Capillary zone electrophoresis and capillary zone electrophoresis-electrospray ionization mass spectrometry studies on the behavior of anticancer cis- and trans-[dihalidobis(2-propanone oxime)platinum(II)] complexes in aqueous solutions.
Capillary zone electrophoresis and capillary zone electrophoresis-electrospray ionization mass spectrometry studies on the behavior of anticancer cis- and trans-[dihalidobis(2-propanone oxime)platinum(II)] complexes in aqueous solutions.
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毛细管区带电泳和毛细管区带电泳-电喷雾电离质谱研究抗癌顺式和反式[二卤化双(2-丙酮肟)铂(II)]配合物在水溶液中的行为。
DOI：
10.1016/j.chroma.2012.07.062
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
C. Hartinger
中科院分区：
文献类型：
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作者：
Gerlinde Grabmann;S. Meier;Y. Y. Scaffidi;M. Galanski;B. Keppler;C. Hartinger
迫切需要具有新作用方式的抗癌化疗药物来克服副作用、耐药性问题和有限的应用范围。在其他方法中，已建立的化疗药物顺铂的反式配置类似物在生物模型系统中显示出有希望的结果。在此，我们报告了使用毛细管区带电泳 (CZE) 和 CZE 联用电喷雾电离质谱 (CZE-ESI-MS) 对顺式和反式[二卤化双(2-丙酮肟)铂(II)] (halido=Cl−, Br−, I−) 配合物在磷酸盐缓冲液中稳定性的比较研究。所使用的条件模拟了细胞质中的条件，这对于激活铂类抗癌剂与最终目标 DNA 的反应非常重要。 Pt 中心的构型（即顺式或反式）解释了化合物不同的降解动力学，此外还观察到卤化物离去基团的显着影响，在顺式配合物的情况下，Br−、Cl− 和 I− 的伪一级速率常数分别为 0.268、0.191 和 0.142h−1。与顺式异构体相比，反式异构体的降解速度明显更快，这也导致了不同的产物，其特征是 CZE 与 ESI-MS 的连字符。
Anticancer chemotherapeutics with new modes of action are in great demand to overcome adverse effects, resistance problems and a limited application range. Among other approaches, trans-configured analogs of the established chemotherapy drug cisplatin show promising results in biological model systems. Herein we report on comparative studies on the stability of cis- and trans-[dihalidobis(2-propanone oxime)platinum(II)] (halido=Cl−, Br−, I−) complexes in phosphate buffer, using capillary zone electrophoresis (CZE) and CZE hyphenated to electrospray ionization-mass spectrometry (CZE–ESI-MS). The used conditions simulate those in the cytoplasm, being of importance for the activation of platinum anticancer agents for their reaction with DNA, the ultimate target. The configuration of the Pt center, i.e., cis or trans, accounts for the differing degradation kinetics of the compounds and in addition a significant influence of the halido leaving group was observed, with in case of the cis complexes pseudo first order rate constants of 0.268, 0.191 and 0.142h−1for Br−, Cl−, and I−, respectively. Degradation of the trans isomers was significantly faster compared to their cis-configured counterparts also leading to different products which were characterized by hyphenation of CZE to ESI-MS.