Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Tongjiaxiang, Nanjing 210009, China.
Bioorg Med Chem. 2010 Jun 15;18(12):4167-77. doi: 10.1016/j.bmc.2010.05.024. Epub 2010 May 11.
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.
有丝分裂纺锤体蛋白（KSP）抑制剂是一类很有前途的抗癌药物，它们会导致细胞有丝分裂停滞，因为它们无法形成功能正常的双极有丝分裂纺锤体。在这里，我们报告了一系列基于已知 KSP 抑制剂 HR22C16 结构的新型四氢-β-咔啉类似物的合成和生物学评价。在 KSP ATP 酶测定中，优选化合物 11b、12a 和 19b 被鉴定为有效的抑制剂，并且在 A549 细胞中具有良好的抗增殖活性。
