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

文献类型：期刊论文

作者Zhou, Yeheng1,2; Sun, Wei1; Peng, Jiale2; Yan, Hui1; Zhang, Li2; Liu, Xingyong2; Zuo, Zhili1,2,3,4
刊名BIOORGANIC CHEMISTRY
出版日期2019-12-01
卷号93页码:13
ISSN号0045-2068
关键词Acetylcholinesterase Drug design N-acylhydrazone Dementia Copper-chelating N-Benzylpiperidine
DOI10.1016/j.bioorg.2019.103322
通讯作者Zuo, Zhili(zuozhili@mail.kib.ac.cn)
英文摘要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.
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000499717000045
源URL[http://ir.kib.ac.cn/handle/151853/70699]  
专题昆明植物研究所_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.Sichuan Univ Sci & Engn, Sch Chem Engn, Zigong 643000, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Yunnan Key Lab Nat Med Chem, Kunming 650201, Yunnan, 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.

入库方式： OAI收割

来源：昆明植物研究所

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