Benzimidazole derivatives as potent α-amylase inhibitors: synthesis, characterization and in vitro α-amylase inhibition

This study aims to evaluate the α-amylase inhibitory potential of newly synthesized benzimidazole derivatives, assessing their viability as prospective antidiabetic agents. A series of 2-(4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-N-phenylacetamide derivatives (7a–7j) were synthesized via an efficient synthetic route. The structural elucidation of these compounds was accomplished using advanced spectroscopic techniques, including mass spectrometry, FT-IR, 1H & 13C NMR, and elemental analysis. The α-amylase inhibitory activity of the synthesized compounds was evaluated in vitro, with IC₅₀ values determined to quantify their efficacy. To gain insights into the molecular interactions, molecular docking studies were conducted, followed by extensive molecular dynamics (MD) simulations. All synthesized derivatives exhibited varying degrees of α-amylase inhibitory activity, with IC₅₀ values ranging from 1.10 ± 0.05 to 12.50 ± 0.30 μM. Notably, compounds 7b, 7c, and 7i demonstrated superior inhibitory effects, with IC₅₀ values of 1.20 ± 0.05, 1.40 ± 0.10, and 1.10 ± 0.05 μM, respectively, surpassing the standard drug acarbose (IC₅₀ = 1.70 ± 0.10 μM). The synthesized benzimidazole derivatives, notably compounds 7b, 7c, and 7i, demonstrated potent α-amylase inhibitory activity, surpassing the standard drug acarbose. These findings highlight their potential as lead compounds for developing novel antidiabetic agents.