Thiazolidine-2,4-dione derivatives as potential α-glucosidase inhibitors: Synthesis, inhibitory activity, binding interaction and hypoglycemic activity

• Published in: Bioorganic chemistry 2024-03, Vol.144, p.107177-107177, Article 107177
• Main Authors: Li, Mengyue, Sun, Jinping, Liang, Bingwen, Min, Xiaofeng, Hu, Jinhui, Wu, Rihui, Xu, Xuetao
• Format: Article
• Language: English
• Subjects: Binding interaction; Hypoglycemic activity; Inhibitors; Thiazolidine-2,4-dione; α-Glucosidase
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107177

[Display omitted] •Novel thiazolidine-2,4-dione derivatives (C1 ∼ 36) were synthesized as potential α-glucosidase inhibitors.•The inhibition action of C23 was investigated by multispectral methods along with docking study.•C23 presented in vivo hypoglycemic activity in glucose tolerance mice. In order to find effective α-glucosidase inhibitors, a series of thiazolidine-2,4-dione derivatives (C1 ∼ 36) were synthesized and evaluated for α-glucosidase inhibitory activity. Compared to positive control acarbose (IC50 = 654.35 ± 65.81 μM), all compounds (C1 ∼ 36) showed stronger α-glucosidase inhibitory activity with IC50 values of 0.52 ± 0.06 ∼ 9.31 ± 0.96 μM. Among them, C23 with the best anti-α-glucosidase activity was a reversible mixed-type inhibitor. Fluorescence quenching suggested the binding process of C23 with α-glucosidase in a static process. Fluorescence quenching, CD spectra, and 3D fluorescence spectra results also implied that the binding of C23 with α-glucosidase caused the conformational change of α-glucosidase to inhibit the activity. Molecular docking displayed the binding interaction of C23 with α-glucosidase. Compound C23 (8 ∼ 64 μM) showed no cytotoxicity against LO2 and 293 cells. Moreover, oral administration of C23 (50 mg/kg) could reduce blood glucose and improve glucose tolerance in mice.