1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy
文献类型：期刊论文
| 作者 | Jiang, Junhang1; Zhang, Hao2; Wang, Chongqing1; Zhang, Qingsen1; Fang, Shaoyu1; Zhou, Ruolan1; Hu, Jian1; Zhu, Ju1; Zhou, Youjun1; Luo, Cheng2
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2019-09-01 |
| 卷号 | 177页码:448-456 |
| 关键词 | Microtubule-targeting agents Colchicine site inhibitors Cis-trans photoisomerization X-ray co-crystal structure Water-soluble prodrug |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2019.04.040 |
| 通讯作者 | Zhou, Youjun(zhuoyoujun@smmu.edu.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Zheng, Canhui(canhuizheng@smmu.edu.cn) |
| 英文摘要 | The colchicine site inhibitors (CSIs) showed promising prospects as antitumor agents due to their vascular disrupting activities besides antimitotic activities. 1-Phenyl-dihydrobenzoindazole was found as a novel scaffold of CSI without the cis-trans isomerization problem. The X-ray co-crystal structure of the lead compound with tubulin was determined, which revealed the binding mode including special waterbridged hydrogen bonds. The structure also provided guidance for the structural optimization of this type of CSI, which led to the discovery of the most potent inhibitor A3, with growth IC50 lower than 1 nM against human colon cancer cell lines and tubulin polymerization IC50 of 1.6 mu M. In addition, its water-soluble prodrug B1 showed good in vivo antitumor activity on two human colon cancer xenograft nude mice models, encouraging further study of this type of antitumor compound. (C) 2019 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | TUBULIN POLYMERIZATION ; BINDING ; AGENTS ; MITOSIS ; TARGET ; DRUGS |
| 资助项目 | National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[81430084] ; National Natural Science Foundation of China[21572266] ; Shanghai Rising Star Program of China[16QA1404800] ; K. C. Wong Education Foundation ; Chinese Academy of Sciences[XDA12020353] ; Chinese Academy of Sciences[XDA12050401] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000474316600031 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/289331]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Youjun; Luo, Cheng; Zheng, Canhui |
| 作者单位 | 1.Second Mil Med Univ, Sch Pharm, 325 Guohe Rd, Shanghai 200433, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Junhang,Zhang, Hao,Wang, Chongqing,et al. 1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,177:448-456. |
| APA | Jiang, Junhang.,Zhang, Hao.,Wang, Chongqing.,Zhang, Qingsen.,Fang, Shaoyu.,...&Zheng, Canhui.(2019).1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,177,448-456. |
| MLA | Jiang, Junhang,et al."1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 177(2019):448-456. |
入库方式： OAI收割
来源：上海药物研究所
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