Discovery of a new template for anticancer agents: 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl-cytosine (2'-F-4'-seleno-ara-C).

Abstract

The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).

• Authors: Lak Shin Jeong, Dilip K Tosh, Won Jun Choi, Sang Kook Lee, You-Jin Kang, Sun Choi, Jin Hee Lee, Hankil Lee, Hyuk Woo Lee, Hea Ok Kim
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 17 Pg. 5303-6 (Sep 10 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19691349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosylcytosine
• Antineoplastic Agents
• Organoselenium Compounds
• Cytarabine
• Cytosine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cytarabine (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Cytosine (chemical synthesis, chemistry, pharmacology)
• Drug Discovery
• Halogenation
• Humans
• Inhibitory Concentration 50
• Models, Molecular
• Molecular Conformation
• Organoselenium Compounds (chemical synthesis, chemistry, pharmacology)