Novel N '-substituted benzylidene benzohydrazides linked to 1,2,3-triazoles: potent alpha-glucosidase inhibitors

Herein, various N '-substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and screened for their inhibitory activity toward alpha-glucosidase. The structure of derivatives was confirmed using H-1- and C-13-NMR, FTIR, Mass spectrometry, and elemental analysis. All derivatives exhibited good inhibition with IC50 values in the range of 0.01 to 648.90 mu M, compared with acarbose as the positive control (IC50 = 752.10 mu M). Among them, compounds 7a and 7h showed significant potency with IC50 values of 0.02 and 0.01 mu M, respectively. The kinetic study revealed that they are noncompetitive inhibitors toward alpha-glucosidase. Also, fluorescence quenching was used to investigate the interaction of three inhibitors 7a, 7d, and 7h, with alpha-glucosidase. Accordingly, the binding constants, the number of binding sites, and values of thermodynamic parameters were determined for the interaction of candidate compounds toward the enzyme. Finally, the in silico cavity detection plus molecular docking was performed to find the allosteric site and key interactions between synthesized compounds and the target enzyme.

Automated summary

In this study, various N'-substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and evaluated for their inhibitory activity against alpha-glucosidase. The structures of the derivatives were confirmed using multiple spectroscopic techniques. All derivatives exhibited potent inhibition, with IC50 values ranging from 0.01 to 648.90 μM, compared to acarbose as the positive control (IC50 = 752.10 μM). Compounds 7a and 7h showed significant potency, with IC50 values of 0.02 and 0.01 μM, respectively. Further studies revealed that these compounds are noncompetitive inhibitors of alpha-glucosidase. Fluorescence quenching and molecular docking were also used to investigate the interaction and binding mechanisms between the inhibitors and the target enzyme.