纺锤体驱动蛋白抑制剂的设计、合成与生物活性研究  

Design, Synthesis and Biological Evaluation of Novel KSP Inhibitors

作　　者：阮秀琴[1] 尤启冬[1] 杨蕾[2] 吴梧桐[2] 

机构地区：[1]中国药科大学江苏省肿瘤发生与干预重点实验室 [2]中国药科大学生命科学与技术学院,南京210009

出　　处：《化学学报》2008年第14期1731-1734,共4页Acta Chimica Sinica

基　　金：国家自然科学基金(No.30772824);高等学校博士学位点专项科研基金(No.20060316006);江苏省“六大人才高峰”(No.06-c-023)资助项目

摘　　要：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=0.065μmol?L-1,优于阳性对照物Monastrol100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.The kinesin spindle protein （KSP/Eg5） is a potential target in cancer therapy, which has attracted great interest in discovery of compounds that inhibit KSP. Here, a series of 4-oxo-tetrahydro-β-carline derivatives 9a-9f have been designed and synthesized as a novel class of KSP inhibitor, and evaluated for their inhibition aganist KSP. All compounds inhibited ATPase activity with ICs0 below that of the analog Monastrol. 9c has an IC50=0.065 umolo·L^-1 for inhibition of KSP, 〉 100-fold more active than Monastrol. The research results provide new candidate molecules for study of anticancer drugs.

关 键 词：纺锤体驱动蛋白 4-氧基-β-四氢咔啉 抗肿瘤 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]