Simple isolation of antimycin A1 and some of its toxicological properties

An unidentified actinomycete, RTI 246, was found to produce antimycin A(1) in high yield on a high protein cereal medium. The antibiotic compound was extracted from the cells and isolated in pure form by crystallization. It was identified by ultraviolet, infrared, nuclear magnetic resonance, and mass spectroscopy and by alkaline hydrolysis to antimycic acid and a neutral lactone. The intravenous LD(50) was 1.0 mg/kg in white mice, whereas the intraperitoneal LD(50) was 1.50 +/- 0.19 mg/kg. Animals receiving an intraperitoneal injection displayed an incoordination of the hind limbs and impaired reflexes before showing signs of respiratory distress. These findings indicated that antimycin A(1) possesses a neurotoxic property separate from its well-documented property as a respiratory poison.