title: One-electron reduction characteristics of N(3)-substituted 5-fluorodeoxyuridines synthesized as radiation-activated prodrugs.
abstract: We designed and synthesized N(3)-substituted 5-fluorodeoxyuridines as radiation-activated prodrugs of the antitumor agent, 5-fluorodeoxyuridine (5-FdUrd). A series of 5-FdUrd derivatives possessing a 2-oxoalkyl group at the N(3)-position released 5-FdUrd in good yield via one-electron reduction initiated by hypoxic irradiation. Cytotoxicity of the 5-FdUrd derivative possessing the 2-oxocyclopentyl group (3d) was low, but was enhanced by hypoxic irradiation resulting in 5-FdUrd release.
authors.affiliation: Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tanabe
authors.forename: Youhei
authors.initials: Y
authors.lastname: Mimasu
authors.forename: Akira
authors.initials: A
authors.lastname: Eto
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tachi
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Mayuko
authors.initials: M
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatta
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Nishimoto
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D007834:Lasers; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005467:Floxuridine