| Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors | |
Shao, Li-Dong1; Su, Jia1; Ye, Baixin2,3; Liu, Jiang-Xin1; Zuo, Zhi-Li1 ; Li, Yan1; Wang, Yue-Ying2,3; Xia, Chengfeng1; Zhao, Qin-Shi1,4
| |
| 2017-11-09 | |
| 发表期刊 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| ISSN | 0022-2623 |
| 卷号 | 60期号:21页码:9053-9066 |
| 摘要 | Previously, vibsanin B (ViB) was found to preferentially target HSP90 beta compared to HSP90 alpha. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90 beta-NTD, MD, CTD, and full-length HSP90 beta, molecular docking of ViB and its derivatives to the HSP90 CTD, and a inhibition assay of interaction of the HSP90 beta CTD with GST-tagged cyclophilin 40 (Cyp40) by ViB derivatives, suggest that ViB can directly bind to the HSP90 C-terminus. On the basis of the docking predictions and primary structure-activity relationships (SARs), a series of ViB analogues devised with focus on the C18 position, along with compounds derivatized at the C4, C7, and C8 positions, were designed and chemically synthesized. Compound 12f (IC50 = 1.12 mu M against SK-BR-3) exhibits great potency with drug-like properties. Overall, our findings demonstrate that compounds with the vibsanin B scaffold are a new class of HSP90 C-terminal inhibitors with considerable potential as anticancer agents. |
| DOI | 10.1021/acs.jmedchem.7b01395 |
| 语种 | 英语 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/60372 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, State Key Lab Med Genom, Shanghai 200025, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, Shanghai Inst Hematol, Shanghai 200025, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shao, Li-Dong,Su, Jia,Ye, Baixin,et al. Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60(21):9053-9066. |
| APA | Shao, Li-Dong.,Su, Jia.,Ye, Baixin.,Liu, Jiang-Xin.,Zuo, Zhi-Li.,...&Zhao, Qin-Shi.(2017).Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,60(21),9053-9066. |
| MLA | Shao, Li-Dong,et al."Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 60.21(2017):9053-9066. |
| 条目包含的文件 | 下载所有文件 | |||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| shao2017.pdf（5724KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | 浏览 下载 | |
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。
修改评论