Synthesis, biological evaluation and molecular docking studies of flavone and isoflavone derivatives as a novel class of KSP (kinesin spindle protein) inhibitors

被引：7
作者：
Dong, Jing-Jun [1 ]
Li, Qing-Shan [1 ,2 ]
Liu, Zhi-Peng [1 ]
Wang, Shu-Fu [1 ]
Zhao, Meng-Yue [1 ]
Yang, Yong-Hua [1 ]
Wang, Xiao-Ming [1 ]
Zhu, Hai-Liang [1 ]
机构：
[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
[2] Hefei Univ Technol, Sch Med Engn, Hefei 230009, Peoples R China
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 70卷
关键词：
KSP; Flavone; Isoflavone; Antimitotic; Kinesin inhibitor; Monoastral spindles; MITOTIC MOTOR PROTEIN; MICROTUBULES; ACTIVATION; DESIGN; CANCER; CELLS; BLOCK; EG5;
D O I：
10.1016/j.ejmech.2013.09.042
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The kinesin spindle protein (KSP) is involved in the formation of bipolar mitotic spindle during cell division and it becomes a new target to overcome the neurotoxicity of MTs inhibitors. A series of flavone and isoflavone derivatives (1a-7c) have been designed, synthesized and evaluated as potential KSP inhibitors. Among them, 2c displayed the most potent inhibitory activity in vitro, which inhibited the growth of MCF-7 and Hela cell lines with IC50 values of 4.8 and 4.3 p,M, respectively, and also exhibited significant KSP inhibitory activity (IC50 = 0.023 mu M). The new compounds can induce irregular monoastral spindles, the characteristic phenotype for KSP inhibiting agents. Docking simulation was further performed to determine the probable binding model. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：427 / 433
页数：7
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