338 



DESCRIPTIONS OF ANTIBIOTICS 



acetone-eluates in the cold and recrystallized from 

 50 per cent aqueous acetone. 



Chemical and physical properties: Long; needles; 

 m.p. 18-t-190°C (decomi)osition) with yellowing at 

 125-130°C. Soluble in chloroform, acetone, ethanol, 

 and n-butanol. Slightly soluble in anhydrous 

 methanol and ethyl acetate. Insoluble in water, 

 benzene, ether, and petroleum ether. Electropho- 

 retic paper chromatography indicates that the 

 antibiotic is neutral or weakly basic. Negative 

 ninhydrin, Fehling, biuret, Molisch, Hopkins- 

 Cole, Millon, Ehrlich (p-dimethylbenzaldehyde), 

 and FeCls reactions. Thermostable in a wide pH 

 range. No characteristic ultraviolet absorption. 

 Infrared absorption spectrum given in reference 1 . 



Biological activity: Active on a certain phage- 

 sensitive strain of E. coli B and moderately active 

 on Sal. enteritidis, but not other salmonellae 

 tested. Moderately active on B. anthracis, Sar- 

 €ina Intea, and Micrococcus citreus. Not active on 

 Staph, aureus, Shigella sonnei, Ps. aeruginosa, 

 or Pr. vulgaris. Prevents placpie formation by Ts 

 and Tt coliphages in the presence of host E. coli 

 B, l)ut at concentrations slightly lower than those 

 reciuired to inhibit the host. Not active on free 

 phage, and does not prevent absorption of Tj . 

 Action (using Ts phage) shown not to be on 

 intracellular phage synthesis, but the inhibition 

 of lysis of the host cell, thus preventing release of 

 intracellular phage (2). 



References: 



1. Hamada, M. J. Antibiotics (Japan) lOA: 



74-79, 1957. 



2. Higo, N. Japan. J. Microbiol. 2: 203-215, 



1958. 



Phalaniyciii 



Produced by: Streptomyces noursei. This strain is 

 a variant of the nystatin-producer. 



Method of crtractiou: Broth-filtrate frozen, then 

 thawed. First two sevenths of melt, containing 

 most of the antibiotic, extracted with ethyl acetate 

 -at pH 7.5 to 8.0. Extract concentrated in vacuo. 

 Residue taken up in methanol, cooled, filtered, 

 and concentrated in vacuo. Chloroform solution of 

 residue washed with water and concentrated in 

 vacuo. Residue washed with ether and extracted 

 with ethyl acetate. Crystallized from acetone. 

 Can also be extracted from mycelium (1, 2). 



Chemical and physical properties: Fragile, long, 

 sharp-pointed hexagonal plates. No characteristic 

 melting point; gradually decomposes but does 

 not melt when heated to 285°C. Soluble in lower 

 alcohols, esters, chloroform, and acetone. Slightly 

 soluble in benzene, ether, and water. No charac- 



teristic ultraviolet spectrum. Infrared data given 

 in reference 2. Tests indicate the presence of un- 

 saturation, enolic function, and primary or sec- 

 ondary alcoholic function. Negative biuret, nin- 

 hydrin, Sakaguchi, Molisch, Millon, and FeClj 

 tests, as well as tests for organic base and methyl 

 ketone. Relatively stable from pH 2.5 to 7.0. C = 

 53.5%; H = 5.45%; N = 13.65%; S = 5.11% 

 (4); or C = 50.10%; H = 4.78%; S = 3.67%; N = 

 14.98%. C36H41O14N9S (2). Does not contain the 

 same amino acids as bryamycin (4). 



Biological activity: Active on gram-positive 

 bacteria, including mycobacteria and nocardiae. 

 Inactive on gram-negative l)acteria and fungi 

 (1). Tests with pure material failed to confirm 

 earlier reports on in vivo activity on Streptococcus 

 henwlyticus (Grovip A) infections in mice (3). 



Toxicity: Mice tolerate > 115.7 mg per kg sub- 

 cutaneously, and >29 mg per kg intraperitoneally, 

 of the crude material. An oral dose of about 1 

 gm per kg of purified phalamycin tolerated by 

 mice, possibly as a resvUt of poor al)sorption (3). 



References: 



1. Brown, R. and Hazen, E. L. Antibiotics & 



Chemotherapy 3 : 818-821 , 1953. 



2. Brown, R. Ann. Rept. Div. Lali. and Re- 



search, N.Y. State Dept. Health. 18-19, 

 1956. 



3. Hazen, E. L. Ann. Rept. Div. Lab. and 



Research, N. Y. State Dept. Health 19-20, 

 1956. 



4. British Patent 790,521, February 12, 1958. 



Phleoniycin 



Produced hi/: Streptomyces verticillus (3). Broth 

 contains two other antibiotics active on B. subtilis 

 but ina-itive on Staph, aureus or Mycobacterium 

 607 (4). 



Method of extraction: Adsorl)ed from broth at 

 pH 7.0 onto Amberlite IRC-50 (Na+ phase) and 

 eluted with 10 per cent NaCl. Active fractions 

 pooled and concentrated in vacuo. Concentrate 

 cooled, filtered to remove the salts, and acetone 

 added to precipitate phleomycin. Reprecipitated 

 from a concentrated methanolic solution by addi- 

 tion of ether. Purification by chromatography on 

 alumina with 80 per cent methanol as solvent and 

 developer. Prepared as a reineckate (1, 3). Rei- 

 neckate washed with ammonia-acetone to give 

 base. Purified by chromatography on alumina 

 (water-methanol, 1:2 to 3) (4). 



Chemical and physical properties: Hydrochloride: 

 White, amorphous, hygroscopic powder. Soluble 

 in water, dilute ethanol, and methanol. Slightly 

 soluble in ethanol. Insoluble in acetone, ether, 



