Novel Vilazodone Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation
文献类型：期刊论文
| 作者 | Li, Xiaokang3; Wang, Huan1,2; Xu, Yixiang3; Liu, Wenwen3; Gong, Qi1; Wang, Wei1; Qiu, Xiaoxia3; Zhu, Jin3; Mao, Fei3; Zhang, Haiyan1
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| 刊名 | ACS CHEMICAL NEUROSCIENCE
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| 出版日期 | 2017-12 |
| 卷号 | 8期号:12页码:2708-2721 |
| 关键词 | Alzheimer's disease depression multitarget-directed ligand ChE inhibition 5-HT1A agonist 5-HT reuptake inhibition |
| ISSN号 | 1948-7193 |
| DOI | 10.1021/acschemneuro.7b00259 |
| 文献子类 | Article |
| 英文摘要 | Depression is one of the most frequent psychiatric complications of Alzheimer's disease (AD), affecting up to 50% of the patients. A novel series of hybrid molecules were designed and synthesized by combining the pharmacophoric features of vilazodone and tacrine as potential multitarget-directed ligands for the treatment of AD with depression. In vitro biological assays were conducted to evaluate the compounds; among the 30 hybrids, compound 1e showed relatively balanced profiles between acetylcholinesterase inhibition (IC50 = 3.319 +/- 0.708 mu M), 5-HT1A agonist (EC50 = 107 +/- 37 nM), and 5-HT reuptake inhibition (IC50 = 76.3 +/- 33 nM). Compound 1e displayed tolerable hepatotoxicity and moderate hERG inhibition activity, and could penetrate the blood-brain barrier in vivo. Furthermore, an oral intake of 30 mg/kg 1e center dot HCl could significantly improve the cognitive function of scopolamine-induced amnesia mice and alleviate the depressive symptom in tail suspension test. The effectivity of 1e validates the rationality of our design strategy. |
| WOS关键词 | SEROTONIN REUPTAKE INHIBITORS ; PROVISIONAL DIAGNOSTIC-CRITERIA ; TAIL SUSPENSION TEST ; 5-HT1A AGONISTS ; BRAIN EXPOSURE ; SYMPTOMS ; DEMENTIA ; ACETYLCHOLINESTERASE ; MICE ; BUTYRYLCHOLINESTERASE |
| 资助项目 | 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 ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000418786100019 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272362]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Mao, Fei; Zhang, Haiyan; Li, Jian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Xiaokang,Wang, Huan,Xu, Yixiang,et al. Novel Vilazodone Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation[J]. ACS CHEMICAL NEUROSCIENCE,2017,8(12):2708-2721. |
| APA | Li, Xiaokang.,Wang, Huan.,Xu, Yixiang.,Liu, Wenwen.,Gong, Qi.,...&Li, Jian.(2017).Novel Vilazodone Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation.ACS CHEMICAL NEUROSCIENCE,8(12),2708-2721. |
| MLA | Li, Xiaokang,et al."Novel Vilazodone Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation".ACS CHEMICAL NEUROSCIENCE 8.12(2017):2708-2721. |
入库方式： OAI收割
来源：上海药物研究所
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