Reductive activation of 5-fluorodeoxyuridine prodrug possessing azide methyl group by hypoxic X-irradiation

  • Bioorg Med Chem Lett. 2012 Feb 15;22(4):1682-5. doi: 10.1016/j.bmcl.2011.12.106.
Kazuhito Tanabe  1 ,  Jin Ishizaki ,  Yuichirou Ando ,  Takeo Ito ,  Sei-ichi Nishimoto
Affiliations
  • 1. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, Japan. [email protected]
PMID: 22248856 DOI: 10.1016/j.bmcl.2011.12.106
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.