Comparison in vitro and in silico studies of phenolic acids and flavonoids on α-glucosidase inhibition

Context: Inhibiting α-glucosidase activity has been proven to regulate hyperglycemia for treating diabetes, particularly type 2 diabetes mellitus (T2DM). Plant secondary metabolites consist of phenolic acids and flavonoids, which have been identified as α-glucosidase inhibitory agents. Aims: To assess the ability of the tested phenolic acids and flavonoids as α-glucosidase inhibitors and to predict their binding interactions with α-glucosidase, as well as their pharmacokinetic properties. Methods: The tested phenolic acids and flavonoids were evaluated for α-glucosidase inhibition by in vitro study, and their binding interactions were observed by an in silico molecular docking study utilizing AutoDock 4.2 software, while their pharmacokinetic properties were predicted using SwissADME and pkCSM online software. Results: The results displayed that quercetin (QE; IC50 = 0.85 μg/mL) and gallic acid (GA; IC50 = 26.19 μg/mL) significantly inhibited α-glucosidase activity than acarbose (IC50 = 139.4 μg/mL). Molecular docking analysis revealed that QE exhibited a higher binding affinity (ΔG; -7.53 kcal/mol) compared to acarbose (ΔG; -7.00 kcal/mol). This suggested that QE formed more favorable interactions with the enzyme, as evidenced by its binding to catalytic residues D215 and D352. In contrast, acarbose interacted with only one catalytic amino acid, i.e., D215. Furthermore, GA displayed a lower binding affinity (ΔG; -4.63 kcal/mol) than acarbose and bound to a distinct site on the α-glucosidase involving amino acids K156, S241, and D242. The pharmacokinetic properties predictions revealed that the potential compounds could bind and inhibit the α-glucosidase and were not toxic. Conclusions: Therefore, this study is useful for modifying the structures of phenolic acids and flavonoids to improve their ability to inhibit the α-glucosidase activity.