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Monday 24 September 2007

Antifungal canthin-6-one series accumulate in lipid droplets and affect fatty acid metabolism in Saccharomyces cerevisiae.

By: Lagoutte D, Nicolas V, Poupon E, Fournet A, Hocquemiller R, Libong D, Chaminade P, Loiseau PM.

Biomed Pharmacother 2007 Aug;(): [Epub ahead of print]

The mechanism of action of antifungal canthin-6-one series was investigated in Saccharomyces cerevisiae. After a rapid uptake, a preferential accumulation of the drug within lipid droplets was observed. The antifungal action of canthin-6-one was found as reversible. Canthin-6-one did not exhibit affinity for sterols, and membrane ergosterol was not necessary for the antifungal activity since the MICs were similar on an ergosterol-deleted and the wild-type S. cerevisiae clones. Relative amount of unsaturated alkyl chain fatty acids was significantly enhanced suggesting a stimulation of desaturase enzyme systems. No synergistic effect was observed between canthin-6-one and amphotericin B, ketoconazole and caspofungine. Canthin-6-one should now be evaluated in vivo against fungal pathogens.

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