Novel Benzimidazole-Endowed Chalcones as α-Glucosidase and α-Amylase Inhibitors: An Insight into Structural and Computational Studies

In search of novel antidiabetic agents, we synthesized a new series of chalcones with benzimidazole scaffolds by an efficient 'one-pot' nitro reductive cyclization method and evaluated their α-glucosidase and α-amylase inhibition studies. The 'one-pot' nitro reductive cyclization method offered a simple route for the preparation of benzimidazoles with excellent yield and higher purity compared to the other conventional acid- or base-catalyzed cyclization methods. H, C NMR, IR, and mass spectrum data were used to characterize the compounds. Single-crystal XRD data confirmed the 3D structure of compound which was crystalized in the P1¯ space group of the triclinic crystal system. Hirshfeld surface analysis validates the presence of O-H..O, O-H…N, and C-H…O intermolecular hydrogen bonds. From the DFT calculations, the energy gap between the frontier molecular orbitals in was found to be 3.791 eV. From the series, compound emerged as a potent antidiabetic agent with IC = 22.45 ± 0.36 µg/mL and 20.47 ± 0.60 µg/mL against α-glucosidase and α-amylase enzymes, respectively. The in silico molecular docking studies revealed that compound has strong binding interactions with α-glucosidase and α-amylase proteins. Molecular dynamics studies also revealed the stability of compound with α-glucosidase and α-amylase proteins.