2. Academic Validation
  3. Synthesis and biological evaluation of indole derivatives containing thiazolidine-2,4-dione as α-glucosidase inhibitors with antidiabetic activity

Synthesis and biological evaluation of indole derivatives containing thiazolidine-2,4-dione as α-glucosidase inhibitors with antidiabetic activity

  • Eur J Med Chem. 2023 Nov 24:264:115957. doi: 10.1016/j.ejmech.2023.115957.
Chunmei Hu 1,  Bingwen Liang 1,  Jinping Sun 1,  Jiangyi Li 1,  Zhuang Xiong 1,  Shao-Hua Wang 2,  Xu Xuetao 3
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 School of Pharmacy & State Key Laboratory of Applied Organic Chemistry & Collaborative Innovation Center for Northwestern Chinese Medicine, Lanzhou University, Lanzhou, 730000, 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].
PMID: 38029465 DOI: 10.1016/j.ejmech.2023.115957
Abstract

In order to develop potential α-glucosidase inhibitors with antidiabetic activity, twenty-six indole derivatives containing thiazolidine-2,4-dione were synthesized. All compounds presented potential α-glucosidase inhibitory activities with IC50 values ranging from 2.35 ± 0.11 to 24.36 ± 0.79 μM, respectively compared to acarbose (IC50 = 575.02 ± 10.11 μM). Especially, compound IT4 displayed the strongest α-glucosidase inhibitory activity (IC50 = 2.35 ± 0.11 μM). The inhibition mechanism of compound IT4 on α-glucosidase was clarified by the investigation of kinetics studies, fluorescence quenching, CD spectra, 3D fluorescence spectra, and molecular docking. In vivo antidiabetic experiments demonstrated that oral administration of compound IT4 would suppress fasting blood glucose level and ameliorate their glucose tolerance and dyslipidemia in diabetic mice.

Keywords

Antidiabetic activity; Indole; Inhibition mechanism; Thiazolidine-2,4-dione; α-Glucosidase.

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