[{顺式-PtCl(NH3)2}2µ{反式-Pt(3-羟基吡啶)2(H2N(CH2)6NH2)2}]Cl4 在人卵巢肿瘤模型中的合成与活性。

Synthesis and activity of [{Cis-PtCl(NH3)2}2µ{trans-Pt(3-Hydroxypyridine)2(H2N(CH2)6NH2)2}]Cl4 in the human ovarian tumour models.

机构信息

Discipline of Biomedical Science, School of Medical Sciences, The University of Sydney, Cumberland Campus C42, 75 East Street, Lidcombe, NSW 1825, Australia.

出版信息

Med Chem. 2012 May;8(3):384-91. doi: 10.2174/157340612800786642.

DOI:10.2174/157340612800786642

PMID:22530892

Abstract

A novel trinuclear platinum compound with a cis-geometry for terminal metal centres coded as QH1 has been synthesized, characterized and investigated for activity against the human ovarian A2780, A2780cisR and A2780ZD0473R cancer cell lines. The cellular accumulation of platinum, level of platinum-DNA binding and the nature of interaction of the compound with pBR322 plasmid DNA have also been determined. QH1 is found to be more active against the resistant cell lines than the parent cell line, thus indicating that the compound has been able to overcome mechanisms of resistance operating in the A2780cisR and A2780ZD0473R cell lines. The high activity of QH1 is associated with high platinum accumulation and high level of platinum-DNA binding in all the three ovarian cancer cell lines. Provided QH1 has the right toxicity profile and its in vitro activity is matched with sufficient activity in vivo, the compound has the potential for development as a novel platinum-based anticancer drug targeted to the ovarian cancer.

摘要

一种新型的顺式几何三核铂配合物，其末端金属中心编码为 QH1，已被合成、表征，并针对人卵巢 A2780、A2780cisR 和 A2780ZD0473R 癌细胞系进行了活性研究。还确定了铂在细胞内的积累、铂-DNA 结合水平以及该化合物与 pBR322 质粒 DNA 的相互作用性质。与亲本细胞系相比，QH1 对耐药细胞系更具活性，这表明该化合物已能够克服 A2780cisR 和 A2780ZD0473R 细胞系中存在的耐药机制。QH1 的高活性与铂在所有三种卵巢癌细胞系中的高积累和高水平的铂-DNA 结合有关。如果 QH1 具有合适的毒性特征，并且其体外活性与体内足够的活性相匹配，那么该化合物有可能被开发为针对卵巢癌的新型铂类抗癌药物。