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

Abstract

Herein, we have designed and synthesized sixteen novel 2,3-diarylthiazolidin-4-one derivatives 6a-p and tested their activity as α-Glucosidase inhibitors. Target compounds 6a-p were characterized using spectroscopic methods (¹H-NMR, ¹³C-NMR, MS, IR), elemental analysis, and melting point. α-Glucosidase inhibition activity was evaluated using the α-Glucosidase enzyme inhibition kit. All 6a-p showed higher α-Glucosidase inhibition activity (90 to 704 µM) in comparison to acarbose as a standard (IC₅₀: 750 µM). 6p, 6m, and 6f exerted the best activity with the IC₅₀ value of 90, 100, and 149 µM 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 µM.

Keywords:

• α-Glucosidase
• bioassay
• inhibitors
• synthesis
• thiazolidine

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by Research Council of Tehran University of Medical Sciences.