• 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 of novel S-linked dihydroartemisinin derivatives and evaluation of their anticancer activity
【24h】

Synthesis of novel S-linked dihydroartemisinin derivatives and evaluation of their anticancer activity

机译：新型S型二氢氨基素蛋白衍生物的合成及其抗癌活性的评价

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

We report herein the synthesis and anticancer activity of a set of novel S-linked artemisinins bearing an aliphatic/aromatic/heterocyclic nucleus as a substituent on the sulfur. The compounds were prepared from artemisinin via its lactol-form by an acid-catalyzed condensation of the desired thiol with the lactol. Both the C-10-alpha- and beta-configured thiol ethers were synthesized with a view to making them available for the anticancer activity evaluation using a variety of cell lines. The results show that many of the synthetic derivatives studied possessed good potential as anticancer agents. In order to draw more information on the origin of the anticancer activity, one of the compounds (9a), that showed a broad-spectrum activity in terms of reducing the viability of most of the cell lines studied, in particular proven to be most effective against Prostate (PC-3) cells, was studied in detail to find the underlying mechanism of its action by KIT assay, immunoblotting, flow cytometry and microscopy. Pretreatment of the PC-3 cells with N-acetyl cysteine affected the efficacy of 9a, suggesting the role of reactive oxygen species in reducing their viability. Cell cycle analysis showed increase in G1 phase that was indicative of G1 cell cycle arrest. Wound healing assay revealed anti-migratory effect of 9a Quantitative PCR and western blot analysis showed changes in the gene expression of PCNA, E2F1, Pin1, cyclinD1, phospho-c-jun, c-Myc, eIF4E and other genes involved in proliferation and maintaining the transformed phenotype of prostate cancer cells. Here we report the anti proliferative property of 9a with a vital and potent target(s) in prostate cancer cells with one of such targets being Pin1 belonging to the parvulin family of PPIases. The results suggest that 9a could be a promising agent in combating prostate cancer. (C) 2019 Elsevier Masson SAS. All rights reserved.
机译：我们在本文中报告了一组新的S-Latched野生蛋白的合成和抗癌活性，其载有脂族/芳族/杂环核作为硫的取代基。通过酸催化硫醇与乳糖醇的酸催化的缩合，通过其乳糖形式制备该化合物。通过使用各种细胞系来合成C-10-α-和β构造的硫醇醚，以使它们可用于抗癌活性评估。结果表明，许多研究的合成衍生物具有良好的抗癌剂潜力。为了绘制关于抗癌活性的来源的更多信息，其中一种化合物（9a），其显示在降低研究的大多数细胞系的生存能力方面，特别证明是最有效的针对前列腺（PC-3）细胞进行详细研究，以通过套件测定，免疫印迹，流式细胞术和显微镜找到其作用的潜在机制。具有N-乙酰半胱氨酸的PC-3细胞的预处理影响了9A的功效，表明反应性氧物种在降低其活力方面的作用。细胞循环分析显示出G1相增加，其指示G1细胞周期停滞。伤口愈合测定显示出9a定量PCR的抗迁移效果，Western印迹分析显示PCNA，E2F1，Pin1，CyclinD1，磷酸-C-Jun，C-Myc，EIF4e等基因的变化，涉及增殖和维持的其他基因前列腺癌细胞的转化表型。在这里，我们将9A的抗增殖性能报告在前列腺癌细胞中具有重要和有效的靶标，其中一种靶标在属于PLVURIN家族的PIN1。结果表明，9A可能是对抗前列腺癌的有希望的剂。 （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