title: Multifaceted Studies of the DNA Interactions and In Vitro Cytotoxicity of Anticancer Polyaromatic Platinum(II) Complexes.
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(PL )(SS-dach)]Cl2 , where PL 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.
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia.
authors.forename: Benjamin J
authors.identifier: http://orcid.org/0000-0001-9201-6242
authors.initials: BJ
authors.lastname: Pages
authors.affiliation: Calvary Mater Newcastle, Waratah, NSW 2298, Australia.
authors.forename: Jennette
authors.initials: J
authors.lastname: Sakoff
authors.affiliation: Calvary Mater Newcastle, Waratah, NSW 2298, Australia.
authors.forename: Jayne
authors.initials: J
authors.lastname: Gilbert
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, West Midlands, CV47AL, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Rodger
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, West Midlands, CV47AL, UK.
authors.forename: Nikola P
authors.identifier: http://orcid.org/0000-0002-2882-5253
authors.initials: NP
authors.lastname: Chmel
authors.affiliation: ISA, Department of Physics and Astronomy, Aarhus University, Aarhus, 8000, Denmark.
authors.forename: Nykola C
authors.initials: NC
authors.lastname: Jones
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Sharon M
authors.identifier: http://orcid.org/0000-0002-3516-1387
authors.initials: SM
authors.lastname: Kelly
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia.
authors.forename: Dale L
authors.identifier: http://orcid.org/0000-0001-5142-7555
authors.initials: DL
authors.lastname: Ang
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia. j.aldrich-wright@westernsydney.edu.au.
authors.forename: Janice R
authors.identifier: http://orcid.org/0000-0002-6943-6908
authors.initials: JR
authors.lastname: Aldrich-Wright
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002151:Calorimetry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry; D013058:Mass Spectrometry; D010618:Phenanthrolines / Q000737:chemistry; D010984:Platinum / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D010618:Phenanthrolines; D010984:Platinum; D015082:2,2'-Dipyridyl; D004247:DNA; C025205:1,10-phenanthroline
keywords: Anticancer agents; DNA; biophysical chemistry; platinum; spectroscopy