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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Organoruthenium(II) complexes attenuate stress in Caenorhabditis elegans through regulating antioxidant machinery
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Organoruthenium(II) complexes attenuate stress in Caenorhabditis elegans through regulating antioxidant machinery

机译：通过调节抗氧化机械，有机素烯（II）复合物抑制Caenorhabditis的胶带杆菌的胁迫

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The 1:1 stoichiometric reactions of 3-methoxy salicylaldehyde-4(N)-substituted thiosemicarbazones (H2L1-4) with [RuCpCI(PPh3)(2)] was carried out in methanol. The obtained complexes (1-4) were characterized by analytical, IR, absorption and H-1 NMR spectroscopic studies. The structures of ligand [H-2-3MSal-etsc] (H2L3) and complex [RuCp(Msal-etsc) (PPh3)] (3), were characterized by single crystal X-ray diffraction studies. The interaction of the ruthenium(II) complexes (1-4) with calfthymus DNA (CT-DNA) has been explored by absorption and emission titration methods. Based on the observations, an intercalative binding mode of DNA has been proposed. The protein binding abilities of the new complexes were monitored by quenching the tryptophan and tyrosine residues of BSA, as model protein. From the studies, it was found that the new ruthenium metallacycles exhibited better affinity than their precursors. The free radical scavenging assay suggests that all complexes effectively scavenged the DPPH radicals as compared to that of standard control ascorbic acid and scavenging activities of complexes are in the order of 4 > 2 >3 > 1. In addition, ruthenium(II) complexes (2-4) also exhibited an excellent in vivo antioxidant activity as it was able to increase the survival of worms exposed to lethal oxidative and thermal stresses possibly through reducing the intracellular ROS levels. It was interesting to note that complexes 2-4 failed to increase the lifespan of rnev-1 mutant worms having shortened lifespan due to the over production of free radicals. This data confirmed that complexes 2-4 conferred stress resistance in C. elegans, but they also require an endogenous detoxification mechanism for doing so. The genetic and reporter gene expression analysis revealed that complexes 2-4 maintained the intracellular redox status and offered stress protection through transactivation of antioxidant defence machinery genes gst-4 and sod-3 which are directly regulated by SKN-1 and DAF-16 transcription factors, respectively. Altogether, our results suggested that complexes 2-4 might play a crucial role in stress modulation and they perhaps exert almost similar effects in higher models, which is an important issue to be validated in future. (C) 2019 Elsevier Masson SAS. All rights reserved.
机译：用[RUCPCI（PPH3）（2）]在甲醇中进行3-甲氧基水杨醛-4（N） - 取出的硫代吡啶脱氨酸（H2L1-4）的1：1化学计量反应。通过分析，IR，吸收和H-1 NMR光谱研究表征了所得复合物（1-4）。通过单晶X射线衍射研究表征配体[H-2-3MSAL-ETESC]（H2L3）和复合物[RUCP（MSAL-ETSC）（PPH3）]（3）的结构。通过吸收和排放滴定方法探索了钌（II）配合物（1-4）与钙霉素DNA（CT-DNA）的相互作用。基于观察结果，已经提出了DNA的插入结合模式。通过淬火BSA的色氨酸和酪氨酸残基来监测新复合物的蛋白质结合能力，作为模型蛋白。从研究来看，发现新的钌金属族的亲和力比其前体更好。自由基清除测定表明，与标准对照抗坏血酸相比，所有复合物都会有效地清除DPPH激进酸，并且复合物的清除活性为4> 2> 3> 1.此外，钌（II）复合物（ 2-4）也表现出优异的体内抗氧化活性，因为它能够增加暴露于致命氧化和热应力的蠕虫的存活，可能通过降低细胞内ROS水平。值得注意的是，复合物2-4未能增加由于过度生产自由基而缩短了寿命的RNEV-1突变蠕虫的寿命。该数据证实，复合物2-4在C.秀丽隐杆线上赋予应力阻力，但它们也需要内源性排毒机制来做。遗传和报告基因表达分析显示，复合物2-4维持细胞内氧化还原状态，并通过转基因通过SKN-1和DAF-16转录因子进行直接调节的抗氧化防御机械基因GST-4和SOD-3的转移来提供应力保护， 分别。完全是我们的结果表明，复合物2-4可能在压力调制中发挥至关重要的作用，他们可能在更高模型中发挥几乎类似的效果，这是未来验证的一个重要问题。 （c）2019年Elsevier Masson SAS。版权所有。

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