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

ELEJALDE, NERITH-ROCIO; MACÍAS, MARIO; CASTILLO, JUAN-CARLOS; SORTINO, MAXIMILIANO; SVETAZ, LAURA; ZACCHINO, SUSANA; PORTILLA, JAIME

ChemistrySelect

Wiley-VCH Verlag GmbH & Co.

Lugar: Weinheim; Año: 2018 vol. 3 p. 5220 - 5227

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 a-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 mg/mL for some of them. The difluorinated compound 5e showed the best activity against C. neoformans, followed by the dichlorinated derivative 5b. The difluorinated compound 5e showed the best activity against C. neoformans, followed by the dichlorinated derivative 5b.