Design, Synthesis, Antiviral, and Cytotoxic Evaluation of Novel Phosphonylated 1,2,3-Triazoles as Acyclic Nucleotide Analogues

Abstract

The 1,3-dipolar cycloaddition of diethyl 2-azidoethyl-, 3-azidopropyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropylphosphonates with selected N-propargyl nucleobases gave a series of the phosphonylated 1,2,3-triazole acyclonucleosides in which the phosphonate residue and nucleobases were linked by three- and four-carbon chains. Under standard conditions (TMSBr, ethanol), all synthesized O,O-diethylphosphonates were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses. Unfortunately, no antiviral activity was observed at 100 μM.

Keywords:

• Phosphonylated nucleosides
• azidophosphonates
• 1,3-dipolar cycloaddition 1,4-disubstituted-1,2,3-triazoles
• phosphonic acid

Acknowledgments

The authors wish to express their gratitude to Mrs. Małgorzata Pluskota, Leen Ingels, Leentje Persoons, Frieda De Meyer, Lies Van den Heurck, and Mr. Steven Carmans for their excellent technical assistance. Preliminary experiments in this project were conducted by Ms. Agnieszka Monińska and Ms. Agnieszka Olczyk-Dziedzińska. This work was supported by the National Science Centre under Decision UMO-2011/01/D/NZ4/01276. The virological part of this work was supported by the K.U.Leuven (GOA no. 10/014).