DESCRIPTIONS OF ANTIBIOTICS 



181 



Toxicitij: LDjo (mice) 3.5 gm per kg intraven- 

 ously and 20 gm per kg subcutaneously (7). 

 References: 



1. Tejera, E. et al. Antibiotics & Chemo- 



therapy 2: 333, 1952. 



2. Grundy, W. E. et al. Antiliiotics & Chemo- 



therapy 2: 399-408, 1952. 



3. Hwang, K. Antibiotics tt Chemotherapy 



2:453-459, 1952. 



4. Sobin, B. A. J. Am. Chem. Soc. 74: 



2947-2948, 1952. 



5. Schenck, J. R. and DeRose, A. F. Arch. 



Biochem. Biophys. 40: 263-2(>9, 1952. 



6. McLamore, W. M. et al. J. Am. Chem. 



Soc. 75: 105-115, 1953. 



7. Miyake, A. et al. Pharm. Bull. (Tokyo) 



1: 84-88, 1953. 



8. Miyake, A. Pharm. Bull. (Tokyo) I: 



89-93, 1953. 



9. Okami, Y. et al . Japan. J. Aled. Sci. & 



Biol. 6: 87-90, 1953. 



10. Maeda, K. Japan. J. Med. Sci. & Biol. 



6: 143-149, 1953. 



11. Umezavva, H. et al. Japan. J. Met!. Sci. 



& Biol. 6: 395-403, 1953. 



12. Hamada, Y. et al. J. Antibiotics (Japan) 



6A: 159-162, 1953. 



13. DeBoer, C. et al. Antil)iotics Ann. 88(5- 



892, 1955-1956. 



14. British Patent 729,208, May 4, 1955. 



15. Personal communication, Chas. Pfizer and 



Company, January, 1960. 



Akla> ill 



Produced by: Streptomyces sp. 



Method of extraction: I. Culture Huid and my- 

 celium adjusted to pH 2.0, heated at 80°C for 10 

 minutes, cooled, and filtered. Mycelium retreated 

 with HCl at pH 2.0 with heating. Combined ex- 

 tracts adjusted to pH 5.0 and extracted with 

 chloroform. Chloroform extracts back-extracted 

 with water at pH 2.0. II. Aqueou.s extract ad- 

 justed with NaOH to pH 9.0 under a stream of 

 nitrogen and extracted with benzene. Benzene 

 reextracted with water at pH 2.0. Process re- 

 peated once. Lyophilization of the final aqueous 

 acidic extract yields crude aklavin hydrochloride. 



Chemical and physical properties: Crude aklavin 

 hydrochloride is very soluble in water, ethanol, 

 chloroform, dioxane, and pyridine; soluble in 

 acetone; and moderately soluble in ethyl acetate. 

 Concentrated HCl solution is yellow; concen- 

 trated H2SO4 solution intensely reddish purple. 

 A purplish pink color in alkaline solution is re- 

 versibly changed to yellow by Na2S204 . Addition 



of NH4OH to an ethanol solution of the purple- 

 blue magnesium acetate-aklavin complex pro- 

 duces a stable magenta-colored precipitate. 

 Ultraviolet absorption maxima at 228, 258, and 

 288 mix, and a visible light peak at 427 m/u. The 

 crude antibiotic appears to contain several frac- 

 tions, as shown by covmtercurrent distribution 

 (ethyl acetate and 0.2 M phosphate buffer, 

 pH 6.3). Melting points of crystalline salts: 168 

 or 1S8°C (picrate); 197°C (helianthate) ; 168 or 

 170°C (hydrochloride). Activity lost in alkaline 

 solution on exposure to air; diff'usibility in agar 

 media doubled by heating at 80°C for 10 minutes. 

 C36H40O18N4 (picrate): C = 52.80%; H = 4.97%; 

 O = 35.22%.; N = 6.85%. Formula of base: CsoH.-,,- 

 (JuN or a multiple. Acid hydrolysis indicates that 

 the antibiotic is made up of two moieties: a non- 

 l:)asic, water-insoluble moiety, and a colorless, 

 water-soluble basic structure. 



Biological activity: Active on a variety of bac- 

 teriophages; stimulates others. Some phages 

 stimulated by aklavin in phage-host system 

 are inhibited when free. Other phages that are 

 completely inhibited in phage-host system are 

 more resistant when free. Higher aklavin concen- 

 trations usually required for inactivation of free 

 phage than i)hage in phage-host system. Active 

 on some gram-negative and gram-positive bac- 

 teria, mycobacteria, fungi, and viru.ses. Mod- 

 erately virucidal for eastern equine encephalo- 

 myelitis virus (EEE), slightly for PR 8 influenza, 

 and not virucidal for MM virus or the Lansing 

 strain. Inhibits Y-SK poliomyelitis virus in 

 tissue culture. Active on EEE inoculated into 

 mice when a mixture of equal volumes of virus 

 (0.1 per cent) and antibiotic (0.01 mg ])er ml) 

 stood for 1 hour before inoculation. 



Toxicity: LDo (mice) 150 mg per kg intrave- 

 nously; 100 mg per kg given intraperitoneally is 

 not tolerated. 



Reference: 1. Strelitz, F. et al. J. Bacteriol. 

 72: 90-94, 1956. 



Alazopeptiii 



Produced by: Streptomyces griseoplanus (2). 



Synontjm: Distantly related to azaserine and 

 DON, which are diazo derivatives of amino acids. 

 Alazopeptin contains diazo groups in a peptide 



(!)• 



Method of extraction: Broth stirred with acti- 

 vated carbon. Antibiotic eluted with 50 per cent 

 acetone. Eluates concentrated in vacuo, residual 

 solution adjusted to pH 9.0 and extracted with 

 butanol containing 2 per cent Arquad 2C. Back- 

 extracted into water at pH 2.0 to 2.5. Aqueous 



