Synthesis and in vitro Antifungal Evaluation of Novel N-Substituted 4-Aryl-2-methylimidazoles

Abstract

An efficient and regioselective synthesis of novel 4-aryl-2-methyl-N-phenacylimidazoles 5 by a microwave-assisted pseudo-tricomponent reaction between acetamidine hydrochloride (3) and α-bromoacetophenones 2 has been developed. The reduction of the carbonyl group of the ketones 5 offered the corresponding N-(2-hydroxyethyl)imidazoles 6 in good yields. Novel N-substituted imidazoles 5 and 6 were tested for antifungal activity against two clinically important fungi Candida albicans and Cryptococcus neoformans. The results showed that all compounds displayed very low activity against C. albicans. In contrast, compounds 5 and 6 were active against C. neoformans. Among them, ketones 5 showed better activity than alcohols 6, with IC50 values as low as 15.6 μg/mL for some of them. The difluorinated compound 5 e showed the best activity against C. neoformans, followed by the dichlorinated derivative 5 b. The difluorinated compound 5 e showed the best activity against C. neoformans, followed by the dichlorinated derivative 5 b.