Alpha-Glucosidase inhibition activity and in silico study of 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one, a synthetic derivative of flavone

Abstract

A synthetic flavone derivative 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one (BDC) was synthesized by the one pot reaction method and assessed for alpha-glucosidase inhibitory activity. The BDC demonstrated dose dependent inhibition of alpha-glucosidase activity. A maximum inhibition (99.3 plus or minus 0.26 percent) of alpha-glucosidase was observed at 27.6 micro M. The maximum alpha-glucosidase inhibitory activity depicted by BDC 27.6 micro M concentration was 22.4 fold over the maximum inhibition observed with acarbose (97.72 plus or minus 0.59 percent at 669.57 micro M), a standard commercial anti-diabetic drug. In contrast to acarbose that depicted competitive type inhibition, kinetic studies of alpha-glucosidase inhibition by BDC demonstrated non-competitive inhibition with Km of 0.71 mM-1 and a Vmax of 0.028 mmol/min. In silico studies suggest allosteric interaction of BDC with alpha-glucosidase at a minimum binding energy (Delta G) of -8.64 kcal/mol and Ki of 465.3 nM, whereas, acarbose interacted at the active site of alpha-glucosidase with Delta G of -9.23 kcal/mol and Ki of 172 nM. Thus BDC significantly inhibited alpha-glucosidase in comparison to acarbose. Moreover, BDC has been endorsed for drug likeness by evaluating it as per Lipinski rule of five. Thus, BDC can be a lead compound for the management of type-2 diabetes mellitus.