Synthesis and cytotoxic activity of various 5-[alkoxy-(4-nitro-phenyl)-methyl]-uracils in their racemic form.

Abstract

The preparation of various 5-[alkoxy-(4-nitro-phenyl)-methyl]-uracils with alkyl chain lengths C(1)-C(12) is described. The synthesis is based on the preparation of 5-[chloro-(4-nitro-phenyl)-methyl]-uracil and subsequent substitution of chlorine with appropriate alcohols. The resulting ethers were tested for their cytotoxic activity in vitro against five cancer cell lines. The compounds were less active in lung resistance protein expressing cell lines, suggesting the involvement of this multidrug resistant protein in control of the biological activity. Cytotoxic substances induced rapid inhibition of DNA and modulation of RNA synthesis followed by induction of apoptosis. The data indicate that the biological activity of 5-[alkoxy-(4-nitro-phenyl)-methyl]-uracils depends on the alkyl chain length.

• Authors: Lucie Spácilová, Petr Dzubák, Marián Hajdúch, Sona Krupková, Pavel Hradil, Jan Hlavác
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 23 Pg. 6647-50 (Dec 01 2007) ISSN: 1464-3405 [Electronic] England
• PMID: 17935983 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alcohols
• Antineoplastic Agents
• Cytotoxins
• alkoxyl radical
• Uracil

Topics

• Alcohols (chemical synthesis, toxicity)
• Antineoplastic Agents (chemical synthesis, toxicity)
• Cell Line, Tumor
• Cytotoxins (chemical synthesis, toxicity)
• Humans
• K562 Cells
• Stereoisomerism
• Uracil (analogs & derivatives, chemical synthesis, toxicity)