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

被引：31

作者：

Meng, Tao ^{[1
]}

Wang, Wei ^{[2
]}

Zhang, Zhixiang ^{[2
]}

Ma, Lanping ^{[1
]}

Zhang, Yongliang ^{[1
]}

Miao, Zehong ^{[2
]}

Shen, Jingkang ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Div Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 02期

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; MICROTUBULE INHIBITORS; MITOTIC SPINDLE; BINDING; COLCHICINE; CELLS; APOPTOSIS; MITOSIS; DRUGS; SITE;

D O I：

10.1016/j.bmc.2013.12.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：848 / 855

页数：8

共 26 条

[1] Selective Targeting of Tumorigenic Cancer Cell Lines by Microtubule Inhibitors [J].