Multifaceted Studies of the DNA Interactions and In Vitro Cytotoxicity of Anticancer Polyaromatic Platinum(II) Complexes

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• 作者：Benjamin J. Pages ; Dr. Jennette Sakoff ; Dr. Jayne Gilbert ; Prof. Alison Rodger ; Dr. Nikola P. Chmel ; Nykola C. Jones ; Dr. Sharon M. Kelly ; Dale L. Ang and Prof. Janice R. Aldrich-Wright
• 刊名：Chemistry - A European Journal
• 出版年：2016
• 出版时间：June 20, 2016
• 年：2016
• 卷：22
• 期：26
• 页码：8943-8954
• 全文大小：3656K
• ISSN：1521-3765

文摘

This study reports a detailed biophysical analysis of the DNA binding and cytotoxicity of six platinum complexes (PCs). They are of the type [Pt(P_L)(SS-dach)]Cl₂, where P_L is a polyaromatic ligand and SS-dach is 1S,2S-diaminocyclohexane. The DNA binding of these complexes was investigated using six techniques including ultraviolet and fluorescence spectroscopy, linear dichroism, synchrotron radiation circular dichroism, isothermal titration calorimetry and mass spectrometry. This portfolio of techniques has not been extensively used to study the interactions of such complexes previously; each assay provided unique insight. The in vitro cytotoxicity of these compounds was studied in ten cell lines and compared to the effects of their R,R enantiomers; activity was very high in Du145 and SJ-G2 cells, with some submicromolar IC₅₀ values. In terms of both DNA affinity and cytotoxicity, complexes of 5,6-dimethyl-1,10-phenanthroline and 2,2′-bipyridine exhibited the greatest and least activity, respectively, suggesting that there is some correlation between DNA binding and cytotoxicity.