Benzimidazole-1,2,3-triazole-piperazine Hybrids: Design, Synthesis, Antidiabetic Evaluation and Molecular Modelling Studies

Sixteen new benzimidazole hybrids containing 1,2,3-triazole and piperazine scaffolds have been synthesized by click reaction. The synthesized hybrids were characterized by various spectroscopic techniques like IR, NMR and HRMS, and further examined in-vitro for their α-amylase and α-glucosidase inhibitory potential. The hybrid 5p was active against α-amylase with IC50 value of 0.0327 µmol/mL and hybrids 5h, 5o and 5p were active against α-glucosidase with IC50 values of 0.0154, 0.0156 and 0.0144 µmol/mL, respectively, comparable to acarbose. Docking analysis of α-glucosidase with 5o and 5p showed effective binding to hydrophobic cavity and form hydrogen bonding with the His348 and Arg439 residues. DFT and molecular electrostatic potential studies supported in-silico and in-vitro biological screening results. The pharmacological profile revealed that 5o and 5p might be the possible lead compounds for the treatment of diabetes.