Imidazolium salts with antifungal potential against multidrug-resistant dermatophytes

AimsTo investigate the antidermatophytic action of a complementary set imidazolium salts (IMS), determining structure-activity relationships and characterizing the IMS toxicological profiles. Methods and ResultsThe susceptibility evaluation of 45 dermatophytic clinical isolates, treated invitro with eleven different IMS (ionic compounds) and commercial antifungals (nonionic compounds), was performed by broth microdilution, following the standard norm of CLSI M38-A2. All dermatophytes were inhibited by IMS, where the lowest minimum inhibitory concentration (MIC) values were observed for salts with n-hexadecyl segment in the cation side chain, containing either the chloride or methanesulfonate anion. 1-n-Hexadecyl-3-methylimidazolium chloride (C(16)MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C(16)MImMeS) acted as fungicides, even in extremely low concentrations, wherein C(16)MImMeS exerted this effect on 100% of the tested dermatophytes. Some of these IMS provoked evident alterations on the fungi cell morphology, causing a total cell damage of 70%. Importantly, none of the screened IMS were cytotoxic, mutagenic or genotoxic to human leucocyte cells. ConclusionsThis report demonstrates for the first time the strong antifungal potential of IMS against multidrug-resistant dermatophytes, without presenting toxicity to human leucocyte cells at MIC. Significance and Impact of the StudyThe expressive antifungal activity of IMS, combined with the invitro nontoxicity, makes them promising compounds for the safe and effective treatment of dermatophytoses, mainly when this skin mycosis is unresponsive to conventional drugs.