FR901469, a Novel Antifimgal Antibiotic from an Unidentified Fungus No.11243

II. In Vitro and In Vivo Activities

Abstract

FR901469 is a water-soluble macrocyclic lipopeptidolactone (C₇₁H₁₁₆N₁₄O₂₃) that has inhibitory activity against 1, 3-β-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16μg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED₅₀s of 0.32 and 0.2mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells is about 30-fold weaker than that of amphotericin B.