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.
Zakula
D
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Anti-infective Research Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Capobianco
J O
JO
Goldman
R C
RC
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D058886:Sterol 14-Demethylase
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase