Molecular docking studies for discovery of plant-derived α-glucosidase inhibitors

The identification of naturally occurring α-glucosidase inhibitors has been actively pursued with the aim of developing therapeutics for the treatment of type 2 diabetes mellitus. To identify α-glucosidase inhibitors, we screened 40 natural compounds, including flavonoids and phenolics, using the structure-based molecular docking approach. The rank of each compound was determined on the basis of the binding free energy of the lowest energy cluster. Results showed that all the tested compounds exhibited a binding energy ranging from -8.2 kcal/mol to -3.6 kcal/mol, indicating the variation in antidiabetic potential of tested compounds. The top-screened compounds were rutin, quercetin, and myricetin, which exhibited higher inhibitory activities (IC50 = 1.0 to 84.1 μg/mL) against αglucosidase than acarbose (IC50 = 140.5 μg/mL), a reference inhibitor. We also demonstrated that a variety of inhibitory actions (competitive and noncompetitive inhibition) exist among these compounds. Our results suggest that rutin, quercetin, and myricetin can be used to further develop potent α-glucosidase inhibitors. Keyword: α-glucosidase, molecular docking, rutin, quercetin, myricetin. Abbreviations: T2DM_Type 2 diabetes mellitus; pNPG_p-nitrophenyl glucopyranoside.