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

• Published in: European journal of medicinal chemistry 2024-01, Vol.264, p.115957-115957, Article 115957
• Main Authors: Hu, Chunmei, Liang, Bingwen, Sun, Jinping, Li, Jiangyi, Xiong, Zhuang, Wang, Shao-Hua, Xuetao, Xu
• Format: Article
• Language: English
• Subjects: alpha-Glucosidases - metabolism; Animals; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Glycoside Hydrolase Inhibitors - pharmacology; Hypoglycemic Agents - pharmacology; Indoles - pharmacology; Mice; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Thiazolidines
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2023.115957

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 IC values ranging from 2.35 ± 0.11 to 24.36 ± 0.79 μM, respectively compared to acarbose (IC  = 575.02 ± 10.11 μM). Especially, compound IT4 displayed the strongest α-glucosidase inhibitory activity (IC  = 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.