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

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.

• Authors: Kenzo Fujimoto, Yu-ki Takematsu, Atsuo Shigeno, Mirei Furusawa, Takashi Sakamoto
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 24 Issue 16 Pg. 3736-8 (Aug 15 2014) ISSN: 1464-3405 [Electronic] England
• PMID: 25080163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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