文献类型：期刊文献

英文题名：Tacrine-propargylamine derivatives with improved acetylcholinesterase inhibitory activity and lower hepatotoxicity as a potential lead compound for the treatment of Alzheimer's disease

作者：Mao, Fei[1,2];Li, Jianheng[1];Wei, Hui[3];Huang, Ling[1];Li, Xingshu[1]

机构：[1]Sun Yat Sen Univ, Sch Pharmaceut Sci, Inst Drug Synth & Pharmaceut Proc, Guangzhou 510275, Guangdong, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Guangdong Pharmaceut Univ, Sch Chem & Chem Engn, Guangzhou, Guangdong, Peoples R China

年份：2015

卷号：30

期号：6

起止页码：995

外文期刊名：JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000369915500018)】；

基金：We thank the National Natural Science Foundation of China (No. 21302235, 20972198), Ph.D. Programs Foundation of Ministry of Education of China (20120171120045) and the Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation (2011A060901014) for financial support of this study.

语种：英文

外文关键词：Alzheimer's disease; cholinesterase inhibitor; hepatotoxicity; neurotoxicity

摘要：A series of tacrine-propargylamine derivatives were synthesised and evaluated as possible anti-Alzheimer's disease (AD) agents. Among these derivatives, compounds 3a and 3b exhibited superior activities and a favourable balance of AChE and BuChE activities (3a: IC50 values of 51.3 and 77.6 nM; 3b: IC50 values of 11.2 and 83.5 nM). Compounds 3a and 3b also exhibited increased hAChE inhibitory activity compared with tacrine by approximately 5- and 28-fold, respectively, and low neurotoxicity. Importantly, these compounds also had lower hepatotoxicity than tacrine. Based on these results, compounds 3a and 3b could be considered as potential lead compounds for the treatment of AD and other AChE related diseases, such as schizophrenia, glaucoma and myasthenia gravis.