化学
单胺类神经递质
IC50型
单胺氧化酶
药理学
体外
基因亚型
活性氧
抑制性突触后电位
中枢神经系统
生物化学
酶
血清素
受体
基因
医学
内科学
作者
Kaicheng Zhang,Yang Liu,Hongyan Jia,Hanxun Wang,Minghua Deng,Yaoyang Liu,Xueqi Zhao,Xiaomeng Xiu,Zhenli Li,Huali Yang,Maosheng Cheng
标识
DOI:10.1016/j.bioorg.2023.106441
摘要
A novel series of N-methyl-propargylamine derivates were designed, synthesized, and evaluated as isoform-selective monoamine oxidases (MAO) inhibitors for the treatment of nervous system diseases. The in vitro studies showed some of the compounds exhibited considerable MAO-A selective inhibitory activity (IC50 of 14.86–17.16 nM), while some of the others exhibited great MAO-B selective inhibitory activity (IC50 of 4.37–17.00 nM). Further studies revealed that compounds A2 (IC50 against MAO-A: 17.16 ± 1.17 nM) and A5 (IC50 against MAO-B: 17.00 ± 1.10 nM) had significant abilities to protect PC12 cells from H2O2-induced apoptosis and reactive oxygen species (ROS) production. The parallel artificial membrane permeability assay showed A2 and A5 would be potent to cross the blood–brain barrier. The results indicated that A2 showed potential use in the therapy of MAO-A related diseases, such as depression and anxiety; while A5 exhibited promising ability in the treatment of MAO-B related diseases, such as Alzheimer’s disease and Parkinson’s disease.
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