title: Bioreductively-activated prodrugs for targeting hypoxic tissues: elimination of aspirin from 2-nitroimidazole derivatives.
abstract: 2-Nitroimidazoles were synthesised substituted with aspirin or salicylic acid, as leaving groups linked through the (imidazol-5-yl)methyl position. Activation of aqueous solutions by CO2*- (a model one-electron reductant) resulted in release of aspirin or salicylate, probably via the 2-hydroxyaminoimidazole. The analogous 2-nitroimidazole with bromide as leaving group eliminated bromide in < 1 ms via the radical-anion.
authors.affiliation: Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Everett
authors.forename: M A
authors.initials: MA
authors.lastname: Naylor
authors.forename: K B
authors.initials: KB
authors.lastname: Patel
authors.forename: M R
authors.initials: MR
authors.lastname: Stratford
authors.forename: P
authors.initials: P
authors.lastname: Wardman
mesh_terms: D000818:Animals; D001241:Aspirin / Q000737:chemistry*; D001965:Bromides / Q000737:chemistry; D015687:Cell Hypoxia / Q000187:drug effects*; D006801:Humans; D009593:Nitroimidazoles / Q000138:chemical synthesis*; D011355:Prodrugs / Q000737:chemistry*; D012459:Salicylates / Q000737:chemistry; D013997:Time Factors
chemical_list: D001965:Bromides; D009593:Nitroimidazoles; D011355:Prodrugs; D012459:Salicylates; D001241:Aspirin