Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy.
J Inorg Biochem. 2012 Dec;117:131-9. doi: 10.1016/j.jinorgbio.2012.09.004. Epub 2012 Sep 13.
Zinc is one of the most important trace elements in the body and it is essential as a cofactor for the structure and function of a number of cellular molecules including enzymes, transcription factors, cellular signalling proteins and DNA repair enzymes. On the other hand, recent studies have shown that zinc could play a role both in the development of various cancers and in the induction of apoptosis in some cell types, however, no established common relationships of zinc with cancer development and progression have been identified. To date, in our research group different metal-dithiocarbamato complexes have been designed that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. On the basis of the obtained encouraging achievements with other metals (such as gold and copper) we have decided to enlarge the studies to the complexes of zinc(II) using the same ligands. Hereby, we report the results on the synthesis and characterisation of ZnL(2) complexes with five different dithiocarbamato derivatives, such as dimethyl-(DMDT), pyrrolidine-(PyDT), methyl-(MSDT), ethyl-(ESDT) and tert-butyl-(TSDT) sarcosinedithiocarbamate. All the obtained compounds have fully been characterised by means of several spectroscopic techniques. In addition, the crystal structure of Zn(MSDT)(2) dinuclear complex is also reported. In order to evaluate the in vitro cytotoxic properties, some biological assays have been carried out on a panel of human tumour cell lines sensible and resistant to cisplatin. Some of the tested compounds show cytotoxicity levels comparable or even greater than the reference drug (cisplatin).
锌是体内最重要的微量元素之一,作为许多细胞分子(包括酶、转录因子、细胞信号蛋白和 DNA 修复酶)的结构和功能的辅助因子,锌是必需的。另一方面,最近的研究表明,锌可能在各种癌症的发展和某些细胞类型的细胞凋亡诱导中发挥作用,但是,尚未确定锌与癌症发展和进展的明确的普遍关系。迄今为止,我们的研究小组设计了不同的金属-二硫代氨基甲酸盐配合物,这些配合物有望与顺铂具有相似的主要特征,同时具有更高的活性、改善的选择性和生物利用度,以及更低的副作用。基于我们在其他金属(如金和铜)方面取得的令人鼓舞的成果,我们决定将研究扩大到使用相同配体的锌(II)配合物。在此,我们报告了具有五个不同二硫代氨基甲酸盐衍生物(如二甲氨基(DMDT)、吡咯烷(PyDT)、甲基(MSDT)、乙基(ESDT)和叔丁基(TSDT))的 ZnL(2)配合物的合成和特性。所有获得的化合物都通过多种光谱技术进行了充分的表征。此外,还报道了Zn(MSDT)(2)双核配合物的晶体结构。为了评估体外细胞毒性特性,在对顺铂敏感和耐药的人肿瘤细胞系中进行了一些生物学测定。一些测试化合物的细胞毒性水平与参考药物(顺铂)相当或甚至更高。