1. 5-Alkynyl-2′-deoxyuridines: Chromatography-Free Synthesis and Cytotoxicity Evaluation Against Human Breast Cancer Cells
- Author
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Roman Dembinski, Ingo Ott, Srinivasarao Meneni, Craig D. Sergeant, Adam Sniady, and Ronald Gust
- Subjects
Magnetic Resonance Spectroscopy ,Spectrophotometry, Infrared ,Trimethylsilyl ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Alkyne ,Sonogashira coupling ,Antineoplastic Agents ,Breast Neoplasms ,Biochemistry ,Chemical synthesis ,Article ,Coupling reaction ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Cytotoxicity ,Molecular Biology ,chemistry.chemical_classification ,Organic Chemistry ,General Medicine ,Deoxyuridine ,In vitro ,MCF-7 ,chemistry ,Molecular Medicine ,Female ,Spectrophotometry, Ultraviolet ,Drug Screening Assays, Antitumor ,Nucleoside - Abstract
Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC(50) (microM) 0.4+/-0.3 for MCF-7 and 4.4+/-0.4 for MDA-MB-231.
- Published
- 2007
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