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 α-glucosidase and α-amylase showing IC50 values ranging from 9.20 ± 0.10 to 38.30 ± 0.40 μM (for α-glucosidase) and 5.20 ± 0.30 to 18.20 ± 0.30 μM (for α-amylase), all analogues show good inhibitory capability when compared to the reference medication acarbose (IC₅₀ = 38.45 ± 0.80 & 11.12 ± 0.15 μM, respectively). The strongest inhibitor among the series for α-amylase analogues was 3 (IC₅₀ = 5.20±0.30 μM), whereas the strongest inhibitor in the series for α-glucosidase was analog 6 (IC₅₀ = 9.20 0.10 μM). All other analogs showed excellent potency against the α-glucosidase enzyme while in case of α-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.