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

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

  • Bioorg Chem. 2024 Mar:144:107177. doi: 10.1016/j.bioorg.2024.107177.
Mengyue Li 1,  Jinping Sun 1,  Bingwen Liang 1,  Xiaofeng Min 1,  Jinhui Hu 2,  Rihui Wu 3,  Xuetao Xu 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China.
  • 2 Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China. Electronic address: [email protected].
  • 3 Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China. Electronic address: [email protected].
  • 4 Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China. Electronic address: [email protected].
PMID: 38335756 DOI: 10.1016/j.bioorg.2024.107177
Abstract

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.

Keywords

Binding interaction; Hypoglycemic activity; Inhibitors; Thiazolidine-2,4-dione; α-Glucosidase.

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