Cs2CO3-promoted one-pot synthesis of novel tetrahydrobenzofuran-4(2H)-ones: In vitro antimicrobial, antimalarial activity and in silico docking study

Abstract

A diverse set of tetrahydrobenzofuran-4(2H)-one derivative 4(a-o) were synthesized using a one-pot treatment of dimedone, 3-(1H-imidazol-1-yl)benzaldehyde, and different phenacyl bromide by utilizing cesium carbonate as a cost-effective catalyst in acetonitrile under mild reaction condition. During the synthesis of compounds, two carbon–carbon (C–C) bonds and one carbon–oxygen (C–O) bond are formed. All the compounds were obtained with moderate to good yield. The synthesized compounds underwent screening to assess their antimicrobial and antimalarial properties. Compounds 4 l (117 µM) and 4d (145 µM) exhibited the highest potency against A. baumannii and Car. Resistant P. aeruginosa in comparison to the standard drug chloramphenicol (155 µM), respectively. Compound 4 l (234 µM) displayed the highest efficacy against C. albicans than that of the standard drug, fluconazole (327 µM) while 4f (1018 µM) showed greater efficacy against A. niger than griseofulvin (1417 µM). In addition, all the titled compounds displayed good antimalarial activity. Among them, 4f (1.60 µM) has the highest efficacy against P. falciparum than quinine (2.71 µM). Since compound 4 l exhibits a strong antibacterial and fungal action among all synthetics, it shows remarkable binding affinities of −8.4 kcal mol−1 and −9.1 kcal mol−1 with A. baumannii and C. albicans respectively.

Keywords

• Multicomponent reactions
• Tetrahydrobenzofuran-4(2H)-one
• Cs2CO3
• Antimicrobial
• Antimalarial
• Molecular docking