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首页> 外文期刊>Chemistry: A European journal >Loss of Am mine from Platinum(II)Complexes:Implications for Cisplatin InactIVation,Storage,and Resistance
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Loss of Am mine from Platinum(II)Complexes:Implications for Cisplatin InactIVation,Storage,and Resistance

机译：铂（II）配合物对我的损失：顺铂失活，储存和抗性的意义

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Potential consequences of the binding of the anticancer drug cis-platin to various biomolecules in the cell have been investigated by using a combined density functional theory and continuum dielectric model approach.Since the ammine ligands remain coordinated at the metal upon formation of the most frequent DNA adducts,whereas they were found to be displaced from the metal upon formation of drug metabolites,we have analyzed the factors governing ammine loss from platinum(II)complexes as a possible pathway of cisplatin inactIVa-tion.The calculations systematically show the effect of 1)the trans ligand,2)the charge of complex,3)the nucle-ophile,and 4)the environment on the thermodynamic instability and kinetic lability of the platinum-ammine bonds.After initial binding of cisplatin hydrolysis products to thioethers or thiols,loss of the ammine trans to this sulfur ligand rather than replacement of the sulfur ligand itself by other nucleo-philes like guanine-N7 is predicted to be the predominant reaction.The results of this study contribute to an understanding of the modes of cisplatin inactIVation prior to DNA binding,for example,by elevated glutathione levels in cisplatin-resistant cancer cells.
机译：通过结合使用密度泛函理论和连续介电模型方法研究了抗癌药顺铂与细胞中各种生物分子结合的潜在后果，因为胺配体在形成最频繁的DNA时在金属上保持配位加合物，尽管发现它们在形成药物代谢物时会从金属中置换出来，但我们已分析了控制铂（II）络合物中氨损失的因素，这是顺铂失活的可能途径。计算系统地显示了1的作用。 ）反式配体; 2）配合物的电荷; 3）亲核剂; 4）环境对铂-氨键的热力学不稳定性和动力学稳定性的影响。顺铂水解产物与硫醚或硫醇的初始结合后，氨的反式丢失到该硫配体上，而不是被诸如鸟嘌呤-N7之类的其他亲核试剂取代硫配体本身是这项研究的结果有助于了解DNA结合之前顺铂失活的模式，例如通过提高顺铂耐药性癌细胞中的谷胱甘肽水平。

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