Abstract

Mansa Shrivastava, Anju Daharia*

ABSTRACT

A novel series of benzimidazole derivatives (3a-f) was rationally designed and synthesized to explore their potential as α-glucosidase inhibitors for the management of hyperglycaemia. The synthesized compounds were structurally characterized using FTIR, 1H NMR, 13C NMR, and mass spectrometry, confirming the presence of key functional groups including hydroxyl (-OH), carbonyl (C=O), and imine (C=N) moieties. The in vitro α-glucosidase inhibitory activity was assessed using acarbose as the standard reference drug. Among the tested derivatives, compound 3f exhibited the highest inhibitory activity (IC50 = 25.57 ± 3.09 µM), followed by 3c (IC50 = 30.35 ± 3.42 µM) and 3a (IC50 = 37.32 ± 2.61 µM), all demonstrating superior potency compared to acarbose (IC50 = 43.52 ± 2.76 µM). Structure-activity relationship (SAR) analysis suggested that electron-donating substituents enhance inhibitory potential, whereas electron-withdrawing groups reduce activity. To further elucidate the binding interactions, molecular docking studies were performed using the crystal structure of α-glucosidase (PDB ID: 3A4A). The docking scores ranged from -8.93126 to -12.0635 kcal/mol, with compounds 3f (-12.0635 kcal/mol) and 3d (-11.6917 kcal/mol) exhibiting the most favourable binding affinities and stable interactions within the enzyme active site, comparable to the standard drug. These findings highlight the potential of benzimidazole-based scaffolds, particularly compound 3f, as promising candidates for the development of effective α-glucosidase inhibitors for diabetes management.