Nardon Chiara, Chiara Federica, Brustolin Leonardo, Gambalunga Alberto, Ciscato Francesco, Rasola Andrea, Trevisan Andrea, Fregona Dolores
Department of Chemical Sciences, University of Padova Via F. Marzolo 1, 35131, Padova, Italy.
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova Via Giustiniani 2, 35128, Padova, Italy.
ChemistryOpen. 2015 Apr;4(2):183-91. doi: 10.1002/open.201402091. Epub 2015 Feb 19.
Transition metals offer many possibilities in developing potent chemotherapeutic agents. They are endowed with a variety of oxidation states, allowing for the selection of their coordination numbers and geometries via the choice of proper ligands, leading to the tuning of their final biological properties. We report here on the synthesis, physico-chemical characterization, and solution behavior of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [Au(III)Br2(PDT)] and [Au(III)Cl2(PDT)]. We found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [Au(III)Br2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death. More efficient antineoplastic strategies are required for the widespread burden that is cancer. In line with this, our results indicate that [Au(III)Br2(PDT)] is a promising antineoplastic agent that targets cellular components with crucial functions for the survival of tumor cells.
过渡金属在开发有效的化疗药物方面提供了许多可能性。它们具有多种氧化态，通过选择合适的配体可以选择其配位数和几何构型，从而调节其最终的生物学性质。我们在此报告两种金（III）吡咯烷二硫代氨基甲酸盐（PDT），即[Au(III)Br2(PDT)]和[Au(III)Cl2(PDT)]的合成、物理化学表征及溶液行为。我们发现，对于几种癌细胞系，溴化物衍生物在诱导细胞死亡方面比氯化物衍生物更有效。[Au(III)Br2(PDT)]引发氧化应激，对通透性转换孔产生影响，通透性转换孔是一种线粒体通道，其开放会导致细胞死亡。对于癌症这种广泛存在的负担，需要更有效的抗肿瘤策略。与此一致的是，我们的结果表明[Au(III)Br2(PDT)]是一种有前景的抗肿瘤药物，它靶向对肿瘤细胞存活具有关键功能的细胞成分。
