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

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 t...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2014-08, Vol.24 (16), p.3736-3738
Main Authors: Fujimoto, Kenzo, Takematsu, Yu-ki, Shigeno, Atsuo, Furusawa, Mirei, Sakamoto, Takashi
Format: Article
Language:English
Subjects:
5-Fluorouracil
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cancer cells
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
Photoirradiation
Prodrug
Prodrugs - chemical synthesis
Prodrugs - chemistry
Prodrugs - pharmacology
Structure-Activity Relationship
Uracil - analogs & derivatives
Uracil - chemistry
Uracil - pharmacology
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Summary: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(AFUIUA), 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(AFUIUA) having a phosphorothioate backbone clearly suppresses the proliferation of HeLa cells in a photo-responsive manner.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2014.07.002