Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as beta-Amyloid Peptide Aggregation Inhibitors
文献类型：期刊论文
| 作者 | Zhou, Yu2 ; Jiang, Chunyi2; Zhang, Yaping1; Liang, Zhongjie2; Liu, Wenfeng2,3; Wang, Liefeng4; Luo, Cheng2; Zhong, Tingting1; Sun, Yi1; Zhao, Linxiang3
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2010-08-12 |
| 卷号 | 53期号:15页码:5449-5466 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm1000584 |
| 文献子类 | Article |
| 英文摘要 | The aggregation of A beta is a crucial step in the etiology of Alzheimer's disease. Our previous work showed that A beta undergoes alpha-helix/beta-sheet intermediate structures during the conformational transition, and an A beta aggregation inhibitor (1) was discovered by targeting the intermediates. Here, structure optimization toward compound 1 was performed and 34 novel derivatives were designed and synthesized. Nine compounds showed more effective inhibitory activity than the hit compound 1 in ThT fluorescence assay. Among them, compound 43 demonstrated more excellent inhibitory potency, which not only can suppress the aggregation of A beta but also can dissolve the preformed fibrils as shown by CD spectroscopy, PICUP and AFM assays. Cellular assay indicated that 43 has no toxicity to neuronal cells, moreover, can effectively inhibit A beta(1-42)-induced neutrotoxicity and increase the cell viability. Together, on the basis of these positive results, these novel chemical structures may provide a promising potential for therapeutic applications in AD and other types of neurodegenerative disorders. |
| WOS关键词 | ALZHEIMERS-DISEASE ; CONFORMATIONAL TRANSITION ; TOXICITY ; OLIGOMERIZATION ; CYCLODEXTRIN ; PROTEINS ; FIBRILS ; BINDING ; DESIGN ; TARGET |
| 资助项目 | CAS[00000000] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[20872153] ; National Natural Science Foundation of China[30670425] ; Ministry of Science and Technology[2009CB940900] ; Ministry of Science and Technology[2006AA020602] ; Ministry of Science and Technology[2008AA02Z138] ; National S&T Major Projects[2009ZX09301-001] ; National S&T Major Projects[2009ZX09501-001] ; National S&T Major Projects[2009ZX09501-010] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000280523300006 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278800]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 药理学第一研究室 |
| 通讯作者 | Zhou, Naiming |
| 作者单位 | 1.Zhejiang Univ, Inst Biochem, Coll Life Sci, Hangzhou 310058, Zhejiang, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Liaoning, Peoples R China; 4.Tongji Univ, Lab Receptor Based Biomed, Sch Life Sci & Technol, Shanghai 200092, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Yu,Jiang, Chunyi,Zhang, Yaping,et al. Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as beta-Amyloid Peptide Aggregation Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2010,53(15):5449-5466. |
| APA | Zhou, Yu.,Jiang, Chunyi.,Zhang, Yaping.,Liang, Zhongjie.,Liu, Wenfeng.,...&Liu, Hong.(2010).Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as beta-Amyloid Peptide Aggregation Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,53(15),5449-5466. |
| MLA | Zhou, Yu,et al."Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as beta-Amyloid Peptide Aggregation Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 53.15(2010):5449-5466. |
入库方式： OAI收割
来源：上海药物研究所
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