Design, synthesis, biological evaluations and in silico studies of sulfonate ester derivatives of 2-(2-benzylidenehydrazono)thiazolidin-4-one as potential α-glucosidase inhibitors

A novel series of hydrazolyl linked sulfonate ester analogues of 4-thiazolidinone nucleus has been rationally designed, synthesized and characterized by various spectroscopic techniques including H-1 NMR, C-13 NMR and mass spectrometry. All of the synthesized derivatives were tested for in vitro alpha-glucosidase inhibitory activities and antioxidant potential. The investigated compounds displayed appreciable alpha- glucosidase inhibition with IC50 values ranging from 42.80 +/- 0.48 to 599.04 +/- 1.26 mu M in comparison to acarbose (478.07 +/- 1.53 mu M) and structure-activity relationship was established. Further, the safety profile of the most potent derivative (7d) was assessed by MTT assay in normal HEK cells. In vivo disaccharide loading test endorsed the higher efficacy of (7d) over acarbose (at a dose of 20 mg/kg of body weight) for reduction of postprandial hyperglycemia after sucrose administration. In silico procedures i.e. homology modeling, molecular docking, molecular dynamic simulations, binding free energy calculations and ADME predictive studies further justified the results of in vitro and in vivo biological investigations. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A novel series of hydrazolyl linked sulfonate ester analogues of 4-thiazolidinone nucleus were designed, synthesized and characterized using various spectroscopic techniques. In vitro studies showed appreciable alpha-glucosidase inhibitory activities of the synthesized derivatives compared to acarbose, and structure-activity relationship was established. Further in vivo experiments demonstrated the higher efficacy of the most potent derivative over acarbose in reducing postprandial hyperglycemia.