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Antimicrobial Agents and Chemotherapy, 07 1995, 1538-1541, Vol 39, No. 7
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

Inhibition of sterol 4-demethylation in Candida albicans by 6-amino-2-n- pentylthiobenzothiazole, a novel mechanism of action for an antifungal agent

T Kuchta, C Leka, P Farkas, H Bujdakova, E Belajova and NJ Russell
Food Research Institute, Bratislava, Slovakia.

The effects of 6-amino-2-n-pentylthiobenzothiazole (APB), a new antifungal agent, on ergosterol biosynthesis in Candida albicans and Saccharomyces cerevisiae were studied, using [14C]acetate incorporation. In C. albicans, the inhibition of growth was accompanied by a marked inhibition of acetate incorporation in 4-desmethylsterols, with a significant portion of the radiolabel being incorporated in 4,4- dimethylsterols, lanosterol, and 4,4-dimethylzymosterol and minor amounts being incorporated in 4-methylsterols and squalene. The data are interpreted as evidence of a block of the ergosterol biosynthesis pathway at the level of 4-demethylation of 4,4-dimethylzymosterol, with partial inhibition of lanosterol 14-dimethylation and squalene epoxidation also being possible. In 6-amino-2-n-pentylthiobenzothiazole- treated S. cerevisiae, a significant amount of the radiolabel was incorporated also in 4-methylsterols, 4-methylzymosterol, and 4- methylfecosterol, indicating that in this microorganism there are different sensitivities of the two 4-demethylations and that the pathway is blocked at the level of 4-demethylation of 4-methylsterols.