| 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
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| Corresponding Author | Zuo, Zhili(zuozhili@mail.kib.ac.cn) |
| 2019-12-01 | |
| Source Publication | BIOORGANIC CHEMISTRY
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| ISSN | 0045-2068 |
| Volume | 93Pages:13 |
| Abstract | 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. |
| Keyword | Acetylcholinesterase Drug design N-acylhydrazone Dementia Copper-chelating N-Benzylpiperidine |
| DOI | 10.1016/j.bioorg.2019.103322 |
| Indexed By | SCI ; SCI |
| Language | 英语 |
| WOS ID | WOS:000499717000045 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://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 Author | Zuo, Zhili |
| Affiliation | 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 |
| 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. |
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| Zhou-2019-Design, sy（4739KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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