Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease
文献类型：期刊论文
| 作者 | Xu, Yi-xiang2; Wang, Huan1,3; Li, Xiao-kang2; Dong, Sheng-nan1; Liu, Wen-wen2; Gong, Qi1; Wang, Tian-duan-yi2; Tang, Yun2; Zhu, Jin2; Li, Jian2 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2018 |
| 卷号 | 143页码:33-47 |
| 关键词 | Multifunctional agents AChE inhibitors MAO-B inhibitors Metal chelating agents Alzheimer's disease |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2017.08.025 |
| 文献子类 | Article |
| 英文摘要 | A series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-3) were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy, and their potential was evaluated through various biological experiments. Among these derivatives, compound 1b displayed good selective inhibitory activity against AChE (vs BuChE, IC50 = 0.324 M, SI > 123) and MAO-B (vs MAO-A, IC50 = 1.427 mu M, SI > 35). Molecular docking study showed that the pyrimidinylthiourea moiety of lb could bind to the catalytic active site (CAS) of AChE, and the propargylamine moiety interacted directly with the flavin adenine dinucleotide (FAD) of MAO-B. Moreover, 1b demonstrated mild antioxidant ability, good copper chelating property, effective inhibitory activity against Cu2+-induced A beta(1-42) aggregation, moderate neuroprotection, low cytotoxicity, and appropriate blood-brain barrier (BBB) permeability in vitro and was capable of ameliorating scopolamine-induced cognitive impairment in mice. These results indicated that 1b has the potential to be a multifunctional candidate for the treatment of Alzheimer's disease. (C) 2017 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | A-BETA PEPTIDE ; MONOAMINE-OXIDASE ; AMYLOID-BETA ; NEURODEGENERATIVE DISEASES ; CHOLINESTERASE-INHIBITORS ; CHELATION-THERAPY ; OXIDATIVE STRESS ; DIRECTED LIGANDS ; HYPOTHESIS ; ACETYLCHOLINESTERASE |
| 资助项目 | National Natural Science Foundation of China[21702061] ; National Natural Science Foundation of China[21672064] ; National Natural Science Foundation of China[81522045] ; Yang-Fan Program from the Science and Technology Commission of Shanghai[17YF1403600] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000428216700004 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272321]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Li, Jian; Zhang, Hai-yan; Mao, Fei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Yi-xiang,Wang, Huan,Li, Xiao-kang,et al. Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,143:33-47. |
| APA | Xu, Yi-xiang.,Wang, Huan.,Li, Xiao-kang.,Dong, Sheng-nan.,Liu, Wen-wen.,...&Mao, Fei.(2018).Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,143,33-47. |
| MLA | Xu, Yi-xiang,et al."Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 143(2018):33-47. |
入库方式： OAI收割
来源：上海药物研究所
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