Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-A beta Aggregation Activity through Molecular Docking-Based Virtual Screening
文献类型：期刊论文
| 作者 | Liu, Guangpu1; Jiao, Yang2; Lin, Yongqiang2; Hao, Haifang3; Dou, Yanli2,4; Yang, Juan4; Jiang, Cheng-Shi3; Chang, Ping1 |
| 刊名 | CHEMICAL & PHARMACEUTICAL BULLETIN
 |
| 出版日期 | 2020-02-01 |
| 卷号 | 68期号:2页码:161-166 |
| 关键词 | selective acetylcholinesterase inhibitor amyloid beta aggregation neuroprotectant molecular docking molecular dynamics simulation |
| ISSN号 | 0009-2363 |
| 通讯作者 | Chang, Ping(changping_qilu@163.com) |
| 英文摘要 | Discovery of novel multifunctional inhibitors targeting acetylcholinesterase (AChE) has becoming a hot spot in anti-Alzheimer's disease (AD) drug development. In the present study, four potent small molecule inhibitors (A01, A02, A03 and A04) of AChE with new chemical scaffold were identified. Inhibitor A03 displayed the most potent inhibition activity on AChE at enzymatic level with IC50 value of 180 nM, and high selectivity towards AChE over butyrylcholinesterase (BChE) by more than 100-fold. The binding modes of compounds A01-A04 were carefully analyzed by molecular docking and molecular dynamics (MD) simulation to provide informative clues for further structure modification. Finally, the anti-amyloid beta (A beta) aggregation and neuroprotective activity were also well investigated. Our findings highlighted the therapeutic promise of AChE inhibitors A01-A04 for AD treatment. |
| WOS关键词 | AMYLOID AGGREGATION ; ALZHEIMERS-DISEASE ; POTENT INHIBITORS ; ACCURATE DOCKING ; DESIGN ; DERIVATIVES ; MECHANISM ; ANALOGS ; GLIDE ; RING |
| 资助项目 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd.[YWJKJIHKYJJ-Q1115] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000511239600008 |
| 出版者 | PHARMACEUTICAL SOC JAPAN |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/281672]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chang, Ping |
| 作者单位 | 1.Shandong Univ, Qilu Hosp, Dept Pharm, 107 Wenhua Xilu, Jinan 250012, Peoples R China 2.Shandong Inst Food & Drug Control, 2749 Xinluo St, Jinan 250012, Peoples R China 3.Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Guangpu,Jiao, Yang,Lin, Yongqiang,et al. Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-A beta Aggregation Activity through Molecular Docking-Based Virtual Screening[J]. CHEMICAL & PHARMACEUTICAL BULLETIN,2020,68(2):161-166. |
| APA | Liu, Guangpu.,Jiao, Yang.,Lin, Yongqiang.,Hao, Haifang.,Dou, Yanli.,...&Chang, Ping.(2020).Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-A beta Aggregation Activity through Molecular Docking-Based Virtual Screening.CHEMICAL & PHARMACEUTICAL BULLETIN,68(2),161-166. |
| MLA | Liu, Guangpu,et al."Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-A beta Aggregation Activity through Molecular Docking-Based Virtual Screening".CHEMICAL & PHARMACEUTICAL BULLETIN 68.2(2020):161-166. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。