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 Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Organic
WOS IDWOS:000499717000045
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Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
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
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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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