Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents

doi:10.2147/DDDT.S65997

科研成果详情

题名	Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents
作者	Chen, Gaozhi1; Jiang, Lili 2; Dong, Lili 2; Wang, Zhe1; Xu, Fengli2; Ding, Ting 3; Fu, Lili1; Fang, Qilu 1; Liu, Zhiguo1,4; Shan, Xiaoou2; Liang, Guang1
发表日期	2014-12-31
发表期刊	DRUG DESIGN DEVELOPMENT AND THERAPY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	anti-inflammation macrophages sepsis
其他关键词	ACETYL SALICYLIC-ACID ; KINASE INHIBITORS ; SEVERE SEPSIS ; DISCOVERY ; DRUGS ; MORTALITY ; TOXICITY ; CURCUMIN ; STRESS ; TRIAL
摘要	Sepsis, a typically acute inflammatory disease, is the biggest cause of death in ICU (intensive care unit). Novel anti-inflammatory alternatives are still in urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza-2-oxindole derivatives based on the skeleton of tenidap, and their anti-inflammatory activity was determined by evaluating the inhibitory potency against lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure-activity relationship) analysis revealed that a high molecular polarizability and low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the expression of TNF-alpha, IL-6, COX-2, PGES, and iNOS in LPS-stimulated macrophages, and 7i exhibited a significant protection from LPS-induced septic death in mouse models. These data present a series of new indole-2-one compounds with potential therapeutic effects in acute inflammatory diseases.
资助项目	National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [21272179, 21202124]; High-level Innovative Talent Funding of Zhejiang Department of Health; Project of Wenzhou SciTech Bureau [Y20120061]; Zhejiang Natural Science Funding [Q12H300009]; Qianjiang Talent Project of Zhejiang Province [2013R10020]; SRF for ROCS and SEMScientific Research Foundation for the Returned Overseas Chinese Scholars; Zhejiang Key Group Project in Scientific Innovation [2010R50042]
出版者	DOVE MEDICAL PRESS LTD
出版地	ALBANY
ISSN	1177-8881
卷号	8 页码:1869-1892
DOI	10.2147/DDDT.S65997
页数	24
WOS类目	Chemistry, Medicinal ; Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000343104400001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	25378906
PMC记录号	PMC4207570
SCOPUSEID	2-s2.0-84908068831
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Pharmacology;Pharmaceutical Science;Drug Discovery
引用统计	被引频次：8[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/15020
专题	药学院（分析测试中心）附属第二医院药学院（分析测试中心）_药学系第二临床医学院、附属第二医院、育英儿童医院第二临床医学院、附属第二医院、育英儿童医院_儿科学
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Lishui,China; 2.Department of Pediatrics,The 2nd Affiliated Hospital,Wenzhou Medical University,Lishui,China; 3.Department of Pharmacy,The 5th Affiliated Hospital,Wenzhou Medical University,Lishui,China; 4.Wenzhou Undersun Biotchnology Co. Ltd,Wenzhou,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	Chen, Gaozhi,Jiang, Lili,Dong, Lili,et al. Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2014,8:1869-1892.
APA	Chen, Gaozhi., Jiang, Lili., Dong, Lili., Wang, Zhe., Xu, Fengli., ... & Liang, Guang. (2014). Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents. DRUG DESIGN DEVELOPMENT AND THERAPY, 8, 1869-1892.
MLA	Chen, Gaozhi,et al."Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents".DRUG DESIGN DEVELOPMENT AND THERAPY 8(2014):1869-1892.