Synthesis and biological evaluation of some novel 1-alkyl-3-methylimidazolium carboxylate ionic liquids as potential antifungal agents

In an effort to discover lead compounds that may be of importance as potent antifungal agents, a series of novel 1-alkyl-3-methylimidazolium carboxylate ionic liquids were efficiently synthesized through a solvent-free ultrasound-assisted quaternization reaction of 1-methylimidazole and alkyl bromides RBr (R = hexyl, octyl) followed by an anion exchange process with selected carboxylate anions (cinnamate, salicylate, crotonate, and oxalate). Quantitative yields obtained were in the range of 86-94%. Structure characterization was done using FT-IR, H-1-NMR, and C-13-NMR spectroscopic techniques. All the synthesized compounds showed in vitro antifungal activity against the fungus Candida albicans with the minimum inhibitory concentrations found to be less than or equal to 1%. Preliminary cytotoxicity assays (trypan blue exclusion and MTT) were performed on all ionic liquids and findings revealed higher lymphocyte viability in 1-hexyl-3-methylimidazolium carboxylate ionic liquids than in 1-octyl-3-methylimidazolium counterparts. No extensive toxicity effect was observed with the carboxylate anion variation. Among the tested compounds, 1-hexyl-3-methylimidazolium crotonate and 1-hexyl-3-methylimidazolium oxalate exhibited the lowest cytotoxicity in the trypan blue exclusion and MTT assays, respectively. Together, our results highlight the potential of carboxylate-based ionic liquids in the development of next-generation antifungal drugs.