Bioreductively-activated prodrugs for targeting hypoxic tissues: elimination of aspirin from 2-nitroimidazole derivatives.
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.
Everett
S A
SA
Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, UK.
Naylor
M A
MA
Patel
K B
KB
Stratford
M R
MR
Wardman
P
P
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
D001965:Bromides; D009593:Nitroimidazoles; D011355:Prodrugs; D012459:Salicylates; D001241:Aspirin