title: Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones.
abstract: A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol-3-yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug.
authors.affiliation: School of Pharmacy, University of Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jaffar
authors.forename: S A
authors.initials: SA
authors.lastname: Everett
authors.forename: M A
authors.initials: MA
authors.lastname: Naylor
authors.forename: S G
authors.initials: SG
authors.lastname: Moore
authors.forename: S
authors.initials: S
authors.lastname: Ulhaq
authors.forename: K B
authors.initials: KB
authors.lastname: Patel
authors.forename: M R
authors.initials: MR
authors.lastname: Stratford
authors.forename: J
authors.initials: J
authors.lastname: Nolan
authors.forename: P
authors.initials: P
authors.lastname: Wardman
authors.forename: I J
authors.initials: IJ
authors.lastname: Stratford
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001168:Arthritis / Q000378:metabolism; D001241:Aspirin / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D011809:Quinones / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship