...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors
【24h】

Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors

机译：发现新型2,4-二取代的嘧啶作为极光激酶抑制剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a showed the moderate to high anti-proliferative activities against A549 (IC50 = 12.05 +/- 0.45 mu M), HCT-116 (IC50 = 1.31 +/- 0.41 mu M) and MCF-7 (IC50 = 20.53 +/- 6.13 mu M) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the proapoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor.
机译：为了探索新的极光激酶抑制剂，设计了一系列新的2,4-二取代的嘧啶，并在癌细胞系（A549，HCT-116和MCF-7）中，合成和评估它们的体外抗增殖活性。（A549，HCT-116和MCF-7） 。其中，化合物12a显示，对A549（IC50 = 12.05 +/-0.45μm），HCT-116（IC50 = 1.31 +/-0.41μm）和MCF-7（IC50 = 20.53的高抗增殖活性+/-6.13μm）细胞，以及Aurora A和极光B的抑制活动，分别具有309nm和293nm的IC 50值。此外，通过上调促凋亡蛋白Bax并在HCT-116细胞中降低抗凋亡蛋白Bcl-XL，化合物12a诱导细胞凋亡。此外，分子对接研究表明，化合物12a具有良好的含有极光A和极光B的结合模式，并且生物信息学预测发现化合物12a使用Swissadme表现出良好的药物象征。总之，这些结果表明12A可以是潜在的抗癌化合物，值得进一步发展为极光激酶抑制剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号