title: Bioreductive fluorescent markers for hypoxic cells: a study of 2-nitroimidazoles with 1-substituents containing fluorescent, bridgehead-nitrogen, bicyclic systems.
abstract: The oxygen-sensitive bioreductive binding of 2-nitroimidazoles labeled with fluorescent side chains has been used to stain hypoxic mammalian cells selectively. Several novel compounds were synthesized with a 1-substituent containing a fluorescent, bicyclic system having a bridgehead-nitrogen atom. Additional amine and secondary alcohol substituents were also included in the link between the fluorophor and the nitroimidazole to improve water solubility. Their ability to discriminate between hypoxic and oxic cells was compared by flow cytometric analysis. A wide range of cellular fluorescence and hypoxic-oxic differentials in fluorescence was observed when compounds with indolizine fluorophors were incubated with cells, and one such compound was considered suitable for further evaluation in vivo. Two compounds with bimane fluorophors gave very little cellular fluorescence when incubated with hypoxic cells.
authors.affiliation: Gray Laboratory of the Cancer Research Campaign, Mount Vernon Hospital, Northwood, Middlesex, U.K.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodgkiss
authors.forename: R W
authors.initials: RW
authors.lastname: Middleton
authors.forename: J
authors.initials: J
authors.lastname: Parrick
authors.forename: H K
authors.initials: HK
authors.lastname: Rami
authors.forename: P
authors.initials: P
authors.lastname: Wardman
authors.forename: G D
authors.initials: GD
authors.lastname: Wilson
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction
chemical_list: D005456:Fluorescent Dyes; D009593:Nitroimidazoles