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非甾体类抗炎药萘普生与钴(II)配合物的生物学评价。

Biological evaluation of cobalt(II) complexes with non-steroidal anti-inflammatory drug naproxen.

机构信息

Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124 Thessaloniki, Greece.

出版信息

J Inorg Biochem. 2012 Feb;107(1):54-64. doi: 10.1016/j.jinorgbio.2011.10.014. Epub 2011 Nov 3.

Abstract

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug naproxen in the presence or absence of nitrogen-donor heterocyclic ligands (pyridine, 2,2'-bipyridine or 1,10-phenanthroline) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated naproxen acts as monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structure of [bis(aqua)bis(naproxenato)bis(pyridine)cobalt(II)], 2 has been determined by X-ray crystallography. The EPR spectrum of complex 2 in frozen solution reveals that it retains its structure. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [(2,2'-bipyridine)bis(methanol)bis(naproxenato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Naproxen and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin proteins having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals.

摘要

钴(II)配合物与非甾体抗炎药萘普生在存在或不存在氮供杂环配体(吡啶、2,2'-联吡啶或 1,10-菲啰啉)的情况下合成,并通过物理化学和光谱技术进行了表征。去质子化的萘普生作为单齿配体通过羧基氧与 Co(II)离子配位。[双(水)双(萘普生)双(吡啶)钴(II)],2 的晶体结构通过 X 射线晶体学确定。配合物 2 在冷冻溶液中的 EPR 光谱表明它保留了其结构。配合物与小牛胸腺 DNA(CT DNA)相互作用的紫外研究表明,配合物可以与 CT DNA 结合,[(2,2'-联吡啶)双(甲醇)双(萘普生)钴(II)]对 CT DNA 的结合常数最高。在 DMSO 溶液中和在含有 150 mM NaCl 和 15 mM 三钠柠檬酸盐的 1/2 DMSO/缓冲液(pH 7.0)溶液中 CT DNA 存在下记录的配合物的循环伏安图表明,它们可以通过嵌入结合模式与 CT DNA 结合,这也通过 DNA 溶液粘度测量得到了验证。与溴化乙锭(EB)的竞争性研究表明,配合物可以置换与 DNA 结合的 EB,表明它们与 DNA 强烈竞争与 EB 结合。萘普生及其钴(II)配合物与人或牛血清白蛋白蛋白具有良好的结合倾向,具有相对较高的结合常数值。还评估了化合物的抗氧化活性,表明它们对羟基自由基和超氧自由基具有高清除活性。

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