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
ISSN0022-2623
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.
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
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请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Shao, Li-Dong]的文章
[Su, Jia]的文章
[Ye, Baixin]的文章
百度学术
百度学术中相似的文章
[Shao, Li-Dong]的文章
[Su, Jia]的文章
[Ye, Baixin]的文章
必应学术
必应学术中相似的文章
[Shao, Li-Dong]的文章
[Su, Jia]的文章
[Ye, Baixin]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

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。