生物活性
IC50型
铅化合物
立体化学
细胞毒性
结构-活动关系
组合化学
效力
生物化学
化学合成
作者
Wen Luo,Jianwu Lv,Ting Wang,Zhi-Yang Zhang,Heng Guo,Zhiyi Song,Chaojie Wang,Jing Ma,Yiping Chen
标识
DOI:10.1016/j.bmc.2019.115190
摘要
A novel series of graveolinine derivatives were synthesized and evaluated as potential anti-Alzheimer agents. Compound 5f exhibited the best inhibitory activity for acetylcholinesterase (AChE) and had surprisingly potent inhibitory activity for butyrylcholinesterase (BuChE), with IC50 values of 0.72 μM and 0.16 μM, respectively. The results from Lineweaver–Burk plot and molecular modeling study indicated non-competitive inhibition of AChE by compound 5f. In addition, these derivatives showed potent self-induced β-amyloid (Aβ) aggregation inhibition. Moreover, 5f didn’t show obvious toxicity against PC12 and HepG2 cells at 50 μM. Finally, in vivo studies confirmed that 5f significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, these graveolinine derivatives should be thoroughly and systematically studied for the treatment of Alzheimer’s disease.
科研通智能强力驱动
Strongly Powered by AbleSci AI