Design, Synthesis and Bioactivity Investigation of Novel 2,3-Diarylthiazolidine-4-Ones as Potent alpha-Glucosidase Inhibitors

Herein, we have designed and synthesized sixteen novel 2,3-diarylthiazolidin-4-one derivatives 6a-p and tested their activity as alpha-Glucosidase inhibitors. Target compounds 6a-p were characterized using spectroscopic methods (H-1-NMR, C-13-NMR, MS, IR), elemental analysis, and melting point. alpha-Glucosidase inhibition activity was evaluated using the alpha-Glucosidase enzyme inhibition kit. All 6a-p showed higher alpha-Glucosidase inhibition activity (90 to 704 mu M) in comparison to acarbose as a standard (IC50: 750 mu M). 6p, 6m, and 6f exerted the best activity with the IC50 value of 90, 100, and 149 mu M respectively. Enzyme kinetic studies showed a competitive mode of inhibition for the most active compound, 6p; molecular docking study revealed the mode of interactions between the most active compounds and enzyme active site. To evaluate the cytotoxicity profile of the synthesized compounds, an MTT assay was done on three different cell lines which showed all 6a-p are safe and nontoxic with IC50 values higher than 750 mu M.