Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid as proteasome inhibitors
文献类型：期刊论文
| 作者 | Zhang, Jiankang2; Cao, Jiayi1; Xu, Lei1; Zhou, Yubo1 ; Liu, Tao2; Li, Jia1; Hu, Yongzhou2
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2014-06-01 |
| 卷号 | 22期号:11页码:2955-2965 |
| 关键词 | Proteasome inhibitors beta-Amino acid Epoxyketone Anti-cancer Drug design SARs |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2014.04.011 |
| 文献子类 | Article |
| 英文摘要 | A series of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome inhibitory activities and selected compounds were tested for their anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and NCI-H929. Among them, eleven compounds exhibited proteasome inhibitory rates of more than 50% at the concentration of 1 mu g/mL and nine compounds showed anti-proliferation activities with IC50 values at low micromolar level. Compound 20h displayed the most potent proteasome inhibitory activities (IC50: 0.11 +/- 0.01 mu M) and anti-proliferation activities with IC50 values at 0.23 +/- 0.01 and 0.17 +/- 0.02 mu M against two tested cell lines. Additionally, the poly-ubiquitin accumulation in the western blot analysis supported that proteasome inhibition in a cellular system was induced by compound 20h. All these experimental results confirmed that b-amino acid can be introduced as a building block for the development of proteasome inhibitors. (C) 2014 Elsevier Ltd. All rights reserved. |
| WOS关键词 | 26S PROTEASOME ; CARFILZOMIB ; AGENTS ; SYSTEM ; TARGET |
| 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 ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000335451500005 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277061]  |
| 专题 | 国家新药筛选中心 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 药物安全性评价中心 |
| 通讯作者 | Li, Jia |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Jiankang,Cao, Jiayi,Xu, Lei,et al. Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid as proteasome inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2014,22(11):2955-2965. |
| APA | Zhang, Jiankang.,Cao, Jiayi.,Xu, Lei.,Zhou, Yubo.,Liu, Tao.,...&Hu, Yongzhou.(2014).Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid as proteasome inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,22(11),2955-2965. |
| MLA | Zhang, Jiankang,et al."Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid as proteasome inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 22.11(2014):2955-2965. |
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。