Reductive activation of 5-fluorodeoxyuridine prodrug possessing azide methyl group by hypoxic X-irradiation
Kazuhito Tanabe1, Jin Ishizaki, Yuichirou Ando
1Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, Japan. tanabeka@scl.kyoto-u.ac.jp
Bioorganic & Medicinal Chemistry Letters
|January 18, 2012
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.


