Potent α-amylase inhibitors and radical (DPPH and ABTS) scavengers based on benzofuran-2-yl(phenyl)methanone derivatives: Syntheses, in vitro, kinetics, and in silico studies

Abstract

Thirty benzofuran-2-yl(phenyl)methanones 1-30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K₂CO₃ in acetonitrile at room temperature to afford the desired benzofurans 1-30. All compounds were screened for their in vitro α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC₅₀ values ranges for α-amylase inhibition (IC₅₀ = 18.04-48.33 µM), DPPH (IC₅₀ = 16.04-32.33 µM) and ABTS (IC₅₀ = 16.99-33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC₅₀ = 16.08 ± 0.07 µM) for α-amylase, ascorbic acid (IC₅₀ = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein-ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18-20, 22, and 25-30 were structurally new.

Keywords: ABTS; Benzofuran; DPPH; Docking studies; In vitro; Kinetics; Radical scavengers; Synthesis; α-amylase.