TY - JOUR
T1 - Multifaceted studies of the DNA interactions and in vitro cytotoxicity of anticancer polyaromatic platinum(II) complexes
AU - Pages, Benjamin J.
AU - Sakoff, Jennette
AU - Gilbert, Jayne
AU - Rodger, Alison
AU - Chmel, Nikola P.
AU - Jones, Nykola C.
AU - Kelly, Sharon M.
AU - Ang, Dale L.
AU - Aldrich-Wright, Janice R.
PY - 2016
Y1 - 2016
N2 - This study reports a detailed biophysical analysis of the DNA binding and cytotoxicity of six platinum complexes (PCs). They are of the type [Pt(PL)(SS-dach)]Cl2, where PLis 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 IC50values. 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.
AB - This study reports a detailed biophysical analysis of the DNA binding and cytotoxicity of six platinum complexes (PCs). They are of the type [Pt(PL)(SS-dach)]Cl2, where PLis 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 IC50values. 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.
KW - DNA
KW - antineoplastic agents
KW - dichroism
KW - physical biochemistry
KW - platinum
KW - spectrum analysis
UR - http://hdl.handle.net/1959.7/uws:36461
U2 - 10.1002/chem.201601221
DO - 10.1002/chem.201601221
M3 - Article
SN - 0947-6539
VL - 22
SP - 8943
EP - 8954
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
IS - 26
ER -