Marzano C, Trevisan A, Giovagnini L, Fregona D
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
Toxicol In Vitro. 2002 Aug;16(4):413-9. doi: 10.1016/s0887-2333(02)00022-x.
New mixed dithiocarbamate-amino Pt(II) complex ([Pt(ESDT)(Py)Cl]) has been recently synthesised with the aim to produce potential anticancer drug able to conjugate cytostatic activity with lack of nephrotoxicity. This complex contains: (1) an amino ligand; (2) a good leaving group (halide); and (3) an S-containing chelating agent potentially able to protect the metal centre from its interaction with S-containing protein-legating sites that are believed to be at the basis of the nephrotoxicity of Pt(II)-based drugs. This complex has been found to be effective as an antiproliferative agent (more active than cis-platin) towards a normal human adenocarcinoma cell line and the corresponding cis-platin-resistant C13 strain. Toxicity tests on the kidney were performed by means of a renal cortical slice model. The slices, prepared with a Brendel-Vitron slicer, were incubated with different doses (0.125-5.0 x 10(-4) M, final concentration) of [Pt(ESDT)(Py)Cl] or cis-platin dissolved in methyl sulphoxide. The platinum(II) complex showed very low renal cytotoxicity as compared with cis-platin; in particular, lipid peroxidation induced by cis-platin appeared about five-fold higher than that induced by [Pt(ESDT)(Py)Cl]. In conclusion, besides being less toxic for the kidney, the results showed that the new synthesised platinum(II) complex appeared in vitro more effective than cis-platin when tested on sensitive and resistant cis-platin tumour cell lines.
新型二硫代氨基甲酸盐 - 氨基铂（II）混合配合物（[Pt(ESDT)(Py)Cl]）最近已被合成，目的是制备一种潜在的抗癌药物，该药物能够将细胞抑制活性与无肾毒性相结合。这种配合物包含：（1）一个氨基配体；（2）一个良好的离去基团（卤化物）；以及（3）一种含硫螯合剂，它可能能够保护金属中心，使其不与含硫蛋白质连接位点相互作用，而这些位点被认为是铂（II）类药物肾毒性的基础。已发现这种配合物作为抗增殖剂（比顺铂更具活性）对正常人腺癌细胞系和相应的顺铂耐药C13菌株有效。通过肾皮质切片模型对肾脏进行毒性测试。用Brendel - Vitron切片机制备的切片，与溶解在二甲基亚砜中的不同剂量（0.125 - 5.0×10⁻⁴ M，终浓度）的[Pt(ESDT)(Py)Cl]或顺铂一起孵育。与顺铂相比，铂（II）配合物显示出非常低的肾细胞毒性；特别是，顺铂诱导的脂质过氧化作用比[Pt(ESDT)(Py)Cl]诱导的高出约五倍。总之，除了对肾脏毒性较小外，结果表明，在对敏感和顺铂耐药的肿瘤细胞系进行测试时，新合成的铂（II）配合物在体外比顺铂更有效。
