One-electron reduction characteristics of N(3)-substituted 5-fluorodeoxyuridines synthesized as radiation-activated prodrugs.
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.
Tanabe
Kazuhito
K
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
Mimasu
Youhei
Y
Eto
Akira
A
Tachi
Yukihiro
Y
Sakakibara
Shingo
S
Mori
Mayuko
M
Hatta
Hiroshi
H
Nishimoto
Sei-ichi
S
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
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005467:Floxuridine