文献类型：期刊文献

英文题名：Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetyicholinesterase (AChE) and Phosphodiesterase 5 (PDE5)

作者：Ni, Wei[1];Wang, Huan[2,3];Li, Xiaokang[1];Zheng, Xinyu[1];Wang, Manjiong[1];Zhang, Jian[2,4];Gong, Qi[2,4];Ling, Dazheng[1];Mao, Fei[1];Zhang, Haiyan[2,4];Li, Jian[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China;[3]Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;[4]Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

年份：2018

卷号：9

期号：7

起止页码：1625

外文期刊名：ACS CHEMICAL NEUROSCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000439531400013)】；

基金：Financial support for this research provided by the National Key R&D Program of China (Grant 2017YFB0202600), the National Natural Science Foundation of China (Grants 21702061, 21672064, 81522045), the Shanghai Sailing Program (Grant 17YF1403600), the "Shu Guang" project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (Grant 14SG28), and the Fundamental Research Funds for the Central Universities are gratefully acknowledged.

语种：英文

外文关键词：Multifunctional agents; AChE inhibitors; PDE5 inhibitors; Alzheimer's disease

摘要：On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer's disease (AD), and the lead compound 2 has proven this method was feasible in AD mouse models. In this study, our work focused on exploring alternative novel tadalafil derivatives (3a-s). Among the 19 analogues, compound 3c exhibited good selective dual-target AChE/PDE5 inhibition and good blood-brain barrier (BBB) permeability. Moreover, its citrate (3c center dot Cit) possessed improved water solubility and good effects against scopolamine-induced cognitive impairment with inhibition of cortical AChE activities and enhancement of cAMP response element-binding protein (CREB) phosphorylation ex vivo.