Synthesis, in vitro, and in silico evaluation of Indazole Schiff bases as potential α-glucosidase inhibitors

Abstract

Indazole Schiff bases were synthesized 1–24 and structurally characterized by different spectroscopic techniques such as EI-MS, HREI-MS, 1H- and 13C-NMR. Stereochemistry of azomethine moiety in synthesized compounds was confirmed by 2D-NOESY. Among the twenty-four compounds, fourteen compounds 1–5, 7, 9–14, 17, and 20 are structurally new. Compounds 1–24 were screened for in vitro α-glucosidase enzyme inhibitory activity. All compounds were In vitro α-glucosidase inhibitory assay results identified a number of molecules including 1, 2, 4, 7, 9, 10, 12, 13, 18, 19, 21, and 23 as potent α-glucosidase inhibitors with IC50 values 9.4 ± 0.1 to 303.7 ± 0.1 μM as compared to the standard acarbose (IC50 = 750 ± 10 µM). Compound 1 (IC50 = 9.43 ± 0.1 µM) was found to be the most potent molecule of this library. Kinetic studies on most active compound 1 suggested the competitive inhibition mechanism. In silico studies indicated the interaction details between analogs (ligands) and active site of α-glucosidase enzyme.