Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities

Abstract

Cispentacin ((-)-(1R, 2S)-2-aminocyclopentane-1-carboxylic acid) is a new antifungal antibiotic possessing potent anti-Candida activity. The 50% inhibitory concentration (IC50) and IC100 values of cispentacin against clinical isolates of Candida albicans were in the ranges 6.3 ~12.5 and 6.3~50 μg/ml, respectively, by turbidimetric measurement in yeast nitrogen base glucose medium. No significant activity was seen against any yeasts and molds when tested by the agar dilution method using three different agar media; KNOPF'S agar, yeast extract-glucose-peptone agar and Sabouraud dextrose agar. This antibiotic demonstrated good therapeutic efficacy against a systemic Candida infection in mice by both parenteral and po administrations. The 50% protection dose (PD50) values after single iv and po administrations were 10 and 30 mg/kg, respectively. It was also effective in a systemic infection with Cryptococcus neoformans and in both lung and vaginal infections with C. albicans in mice. Cispentacin did not induce acute lethal toxicity at 1,000 mg/kg by iv injection and 1,500 mg/kg by ip and po administrations in mice. © 1989, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.