Novel N′-substituted benzylidene benzohydrazides linked to 1,2,3-triazoles: potent α-glucosidase inhibitors
Mina Saeedi, Roshanak Hariri, Aida Iraji, Ali Ahmadi, Somayeh Mojtabavi, Shiva Golshani, Mohammad Ali Faramarzi, Tahmineh Akbarzadeh
Abstract
Abstract Herein, various N′ -substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and screened for their inhibitory activity toward α-glucosidase. The structure of derivatives was confirmed using 1 H- and 13 C-NMR, FTIR, Mass spectrometry, and elemental analysis. All derivatives exhibited good inhibition with IC 50 values in the range of 0.01 to 648.90 µM, compared with acarbose as the positive control (IC 50 = 752.10 µM). Among them, compounds 7a and 7h showed significant potency with IC 50 values of 0.02 and 0.01 µM, respectively. The kinetic study revealed that they are noncompetitive inhibitors toward α-glucosidase. Also, fluorescence quenching was used to investigate the interaction of three inhibitors 7a , 7d , and 7h, with α-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.