Nanoemulsion Improves the Antifungal Activity of Allylic Thiocyanates against Yeasts and Filamentous Pathogenic Fungi

We report the antifungal and antichemotactic activities of a series of allylic thiocyanates with low toxicity. We also show improved antifungal activity of the most promising compound when used in a nanoemulsion (NE). The 4-chlorophenyl-substituted allylic thiocyanate (compound 11) exhibited a broad spectrum of antifungal activity and showed antichemotactic effects with 100% reduction in leucocyte migration. Minimal inhibitory concentrations ranged from 25 to 50 mu g mL(-1), and the mechanism of action was related to complexation with fungal ergosterol. The NE containing compound 11 enhanced the antifungal activity approximately 64-fold for dermatophytes and 4-fold for Candida spp.. Compound 11 was not mutagenic and did not cause cell death or significant haemoloysis, although it exhibited mild dose-dependent DNA damage. It was not an irritant for chorioallantoic membrane of fertile white eggs and exhibited 100% inhibition of fungal growth in an in vivo model of dermatophytosis. Our data indicate that allylic thiocyanates are very promising for the antifungal potential in nanostructured systems, with associated anti-inflammatory effect.