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| Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment | |
| Wang, Lijun1,2; Guo, Chuanlong1,2,5,6; Li, Xiuxue1,2; Yu, Xuemin4; Li, Xiangqian1,2; Xu, Kuo1,2; Jiang, Bo1,2; Jia, Xiaoling1,2; Li, Chao1,2; Shi, Dayong1,2,3 | |
| 2019-09-01 | |
| 发表期刊 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| ISSN | 0223-5234 |
| 卷号 | 177页码:153-170 |
| 通讯作者 | Wang, Lijun(wanglijun@qdio.ac.cn) ; Shi, Dayong(shidayong@qdio.ac.cn) |
| 摘要 | The eukaryotic initiation factor 4E (eIF4E) is an emerging anticancer drug target for specific anticancer therapy as a promising approach to overcome drug resistance and promote chemotherapy antitumor efficacy. A series of bromophenol-thiazotylhydrazone hybrids were designed, synthesized and evaluated for their antitumor activities. Among of them, the most potent compound 3e (EGPI-1) could inhibit the eIF4E/eIF4G interaction. Further mechanism study demonstrated EGPI-1 played an antitumor role in multiple modes of action including regulating the activity of elF4E by inhibiting the phosphorylation of eIF4E and 4EBPI, disrupting mitochondrial function through the mTOR/4EBP1 signaling pathway, and inducing autophagy, apoptosis and ROS generation. Moreover, EGPI-1 showed good safety and favorable pharmacokinetic properties in vivo. These observations demonstrate that EGPI-1 may serve as an excellent lead compound for the development of new anticancer drugs that target the eIF4E/eIF4G interface and as a chemical genetic probe to investigate the role of the eIF4E in biological processes and human diseases. (C) 2019 Elsevier Masson SAS. All rights reserved. |
| 关键词 | Bromophenol-thiazolylhydrazone hybrids Synthesis Multifunctional agents eIF4E/eIF4G interaction Autophagy ROS |
| DOI | 10.1016/j.ejmech.2019.05.044 |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助项目 | National Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; National Natural Science Foundation of China[81600782] ; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Project of Discovery, Evaluation and Transformation of Active Natural Com-pounds, Strategic Biological Resources Service Network Program of Chinese Academy of Sciences[ZSTH-026] ; National Program for Support of Top-notch Young Professionals ; Taishan scholar Youth Project of Shandong province ; National Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; National Natural Science Foundation of China[81600782] ; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Project of Discovery, Evaluation and Transformation of Active Natural Com-pounds, Strategic Biological Resources Service Network Program of Chinese Academy of Sciences[ZSTH-026] ; National Program for Support of Top-notch Young Professionals ; Taishan scholar Youth Project of Shandong province |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Medicinal |
| WOS记录号 | WOS:000474316600010 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/161927 |
| 专题 | 实验海洋生物学重点实验室 |
| 通讯作者 | Wang, Lijun; Shi, Dayong |
| 作者单位 | 1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Shandong, Peoples R China 2.Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao 266071, Shandong, Peoples R China 3.Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China 4.Shandong Univ, Qilu Hosp, Dept Otorhinolaryngol, Qingdao 266000, Shandong, Peoples R China 5.Qingdao Univ Sci & Technol, Dept Pharm, Coll Chem Engn, Qingdao 266042, Shandong, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 第一作者单位 | 中国科学院海洋研究所 |
| 通讯作者单位 | 中国科学院海洋研究所 |
| 推荐引用方式 GB/T 7714 | Wang, Lijun,Guo, Chuanlong,Li, Xiuxue,et al. Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,177:153-170. |
| APA | Wang, Lijun.,Guo, Chuanlong.,Li, Xiuxue.,Yu, Xuemin.,Li, Xiangqian.,...&Shi, Dayong.(2019).Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,177,153-170. |
| MLA | Wang, Lijun,et al."Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 177(2019):153-170. |
| 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 | ||
| Wang-2019-Design-syn（4835KB） | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | 浏览 | |
| Design, synthesis an（4835KB） | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | 浏览 | |
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