Discovery of tetrahydro-β-carbolines as inhibitors of the mitotic kinesin KSP
Discovery of tetrahydro-β-carbolines as inhibitors of the mitotic kinesin KSP
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DOI：
10.1016/j.bmc.2010.05.024
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发表时间：
2010-06-15
影响因子：
3.5
通讯作者：
You, Qi-Dong
中科院分区：
文献类型：
--
作者：
Liu, Fei;Yu, Li-Qin;You, Qi-Dong
驱动蛋白纺锤体蛋白 (KSP) 抑制剂是一类很有前途的抗癌药物，可导致细胞因无法形成功能性双极有丝分裂纺锤体而导致有丝分裂停滞。在此，我们报告了基于已知 KSP 抑制剂 HR22C16 结构的一系列新型四氢-β-咔啉类似物的合成和生物学评价。优选的化合物11b、12a和19b在KSP ATP酶测定中被鉴定为有效抑制剂，在A549细胞中具有良好的抗增殖活性。 (C) 2010 Elsevier Ltd. 保留所有权利。
Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the synthesis and biological evaluation of a novel series of tetrahydro-beta-carboline analogs based on the structure of the known KSP inhibitor HR22C16. Preferred compounds 11b, 12a and 19b were identified as potent inhibitors in a KSP ATPase assay with good anti-proliferative activity in A549 cells. (C) 2010 Elsevier Ltd. All rights reserved.