- 

 cinoma (5). 



Toxicity: MLD (mice) about 10 mg per kg in- 

 travenously (1). 



Refetences: 



1. Umezawa, H. cl al. J. Antil)iotics (Japan) 



6A: 45-51, 1953. 



2. Osato, T. et al. J. Antibiotics (Japan) 6A: 



52-56, 1953. 



3. Okami, Y. et al. J. Antiliiotics (Japan) 



6A: 153-157, 1953. 



4. Okami, Y. et al. J. Antibiotics (Japan) 



8A: 126-131, 1955. 



5. Nakamura, S. J. Antibiotics (Japan) 9A: 



207-209, 1956. 



6. Umezawa, H. Giorn. microl)iol. 2: 160- 



193, 1956. 



Antitumor Substance 1418 Al 



Produced by: Streptomyces sp. 



Remarks: Not sufficiently characterized to per- 

 mit differentiation from certain other antibiotics 

 having antitumor activity and ultraviolet spectra 

 of a similar nature. Authors (1) state that it differs 

 from cellocidin and lenamycin. 



Method of extraction: Extraction of broth-filtrate 

 at pH 2.0 or 7.0 with butanol. Extract evaporated, 

 residual syrup washed with ether. Taken up in 

 benzene, concentrated, and filtered to remove 

 white precipitate of trans-cinnamic acid amide. 

 Subjected to countercurrent distribution (76 per 

 cent methanol-benzene-chloroform, 2:1:1). 



