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Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment

文献类型：期刊论文

作者Liu, Wenwen2; Wang, Huan1,3; Li, Xiaokang2; Xu, Yixiang2; Zhang, Jian3; Wang, Wei3; Gong, Qi3; Qiu, Xiaoxia2; Zhu, Jin2; Mao, Fei2
刊名BIOORGANIC & MEDICINAL CHEMISTRY
出版日期2018-07-23
卷号26期号:12页码:3117-3125
ISSN号0968-0896
关键词Depression Cognitive impairment Multitarget-directed ligand 5-HT1A agonist 5-HT reuptake inhibition ChE inhibition
DOI10.1016/j.bmc.2018.04.037
文献子类Article
英文摘要Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodonetacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50 = 0.36 +/- 0.08 nM; 2a, EC50 = 0.58 +/- 0.14 nM) and 5-HT reuptake inhibitory activities (1d, IC50 = 20.42 +/- 6.60 nM; 2a, IC50 = 22.10 +/- 5.80 nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50 = 1.72 +/- 0.217 mu M, BuChE IC50 = 0.34 +/- 0.03 mu M; 2a, AChE IC50 = 2.36 +/- 0.34 mu M, BuChE IC50 = 0.10 +/- 0.01 mu M). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment. (C) 2018 Elsevier Ltd. All rights reserved.
WOS关键词SEROTONIN REUPTAKE INHIBITORS ; ALZHEIMERS-DISEASE ; 5-HT1A AGONISTS ; VASCULAR DEMENTIA ; DRUG DISCOVERY ; OLDER PERSONS ; ACETYLCHOLINESTERASE ; DECLINE ; DYSFUNCTION ; DONEPEZIL
资助项目National Natural Science Foundation of China[21702061] ; National Natural Science Foundation of China[21672064] ; National Natural Science Foundation of China[81522045] ; Shanghai Sailing Program[17YF1403600] ; Fundamental Research Funds for the Central Universities[00000000]
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种英语
出版者PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号WOS:000436779400005
源URL[http://119.78.100.183/handle/2S10ELR8/279653]  
专题药理学第二研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Mao, Fei; Zhang, Haiyan; Li, Jian
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, 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;
推荐引用方式
GB/T 7714		 Liu, Wenwen,Wang, Huan,Li, Xiaokang,et al. Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2018,26(12):3117-3125.
APA Liu, Wenwen.,Wang, Huan.,Li, Xiaokang.,Xu, Yixiang.,Zhang, Jian.,...&Li, Jian.(2018).Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment.BIOORGANIC & MEDICINAL CHEMISTRY,26(12),3117-3125.
MLA Liu, Wenwen,et al."Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment".BIOORGANIC & MEDICINAL CHEMISTRY 26.12(2018):3117-3125.

入库方式： OAI收割

来源：上海药物研究所

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