Synthesis and biological evaluation of 6H-pyrido[2 ',1 ':2,3] imidazo[4,5-c] isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization

doi:10.1016/j.bmc.2013.12.004

	Synthesis and biological evaluation of 6H-pyrido[2 ',1 ':2,3] imidazo[4,5-c] isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization
	Meng, Tao2 ; Wang, Wei 1; Zhang, Zhixiang 1; Ma, Lanping2 ; Zhang, Yongliang 2; Miao, Zehong 1; Shen, Jingkang 2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2014-01-15
卷号	22 期号:2 页码:848-855
关键词	6H-Pyrido[2 ',1 ':2,3]imidazo[4,5-c] isoquinolin-5(6H)-ones Antitumor agents Inhibitors of tubulin polymerization Colchicine binding site
ISSN号	0968-0896
DOI	10.1016/j.bmc.2013.12.004
文献子类	Article
英文摘要	A series of 6H-pyrido[20,10: 2,3] imidazo[4,5-c] isoquinolin-5(6H)-ones have been synthesized and evaluated for their antiproliferative activities. Among them, compounds 2j and 4d displayed potent cytotoxic activities in vitro against HeLa cell line with IC50 values of 0.07 and 0.06 mu M, respectively. In general, the antiproliferative activities are correlated with the inhibitory effect on tubulin polymerization and binding property of the colchicine binding site. In addition, flow cytometry and immunofluorescence analysis revealed selected compounds caused G2/M phase arrest of the cell cycle and disruption of the mitotic spindle assembly, which had correlation with proliferation inhibitory activity. (C) 2014 Published by Elsevier Ltd.
资助项目	National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program', China[2012ZX09103-101-026]
WOS关键词	MICROTUBULE INHIBITORS ; MITOTIC SPINDLE ; BINDING ; COLCHICINE ; CELLS ; APOPTOSIS ; MITOSIS ; DRUGS ; SITE
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000329576400019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277228]
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药理学第一研究室
通讯作者	Ma, Lanping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Meng, Tao,Wang, Wei,Zhang, Zhixiang,et al. Synthesis and biological evaluation of 6H-pyrido[2 ',1 ':2,3] imidazo[4,5-c] isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2014,22(2):848-855.
APA	Meng, Tao.,Wang, Wei.,Zhang, Zhixiang.,Ma, Lanping.,Zhang, Yongliang.,...&Shen, Jingkang.(2014).Synthesis and biological evaluation of 6H-pyrido[2 ',1 ':2,3] imidazo[4,5-c] isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization.BIOORGANIC & MEDICINAL CHEMISTRY,22(2),848-855.
MLA	Meng, Tao,et al."Synthesis and biological evaluation of 6H-pyrido[2 ',1 ':2,3] imidazo[4,5-c] isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization".BIOORGANIC & MEDICINAL CHEMISTRY 22.2(2014):848-855.