• 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 and biological assessment of a ruthenium(II) cyclopentadienyl complex in breast cancer cells and on the development of zebrafish embryos
【24h】

Synthesis and biological assessment of a ruthenium(II) cyclopentadienyl complex in breast cancer cells and on the development of zebrafish embryos

机译：乳腺癌细胞中钌（II）环戊二烯基复合物以及斑马鱼胚胎发育的合成及生物学评估

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

Ruthenium-based complexes currently attract great attention as they hold promise to replace platinum-based drugs as a first line cancer treatment. Whereas ruthenium arene complexes are some of the most studied species for their potential anticancer properties, other types of ruthenium complexes have been overlooked for this purpose. Here, we report the synthesis and characterization of Ru(II) cyclopentadienyl (Cp), Ru(II) cyclooctadienyl (COD) and Ru(III) complexes bearing anastrozole or letrozole ligands, third-generation aromatase inhibitors currently used for the treatment of estrogen receptor positive (ER +) breast cancer. Among these complexes, Ru(II)Cp 2 was the only one that displayed a high stability in DMSO and in cell culture media and consequently, the only complex for which the in vitro and in vivo biological activities were investigated. Unlike anastrozole alone, complex 2 was considerably cytotoxic in vitro (IC50 values < 1 mu M) in human ER + breast cancer (T47D and MCF7), triple negative breast cancer (TNBC) (MBA-MB-231), and in adrenocortical carcinoma (H295R) cells. Theoretical (docking simulation) and experimental (aromatase catalytic activity) studies suggested that an interaction between 2 and the aromatase enzyme was not likely to occur and that the bulkiness of the PPh3 ligands could be an important factor preventing the complex to reach the active site of the enzyme. Exposure of zebrafish embryos to complex 2 at concentrations around its in vitro cytotoxicity IC50 value (0.1-1 mu M) did not lead to noticeable signs of toxicity over 96 h, making it a suitable candidate for further in vivo investigations. This study confirms the potential of Ru(II)Cp complexes for breast cancer therapy, more specifically against TNBCs that are usually not responsive to currently used chemotherapeutic agents. (C) 2020 Elsevier Masson SAS. All rights reserved.
机译：基于钌的复合物目前吸引了很大的关注，因为它们认为将基于铂类药物替换为第一线癌症治疗。虽然钌芳烃配合物是其中一些最具学习的抗癌性质的物种，但是为此目的忽略了其他类型的钌配合物。在这里，我们报告了Ru（II）环戊二烯基（CP），Ru（II）环偶二苯基（Cod）和Ru（III）复合物的合成和表征，其含有Anastrozole或Letrozole配体，目前用于治疗雌激素的第三代芳族酶抑制剂受体阳性（ER +）乳腺癌。在这些配合物中，Ru（II）CP 2是唯一一种在DMSO和细胞培养基中展示高稳定性的CP 2，因此，研究了体外和体内生物活性的唯一复合物。单独不同于Anastrozole，复合物2在人ER +乳腺癌（T47D和MCF7）中的体外（IC50值<1μm）具有大量细胞毒性（IC50值<1μm），三重阴性乳腺癌（TNBC）（MBA-MB-231）和肾上腺导囊（H295R）细胞。理论（对接模拟）和实验（芳族酶催化活性）研究表明，不太可能发生2和芳族酶酶之间的相互作用，并且PPH3配体的大部分可能是预防络合物到达活性位点的重要因素酶。在其体外细胞毒性IC50值（0.1-10μm）周围的浓度下暴露斑马鱼胚胎在其浓度下产生毒性明显的毒性迹象超过96小时，使其成为进一步的体内研究的合适候选者。本研究证实了ru（ii）Cp复合物用于乳腺癌治疗的潜力，更具体地针对通常对目前使用的化学治疗剂的抗旱性而不是反应的TNBC。 （c）2020 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