Novel antifungal agents which inhibit lanosterol 14alpha-demethylase in Candida albicans CCH442.

We have identified four non-azole inhibitors of lanosterol 14a-demethylase in Candida albicans CCH442. The most potent compound, A-39806, had IC50 values for ergosterol inhibition of 0.9 microM (0.3 mg/L) and 1.9 microM (0.6 mg/L) in whole cell and cell-free extract assays, respectively. A-39806 demonstrated broad in-vitro antifungal activity against several Candida species as well as against Cryptococcus albidus and Aspergillus niger. In-vitro antifungal activity was also demonstrated against a fluconazole-resistant clinical isolate of C. albicans.