One-electron reduction characteristics of N(3)-substituted 5-fluorodeoxyuridines synthesized as radiation-activated prodrugs

Bioorg Med Chem. 2003 Oct 15;11(21):4551-6. doi: 10.1016/j.bmc.2003.08.001.

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.

MeSH terms

  • Antimetabolites, Antineoplastic / chemical synthesis*
  • Antimetabolites, Antineoplastic / chemistry*
  • Antimetabolites, Antineoplastic / toxicity
  • Cell Hypoxia
  • Cell Line, Tumor
  • Floxuridine / analogs & derivatives*
  • Floxuridine / toxicity
  • Humans
  • Lasers
  • Oxidation-Reduction
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry*
  • Prodrugs / toxicity

Substances

  • Antimetabolites, Antineoplastic
  • Prodrugs
  • Floxuridine