title: Fragmentation of the quinoxaline N-oxide bond to the ˙OH radical upon one-electron bioreduction.
abstract: The ˙OH radical is released from 3-trifluoromethyl-quinoxaline 1,4-dioxides upon one-electron reduction by cytochrome P450 oxidoreductase. This process effectively competes with back oxidation of the intermediate radical anion by oxygen and underlies the increased aerobic cytotoxicity of such compounds compared to that seen for the related clinical bioreductive benzotriazine drug, tirapazamine.
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. r.anderson@auckland.ac.nz.
authors.forename: Pooja
authors.initials: P
authors.lastname: Yadav
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Marshall
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hay
authors.forename: Robert F
authors.initials: RF
authors.lastname: Anderson
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry*; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry*; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry; D011810:Quinoxalines / Q000737:chemistry*; D000077704:Tirapazamine; D014227:Triazines / Q000737:chemistry
chemical_list: C510912:(diethoxyphosphoryl)-5-methylpyrroline N-oxide; D000970:Antineoplastic Agents; D010087:Oxides; D011758:Pyrroles; D011810:Quinoxalines; D014227:Triazines; D000077704:Tirapazamine; D017665:Hydroxyl Radical; C003282:quindoxin; D009251:NADPH-Ferrihemoprotein Reductase