β-四氢咔啉衍生物的合成和生物活性  

Synthesis and biological evaluation of tetrahydro-β-carline derivatives

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,江苏南京210009

出　　处：《药学学报》2008年第8期828-832,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30772824);高等学校博士学位点专项科研基金资助项目(20060316006);江苏省“六大人才高峰”项目资助项目(06-c-023)

摘　　要：纺锤体驱动蛋白(kinesin spindle protein,KSP)是有丝分裂过程中二极纺锤体形成和维持所必需的。抑制KSP的功能将导致细胞周期停滞和细胞编程性细胞死亡,并且不干扰微管的其他功能,因而可成为潜在的肿瘤治疗靶点。本文合成了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。Kinesin spindle protein （KSP/Eg5） is essential for the formation and maintenance of bipolar spindles during mitosis. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, a series of tetrahydro-β-carboline derivatives 5a - k were synthesized as kinesin spindle protein inhibitor. Their structures were confirmed with ^1H NMR, ESI-MS and elemental analysis. The synthesized compounds were evaluated for their inhibition of KSP.

关 键 词：β-四氢咔啉 纺锤体驱动蛋白抑制剂 抗肿瘤 

分 类 号：R916.2[医药卫生—药学]