title: Characterisation of radicals formed by the triazine 1,4-dioxide hypoxia-activated prodrug, SN30000.
abstract: The radical species underlying the activity of the bioreductive anticancer prodrug, SN30000, have been identified by electron paramagnetic resonance and pulse radiolysis techniques. Spin-trapping experiments indicate both an aryl-type radical and an oxidising radical, trapped as a carbon-centred radical, are formed from the protonated radical anion of SN30000. The carbon-centred radical, produced upon the one-electron oxidation of the 2-electron reduced metabolite of SN30000, oxidises 2-deoxyribose, a model for the site of damage on DNA which leads to double strand breaks. Calculations using density functional theory support the assignments made.
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. r.anderson@auckland.ac.nz.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Anderson
authors.forename: Pooja
authors.initials: P
authors.lastname: Yadav
authors.forename: Deepa
authors.initials: D
authors.lastname: Patel
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
authors.forename: Smitha R
authors.initials: SR
authors.lastname: Tipparaju
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Guise
authors.forename: Adam V
authors.initials: AV
authors.lastname: Patterson
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
authors.forename: Andrej
authors.initials: A
authors.lastname: Maroz
authors.forename: Sujata S
authors.initials: SS
authors.lastname: Shinde
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hay
mesh_terms: D015687:Cell Hypoxia; D003497:Cyclic N-Oxides / Q000737:chemistry*; D053903:DNA Breaks, Double-Stranded; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011355:Prodrugs / Q000737:chemistry*; D011675:Pulse Radiolysis; D011789:Quantum Theory; D013696:Temperature; D000077704:Tirapazamine; D014227:Triazines / Q000737:chemistry*
chemical_list: C570601:CEN-209; D003497:Cyclic N-Oxides; D005609:Free Radicals; D011355:Prodrugs; D014227:Triazines; D000077704:Tirapazamine