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Multifaceted Studies of the DNA Interactions and In Vitro Cytotoxicity of Anticancer Polyaromatic Platinum(II) Complexes
Author(s) -
Pages Benjamin J.,
Sakoff Jennette,
Gilbert Jayne,
Rodger Alison,
Chmel Nikola P.,
Jones Nykola C.,
Kelly Sharon M.,
Ang Dale L.,
AldrichWright Janice R.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601221
Subject(s) - cytotoxicity , circular dichroism , chemistry , isothermal titration calorimetry , dna , stereochemistry , platinum , fluorescence , ligand (biochemistry) , in vitro , biochemistry , receptor , quantum mechanics , catalysis , physics
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)]Cl 2 , where P L is a polyaromatic ligand and SS ‐dach is 1 S ,2 S ‐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 IC 50 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.