化学
取代基
竞争行为
立体化学
药理学
结构-活动关系
对接(动物)
作用机理
体外
生物化学
医学
心理学
护理部
精神科
侵略
作者
Weiwei Huang,Yi Huang,Jiayan Cui,Yuhang Wu,Fuli Zhu,Jin Huang,Lei Ma
标识
DOI:10.1016/j.bmcl.2022.128547
摘要
A total of 23 compounds based on Osthole skeleton were designed and synthesized. Their agonistic activity for Nrf2 were evaluated by Dual-luciferase Reporter Gene Assay. Most of the compounds showed better activities compared with Osthole, especially O15 and O21. And the median effective concerntration (EC50) values was calculated accordingly, both of which showed remarkable activity for Nrf2. The structure activity relationship study indicated that introduction of the structure of stilbene might be beneficial for enhancement of agonistic properties of Osthole, and the position of the substituent may have a greater effect on the activity than the electron-donating/withdrawing ability of the substituent. Mechanism of the action of selected compound O15 was investigated by molecular docking, cellular thermal shift assay and ubiquitination assay, which suggested the reason why O15 exhibited relatively stronger agonistic activity for Nrf2. Compound O15 and O21 both provided novel methods to investigate Osthole-based compounds as Nrf2 agonists.
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