Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments
Zhou, Yeheng1,4; Sun, Wei1; Peng, Jiale4; Yan, Hui1; Zhang, Li4; Liu, Xingyong4; Zuo, Zhili1,2,3,4
Corresponding AuthorZuo, Zhili(zuozhili@mail.kib.ac.cn)
2019-12-01
Source PublicationBIOORGANIC CHEMISTRY
ISSN0045-2068
Volume93Pages:13
AbstractCholinergic 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.
KeywordAcetylcholinesterase Drug design N-acylhydrazone Dementia Copper-chelating N-Benzylpiperidine
DOI10.1016/j.bioorg.2019.103322
Indexed BySCI ; SCI
Language英语
WOS IDWOS:000499717000045
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/70700
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorZuo, Zhili
Affiliation1.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
Recommended Citation
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.
Files in This Item: Download All
File Name/Size DocType Version Access License
Zhou-2019-Design, sy(4739KB)期刊论文出版稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhou, Yeheng]'s Articles
[Sun, Wei]'s Articles
[Peng, Jiale]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhou, Yeheng]'s Articles
[Sun, Wei]'s Articles
[Peng, Jiale]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhou, Yeheng]'s Articles
[Sun, Wei]'s Articles
[Peng, Jiale]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: Zhou-2019-Design, synthesis and biological eva.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.