A. Fujie et al., FR901469, a novel antifungal antibiotic from an unidentified fungus no.11243 - II. In vitro and in vivo activities, J ANTIBIOT, 53(9), 2000, pp. 920-927
FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23)
that has inhibitory activity against 1,3-beta-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 0.16 mu g/ml, respectively. FR901469 showed excellent efficacy by subcu
taneous injection against both Candida albicans and Aspergillus fumigatus i
n a murine systemic infection mode, with ED(50)s of 0.32 and 0.2 mg/kg, res
pectively. This compound also showed potent anti-Pneumocystis activity in t
he 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.