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化学学报
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化学学报 ›› 2008, Vol. 66 ›› Issue (14): 1731-1734. 上一篇    下一篇

研究论文

纺锤体驱动蛋白抑制剂的设计、合成与生物活性研究

阮秀琴a,b,c 尤启冬*,a,b 杨 蕾d 吴梧桐d   

  1. (a中国药科大学 江苏省肿瘤发生与干预重点实验室 南京 210009)
    (b中国药科大学 药物化学教研室 南京 210009)
    (c中国药科大学 物理化学教研室 南京 210009)
    (d中国药科大学 生命科学与技术学院 南京 210009)
  • 投稿日期:2007-12-10 修回日期:2008-01-22 发布日期:2008-07-28
  • 通讯作者: 尤启冬

Design, Synthesis and Biological Evaluation of Novel KSP Inhibitors

RUAN, Xiu-Qin a,b,c YOU, Qi-Dong *,a,b YANG, Lei d WU, Wu-Tong d   

  1. (a Key Laboratory of Carcinogenesis and Intervention of Jiangsu Province, China Pharmaceutical University,
    Nanjing 210009)
    (b Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009)
    (c Department of Physical Chemistry, China Pharmaceutical University, Nanjing 210009)
    (d School of Life and Technology, China Pharmaceutical University, Nanjing 210009)
  • Received:2007-12-10 Revised:2008-01-22 Published:2008-07-28
  • Contact: YOU, Qi-Dong

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被引次数

12 | 1

纺锤体驱动蛋白(kinesin spindle protein, KSP/Eg5)作为潜在的肿瘤治疗靶点, 使发现KSP抑制剂成为热点. 设计并合成了4-氧基-β-四氢咔啉衍生物作为新型的KSP抑制剂, 并测定了其对KSP的抑制活性, 均优于阳性对照物. 其中化合物9c抑制KSP的IC50＝0.065 μmol•L－1, 优于阳性对照物Monastro l100多倍. 生物活性研究表明为抗肿瘤药物提供了新结构类型的候选化合物.

关键词: 纺锤体驱动蛋白, 4-氧基-β-四氢咔啉, 抗肿瘤

The kinesin spindle protein (KSP/Eg5) is a potential target in cancer therapy.It, which has attracted great interest in discovery of compounds that inhibit KSP. Here, a series of 4-oxo-tetrahydro-β-carline derivatives 9a～94f have been designed and synthesized as a novel class of KSP inhibitor. The synthesized compounds were, and evaluated for their inhibition of aganist KSP. All compounds inhibited ATPase activity with IC50 below that of the analog Monastrol. 9c has an IC50＝0.065 μmol•L－1 for inhibition of KSP, ＞100-fold more active than Monastrol. The research results provide new candidate molecules for study of anticancer drugs.

Key words: kinesin spindle protein, 4-oxo-tetrahydro-β-carline, anticancer