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

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• 作者：Tao Meng ; Wei Wang ; Zhixiang Zhang ; Lanping Ma ; Yongliang Zhang ; Zehong Miao ; Jingkang Shen
• 关键词：6H-Pyrido[2&prime ; 1&prime ; 2 ; 3]imidazo[4 ; 5-c]isoquinolin-5(6H)-ones ; Antitumor agents ; Inhibitors of tubulin polymerization ; Colchicine binding site
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：15 January, 2014
• 年：2014
• 卷：22
• 期：2
• 页码：848-855
• 全文大小：999 K

文摘

A series of 6H-pyrido[2鈥?1鈥?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 渭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.