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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
Source PublicationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN0223-5234
Volume177Pages:153-170
Corresponding AuthorWang, Lijun(wanglijun@qdio.ac.cn) ; Shi, Dayong(shidayong@qdio.ac.cn)
AbstractThe 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.
KeywordBromophenol-thiazolylhydrazone hybrids Synthesis Multifunctional agents eIF4E/eIF4G interaction Autophagy ROS
DOI10.1016/j.ejmech.2019.05.044
Indexed BySCI
Language英语
Funding ProjectNational 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 Research AreaPharmacology & Pharmacy
WOS SubjectChemistry, Medicinal
WOS IDWOS:000474316600010
PublisherELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation statistics
Document Type期刊论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/161927
Collection实验海洋生物学重点实验室
Corresponding AuthorWang, Lijun; Shi, Dayong
Affiliation1.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
First Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Recommended Citation
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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.
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