DESCRIPTIONS OF ANTIBIOTICS 



211 



17. Nakayama, K. et al. J. Antilnotics (Ja- 

 pan) 9A: 63-()6, 195(). 



IS. Sakagami, Y. et al. J. Antil)iotics (Japan) 

 9A: 1-5, 1956. 



19. Nakazawa, K. Meeting Japan Antil)iotic 



Research Assoc. 1953 (as given in refer- 

 ence 18). 



20. Tener, G. M. Doctoral Dissertations U: 



343, 1954 (as given in Velick, S. F. Ann. 

 Rev. Biochem. 25: 284, 1956). 



21. Miyakawa, T. et al. Japan. J. Microliiol. 



2: 53-62, 1958. 



22. Tarnowski, G S. and Stock, C. C. Cancer 



Research 18: (Suppl. I) 25, 1958. 



23. Liu, W. C. Dissertation Abstr. Univer- 



sity of Wisconsin, 19: 662, 1958. 



24. Harada, Y. et al. J. Antilnolics (Japan) 



11 A: 32-35, 1958. 



25. Burger, J. Quoted in reference 2(i. 



26. Strong, F. M. Topics in microbial chem- 



istry. John Wiley and Sons, Inc., New 

 York, 1958, pp. 1-43. 



27. Karasawa, K. et al. J. Gen. A])])l. Micro- 



biol. 5: 13-20, 1959. 



28. Van Tamelen, E. E. et al. J. Am. Chem. 



Soc. 81: 750-751, 1959. 



Anlini> coin 



Produced by: Streptoiiiyces aureus (1). 



Synonyms: Fungicidin RAW; antibiotic C 381. 



Remarks: Following the original description (1) 

 of this antibiotic, the culture ceased to produce 

 the polyene. It was later found that production 

 of one of the components of the original complex 

 could be induced bj- the addition of high concen- 

 trations of CaCl-2 or AlgCle and mevalonic acid 

 to the culture medium (4, 5). 



Method of extraction: Broth extracted with 

 butanol. Extract cooled to precipitate lipid im- 

 ])urities, then concentrated to dryness in vacuo. 

 Residue washed with petroleum ether, then ace- 

 tone, and dried. Residue can also be taken up in 

 ethanol, filtered, and distilled to dryness. Pre- 

 cipitates from an ethanol solution on addition of 

 ice-cold ether (1). 



Chemical and physical properties: Tetraene. 

 Original complex (see "Remarks'") contains two 

 active components, Rf values about 0.55 and 0.45 

 (ethanol- n-butanol-water, 1:5:5). The faster 

 moving component is called antimj'coin A (4, 5). 

 Complex: Soluble in water, ethanol, and physio- 

 logical saline solution. Insoluble in ether, chloro- 

 form, and acetone. Unstable at acid pH; most 

 stable at pH 7.0. Ultraviolet absorption spectrum 

 maxima at 290, 305, and 316 m/x (ethanol) (1, 4). 



Ditl'ers from nystatin and rimocidin (1, 3). Ciude 

 antimycoin A: Brown or gray substance. Soluble 

 in pyridine, butanol, and dimethj-l sulfoxide (5). 



Biological activity: Active on yeasts and fungi, 

 including Cryptococcus. Not active on bacteria or 

 actinomycetes. Prevents C. albicans infection and 

 has some activity on Histoplasma capsulatum in 

 ovo. Active in vivo (mice) on Coccidioides immitis 

 infections (1, 2). 



Toxicity: LD50 (mice) 204 mg per kg intraperi- 

 toneally (1), >532 mg per kg subcutaneously (2). 



References: 



1. Raubitscheck, F. e/ a/. Antil)iotics cV Chem- 



otherapy 2: 179-183, 1952. 



2. Schwartz, J. A. et al. 11th Conf. Tul)erc. 



Vet. Adm. 86-93, 1952. 



3. Oroshnik, W. et al. Science 121: 147-149. 



1955. 



4. Schaffner, C. P. et al. Antiliiotics Ann. 



869-873, 1957-1958. 



5. Steinman, I. D. Thesis, Rutgers University, 



1958. 



Anliphlei Antibiotic I 



Produced by: Streptomyces sp. resembling S. 

 aureus. 



Method of extraction: Broth adjusted to pH 5.0 

 and filtered. Filtrate evaporated in vacuo to dry- 

 ness and extracted with methanol. Extract evap- 

 orated to dryness and re-extracted into methanol. 

 Addition of butanol in excess, concentration 171 

 vacuo of supernatant, and precipitation with ace- 

 tone. Reprecipitated from methanol with acetone. 

 Purified l\v conversion to helianthate, then hj'- 

 drochloride. 



Chemical and physical properties: Basic sub- 

 stance. HCl salt: White amorphous powder. Heli- 

 anthate: Crystalline; m.p. 243-247°C. (decomposi- 

 tion). Negative l)iuret, xanthoproteic, Millon, 

 Sakaguchi, Vole sulfur, Hopkins-Cole, Molisch, 

 glucosamine, and maltol tests. Most stable to 

 boiling at pH 5 to 6; less stable at alkaline than 

 at acid pH. Soluble in anhydrous methanol. 



Biological activity: Active mainly on M. phlei. 

 Less active on M. tuberculosis (human type), M. 

 smegmatis, and M. avium. Very slight activity on 

 B. subtilis and B. anthracis. No activity on gram- 

 negative bacteria. 



Toxicity: Mice tolerate 10 to 20 mg of the crude 

 HCl salt intramuscularly and intravenously. 



Reference: 1. Ouchi, N. Tohoku J. Exptl. Med. 

 55: 355-365, 1952. 



Antiplilei Antibiotic II 



Pioduced by: Streptomyces aureus (2). 

 Synonym: New antiphlei factor (2). 



