Synthesis, In-Vitro Evaluation and Molecular Docking Study of N-Substituted Thiazolidinediones as α-Glucosidase Inhibitors

Thiazolidinedione (TZD) drugs have been shown to improve insulin sensitivity, hyperglycemia, and lipid metabolism in people with type 2 diabetes mellitus. In this study, we have explored the alpha-glucosidase inhibitor action of new N-substituted 5-benzylidene-2,4-thiazolidinedione derivatives. Various substituted benzothiazoles linked to the 5-benzylidene-2,4-TZD with acetamide linker were synthesized and characterized by FTIR, H-1-NMR, C-13-NMR, and mass spectrometry. After the in-silico screening of all the compounds, the IC50 values of 32 compounds were determined using an in vitro alpha-glucosidase assay (maltase yeast extract) with acarbose as a standard drug. All compounds showed varying degrees of alpha-glucosidase inhibitory action as compared to acarbose. When compared to acarbose (IC50=67.06 +/- 1.24 mu M), molecules GB24, GB21, GB16, GB17 and GB25 exhibited very significant inhibitory activity, with IC50 values of 29.91 +/- 0.82, 36.52 +/- 0.49, 39.19 +/- 1.09, 41.35 +/- 1.37 mu M and 60.47 +/- 1.49 respectively. Moreover, a molecular docking study of active compounds was performed to rationalize the in-vitro results and to understand the binding interactions with the target enzyme. Based on the findings, we can predict that these compounds could be taken further for the development of new antidiabetic agents.