Synthesis and anti-tumor activity of EF24 analogues as IKK beta inhibitors

doi:10.1016/j.ejmech.2017.11.077

科研成果详情

题名	Synthesis and anti-tumor activity of EF24 analogues as IKK beta inhibitors
作者	Jin, Rong1,2; Chen, Qiuxiang2,3; Yao, Song 2; Bai, Encheng1,2; Fu, Weitao 2; Wang, Ledan4; Wang, Jiabing 2; Du, Xiaojing1,2; Wei, Tao2; Xu, Haineng 2,5; Jiang, Chengxi 2,5; Qiu, Peihong 2; Wu, Jianzhang2,5; Li, Wulan2,6; Liang, Guang2,5
发表日期	2018-01-20
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	IKK beta inhibitor Synthesis Molecular docking Anti-tumor activity
其他关键词	NF-KAPPA-B ; MONO-CARBONYL ANALOGS ; CURCUMIN ANALOGS ; LEUKEMIA INVOLVEMENT ; MOLECULAR-DYNAMICS ; PATHWAY ; CANCER ; ANTICANCER ; APOPTOSIS ; PERFORMANCE
摘要	EF24 is an IKK beta inhibitor (IC50: 72 mu M) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKK beta were designed and synthesized. Several IKK beta inhibitors with better activities than EF24 were screened out and B3 showed best IKK beta inhibitory (IC50: 6.6 mu M). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-kappa B signal pathway by inhibiting IKK beta phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKK beta-NF-kappa B signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKK beta inhibitor as anti-tumor precursor. (C) 2017 Published by Elsevier Masson SAS.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81703766, 81402839, 81272462]; ZheJiang Province Natural Science Fund of China [LY17H160059, LY15H280014]; Wenzhou Sci-Tech Bureau [Y20170161]; Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
出版地	ISSY-LES-MOULINEAUX
ISSN	0223-5234
EISSN	1768-3254
卷号	144 页码:218-228
DOI	10.1016/j.ejmech.2017.11.077
页数	11
WOS类目	Chemistry, Medicinal
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000425198100017
收录类别	SCIE ; PUBMED ; SCOPUS ; IC
URL	查看原文
PubMed ID	29351887
SCOPUSEID	2-s2.0-85040662018
自科自定义期刊分类	T3(B)类
通讯作者地址	[Wei, Tao]Chemical Biology Research Center,College of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Pharmacology;Drug Discovery;Organic Chemistry
引用统计	被引频次：14[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17447
专题	附属第一医院药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院药学院（分析测试中心）_生物有机与药物化学研究中心第一临床医学院（信息与工程学院）、附属第一医院_计算机与信息管理系
通讯作者	Wei, Tao
作者单位	1.Department of Digestive Diseases,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Chemical Biology Research Center,College of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Ultrasound,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 4.Department of Gynecology and Obstetrics,The 2nd Affiliated Hospital of the Wenzhou Medical University,Wenzhou,325000,China; 5.Wenzhou Biomedical Innovation Center,Wenzhou University and Wenzhou Medical University,Wenzhou,325000,China; 6.College of Information Science and Computer Engineering,The First Clinical Medical College,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 生物有机与药物化学研究中心
通讯作者单位	生物有机与药物化学研究中心
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Jin, Rong,Chen, Qiuxiang,Yao, Song,et al. Synthesis and anti-tumor activity of EF24 analogues as IKK beta inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,144:218-228.
APA	Jin, Rong., Chen, Qiuxiang., Yao, Song., Bai, Encheng., Fu, Weitao., ... & Liang, Guang. (2018). Synthesis and anti-tumor activity of EF24 analogues as IKK beta inhibitors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 144, 218-228.
MLA	Jin, Rong,et al."Synthesis and anti-tumor activity of EF24 analogues as IKK beta inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 144(2018):218-228.