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非甾体抗炎药双氯芬酸与 Cu(II)相互作用。结构与生物学特征。

Non-steroidal anti-inflammatory drug diflunisal interacting with Cu(II). Structure and biological features.

机构信息

Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

J Inorg Biochem. 2011 Dec;105(12):1645-55. doi: 10.1016/j.jinorgbio.2011.09.004. Epub 2011 Sep 10.

DOI:10.1016/j.jinorgbio.2011.09.004
PMID:22071090
Abstract

Copper(II) complexes with the non-steroidal anti-inflammatory drug diflunisal in the presence of N,N-dimethylformamide or nitrogen donor heterocyclic ligands (pyridine, 1,10-phenanthroline, 2,2'-bipyridine or 2,2'-bipyridylamine) have been synthesized and characterized. The deprotonated diflunisal ligands are coordinated to Cu(II) ion through carboxylato oxygen atoms. The crystal structures of [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] 1 and [bis(diflunisal)bis(pyridine)copper(II)], 2 have been determined by X-ray crystallography and are the first reported crystal structures of diflunisal complexes. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) suggests binding of the complexes to CT DNA with the dinuclear [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] compound exhibiting the highest binding constant, K(b). Intercalative binding mode may also be concluded using cyclic voltammetry and solution viscosity measurements of the complexes in the presence of CT DNA. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting competition with EB. Diflunisal and its complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values.

摘要

在 N,N-二甲基甲酰胺或氮供杂环配体(吡啶、1,10-菲啰啉、2,2'-联吡啶或 2,2'-联吡啶胺)存在下,合成并表征了铜(II)配合物与非甾体抗炎药双氯芬酸。去质子化的双氯芬酸配体通过羧基氧原子与 Cu(II)离子配位。通过 X 射线晶体学确定了[四(双氯芬酸)双(N,N-二甲基甲酰胺)二铜(II)]1 和[双(双氯芬酸)双(吡啶)铜(II)]2 的晶体结构,这是双氯芬酸配合物的首个晶体结构报道。复合物与小牛胸腺 DNA(CT DNA)相互作用的 UV 研究表明,复合物与 CT DNA 结合,二核[四(双氯芬酸)双(N,N-二甲基甲酰胺)二铜(II)]化合物具有最高的结合常数 K(b)。也可以通过循环伏安法和在 CT DNA 存在下复合物的溶液粘度测量得出它们的嵌入结合模式。与溴化乙锭(EB)的竞争研究表明,复合物可以取代 DNA 结合的 EB,表明与 EB 竞争。双氯芬酸及其配合物与人或牛血清白蛋白蛋白具有良好的结合倾向,表现出相对较高的结合常数值。

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