化学
代谢稳定性
二甲双胍
药理学
立体化学
生物化学
糖尿病
内分泌学
体外
医学
作者
Lili Wang,Yao Du,Shumin Li,Fei Cheng,Nana Zhang,Rui Chen,Xing Cui,Sheng-Gang Yang,Lingling Fan,Jianta Wang,Bing Guo,Hai Wu,Jiquan Zhang,Lei Tang
标识
DOI:10.1016/j.bioorg.2021.105172
摘要
Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.
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