Relationship between antifungal activity and inhibition of sterol biosynthesis in miconazole, clotrimazole, and 15-azasterol.
AUTOR(ES)
Taylor, F R
RESUMO
The availability of Saccharomyces cerevisiae mutants which are defective in sterol biosynthesis makes it possible to determine whether the ability of several antifungal agents to inhibit cell growth is due to their effect on sterol production. 15-Aza-24-methylene-8,14-cholestadien-3 beta-ol (15-azasterol) is known to block the reduction of the sterol delta 14 bond following C-14 demethylation. This agent inhibits the growth of wild-type S. cerevisiae but does not inhibit the growth of a strain that is defective in the removal of the C-14 methyl group of lanosterol and in the introduction of the 5,6 double bond. 15-Azasterol does not inhibit the growth of a sterol auxotrophic strain growing on an exogenous supply of sterol. Therefore, the effect of 15-azasterol on sterol biosynthesis is clearly the cause of its ability to inhibit growth. On the other hand, growth inhibition by two imidazole antifungal agents, clotrimazole and miconazole, cannot be ascribed to their ability to prevent the removal of the C-14 methyl group of lanosterol, because they inhibit the growth of the sterol auxotrophic strain as well as that of the demethylase mutant.
ACESSO AO ARTIGO
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