Design, synthesis and biological evaluation of novel non-covalent piperidine-containing peptidyl proteasome inhibitors
文献类型：期刊论文
| 作者 | Zhang, Jiankang1; Gao, Lixin2; Xi, Jianjun1; Sheng, Li2; Zhao, Yanmei1; Xu, Lei2; Shao, Yidan1; Liu, Shourong1; Zhuang, Rangxiao1; Zhou, Yubo2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2016-12-01 |
| 卷号 | 24期号:23页码:6206-6214 |
| 关键词 | Proteasome inhibitors Piperidine Non-covalent Anti-cancer SARs |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2016.10.002 |
| 文献子类 | Article |
| 英文摘要 | A series of novel non-covalent piperidine-containing dipeptidyl derivatives were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome chymotrypsin-like inhibitory activities, and selected derivatives were evaluated for the anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and MM-1S. Among all of these compounds, eight exhibited significant proteasome inhibitory activities with IC50 less than 20 nM, and four are more potent than the positive control Carfilzomib. Compound 28 displayed the most potent proteasome inhibitory activity (IC50: 1.4 +/- 0.1 nM) and cytotoxicities with IC50 values at 13.9 +/- 1.8 nM and 9.5 +/- 0.5 nM against RPMI 8226 and MM-1S, respectively. Additionally, the ex vivo blood cell proteasome inhibitory activities of compounds 24 and 27-29 demonstrated that the enzymatic metabolism in the whole blood could be well tolerated. All these experiments confirmed that the piperidine-containing non-covalent proteasome inhibitors are potential leads for exploring new anti-cancer drugs. (C) 2016 Elsevier Ltd. All rights reserved. |
| WOS关键词 | CHYMOTRYPSIN-LIKE ACTIVITY ; HUMAN 20S PROTEASOME ; CANCER-THERAPY ; PROTEOLYTIC PATHWAY ; CRYSTAL-STRUCTURE ; MULTIPLE-MYELOMA ; APPROVAL ; SERIES ; CARFILZOMIB ; COMPLEX |
| 资助项目 | Key Development Program of the Hangzhou Science and Technology Committee[20152013A03] ; Hangzhou Science and Technology Committee[20150733Q49] ; National Natural Science Foundation of China[81473244] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000389519600009 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275784]  |
| 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 药物安全性评价中心 |
| 通讯作者 | Zhuang, Rangxiao; Zhou, Yubo; Li, Jia |
| 作者单位 | 1.Hangzhou Xixi Hosp, Dept Pharmaceut Preparat, Hangzhou 310023, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Jiankang,Gao, Lixin,Xi, Jianjun,et al. Design, synthesis and biological evaluation of novel non-covalent piperidine-containing peptidyl proteasome inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2016,24(23):6206-6214. |
| APA | Zhang, Jiankang.,Gao, Lixin.,Xi, Jianjun.,Sheng, Li.,Zhao, Yanmei.,...&Li, Jia.(2016).Design, synthesis and biological evaluation of novel non-covalent piperidine-containing peptidyl proteasome inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,24(23),6206-6214. |
| MLA | Zhang, Jiankang,et al."Design, synthesis and biological evaluation of novel non-covalent piperidine-containing peptidyl proteasome inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 24.23(2016):6206-6214. |
入库方式： OAI收割
来源：上海药物研究所
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