190 THE ANTIBIOTICS 



Utilization: None. Inactive in vivo; no chemotherapeutic effect in experi- 

 mental tuberculosis in mice. 



Reference: Grundy, W. E., Whitman, S. L., Rdzok, E. G., Rdzok, E. J., 

 Haines, M. E., and Sylvester, J. C., Antibiotics & Chemotherapy, 

 2, 1952, 399-408; Schenck, J. R., and DeRose, A. F., Arch. Biochem. 

 and Biophys., 40, 1952, 263-269; Clark, R. K. Jr., and Schenck, J. R., 

 ibid., 270-276; Hwang, K., Antibiotics & Chemotherapy, 2, 1952, 

 453-459; Sobin, B. A., J. Am. Chem. Soc, 74, 1952, 2247; McLamore, 

 W. M., Celmer, W. D., Bogert, V. V., Pennington, F. C, and Solomons, 

 I. A., ibid., 2246; Tejera, E., et al., Antibiotics & Chemotherapy, 2, 

 1952, 233. 



Amicetin 



Produced by: Streptomyces sp., S. fasciculatus 



Method of extraction: Extraction of clarified fermentation broth with n-butanol 

 at pH 7.5. Concentration by distillation, extraction of the residue 

 with water, lyopbilization of the aqueous solution, which can be 

 further purified by countercurrent distribution between water and 

 methylene chloride. Amicetin can be finally crystallized from water. 



Chemical and physical properties: Crystals melt at 160-165°C. On warming 

 to 50-70° in methanol or water suspension, they are converted to a 

 granular high melting point crystal form of the free base with the prop- 

 erties: m.p. 243-244° [a]™ + 116.5° (c, 0.5 in O.liV hydrochloric acid); 

 solubility in water at 25°, 1-2 mg/ml; only slightly soluble in common 

 organic solvents. Amicetin exhibits characteristic ultraviolet absorp- 

 tion: in neutral aqueous solution at the maximum at 305 m/r, in O.liV 

 hydrochloric acid, at 316 m/z; and in O.liV sodium hydroxide, at 322 

 nux. Titration data and analyses suggest the formula C29H44N6O9 for 

 the free base. 



Biological activity: Active largely against gram-positive bacteria, especially 

 mycobacteria. 



Toxicity: The acute intravenous LD 5 o of amicetin as the citrate complex 

 at pH 6 in mice is approximately 90 mg/kg; the subcutaneous LD B o, 

 600-700 mg/kg. In rats the acute intravenous LD B o is approximately 

 200 mg/kg. Amicetin is especially toxic to guinea pigs: by the sub- 

 cutaneous route it is about forty times as toxic as streptomycin, but 

 on the other hand only about one-tenth as toxic as penicillin to this 

 same species. 



Utilization: No data. 



Reference: DeBoer, C, Caron, E. L., and Hinman, J. W., J. Am. Chem. Soc, 

 75, 1953, 499; McCormick, M. H., and Hoehn, M. M., Antibiotics & 

 Chemotherapy, 2, 1953, 718-720. 



