The Potential of C‐Glycosylflavonoids as α‐Glucosidase Inhibitors Determined by Virtual Screening, Molecular Docking, Molecular Dynamics, and IC50 Studies

Abstract

AbstractInhibition of intestinal α‐glucosidase (αGS), a crucial enzyme in carbohydrate digestion, is an effective therapeutic approach for diabetes mellitus treatment. The C‐glycosylflavonoids (CGFs) are natural compounds with antioxidant, antidiabetic, and anti‐inflammatory activities. The present work seeks an alternative compound among CGFs that can control the blood glucose level by inhibiting αGS enzyme activity. Therefore, ten CGFs were selected and carried out the docking to αGS. The docking outcomes proposed that among selected CGFs, the orientin compound can successfully interact with the key residues of Asp215, Glu277, Asp352, Arg442, and Arg446. Of them, the orientin compound with docking energy of −6.11 Kcal/mol, was subsequently subjected to molecular dynamics simulation (MDs), and in vitro investigation. MDs results indicated that orientin formed a stable complex with αGS enzyme. We also performed molecular mechanics generalized Born and surface area (MM/GBSA) free energy calculation manner on all chosen CGFs along with miglitol as reference. The IC50 value of orientin for αGS inhibition with competitive mode was found to be 0.13 mg/ml. The results highlight that orientin can be considered as a possible compound in treating DM via αGS inhibition. However, further in vitro and in vivo analyses are required to confirm this claim.