Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities.
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 approximately 12.5 and 6.3 approximately 50 micrograms/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: KNOPP'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.
Oki
T
T
Bristol-Myers Research Institute, Ltd., Tokyo Research Center, Japan.
Hirano
M
M
Tomatsu
K
K
Numata
K
K
Kamei
H
H
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D003515:Cycloleucine / Q000494:pharmacology / Q000627:therapeutic use / Q000031:analogs & derivatives; D004353:Drug Evaluation, Preclinical; D005437:Flucytosine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D003515:Cycloleucine; C065594:cispentacin; D000666:Amphotericin B; D005437:Flucytosine