• 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 >Ru(eta6-arene) complexes of combretastatin-analogous oxazoles with enhanced anti-tumoral impact.
【24h】

Ru(eta6-arene) complexes of combretastatin-analogous oxazoles with enhanced anti-tumoral impact.

机译：Ru（ETA6-芳烃）复合物的梳子酸汀类蛋白 - 类似的恶唑，具有增强的抗肿瘤撞击。

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

Oxazole-bridged combretastatin A-4 analogues bind to tubulin and exert anti-vascular and anti-angiogenic effects. When linked to Ru(eta(6)-arene) complex fragments, conjugates with additional cytotoxic activity result which can ruthenate bionucleophiles such as DNA and proteins. For instance, the Ru(II)(p-cymene)(isonicotinate)Cl(2) complex 6a of the known 4-(3,4,5-trimethoxyphenyl)-5-(3-hydroxy-4-methoxyphenyl)-oxazole 4a was far more active than the latter against cells of the p53-competent wild-type form of HCT-116 colon carcinoma at low 0.01 muM concentrations. A fast reaction of 6a with nucleophilic N-acetyl-L-cysteine was observed in NMR studies. The Ru(arene) complexes 6a-c were also more efficacious against combretastatin-refractory p53(+) cells of human HT-29 colon carcinoma when compared to their parent 4-(3,4-dimethoxy-5-methoxy/halo-phenyl)-5-(3-hydroxy-4-methoxyphenyl)-oxazoles 4a-c. These cells are rich in ABC-transporters which are responsible for their multi-drug resistance and for which conjugates 6 are less good substrates than the phenols 4. Unlike 4a, its complex 6a also diminished the motility of human 518A2 melanoma cells in a wound-healing assay which is indicative of anti-metastatic activity in solid tumors. Overall, the Ru(arene) complex conjugates 6 broaden the anti-tumoral spectrum of the combretastatin A-4 analogues 4 considerably.
机译：恶唑桥桥的组合A-4类似物与小管蛋白结合并施加抗血管和抗血管生成效果。当与Ru（eta（6） - rene）复杂的片段，与额外的细胞毒性活性结果的缀合物，其可以钌酸盐如DNA和蛋白质。例如，已知的4-（3,4,5-三甲氧基苯基）-5-（3-羟基-4-甲氧基苯基）-Oxazole的Ru（II）（p-cymene）（Inononotinate）Cl（2）复合物6a在低0.01静脉浓度下，4A对P53态态癌的P53主管野生型形式的细胞的后者更活跃。在NMR研究中观察到6A与亲核酸N-乙酰基-1-半胱氨酸的快速反应。与父母4-（3,4-二甲氧基-5-甲氧基/卤代 - 苯基相比，Ru（arene）复合物6a-c也更有效地针对人HT-29结肠癌的难治性P53（+）细胞。（3,4-二甲氧基-5-甲氧基/卤代苯基）-5-（3-羟基-4-甲氧基苯基） - 恶唑4a-c。这些细胞富含ABC-转运物，其负责它们的多种药物抗性，并且缀合物6的缀合物6比苯酚4较低。与4A不同，其复合物6a还减少了人518A2黑色素瘤细胞在伤口中的运动性降低了愈合测定表明实体瘤中的抗转移活性。总而言之，Ru（芳烃）复合缀合物6大大拓宽了组合酶A-4类似物4的抗肿瘤谱。

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