Synthesis, biological evaluation and molecular docking studies of chromone derivatives as potential α-glucosidase inhibitors

Abstract

A series of chromone derivatives were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity by using in vitro methods and molecular docking studies. Some new synthetic compounds showed excellent α-glucosidase inhibitory activity with IC50 values in the range from 10.9 ± 0.29 to 146.50 ± 0.49 µM. Among them, compound 6m exhibited the most potent α-glucosidase inhibitory activity with an IC50 value of 10.9 ± 0.29 μM. Enzyme kinetic study demonstrated that 6m was a mixed-type inhibitor (Ki = 16.87 μM). Circular dichroism spectra and fluorescence quenching experiments further confirmed that the secondary structure of α-glucosidase was changed by the binding of 6m. Molecular docking studies showed that the aryl groups of 6m interactions with the residues Tyr-71, Phe-157, Phe-177, and Phe-300 formed the CH-π. Cell viability assay has shown that 6m exhibited low cytotoxic activity against human normal cell lines.