Dual-target anti-Alzheimer’s disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity

Journal of Enzyme Inhibition and Medicinal Chemistry

Jianan Guo¹  Zhisheng Mi¹  Xiaoying Jiang¹  Renren Bai¹  Changjun Zhang¹  Yuanyuan Xie²  Bing Gan³  Sihang Yu⁴  Tao Zhou⁵  Jing Su⁵ 

[1] College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China;College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China;Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Chin;College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China;Guiyang Institute for Food and Drug Control, Guiyang, China;Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, China;School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China;

关键词: Alzheimer’s disease;    iron ion chelation;    MAO-B;    coumarin derivatives;    hydroxypyridinone;   

DOI  :  10.1080/14756366.2019.1634703

来源: publisher

【 摘 要 】

MAO-B leads to an increase in the levels of hydrogen peroxide and oxidative free radicals, which contribute to the aetiology of the AD. Thus, both iron ion chelators and MAO-B inhibitors can be used to treat AD. Taking the coumarin derivatives and hydroxypyridinones as the lead compounds, a series of dual-target hybrids were designed and synthesised by Click Chemistry. The compounds were biologically evaluated for their iron ion chelating and MAO-B inhibitory activity. Most of the compounds displayed excellent iron ion chelating activity and moderate to good anti-MAO-B activity. Compounds 27b and 27j exhibited the most potent MAO-B inhibitory activity, with IC50 values of 0.68 and 0.86 μM, respectively. In summary, these dual-target compounds have the potential anti-AD activity.

【 授权许可】

CC BY