• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Synthesis, biological evaluation and mechanism studies of C-23 modified 23-hydroxybetulinic acid derivatives as anticancer agents
【24h】

Synthesis, biological evaluation and mechanism studies of C-23 modified 23-hydroxybetulinic acid derivatives as anticancer agents

机译：C-23改性23-羟基乙酸衍生物作为抗癌剂的合成，生物学评价和机理研究

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

A series of C-23 modified 23-hydroxybetulinic acid (HBA) derivatives were synthesized and evaluated for their antiproliferative activity against a panel of cancer cell lines (A2780, A375, B16, MCF-7 and HepG2). The biological screening results showed that most of the derivatives exhibited more potent antiproliferative activity than HBA, and compound 6e exhibited the most potent activity with IC50 values of 2.14 mu M, 2.89 mu M, and 3.97 mu M against A2780, B16, and MCF-7 cells, respectively. Further anticancer mechanism studies revealed that compound 6e induced the generation of intracellular reactive oxygen species (ROS) and reduction of mitochondrial membrane potential (MMP) of B16 cells in a dose-dependent manner. Moreover, western blot analysis indicated that compound 6e downregulated the expression of anti-apoptotic protein Bcl-2 and upregulated the expression of proapoptotic protein Bax, activation of caspase 3 to induce cell apoptosis. Meanwhile, compound 6e significantly inhibited the phosphorylation of MEK, ERK, and Akt without affecting the expression of MEK, ERK, and Akt. Furthermore, the in vivo anti-tumor activity of 6e was validated (tumor inhibitory ratio of 68.4% at the dose of 30 mg/kg) in mice with B16 melanoma. (C) 2019 Elsevier Masson SAS. All rights reserved.
机译：合成了一系列C-23改性的23-羟基丙酸（HBA）衍生物，并评估其抗增殖活性对癌细胞系（A2780，A375，B16，MCF-7和HepG2）的抗增殖活性。生物筛选结果表明，大多数衍生物表现出比HBA更有效的抗增殖活性，并且化合物6e表现出最有效的活性，IC50值为2.14 mu m，2.89 mu m和3.97 mu m对抗A2780，B16和MCF - 分别为7个细胞。进一步的抗癌机制研究表明，化合物6e以剂量依赖性方式诱导细胞内反应性氧物质（ROS）和减少B16细胞的线粒体膜电位（MMP）。此外，Western印迹分析表明，化合物6e下调了抗凋亡蛋白Bcl-2的表达，并上调了促凋亡蛋白Bax的表达，Caspase 3的激活诱导细胞凋亡。同时，化合物6e显着抑制MEK，ERK和AKT的磷酸化而不影响MEK，ERK和AKT的表达。此外，验证了6e的体内抗肿瘤活性（肿瘤抑制比为B16黑色素瘤的小鼠中的68.4％的68.4％）。 （c）2019年Elsevier Masson SAS。版权所有。

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