Exploration of novel piperazine or piperidine constructed non-covalent peptidyl derivatives as proteasome inhibitors
文献类型：期刊论文
| 作者 | Zhuang, Rangxiao1; Gao, Lixin2; Lv, Xiaoqing3; Xi, Jianjun1; Sheng, Li2; Zhao, Yanmei1; He, Ruoyu1; Hu, Xiaobei2; Shao, Yidan1; Pan, Xuwang1 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-01-27 |
| 卷号 | 126页码:1056-1070 |
| 关键词 | Proteasome inhibitors Piperazine or piperidine Non-covalent Peptidyl derivatives Anti-cancer |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.12.034 |
| 文献子类 | Article |
| 英文摘要 | A series of novel piperazine or piperidine-containing non-covalent peptidyl derivatives possessing a neopentyl-asparagine residue were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were screened for their 20S proteasome chymotrypsin-like inhibitory activities, and 15 ones displayed more potent activities than carfilzomib with IC50 values lower than 10 nM. Subsequently, the most potent 10 analogues were tested for their cytotoxic activities against two multiple myeloma (MM) cell lines RPMI-8226 and MM-1S. Based on these experiments, selected derivatives were further evaluated for their ex vivo and in vivo blood cell proteasome inhibitory activities. The most potential compound 35 (proteasome inhibition IC50: 1.2 +/- 0.1 nM) with potent anti-proliferation (IC50: RPMI-8226 8.4 +/- 0.8 nM; MM-1S: 6.3 +/- 0.8 nM), ex vivo and in vivo activities also had a prolonged half life in plasma, which demonstrated that the enzymatic stabilities of this series of compounds have been improved by constructing a six-membered ring into the peptide skeleton. All the experiments confirmed the correctness of design concept, which made this series of compounds potential leads for exploring new anti-MM drugs. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | MULTIPLE-MYELOMA ; UBIQUITIN SYSTEM ; CANCER-THERAPY ; APPROVAL ; PROTEOLYSIS ; SERIES |
| 资助项目 | Key Development Program of the Hangzhou Science and Technology Committee[20152013A03] ; Key Development Program of the Hangzhou Science and Technology Committee[20142013A60] ; normal project - Hangzhou Science and Technology Committee[20150733Q49] ; National Natural Science Foundation of China[81473244] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000396804600082 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275666]  |
| 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 | Zhou, Yubo; Li, Jia; Zhang, Jiankang |
| 作者单位 | 1.Hangzhou Xixi Hosp, Dept Pharmaceut Preparat, Hangzhou 310023, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Jiaxing Univ, Coll Med, Jiaxing 314001, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhuang, Rangxiao,Gao, Lixin,Lv, Xiaoqing,et al. Exploration of novel piperazine or piperidine constructed non-covalent peptidyl derivatives as proteasome inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,126:1056-1070. |
| APA | Zhuang, Rangxiao.,Gao, Lixin.,Lv, Xiaoqing.,Xi, Jianjun.,Sheng, Li.,...&Zhang, Jiankang.(2017).Exploration of novel piperazine or piperidine constructed non-covalent peptidyl derivatives as proteasome inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,126,1056-1070. |
| MLA | Zhuang, Rangxiao,et al."Exploration of novel piperazine or piperidine constructed non-covalent peptidyl derivatives as proteasome inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 126(2017):1056-1070. |
入库方式： OAI收割
来源：上海药物研究所
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