Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer

doi:10.1016/j.ejmech.2016.10.066

科研成果详情

题名	Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer
作者	Ying, Shilong 1; Du, Xiaojing1,2; Fu, Weitao 1; Yun, Di 1; Chen, Liping 1; Cai, Yuepiao1; Xu, Qing 3; Wu, Jianzhang1; Li, Wulan1,4; Liang, Guang1
发表日期	2017-02-15
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	Design Fibroblast growth factor receptor 1 Gastric cancer Quantitative structure-activity relationship
其他关键词	GENE AMPLIFICATION ; DISCOVERY ; MODE ; FGFR ; OPTIMIZATION ; APATINIB ; THERAPY ; PACKAGE ; AMBER
摘要	Accumulating evidence suggests that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. Based on our previous discovery of two non-ATP competitive FGFR1 inhibitors, A114 and A117, we designed and screened a series of compounds with the framework of bisaryl-1,4-dien-3-one. Among them, D12 and D15 exhibited the most potent FGFR1 inhibitory activity, which was ATP-independent. Furthermore, a quantitative structure-activity relationship analysis of 41 analogs demonstrated that the specific structural substitutions alter their bioactivities. Molecular docking and dynamics simulation analysis indicated the hydrophobic interaction at the FGFR1-D12/D15 interaction was dominant. Evaluation for anti-gastric cancer efficacy of D12 and D15 indicated effective inhibition of cell proliferation, apoptosis induction and cell cycle arrest. Thus, these two FGFR1 inhibitors have therapeutic potential in the treatment of gastric cancer, and this study provides will contribute to the rational design of novel non-ATP competitive FGFR1 inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402839, 81272462, 81473242]; Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [LY17H160059]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129]
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
出版地	ISSY-LES-MOULINEAUX
ISSN	0223-5234
EISSN	1768-3254
卷号	127 页码:885-899
DOI	10.1016/j.ejmech.2016.10.066
页数	15
WOS类目	Chemistry, Medicinal
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000397172800070
收录类别	SCIE ; PUBMED ; SCOPUS ; IC
URL	查看原文
Pubmed记录号	27829519
Scopus记录号	2-s2.0-85008191221
自科自定义期刊分类	T3(B)类
通讯作者地址	[Wu, Jianzhang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical Universtiy,Wenzhou,325035,China
scopus学科分类	Pharmacology;Drug Discovery;Organic Chemistry
引用统计	被引频次：11[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/4271
专题	药学院（分析测试中心）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_计算机与信息管理系第一临床医学院（信息与工程学院）、附属第一医院_内科学_消化内科
通讯作者	Wu, Jianzhang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical Universtiy,Wenzhou,325035,China; 2.Department of Digestive Diseases,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,323000,China; 3.College of Chemistry and Materials Engineering,Wenzhou University,Wenzhou,325035,China; 4.College of Information Science and Computer Engineering,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Ying, Shilong,Du, Xiaojing,Fu, Weitao,et al. Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,127:885-899.
APA	Ying, Shilong., Du, Xiaojing., Fu, Weitao., Yun, Di., Chen, Liping., ... & Liang, Guang. (2017). Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 127, 885-899.
MLA	Ying, Shilong,et al."Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 127(2017):885-899.