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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chmel, Nikola P. Sakoff, Jennette Pages, Benjamin J. Rodger, Alison Jones, Nykola C. Ang, Dale L. Gilbert, Jayne Aldrich-wright, Janice R. Kelly, Sharon M.
Description	Author Affiliation: Pages BJ ( Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia.); Sakoff J ( Calvary Mater Newcastle, Waratah, NSW 2298, Australia.); Gilbert J ( Calvary Mater Newcastle, Waratah, NSW 2298, Australia.); Rodger A ( Department of Chemistry, University of Warwick, Coventry, West Midlands, CV47AL, UK.); Chmel NP ( Department of Chemistry, University of Warwick, Coventry, West Midlands, CV47AL, UK.); Jones NC ( ISA, Department of Physics and Astronomy, Aarhus University, Aarhus, 8000, Denmark.); Kelly SM ( Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.); Ang DL ( Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia.); Aldrich-Wright JR ( Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia. j.aldrich-wright@westernsydney.edu.au.)
Abstract	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 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 $IC_{50}$ 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.
ISSN	09476539
e-ISSN	15213765
Journal	Chemistry - A European Journal
Issue Number	26
Volume Number	22
Language	English
Publisher	Wiley-VCH;ChemPubSoc Europe
Publisher Date	2016-06-20
Publisher Place	Germany
Access Restriction	Open
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Catalysis

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