Discovering novel 3-nitroquinolines as a new class of anticancer agents

doi:10.1111/j.1745-7254.2008.00907.x

	Discovering novel 3-nitroquinolines as a new class of anticancer agents
	Li, Hai-hong 2; Huang, He 2; Zhang, Xiu-hua 1; Luo, Xiao-min2 ; Lin, Li-ping 1; Jiang, Hua-liang2 ; Ding, Jian1 ; Chen, Kaixian2 ; Liu, Hong2
刊名	ACTA PHARMACOLOGICA SINICA
	2008-12
卷号	29 期号:12 页码:1529-1538
关键词	3-nitroquinoline epidermal growth factor receptor tyrosine kinase inhibitor molecular modeling
ISSN号	1671-4083
DOI	10.1111/j.1745-7254.2008.00907.x
文献子类	Article
英文摘要	Aim: To design and synthesize a novel class of antitumor agents, featuring the 3-nitroquinoline framework. Methods: Based on the enzyme-binding features of Ekb1, introducing a nitro group at the 3-position of the quinoline core, a series of novel 3-nitroquinolines was designed and synthesized. The inhibition of epidermal growth factor receptor (EGFR) activity by these compounds was evaluated and analyzed by the sulforhodamine B assay for their inhibitory activities toward human epidermoid carcinoma (A431) cells and breast cancer (MDA-MB-468) cells, which are known to overexpress the EGFR kinase. Results: A series of novel 3-nitroquinoline derivatives were synthesized and evaluated for their antiproliferative effect against the EGFR-overexpressing tumor cell lines. Several compounds for concentration-response studies showed prominent inhibitory activities with IC50 values in the micromolar or nanomolar range. The structure-activity relationship was discussed in terms of the inhibitory activity against the proliferation of 2 human carcinoma cell lines. Conclusion: This study was the first to identify new structural types of antiproliferative agents against the EGFR-overexpressing tumor cell lines by the incorporation of the nitro group at the 3-position of the quinoline core structure, providing promising new templates for the further development of anticancer agents.
资助项目	State Key Program of Basic Research of China[2006BAI01B02] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[20872153] ; 863 Hi-Tech Program of China[2006AA020602]
WOS关键词	GROWTH-FACTOR RECEPTOR ; TYROSINE KINASE INHIBITORS ; SITE INHIBITORS ; EGF-R ; PROTEIN ; ANALOGS ; DESIGN ; CANCER
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3430179
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000261710300017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279413]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室科研与新药推进处
通讯作者	Lin, Li-ping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Li, Hai-hong,Huang, He,Zhang, Xiu-hua,et al. Discovering novel 3-nitroquinolines as a new class of anticancer agents[J]. ACTA PHARMACOLOGICA SINICA,2008,29(12):1529-1538.
APA	Li, Hai-hong.,Huang, He.,Zhang, Xiu-hua.,Luo, Xiao-min.,Lin, Li-ping.,...&Liu, Hong.(2008).Discovering novel 3-nitroquinolines as a new class of anticancer agents.ACTA PHARMACOLOGICA SINICA,29(12),1529-1538.
MLA	Li, Hai-hong,et al."Discovering novel 3-nitroquinolines as a new class of anticancer agents".ACTA PHARMACOLOGICA SINICA 29.12(2008):1529-1538.