Novel coumarin-thiazolidine-2,4‑dione hybrids as potential α-glucosidase inhibitors: Synthesis and bioactivity evaluation

• Published in: Journal of molecular structure 2025-02, Vol.1322, p.140481, Article 140481
• Main Authors: Liang, Bingwen, Li, Jianping, Wu, Simin, Kou, Xianke, Liu, Tongzheng, Xu, Xuetao
• Format: Article
• Language: English
• Subjects: Coumarin; Hypoglycemic activity; Inhibitor; Thiazolidinedione; α-Glucosidase
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.140481

•Coumarin-thiazolidine-2,4‑dione hybrids (BJX1∼20) were synthesized as potential α-glucosidase inhibitors.•The inhibition mechanism of BJX15 was investigated by multispectral methods.•BJX15 presented in vivo hypoglycemic activity. To discover novel α-glucosidase inhibitors, a series of coumarin- thiazolidine-2,4‑dione hybrids (BJX1∼20) were synthesized and assessed their inhibitory activities against α-glucosidase. Compared to acarbose (IC50 = 655.01 ± 52.54 μM), coumarin-thiazolidinedione hybrids (BJX1∼20) displayed stronger α-glucosidase inhibitory activity, with IC50 values ranging from 5.12 ± 0.48 to 24.07 ± 1.96 μM. BJX3, BJX9, and BJX15 exhibited strongest inhibitory activities against α-glucosidase and acted as non-competitive inhibitors. The fluorescence quenching experiment revealed that the interaction between BJX3, BJX9, BJX15, and α-glucosidase followed a static binding process. CD spectra and 3D fluorescence spectra analysis revealed that the binding of BJX3, BJX9, and BJX15 to α-glucosidase induced a conformation change of α-glucosidase, thereby inhibiting its activity. Molecular docking simulation revealed the binding mechanism of BJX3, BJX9, and BJX15 with α-glucosidase. In vitro cytotoxicity assay indicated BJX15 (0∼64 μM) showed no obvious cytotoxicity against HEK 293 cells. In vivo experiments in mice demonstrated the ameliorative effect of orally administered BJX15 (50 mg kg-1) on postprandial hyperglycemia. [Display omitted]