Synthesis, in Vitro Α-Glucosidase, Α-Amylase Inhibitory Potentials and Molecular Docking Study of Benzimidazole Bearing Sulfonamide Analogues

We synthesized fourteen benzimidazole-containing sulfonamide analogs (1-14), characterized them using methods including NMR and HR-EIMS. The synthesized analogs were then tested against the enzymes alpha-glucosidase and alpha-amylase showing IC50 values ranging from 9.20 +/- 0.10 to 38.30 +/- 0.40 mu M (for alpha-glucosidase) and 5.20 +/- 0.30 to 18.20 +/- 0.30 mu M (for alpha-amylase), all analogues show good inhibitory capability when compared to the reference medication acarbose (IC50 = 38.45 +/- 0.80 & 11.12 +/- 0.15 mu M, respectively). The strongest inhibitor among the series for alpha-amylase analogues was 3 (IC50 = 5.20 +/- 0.30 mu M), whereas the strongest inhibitor in the series for alpha-glucosidase was analog 6 (IC50 = 9.20 0.10 mu M). All other analogs showed excellent potency against the alpha-glucosidase enzyme while in case of alpha-amylase analogs showed excellent to moderate potency. The structure-activity relationship was established for determining the increase/decrease in potency due to quantity, type, position, and electron-donating/withdrawing effects of the substituent/s on the phenyl ring. To demonstrate the binding interaction of the most potent analogues with the enzyme's active sites, a molecular docking research was performed.