Department of Integrative Zoology, Institute of Biology, University of Leiden, 2333 AL Leiden, The Netherlands.
Dalton Trans. 2009 Dec 28(48):10799-805. doi: 10.1039/b912378d. Epub 2009 Oct 28.
Gold(I) phosphine complexes exhibit promising properties for anticancer drug development. Here we report on a series of gold(I) phosphine complexes containing a naphthalimide ligand. Strong antiproliferative effects were observed in MCF-7 breast cancer cells as well as in HT-29 colon carcinoma cells. The cellular and nuclear gold levels were increased compared to analogues, in which the naphthalimide ligand was replaced by a chloro ligand. Compound 4a was selected for more detailed biochemical and biological studies, which revealed solvent dependent fluorescence emission, uptake of the compound into the organelles of tumor cells as well as antiangiogenic effects concerning angiogenesis and tumor-induced angiogenesis in vivo. Antiangiogenic properties of 4a were observed in two different zebrafish angiogenesis models, including a tumor-cell induced neovascularization assay.
金（I）膦配合物在抗癌药物开发方面表现出良好的特性。在这里，我们报告了一系列含有萘酰亚胺配体的金（I）膦配合物。在 MCF-7 乳腺癌细胞和 HT-29 结肠癌细胞中观察到强烈的抗增殖作用。与类似物相比，细胞内和核内的金水平增加，类似物中萘酰亚胺配体被氯配体取代。选择化合物 4a 进行更详细的生化和生物学研究，结果表明化合物具有溶剂依赖性荧光发射、进入肿瘤细胞细胞器的摄取以及在体内的抗血管生成作用，包括血管生成和肿瘤诱导的血管生成。在两种不同的斑马鱼血管生成模型中观察到 4a 的抗血管生成特性，包括肿瘤细胞诱导的新血管生成测定。
