Chloroacetamide derivatives as a promising topical treatment for fungal skin infections.

The aim of this study was to evaluate the antifungal potential of 11 chloroacetamide derivatives and derivative incorporated into a film-forming system (FFS) as a potential alternative for the topical treatment of superficial and skin mycoses. The minimum inhibitory concentration (MIC) evaluation followed Clinical and Laboratory Standards Institute protocols M27-A3 (Candida) and M28-A2 (dermatophytes). Compounds 2, 3, and 4 were the most effective against Candida species (MIC range: 25-50 µg/mL) and dermatophytes (MIC range: 3.12-50 µg/mL). Compound 2 maintained its antifungal activity when incorporated in a FFS, with MIC values equivalent to the free compound. In addition, the compound does not act through complexation with ergosterol, suggesting that it may act on other targets of the fungal cell membrane. Chloroacetamide derivatives presented anti-Candida and anti-dermatophytic effectiveness. The FFS containing compound 2 has shown to be superior to traditional topical treatment of superficial and cutaneous fungal infections. It was found that these new chemical entities, with their applicability, are an excellent alternative to the topical treatment of fungal skin infections.