title: Reductive activation of 5-fluorodeoxyuridine prodrug possessing azide methyl group by hypoxic X-irradiation.
abstract: We prepared a 5-fluorodeoxyuridine (5-FdUrd) derivative possessing azide methyl group (N(3)-FdUrd) as a novel radiation-activated prodrug. The parent antitumor agent, 5-FdUrd, was released efficiently from N(3)-FdUrd by hypoxic X-irradiation. On the other hand, the activation of N(3)-FdUrd was suppressed upon X-irradiation under aerobic conditions. A biological assay using A549 cells revealed that the cytotoxicity of N(3)-FdUrd was significantly enhanced by hypoxic X-irradiation.
authors.affiliation: Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, Japan. tanabeka@scl.kyoto-u.ac.jp
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tanabe
authors.forename: Jin
authors.initials: J
authors.lastname: Ishizaki
authors.forename: Yuichirou
authors.initials: Y
authors.lastname: Ando
authors.forename: Takeo
authors.initials: T
authors.lastname: Ito
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Nishimoto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005467:Floxuridine / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects*; D006801:Humans; D008697:Methane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000528:radiation effects*
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D011355:Prodrugs; D005467:Floxuridine; D008697:Methane