ANTIBIOTICS OF ACTINOMYCETES 229 



Production: Strep tomyciu-isoniazid complex, or streptohydrazid in the 

 form of the hydrochloride is prepared by boiling under reflux for 15 

 minutes in absolute methanol a mixture of 5 parts of streptomycin 

 hydrochloride and 1 part of isoniazid. Upon standing in the refrigera- 

 tor large crystals are slowly formed. In order to prepare the sulfate, 

 a mixture of streptomycin trihydrochloride calcium chloride double 

 salt, isoniazid and triethylamine sulfate is stirred in aqueous methanolic 

 solution for 30 minutes. The precipitated CaS0 4 is removed. Methanol 

 is added slowly as the white crystalline product is formed. 



Chemical and physical properties: The hydrochloride and sulfate of the strep- 

 tomycin-isoniazid complex are extremely water soluble and insoluble in 

 most organic solvents. Chemically they are streptomycylideneisonico- 

 tinylhydrazine trihydrochloride (C27H47NioOi 2 Cl 3 ) and streptomycyl- 

 ideneisonicotinylhydrazine sesquisulfate (C23H 4 4Ni Oi2-3/2H 2 SO4). 



Biological activity: Streptohydrazid therapy has been found to be as effective 

 in tuberculosis protection studies in animals as combined streptomycin- 

 isoniazid therapy. 



Utilization: Recommended in the treatment of various forms of tubercu- 

 losis. 



Reference: Pennington, F. C, Guercio, P. A., and Solomons, I. A., J. Am. 

 Chem. Soc, 75, 1953, 2261. 



Streptothricin 



Produced by: Streptomyces lavendulae. 



Synonyms: The following antibiotics are closely related to streptothricin: 

 streptin, lavendulin, streptolin, streptothricin VI, aerothricin and 

 pleocidin. 



Method of extraction: Adsorption on IRC 50 and elution with acid alcohol. 

 Adsorption on Decalso and elution with NH 4 C1. 



Chemical and physical properties: Basic substance. Not inactivated by cys- 

 teine. Contains two amino acids including isolysine and an amino sugar. 

 Soluble in water, insoluble in organic solvents except methanol. Stable. 

 C 2 oH 3 6N 8 9 -3HCl. 



Biological activity: Active against gram-positive and gram-negative bac- 

 teria, mycobacteria, and certain fungi. Not active against rickettsiae 

 and viruses. Little activity against Bacillus cereus-mycoides group. 



Toxicity: LD 60 (mice), intravenous, 250 mg/kg. High delayed toxicity. 



Utilization: Possible use in topical application. 



Reference: Waksman, S. A., and Woodruff, H. B., Proc. Soc. Exptl. Biol. 

 Med., 49, 1942, 207-210; Hutchison, D., Swart, E. A., and Waksman, 

 S. A., Arch. Biochem., 22, 1949, 16-30; Molitor, H., Ann. N. Y. Acad. 

 Sci., 48 (art. 2), 1946, 101-118. 



