Discovery of novel taspine derivatives as antiangiogenic agents.
Discovery of novel taspine derivatives as antiangiogenic agents.
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DOI：
10.1016/j.bmcl.2009.11.073
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发表时间：
2010-01
影响因子：
2.7
通讯作者：
Jie Zhang;Yanmin Zhang;San-qi Zhang;Sicen Wang;Langchong He
中科院分区：
文献类型：
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作者：
Jie Zhang;Yanmin Zhang;San-qi Zhang;Sicen Wang;Langchong He
VEGFR-2在血管发生中起关键作用，并且VEGFR-2的抑制剂可用于治疗癌症。塔斯品碱是通过使用内皮细胞膜色谱法筛选的活性成分之一，并显示对VEGFR-2的抑制作用。在我们的研究中，我们探讨了塔斯品碱的内酯环和联苯骨架如何影响其有效的体外抗癌和抗血管生成活性。因此，我们报告的设计，合成，并初步评估四个新的塔斯品碱衍生物作为VEGFR-2抑制剂。初步生物活性测试表明，其中一个化合物对CACO-2（IC_（50）=52.5nM）和ECV_（304）（IC_（50）=2.67nM）的抑制活性明显优于塔斯品碱。这一结果扩大了人们对塔斯品碱骨架开环衍生物在寻找新的抗血管生成药物方面的兴趣。
VEGFR-2 plays a critical role in vasculogenesis and inhibitors of VEGFR-2 could be used in the treatment of cancer. Taspine was one of the active ingredients screened by using an endothelial cell membrane chromatography and showed inhibition against VEGFR-2. In our research, we explored how the lactone ring and biphenyl scaffold in taspine influence its potent in vitro anticancer and antiangiogenesis activities. Accordingly, we report the design, synthesis, and preliminary evaluation of four novel taspine derivatives as VEGFR-2 inhibitors. The preliminary biological test showed that one of the compounds showed much better inhibitory activities against CACO-2 (IC50=52.5nM) and ECV304 (IC50=2.67nM) than taspine. This result enlarges the interest in ring-opened taspine derivative skeleton in the search of new antiangiogenesis agents.