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Anticancer Activity and Catalytic Potential of Ruthenium(11)-Arene Complexes with N,O-Donor Ligands

机译:钌(11) - o-on on系列配体的抗癌活性和钌(11)的催化潜力

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摘要

The special ability of organometallic complexes to catalyze various transformations might offer new effective mechanisms for the treatment of cancer. Studies that report both the biological properties and the ability of metallic complexes to promote therapeutically relevant catalytic reactions are limited. Herein, we report the anticancer activity and catalytic potential of some ruthenium(II)-arene complexes bearing bidentate Schiff base ligands (2a and 2b) and their reduced analogues (5a and 5b, respectively). In comparison to their Schiff base counterparts 2a and 2b, we demonstrate that amine complexes 5a and 5b display (i) a higher in vitro antiproliferative activity on different human cancer cell lines, (ii) a lower rate of hydrolysis, and (iii) an improved initial catalytic rate for the reduction of NAD(+) to NADH. In contrast to their imine analogues 2a and 2b, we also show that amine complexes 5a and 5b induce the generation of intracellular reactive oxygen species (ROS) in MCF-7 breast cancer cells. Our results highlight the impact that a simple ligand modification such as the reduction of an imine moiety can have on both the catalytic and biological activities of metal complexes. Moreover, the ruthenium complexes reported here display some antiproliferative activity against T47D breast cancer cells, known for their cis-platin resistance.
机译:有机金属配合物催化各种转化的特殊能力可能为治疗癌症提供新的有效机制。报告生物学性质和金属配合物促进治疗相关催化反应的能力的研究有限。在此,我们报告了一些钌(II) - 载体复合物的抗癌活性和催化潜力,其含有双齿席夫碱配体(2a和2b)及其还原的类似物(5a和5b)。与其席夫底座对应2A和2B相比,我们证明胺配合物5A和5B显示(I)在不同人类癌细胞系上的体外抗增殖活性更高,(II)水解率较低,(III)改善NAD(+)对NADH的初始催化率。与其亚胺类似物2a和2b相反,我们还表明胺配合物5a和5b诱导MCF-7乳腺癌细胞中细胞内反应性氧物质(ROS)产生。我们的结果突出了简单配体改性如诸如亚胺部分的减少可以对金属配合物的催化和生物活性的影响。此外,钌配合物报告在此显示出针对T47D乳腺癌细胞的一些抗增殖活性,以其Cis-铂抗性而已知。

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