首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >The role of p53 in the cellular toxicity by active trans-platinum complexes containing isopropylamine and hydroxymethylpyridine.
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The role of p53 in the cellular toxicity by active trans-platinum complexes containing isopropylamine and hydroxymethylpyridine.

机译:P53在含异丙胺和羟甲基吡啶的活性反式铂复合物中P53在细胞毒性中的作用。

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Despite some initial research that reported a lack of activity of trans geometry, complexes with general formula trans-[PtCl2(L)(L')] exhibit an important cytotoxic activity in cisplatin-sensitive and resistant cell lines. Based on the proposed mechanism of action for the trans-platinum compounds, they might form DNA adducts initiating a DNA-damage response and ultimately ending in the activation of the p53 protein. In the present work, we have studied the biochemical properties of the trans-[PtCl2(isopropylamine)(L)] complexes (where L is 3- or 4-(hydroxymethyl)-pyridine) against several cell lines and the relationship between cytotoxicity and the protein p53. Both complexes showed different antitumoral properties depending on the presence or absence of protein p53 in isogenic colon carcinoma HCT116 cell lines. Cell cycle studies with the complexes in these cell lines were performed to investigate their antitumoral activity. Apoptosis was observed to be launched from G1 or G2/M accumulations. Confocal microscopy showed the different behaviour of isogenic tumoral cell lines treated with the trans-platinum complexes. Our data suggest that small differences in the carrier ligands could play an important role in the overall biological effects. The body of the research regarding structure-activity relationships such as the different position of groups in the carrier ligands will provide new rational basis for the design of new platinum antitumor drugs.
机译:尽管有一些初步研究报告缺乏反式几何体的活性,但具有通式转铂敏感和抗性细胞系中的重要细胞毒活性。基于替代铂化合物的提出的作用机制,它们可以形成DNA加合物引发DNA损伤响应并最终在P53蛋白的激活中结束。在本作的工作中,我们研究了反转基[PtCl2(异丙胺)(L)]复合物(其中L是3-或4-(羟甲基) - 吡啶)的生化特性,与几种细胞系和细胞毒性之间的关系蛋白质p53。根据中原结肠癌HCT116细胞系中的蛋白质p53的存在或不存在,两种复合物表现出不同的抗肿瘤性质。进行细胞周期研究这些细胞系中的复合物进行研究以研究其抗肿瘤活性。观察到细胞凋亡从G1或G2 / M累积发射。共聚焦显微镜显示用反式铂复合物处理的中源性肿瘤细胞系的不同行为。我们的数据表明,载体配体的小差异可以在整体生物效应中发挥重要作用。关于载体配体中群体中的不同基位的不同位置的结构的研究体将为新的铂抗肿瘤药物设计提供新的合理基础。

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