Synthesis and antiviral activity of 1,2,3-triazolyl nucleoside analogues with N-acetyl-d-glucosamine residue

Abstract

A series of 1,2,3-triazolyl nucleoside analogues bearing N-acetyl-D-glucosamine residue was synthesized by the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction of N1-ω-alkynyl derivatives of uracil, 6-methyluracil, thymine and 3,4,6-tri-O-acetyl-2-deoxy-2-acetamido-β-D-glucopyranosyl azide. Antiviral assays revealed the lead compound 3f which showed both the same activity against the influenza virus A H1N1 (IC₅₀=70.7 µM) as the antiviral drug Rimantadine in control (IC₅₀=77 µM) and good activity against Coxsackievirus B3 (IC₅₀=13.9 µM) which was one and a half times higher than the activity of the antiviral drug Pleconaril in control (IC₅₀=21.6 µM). According to molecular docking simulations, the antiviral activity of the lead compound 3f against Coxsackie B3 virus can be explained by its binding to a key fragment of the capsid surface of this virus.

Keywords:

• Nucleoside analogues
• 1;2;3-Triazole
• glucosamine
• Influenza virus
• Coxsackie virus
• click chemistry

Acknowledgements

The authors are grateful to the Assigned Spectral-Analytical Center of FRC Kazan Scientific Center of RAS for technical assistance in research.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Funding

The author(s) reported there is no funding associated with the work featured in this article.