Effects of squalene epoxidase inhibitors on Candida albicans

The relationship between sterol biosynthesis inhibition, membrane integrity, and cell growth inhibition in Candida albicans was examined for five squalene epoxidase inhibitors. The compounds were the thiocarbamates tolnaftate and tolciclate and the allylamines naftifine, terbinafine, and SDZ 87-469. All compounds inhibited sterol biosynthesis, with the concentrations that caused a 50% decrease in the total sterol-to-squalene ratio ranging from less than or equal to 0.01 microM for terbinafine and SDZ 87-469 to 500 microM for tolnaftate. At 100 microM, the compounds also caused up to a 30% release of intracellular [14C]aminoisobutyric acid. With terbinafine and SD2 87-469, aminoisobutyric acid release further increased in cells grown at concentrations that inhibited ergosterol biosynthesis. It is suggested that inhibition of ergosterol synthesis may render the C. albicans membrane susceptible to further damage, including direct damage from squalene epoxidase inhibitors.