Abstract
Using a wild-type strain of dimorphic pathogenic fungus Sporothrix schenckii, with both high susceptibility to butenafine and to an allylamine derivative naftifine, and several tolciclate-resistant mutant strains derived therefrom, the mechanism of action by which butenafine inhibits fungal growth was studied. Some of these mutant strains were revealed to be defective in the activity of squalene epoxidation, while others were not. All of the of tolciclate-resistant mutant strains showed cross-resistance to butenafine and naftifine. On the other hand, no significant difference in the response to a direct membrane-damaging action of butenafine in terms of induction of K+-release from the fungal cells was demonstrated between a susceptible wild-type strain and one resistant mutant strain of S. schenckii.
All of these experimental data suggest that in highly susceptible fungi such as S. schenckii, butenafine shares the target of action with thiocarbamates and allylamines, and that inhibition of squalene epoxidation by butenafine is primarily responsible for its antifungal activity.
