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Antiproliferative, DNA binding, and cleavage properties of dinuclear Co(III) complexes containing the bioactive quinizarin ligand.
JBIC Journal of Biological Inorganic Chemistry ( IF 3 ) Pub Date : 2020-02-28 , DOI: 10.1007/s00775-020-01765-4 Hana Crlikova 1 , Hana Kostrhunova 2 , Jitka Pracharova 3 , Máté Kozsup 4 , Sándor Nagy 4 , Péter Buglyó 4 , Viktor Brabec 1, 2 , Jana Kasparkova 1, 2
中文翻译:
含有生物活性奎尼西林配体的双核 Co(III) 复合物的抗增殖、DNA 结合和切割特性。
更新日期:2020-02-28
JBIC Journal of Biological Inorganic Chemistry ( IF 3 ) Pub Date : 2020-02-28 , DOI: 10.1007/s00775-020-01765-4 Hana Crlikova 1 , Hana Kostrhunova 2 , Jitka Pracharova 3 , Máté Kozsup 4 , Sándor Nagy 4 , Péter Buglyó 4 , Viktor Brabec 1, 2 , Jana Kasparkova 1, 2
Affiliation
Abstract
The adverse side effects and acquired resistance associated with the clinical application of traditional platinum-based anticancer drugs have forced investigation of alternative transition metal-based compounds and their cytostatic properties. Over the last years, the anticancer potential of cobalt complexes has been extensively studied, and in-depth analyses of their mode of action have been conducted. In this work, we present antiproliferative activity against human cancer cells of the dinuclear Co(III) complexes bearing the quinizarin ligand and tris(2-aminoethyl)amine (tren, compound 1) or tris(2-pyridylmethyl)amine (tpa, compound 2) co-ligands. To contribute the understanding mechanisms of biological action of these compounds, their association with DNA in the cells, DNA binding in cell-free media, and DNA cleavage capability were investigated in detail. The results demonstrate that both complexes interact with DNA in tumor cells. However, their mechanism of antiproliferative action is different, and this difference is mirrored by distinct antiproliferative activity. The antiproliferative effect of 1 is connected with its ability to intercalate into DNA and subsequently to inhibit activities of DNA processing enzymes. In contrast, the total antiproliferative efficiency of 2, thanks to its redox properties, appears to be connected with its ability to form radicals and, consequently, with the ability of 2 to cleave DNA. Hence, the findings presented in this study may significantly contribute to understanding the antitumor potential of cobalt complexes.Graphic abstract
Dinuclear Co(III) complexes containing the bioactive quinizarin ligand exhibit antiproliferative activity based on distinct mechanism中文翻译:
含有生物活性奎尼西林配体的双核 Co(III) 复合物的抗增殖、DNA 结合和切割特性。