当前位置: X-MOL 学术J. Biol. Inorg. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
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
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。

摘要

与传统铂类抗癌药物的临床应用相关的不良副作用和获得性耐药性迫使人们对替代过渡金属类化合物及其细胞抑制特性进行研究。在过去的几年里,钴配合物的抗癌潜力得到了广泛的研究,并对其作用模式进行了深入的分析。在这项工作中,我们展示了带有 quinizarin 配体和三(2-氨基乙基)胺(tren,化合物1)或三(2-吡啶基甲基)胺(tpa,化合物2) 共配体。为了有助于理解这些化合物的生物作用机制,详细研究了它们与细胞中 DNA 的关联、无细胞培养基中的 DNA 结合以及 DNA 切割能力。结果表明,这两种复合物都与肿瘤细胞中的 DNA 相互作用。然而,它们的抗增殖作用机制不同,这种差异反映在不同的抗增殖活性上。的抗增殖作用1与它的能力插入DNA并随后的DNA加工酶抑制活动连接。相比之下,由于其氧化还原特性,2的总抗增殖效率似乎与其形成自由基的能力有关,因此,与2切割 DNA。因此,本研究中提出的发现可能对理解钴配合物的抗肿瘤潜力有重要贡献。

图形摘要

含有生物活性奎尼西林配体的双核 Co(III) 复合物表现出基于不同机制的抗增殖活性
更新日期:2020-02-28
down
wechat
bug