Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans.
AUTOR(ES)
Ryder, N S
RESUMO
Naftifine, a new antimycotic drug of the allylamine class, is a potent inhibitor of ergosterol biosynthesis in Candida albicans. Treated cells showed a dose-dependent drop in ergosterol content; the level was reduced by 60% at concentrations of greater than 50 mg/liter, causing total inhibition of growth. This inhibition coincided with a heavy accumulation of the sterol precursor squalene. Radiolabeling experiments showed that the inhibition of sterol synthesis was complete within 10 min of exposure of cells to the compound. Control cells incorporated [14C]acetate into nonsaponifiable lipids composed primarily of ergosterol, whereas naftifine-treated cells accumulated only labeled squalene. When the drug was removed by washing cells thoroughly in 1% Tween 80, the accumulated squalene was further metabolized to ergosterol. A similar pattern of inhibition was observed in sterol biosynthesis from [14C]mevalonate in a cell-free system. At 50 mg/liter, naftifine gave greater than 99% inhibition of sterol biosynthesis both in whole cells and in cell extracts of C. albicans. The primary action of naftifine appears to be the blocking of fungal squalene epoxidation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=185557Documentos Relacionados
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