Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study.

Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (-) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives (IC = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and (IC = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure-activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes.