Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments

doi:10.1016/j.bioorg.2019.103322

	Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments
	Zhou, Yeheng 1,4; Sun, Wei1 ; Peng, Jiale 4; Yan, Hui 1; Zhang, Li 4; Liu, Xingyong 4; Zuo, Zhili1,2,3,4
通讯作者	Zuo, Zhili(zuozhili@mail.kib.ac.cn)
	2019-12-01
发表期刊	BIOORGANIC CHEMISTRY
ISSN	0045-2068
卷号	93 页码:13
摘要	Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
关键词	Acetylcholinesterase Drug design N-acylhydrazone Dementia Copper-chelating N-Benzylpiperidine
DOI	10.1016/j.bioorg.2019.103322
收录类别	SCI ; SCI
语种	英语
WOS记录号	WOS:000499717000045
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/70700
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Zuo, Zhili
作者单位	1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Yunnan Key Lab Nat Med Chem, Kunming 650201, Yunnan, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Sichuan Univ Sci & Engn, Sch Chem Engn, Zigong 643000, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Yeheng,Sun, Wei,Peng, Jiale,et al. Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments[J]. BIOORGANIC CHEMISTRY,2019,93:13.
APA	Zhou, Yeheng.,Sun, Wei.,Peng, Jiale.,Yan, Hui.,Zhang, Li.,...&Zuo, Zhili.(2019).Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments.BIOORGANIC CHEMISTRY,93,13.
MLA	Zhou, Yeheng,et al."Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments".BIOORGANIC CHEMISTRY 93(2019):13.

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