Discovery of new multifunctional selective acetylcholinesterase inhibitors: structure-based virtual screening and biological evaluation
文献类型：期刊论文
| 作者 | Jiang, Cheng-Shi2; Ge, Yong-Xi2; Cheng, Zhi-Qiang2; Song, Jia-Li2; Wang, Yin-Yin2; Zhu, Kongkai1,2; Zhang, Hua2 |
| 刊名 | JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
 |
| 出版日期 | 2019-05-01 |
| 卷号 | 33期号:5页码:521-530 |
| 关键词 | AChE inhibitor Pharmacophore model Molecular docking Anti-A aggregation Neuroprotective activity |
| ISSN号 | 0920-654X |
| DOI | 10.1007/s10822-019-00202-2 |
| 通讯作者 | Zhu, Kongkai(hkhhh.k@163.com) ; Zhang, Hua(bio_zhangh@ujn.edu.cn) |
| 英文摘要 | Although the mechanism of Alzheimer's disease (AD) is still not fully understood, the development of multifunctional AChE inhibitors remains a research focus for AD treatment. In this study, 48 AChE candidate inhibitors were picked out from SPECS database through a pharmacophore- and molecular docking-based virtual screening. The biological evaluation results indicated that four compounds 7, 29, 41 and 48 with different scaffolds exhibited potent and selective AChE inhibitory activity, with the best IC50 value of 1.62 +/- 0.11 M obtained for 48. Then their mechanism of action, the inhibition on A aggregation, neurotoxicity, and neuroprotective activity against A-induced nerve cell injury were well studied. The binding mode of 48 with AChE was also proposed. The present bioassay results indicated that these multifunctional AChE inhibitors were worth for further structural derivatization to make them the anti-AD lead compounds. |
| WOS关键词 | ALZHEIMERS-DISEASE ; ACCURATE DOCKING ; DERIVATIVES ; DESIGN ; CHOLINESTERASE ; AGGREGATION ; CANDIDATES ; ANALOGS ; TARGET ; GLIDE |
| 资助项目 | National Natural Science Foundation of China[21672082] ; National Natural Science Foundation of China[81803438] ; Shandong Key Development Project[2016GSF201209] ; Young Taishan Scholars Program[tsqn20161037] ; Natural Science Foundation of Shandong Province[ZR201807060857] ; Natural Science Foundation of Shandong Province[ZR2017BH038] ; Natural Science Foundation of Shandong Province[JQ201721] ; Shandong Talents Team Cultivation Plan of University Preponderant Discipline[10027] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000467423700006 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/289853]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhu, Kongkai; Zhang, Hua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Cheng-Shi,Ge, Yong-Xi,Cheng, Zhi-Qiang,et al. Discovery of new multifunctional selective acetylcholinesterase inhibitors: structure-based virtual screening and biological evaluation[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,2019,33(5):521-530. |
| APA | Jiang, Cheng-Shi.,Ge, Yong-Xi.,Cheng, Zhi-Qiang.,Song, Jia-Li.,Wang, Yin-Yin.,...&Zhang, Hua.(2019).Discovery of new multifunctional selective acetylcholinesterase inhibitors: structure-based virtual screening and biological evaluation.JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,33(5),521-530. |
| MLA | Jiang, Cheng-Shi,et al."Discovery of new multifunctional selective acetylcholinesterase inhibitors: structure-based virtual screening and biological evaluation".JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN 33.5(2019):521-530. |
入库方式： OAI收割
来源：上海药物研究所
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