Short oligonucleotide prodrug having 5-fluoro and 5-iodouracil inhibits the proliferation of cancer cells in a photo-responsive manner

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3736-8. doi: 10.1016/j.bmcl.2014.07.002. Epub 2014 Jul 14.

Abstract

Photo-induced C1' hydrogen abstraction of 5-fluoro-2'-deoxyuridine was adopted as the key reaction for releasing 5-fluorouracil (5-FU) anticancer drug from oligonucleotide strands. After photoirradiation following 5-FU release, anticancer activity was expected. We demonstrated that oligonucleotide tetramer, d(A(F)U(I)UA), can release 5-FU under physiological conditions in a photo-responsive manner thorough photo-induced C1' hydrogen abstraction, and that the 5-FU released from d(A(F)U(I)UA) having a phosphorothioate backbone clearly suppresses the proliferation of HeLa cells in a photo-responsive manner.

Keywords: 5-Fluorouracil; Cancer cells; Photoirradiation; Prodrug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fluorouracil / chemistry
  • Fluorouracil / pharmacology*
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry
  • Oligonucleotides / pharmacology*
  • Photochemical Processes
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Structure-Activity Relationship
  • Uracil / analogs & derivatives*
  • Uracil / chemistry
  • Uracil / pharmacology

Substances

  • Antineoplastic Agents
  • Oligonucleotides
  • Prodrugs
  • Uracil
  • 5-iodouracil
  • Fluorouracil