Groessl Michael, Hartinger Christian G, Dyson Paul J, Keppler Bernhard K
Institute of Inorganic Chemistry, University of Vienna, Waehringer Street 42, A-1090 Vienna, Austria.
J Inorg Biochem. 2008 May-Jun;102(5-6):1060-5. doi: 10.1016/j.jinorgbio.2007.11.018. Epub 2007 Dec 14.
Elucidating the mode of action and thereby opening the way to the design of chemotherapeutic agents is one of the major goals of metal-based anticancer research. Hydrolysis and DNA binding play an important role for pharmaceutical formulation and for exerting anticancer activity. Herein, for the first time the application of capillary zone electrophoresis-inductively-coupled plasma mass spectrometry (CZE-ICP-MS) for studying the hydrolytic stability and the binding of the ruthenium anticancer drug candidates KP418, KP1019, and RAPTA-C to dGMP is described. RAPTA-C was found to hydrolyze fastest and showed the highest reactivity toward the DNA model compound, whereas KP418 was the most stable compound in both these respects.
阐明作用模式从而为化疗药物的设计开辟道路是金属基抗癌研究的主要目标之一。水解和与DNA结合对于药物制剂以及发挥抗癌活性起着重要作用。本文首次描述了毛细管区带电泳-电感耦合等离子体质谱法（CZE-ICP-MS）在研究钌抗癌候选药物KP418、KP1019和RAPTA-C与dGMP的水解稳定性及结合方面的应用。结果发现，RAPTA-C水解最快，对DNA模型化合物的反应性最高，而在这两个方面，KP418是最稳定的化合物。
