Rogolino Dominga, Cavazzoni Andrea, Gatti Anna, Tegoni Matteo, Pelosi Giorgio, Verdolino Vincenzo, Fumarola Claudia, Cretella Daniele, Petronini Pier Giorgio, Carcelli Mauro
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale and Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici, Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
Department of Clinical and Experimental Medicine, University of Parma, Italy.
Eur J Med Chem. 2017 Mar 10;128:140-153. doi: 10.1016/j.ejmech.2017.01.031. Epub 2017 Jan 23.
The possibility to influence the physiological concentration of copper ions through the careful choice of ligands is emerging as a novel intriguing strategy in the treatment of pathologies such as cancer and Alzheimer. Thiosemicarbazones play an important role in this field, because they offer a wide variety of potential functionalizations and different kinds of coordination modes. Here we report the synthesis of some 8-hydroxyquinoline thiosemicarbazone ligands containing an ONN'S donor set and their Zn(II) and Cu(II) complexes. The metal complexes were characterized in solution and in the solid state and the X-ray structure of one of the copper(II) complex is reported. The Cu(II) complexes were characterized also by means of quantum mechanical calculations. The Cu(II) complexes displayed cytostatic activity in different cancer cell models. In particular, the most active Cu(II) complex significantly inhibited cell proliferation with an IC value lower than 1 μM; this effect was associated with a block of the cell cycle in the G/M phase. This Cu(II) complex induced neither the production of reactive oxygen species (ROS) nor the accumulation of p53 protein, suggesting the lack of DNA damage.
通过精心选择配体来影响铜离子的生理浓度，正成为治疗癌症和阿尔茨海默病等病症的一种新颖且引人入胜的策略。硫代氨基脲在该领域发挥着重要作用，因为它们提供了多种潜在的功能化方式和不同类型的配位模式。在此，我们报告了一些含有ONN'S供体集的8-羟基喹啉硫代氨基脲配体及其锌（II）和铜（II）配合物的合成。对金属配合物进行了溶液和固态表征，并报道了其中一种铜（II）配合物的X射线结构。还通过量子力学计算对铜（II）配合物进行了表征。铜（II）配合物在不同的癌细胞模型中显示出细胞生长抑制活性。特别是，活性最高的铜（II）配合物以低于1 μM的IC值显著抑制细胞增殖；这种效应与细胞周期在G/M期的阻滞有关。这种铜（II）配合物既不诱导活性氧（ROS）的产生，也不诱导p53蛋白的积累，表明不存在DNA损伤。
