Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity.

Content Provider	Europe PMC
Author	Andreeva, Olga V. Garifullin, Bulat F. Zarubaev, Vladimir V. Slita, Alexander V. Yesaulkova, Iana L. Saifina, Liliya F. Shulaeva, Marina M. Belenok, Maya G. Semenov, Vyacheslav E. Kataev, Vladimir E.
Abstract	AbstractBased on the fact that a search for influenza antivirals among nucleoside analogues has drawn very little attention of chemists, the present study reports the synthesis of a series of 1,2,3-triazolyl nucleoside analogues in which a pyrimidine fragment is attached to the ribofuranosyl-1,2,3-triazol-4-yl moiety by a polymethylene linker of variable length. Target compounds were prepared by the Cu alkyne-azide cycloaddition (CuAAC) reaction. Derivatives of uracil, 6-methyluracil, 3,6-dimethyluracil, thymine and quinazolin-2,4-dione with ω-alkyne substituent at the N1 (or N5) atom and azido 2,3,5-tri-O-acetyl-D-β-ribofuranoside were used as components of the CuAAC reaction. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. The best values of IC50 (inhibiting concentration) and SI (selectivity index) were demonstrated by the lead compound 4i in which the 1,2,3-triazolylribofuranosyl fragment is attached to the N1 atom of the quinazoline-2,4-dione moiety via a butylene linker (IC50 = 30 μM, SI = 24) and compound 8n in which the 1,2,3-triazolylribofuranosyl fragment is attached directly to the N5 atom of the 6-methyluracil moiety (IC50 = 15 μM, SI = 5). According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 4i and 8n against H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRP).Graphic abstractElectronic supplementary materialThe online version of this article (10.1007/s11030-020-10141-y) contains supplementary material, which is available to authorized users.
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ISSN	13811991
Journal	Molecular Diversity [Mol Divers]
Volume Number	25
DOI	10.1007/s11030-020-10141-y
PubMed Central reference number	PMC7490575
Issue Number	1
PubMed reference number	32930935
e-ISSN	1573501X
Language	English
Publisher	Springer International Publishing
Publisher Date	2020-09-15
Publisher Place	Gewerbestrasse 11, Cham, Ch 6330, Switzerland
Access Restriction	Open
Rights License	This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. © Springer Nature Switzerland AG 2020
Subject Keyword	Nucleoside analogues 1,2,3-Triazole Influenza virus Coxsackievirus Click chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Drug Discovery Medicine Molecular Biology Physical and Theoretical Chemistry Information Systems Catalysis Inorganic Chemistry