Applied Chemistry Department, Nanjing University of Finance and Economics, Nanjing 210003, PR China.
J Inorg Biochem. 2010 Nov;104(11):1178-84. doi: 10.1016/j.jinorgbio.2010.07.007. Epub 2010 Jul 18.
Platinum-based anticancer drugs such as cisplatin induce increased oxidative stress and oxidative damage of DNA and other cellular components, while selenium plays an important role in the antioxidant defense system. In this study, the interaction between a platinum(II) methionine (Met) complex [Pt(Met)Cl(2)] and a diselenide compound selenocystine [(Sec)(2)] was studied by electrospray ionization mass spectrometry, high performance liquid chromatography mass spectrometry, and (1)H NMR spectroscopy. The results demonstrate that the diselenide bond in (Sec)(2) can readily and quickly be cleaved by the platinum complex. Formation of the selenocysteine (Sec) bridged dinuclear complex Pt(2)(Met-S,N)(2)(μ-Sec-Se,Cl) and Sec chelated species Pt(Met-S,N)(Sec-Se,N) was identified at neutral and acidic media, which seems to result from the intermediate Pt(Met-S,N)(Sec-Se)Cl. An accelerated formation of S-Se and S-S bonds was also observed when (Sec)(2) reacted with excessive glutathione in the presence of [Pt(Met)Cl(2)]. These results imply that the mechanism of activity and toxicity of platinum drugs may be related to their fast reaction with seleno-containing biomolecules, and the chemoprotective property of selenium agents against cisplatin-induced toxicity could also be connected with such reactions.
铂类抗癌药物如顺铂会引起氧化应激增加和 DNA 及其他细胞成分的氧化损伤，而硒在抗氧化防御系统中发挥着重要作用。在这项研究中，通过电喷雾电离质谱、高效液相色谱-质谱联用和（1）H NMR 光谱研究了铂（II）蛋氨酸（Met）配合物[Pt（Met）Cl2]与二硒化物化合物硒代半胱氨酸[（Sec）2]之间的相互作用。结果表明，（Sec）2 中的二硒键可以被铂配合物快速且容易地断裂。在中性和酸性介质中，形成了硒代半胱氨酸（Sec）桥联双核配合物[Pt2（Met-S，N）2（μ-Sec-Se，Cl]）和 Sec 螯合物种[Pt（Met-S，N）（Sec-Se，N）]），这似乎是由于中间产物[Pt（Met-S，N）（Sec-Se）Cl]+。当（Sec）2 与过量谷胱甘肽在[Pt（Met）Cl2]存在下反应时，也观察到 S-Se 和 S-S 键的加速形成。这些结果表明，铂类药物的活性和毒性机制可能与其与含硒生物分子的快速反应有关，而硒剂对顺铂诱导的毒性的化学保护性质也可能与这些反应有关。
