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

doi:10.1021/acschemneuro.8b00014

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	Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetyicholinesterase (AChE) and Phosphodiesterase 5 (PDE5)
	Ni, Wei 2; Wang, Huan 1,3; Li, Xiaokang 2; Zheng, Xinyu 2; Wang, Manjiong 2; Zhang, Jian 3,4; Gong, Qi 3,4; Ling, Dazheng 2; Mao, Fei 2; Zhang, Haiyan3,4
刊名	ACS CHEMICAL NEUROSCIENCE
	2018-07
卷号	9 期号:7 页码:1625-1636
关键词	Multifunctional agents AChE inhibitors PDE5 inhibitors Alzheimer's disease
ISSN号	1948-7193
DOI	10.1021/acschemneuro.8b00014
文献子类	Article
英文摘要	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.
资助项目	National Key R&D Program of China[2017YFB0202600] ; 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] ; "Shu Guang" project - Shanghai Municipal Education Commission[00000000] ; Shanghai Education Development Foundation[14SG28] ; Fundamental Research Funds for the Central Universities[00000000]
WOS关键词	MULTITARGET-DIRECTED LIGANDS ; BLOOD-BRAIN-BARRIER ; ALZHEIMERS-DISEASE ; MOUSE MODEL ; ACETYLCHOLINESTERASE ACHE ; THERAPEUTIC AGENTS ; ANALOGS ; DESIGN ; MEMORY ; DISCOVERY
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000439531400013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279679]
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	Ni, Wei,Wang, Huan,Li, Xiaokang,et al. Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetyicholinesterase (AChE) and Phosphodiesterase 5 (PDE5)[J]. ACS CHEMICAL NEUROSCIENCE,2018,9(7):1625-1636.
APA	Ni, Wei.,Wang, Huan.,Li, Xiaokang.,Zheng, Xinyu.,Wang, Manjiong.,...&Li, Jian.(2018).Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetyicholinesterase (AChE) and Phosphodiesterase 5 (PDE5).ACS CHEMICAL NEUROSCIENCE,9(7),1625-1636.
MLA	Ni, Wei,et al."Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetyicholinesterase (AChE) and Phosphodiesterase 5 (PDE5)".ACS CHEMICAL NEUROSCIENCE 9.7(2018):1625-1636.