A NEW ANTIBIOTIC, IKARUGAMYCIN

A protozoan Tetrahymena pyriformis W as a test organism can be useful in the preliminary screening for antiprotozoals, especially antitrichomonas agents. By this screening method, ikarugamycin, a new antibiotic with specific antiprotozoal activity was found in the culture of Streptomyces sp. No. 8603 isolated from a soil sample. The morphological characteristics of Streptomyces sp. No. 8603 include formation of gray aerial mycelium, dark brown growth and aerial hyphae forming a long spiral. Strain No. 8603, belonging to a chromogenic type, was identified as a variety of Streptomyces phaeochromogenes and given the name Streptomyces phaeochromogenes var. ikaruganensis SAKAI. Ikarugamycin was isolated as white crystalline needles, decomposing at 252-255°C, and exhibiting optical rotation [α]20D+360° (c 1.10, dimethylformamide). Its molecular formula C29H38O4N2 was given by elementary and mass spectrum analyses. The ultraviolet absorption gave two maximal peaks at 220mμ and 325mμ in methanol. Ikarugamycin showed strong antiprotozoal activities: MIC 0.3-1.25 mcg/ml against Trichomonas vaginalis, MIC 1.0 meg/ml against Tetrahymena pyriformis W and MIC 2-10 meg/ml against Entamoeba histolytica. The median lethal dose of ikarugamycin was 6 mg/kg, determined in mice by intraperitoneal administration. Hexahydro-ikarugamycin was obtained by catalytic hydrogenation of ikarugamycin and its physicochemical and biological properties were investigated. It is similarly active against T. vaginalis as is the antitrichomonas agent, azalomycin F and its acute toxicity (LD50 300 mg/kg, ip, in mice) is less than that of ikarugamycin and azalomycin F.