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首页> 外文期刊>The Open Crystallography Journal >Dinuclear Gold(III) Complexes as Potential Anticancer Agents: Structure, Reactivity and Biological Profile of a Series of Gold(III) Oxo-BridgedDerivatives
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Dinuclear Gold(III) Complexes as Potential Anticancer Agents: Structure, Reactivity and Biological Profile of a Series of Gold(III) Oxo-BridgedDerivatives

机译：双核金（III）配合物作为潜在的抗癌剂：系列金（III）氧桥联衍生物的结构，反应性和生物学特性

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Six homologous gold(III) dinuclear oxo-bridged complexes, of the type [(bipynR)Au(μ-O)2Au(bipynR)][PF6]2,bearing variously substituted 2,2’-bipyridine ligands (bipynR = 2,2’-bipyridine, 4,4’-di-tert-butyl-, 6-methyl-, 6-neopentyl-, 6-o-xylyl- and 6,6’-dimethyl-2,2’-bipyridine), here called Auoxos, were prepared, characterised and recently tested as potential anticancer agents. Crystal structures were obtained for five members of the series that allowed us to perform detailed comparative analyses. Interestingly, the various Auoxos showed an acceptable stability profile in buffer solution and turned out to manifest outstanding antitumor properties in vitro. In particular, one member of this family, Auoxo6(bipynR = 6,6’-dimethyl-2,2’-bipyridine), produced more selective and far greater antiproliferative effects than all other tested Auoxos, qualifying itself as the best “drug candidate”. In turn, COMPARE analysis of the cytotoxicity profiles of five Auoxos, toward an established panel of thirty-six human tumor cell lines, revealed important mechanistic differences; a number of likely biomolecular targets could thus be proposed such as HDAC and PKC. Biophysical studies revealedmarkedly different modes of interaction with calf thymus DNA for two representative Auoxo compounds. In addition, apeculiar reactivity with model proteins was documented on the ground of spectrophotometric and ESI MS data, most likely as the result of redox processes. In view of the several experimental evidences gathered so far, it can be stated that Auoxos constitute a novel family of promising cytotoxic gold compounds with an innovative mechanism of action that merit a more extensive pharmacological evaluation.
机译：六个[[bipynR）Au（μ-O）2Au（bipynR）] [PF6] 2类型的同源金（III）双核氧桥接结构，带有各种取代的2,2'-联吡啶配体（bipynR = 2， 2'-联吡啶，4,4'-二叔丁基-，6-甲基-，6-新戊基-，6-邻-二甲苯基-和6,6'-二甲基-2,2'-联吡啶）制备，表征并最近测试了称为Auoxos的潜在抗癌药。获得了该系列五个成员的晶体结构，使我们能够进行详细的比较分析。有趣的是，各种Auoxos在缓冲溶液中显示出可接受的稳定性，并在体外表现出出色的抗肿瘤特性。特别是，该家族的一个成员Auoxo6（bipynR = 6,6'-二甲基-2,2'-联吡啶）比所有其他经过测试的Auoxos产生了更高的选择性和更大的抗增殖作用，使自己成为最佳“候选药物” ”。反过来，对五个已建立的三十六种人类肿瘤细胞系的Auoxos的细胞毒性谱进行比较分析，发现了重要的机理差异。因此，可以提出许多可能的生物分子靶标，例如HDAC和PKC。生物物理研究表明，两种代表性的Auoxo化合物与小牛胸腺DNA相互作用的模式明显不同。此外，根据分光光度法和ESI MS数据记录了与模型蛋白的非凡反应性，这很可能是氧化还原过程的结果。鉴于到目前为止收集到的一些实验证据，可以说Auoxos构成了一个有希望的细胞毒性金化合物的新家族，其新颖的作用机理值得更广泛的药理学评估。

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