DESCRIPTIONS OF ANTIBIOTICS 



219 



less prisms (7); m.p. 2S1-284°C (decomposition) 

 (1, 4, 7). Soluble in aqueous NaOH and NH4OH 

 (j-ellow solutions). Slightly soluble in methanol, 

 ethanol, propylene glycol, acetone, ethyl acetate, 

 and butjd acetate. Almost insoluble in water, car- 

 bon disulfide, carbon tetrachloride, ether, and 

 petroleum ether (7). Ultraviolet alisorption maxi- 

 mum at 313 (E'JcL 680) or 31-4 mju (£^lcm 905) in 

 ethanol. Infrared spectrum given in reference 7. 

 Optically inactive in methanol. Negative Pauly, 

 Sakaguchi, FeCls , ninhydrin, biuret, Fehling, 

 ^Nlolisch, and Millon tests. After catalytic hydro- 

 genation, gives positive Pauly reaction. No S or 

 halogen (1, 4, 7). At pH 2.0 to 8.0, 50 per cent of 

 the antibiotic activity lost at 100°C in 30 minutes 

 (4). C3H3N3O2 (3): C = 31.89%; H = 2.65%; N = 

 36.75% (7). 2-Nitro-imidazole. Structural formula 

 given in Chapter 6. Acetylaminoazomycin deriva- 

 tive: Fine needles; m.p. 278-279°C (decomposition) 

 (7). 



Biological activity: Inhibits the growth of gram- 

 positive and gram-negative bacteria at 3 to 25 

 fxg per ml. Active on mjcobacteria. No antifungal 

 activity (1). Active on Trichomonas but not Eu- 

 glena gracilis or Tetrahymena geleii (8). Inhibits 

 ascites increase in mice with Ehrlich carcinoma 

 but does not prolong survival time (5). 



Toxicity: LDso (mice) 80 mg per kg intrave- 

 nously (Ij. 



References: 



1. Maeda, K. et al. J. Antibiotics (Japan) ()A: 



182, 1953. 



2. Okami, Y. ct al. J. Antil)iotics (Japan) 7A: 



53-54, 1954. 



3. Nakamura, S. and Umezawa, H. J. Anti- 



biotics (Japan) 8A: 66, 1955. 



4. Osato, T. et al. J. Antibiotics (Japan) 8A: 



105-109, 1955. 



5. Nitta, K. et al. J. Antiliiotics (Japan) 8A: 



120-125, 1955. 



6. Ueda, M. and Umezawa, H. J. Antil)iotics 



(Japan) 8.4: 164-167, 1955. 



7. Nakamura, S. Pharm. Bull. (Tokyo) 3: 



379-383, 1955. 



8. Horie, H. J. Antibiotics (Japan) 9A: 168, 



1956. 



9. Taguchi, H. and Nakano, A. J. Fermenta- 



tion Techno!. 3.5: 191-195, 1957. 



Bacteriolytic Factors 



Produced by: Various species of Streptomyces 

 ■capable of producing enzymatic systems with the 

 capacity to cause the lysis of dead and living l)ac- 

 teria. Hence thej- are designated as bacteriolysins. 

 Actinomj'cetin, described previously, belongs to 



this group of (■()ini)()unds. Theoretically these sub- 

 stances should l)e considered as antibiotics, since 

 they are produced by microorganisms and are able 

 to suppress the growth of and even to kill micro- 

 organisms. 



Method of exiractiun: The best yield of l)acteri- 

 olysin is obtained on semisynthetic medium 

 containing casein hydrolysate as a source of ni- 

 trogen. Production rate is greater at 37°C than 

 at 30°C. The preparation can be concentrated by 

 precipitation with (NH4)..S04 , followed bj- cHaly- 

 sis of the dissolved precipitate. 



Biological activity: Lysis of living bacteria 

 slower than that of dead cells. Highly fibrinolytic, 

 causing hydrolysis of extracts of M antigen from 

 Streptococcus pyogenes. 



Reference: 1. Pakula, R. et al. Acta Microbiol. 

 Polon. 3: 363-371, 1954. 



Baiiiicetiii 



Produced by: Streptomyces plicatus (1). 



Remarks: Produced simultaneoush' with amice- 

 tin and amicetin B (plicacetin) ; differs from ami- 

 cetin in having one less — CH-2 group in the glycosi- 

 dic moiety. 



Synonym: Antil)iotic L) (1). 



Method of extraction: Broth acidified and filtered. 

 Filtrate (pH 5.5) concentrated in vacuo. Concen- 

 trate extracted in a Podl)ielniak extractor with 

 1-butanol at pH 8.6. Extract back-extracted into 

 0.05 .V H0SO4 ; pH of acidic extract adjusted to 

 5.5. Concentration in vacuo. Residue extracted 

 into butanol at pH 8.6. Addition of acetone fol- 

 lowed by butanol-acetone (50:50) gives gelatinous 

 precipitate (I). A water suspension of I stirred 

 with acetone gives a granular precipitate (II), 

 which is a mixture of amicetin and bamicetin. II 

 suspended in dipotassiiun hydrogen phosphate, 

 adjusted to pH 8.2 with HCl, water added, and 

 mixture extracted with chloroform in a Porlbiel- 

 niak extractor. Chloroform-extracts contain the 

 amicetin; the aqueous solution (III), bamicetin. 

 Ill adjusted to pH 5.5 and concentrated in vacuo. 

 Residue extracted with butanol at pH 8.5. Butanol 

 concentrated. Addition of acetone, followed by 

 acidic butanol-acetone gives the hydrochloride. 

 Conversion to the ba.se, followed by treatment 

 with absolute ethanol to give the high melting 

 point form. The ethanol -insoluble powder (IV) 

 leached with water. Purification by dissolving IV 

 in dilute aciueous methanol, lyophilization, and 

 recrystallization from absolute ethanol (2, 3). 



Chemical and physical properties: Dense white 

 microcrystals; m.p. 240-241 °C (decomposition). 

 [a]-;3 = +123° (c = 0.5 per cent in 0.1 A' HCl). Has 



