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

Abstract

A series of chromone hydrazone derivatives 4a–4p have been synthesized, characterized by 1H NMR and 13C NMR and evaluated for theirinvitro α-glucosidase inhibitory activity. Out of these tested compounds, six (4a, 4b, 4d, 4j, 4o and 4p) displayed potent α-glucosidase inhibitory activity with IC50 values in the range of 20.1±0.19μM to 45.7±0.23μM, as compared to the standard drug acarbose (IC50=817.38±6.27μM). Among this series, compound 4d (IC50=20.1±0.19μM) with 4-sulfonamide substitution at phenyl part of hydrazide was found to be the most active compound. Lineweaver-Burk plot analysis indicated that compound 4d is a non-competitive inhibitor of α-glucosidase. The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 4d are interacting with the residues Glu-276, Asp-214, Asp-349 and Arg-439 through hydrogen bonds, arene-anion and arene-cation interactions. In summary, our studies shown that these chromone hydrazone derivatives are a new class of α-glucosidase inhibitors.