Squalenoyl nucleoside monophosphate nanoassemblies: new prodrug strategy for the delivery of nucleotide analogues.

Abstract

4-(N)-1,1',2-trisnor-squalenoyldideoxycytidine monophosphate (SQddC-MP) and 4-(N)-1,1',2-trisnor-squalenoylgemcitabine monophosphate (SQdFdC-MP) were synthesized using phosphoramidite chemistry. These amphiphilic molecules self-assembled to about hundred nanometers size nanoassemblies in aqueous medium. Nanoassemblies of SQddC-MP displayed significant anti-HIV activity whereas SQdFdC-MP nanoassemblies displayed promising anticancer activity on leukemia cells. These results suggested that squalene conjugate of negatively charged nucleotide analogues efficiently penetrated within cells. Thus, we propose a new prodrug strategy for improved delivery of nucleoside analogues to ameliorate their biological efficacy.

• Authors: Joachim Caron, L Harivardhan Reddy, Sinda Lepêtre-Mouelhi, Séverine Wack, Pascal Clayette, Christine Rogez-Kreuz, Rahima Yousfi, Patrick Couvreur, Didier Desmaële
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 9 Pg. 2761-4 (May 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20363623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-HIV Agents
• Antineoplastic Agents
• Nucleosides
• Prodrugs
• Squalene

Topics

• Animals
• Anti-HIV Agents (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Mice
• Nanoparticles (chemistry, ultrastructure)
• Nucleosides (chemical synthesis, chemistry, pharmacology)
• Particle Size
• Prodrugs (chemical synthesis, chemistry, pharmacology)
• Squalene (chemistry)