Design, Synthesis and Biological Evaluation of Peptidyl Epoxyketone Proteasome Inhibitors Composed of beta-amino Acids
文献类型：期刊论文
| 作者 | Zhang, Jiankang1; Han, Mengmeng2; Ma, Xiaodong1; Xu, Lei2; Cao, Jiayi2; Zhou, Yubo2 ; Li, Jia2; Liu, Tao1; Hu, Yongzhou1
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 2014-11 |
| 卷号 | 84期号:5页码:497-504 |
| 关键词 | anti-cancer di- and tripeptides epoxyketone proteasome inhibitors -amino acid |
| ISSN号 | 1747-0277 |
| DOI | 10.1111/cbdd.12342 |
| 文献子类 | Article |
| 英文摘要 | A series of novel di- and tripeptidyl epoxyketone derivatives composed of -amino acids were designed, synthesized and evaluated for their proteasome inhibitory activities and anti-proliferation activities against two multiple myeloma cell lines RPMI 8226 and NCI-H929 and normal cells (peripheral blood mononucleated cells). Among these tested compounds, tripeptidyl analogues showed much more potent activities than dipeptides, and four tripeptidyl compounds exhibited proteasome inhibitory activities with IC50 values ranging from 0.97 +/- 0.05 to 1.85 +/- 0.11m. In addition, all the four compounds showed anti-proliferation activities with IC50 values at low micromolar levels against two multiple myeloma cell lines and weak activities against normal cells. Furthermore, Western blot analysis was performed to verify the proteasome inhibition induced by compounds 21d and 21e. All the experimental results validated that the -amino acid building block has the potential for the development of proteasome inhibitors. |
| WOS关键词 | 20S PROTEASOME ; PERSPECTIVES |
| 资助项目 | National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[91029716] ; National Science and Technology Major Projects for Major New Drugs Innovation and Development[2012ZX09301-001-004] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000343825100001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276858]  |
| 专题 | 药物化学研究室 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 药物安全性评价中心 国家新药筛选中心 |
| 通讯作者 | Liu, Tao |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Jiankang,Han, Mengmeng,Ma, Xiaodong,et al. Design, Synthesis and Biological Evaluation of Peptidyl Epoxyketone Proteasome Inhibitors Composed of beta-amino Acids[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2014,84(5):497-504. |
| APA | Zhang, Jiankang.,Han, Mengmeng.,Ma, Xiaodong.,Xu, Lei.,Cao, Jiayi.,...&Hu, Yongzhou.(2014).Design, Synthesis and Biological Evaluation of Peptidyl Epoxyketone Proteasome Inhibitors Composed of beta-amino Acids.CHEMICAL BIOLOGY & DRUG DESIGN,84(5),497-504. |
| MLA | Zhang, Jiankang,et al."Design, Synthesis and Biological Evaluation of Peptidyl Epoxyketone Proteasome Inhibitors Composed of beta-amino Acids".CHEMICAL BIOLOGY & DRUG DESIGN 84.5(2014):497-504. |
入库方式： OAI收割
来源：上海药物研究所
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