Effects of three azole derivatives on the lipids of different strains of Cryptococcus neoformans

Abstract

The comparative effects of ketoconazole, itraconazole and fluconazole on the lipids of four Cryptococcus neoformans strains were investigated. Quantitative analysis of lipids and sterols was completed, as well as qualitative analysis of sterols by thin-layer chromatography and by the ultraviolet spectrum. Growth of the cryptococcal isolates in the presence of the azoles derivatives concentrations below the minimum inhibitory concentration resulted in significant alterations in the lipid and sterol contents as compared with the control values. Furthermore, lanosterol was detected in these azole-treated cells. These results were in complete agreement with the proposed mechanism of action of azoles, which act through the inhibition of ergosterol biosynthesis, with resultant accumulation of lanosterol. Ketoconazole was found to be the least effective drug, as determined from a comparison of the effect of the three azoles on the sterol content of the four strains. Itraconazole showed to be the most effective drug, probably because of its high lipophilicity, which allows the drug to penetrate into fungi cells more efficiently.