Novel uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, as potential antiviral compounds

Ewelina Król , Gabriela Pastuch-Gawołek , Binay Chaubey , Gabriela Brzuska , Karol Erfurt , Bogusław Szewczyk

Abstract

A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for which new or improved therapeutic options are needed. The antiviral activity of all synthesized compounds was confirmed using pseudo-plaque reduction assays in which a significant arrest of CSFV and HCV growth was observed in the presence of these compounds. Two of the synthesized compounds, 9 and 12, displayed a significant inhibitory effect on HCV and CSFV propagation with IC50 values of 4.9 and 13.5 µM for HCV and 4.2 and 4 µM for CSFV, respectively, with low cytotoxicity. Using various infection and replication models, we have shown that both compounds were able to significantly reduce viral genome replication by up to 90% with IC50 values in the low micromolar range. A structure activity analysis of the synthesized compounds showed that the high antiviral activity was attributed to the hydrophobicity of glycoconjugates and the introduction of elements capable to coordinate metal ions into the spacer connecting the sugar and uridine moiety, which can be useful in the development of new antiviral compounds in the future.
Author Ewelina Król (IFB / IB / LRV)
Ewelina Król,,
- Laboratory of Recombinant Vaccines
, Gabriela Pastuch-Gawołek
Gabriela Pastuch-Gawołek,,
-
, Binay Chaubey (IFB / IB / LRV)
Binay Chaubey,,
- Laboratory of Recombinant Vaccines
, Gabriela Brzuska (IFB)
Gabriela Brzuska,,
- Intercollegiate Faculty of Biotechnology UG
, Karol Erfurt
Karol Erfurt,,
-
, Bogusław Szewczyk (IFB / IB / LRV)
Bogusław Szewczyk,,
- Laboratory of Recombinant Vaccines
Journal seriesMolecules, ISSN , e-ISSN 1420-3049, (A 30 pkt)
Issue year2018
Vol23
No6
Pages1-24
Publication size in sheets1.15
Keywords in Englishhepatitis C virus, classical swine fever virus, antivirals, aryl 1-thioglycoside derivatives, uridine glycoconjugates, analogues of glycosyltransferase substrates
DOIDOI:10.3390/molecules23061435
URL https://www.mdpi.com/1420-3049/23/6/1435/pdf
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)30
ScoreMinisterial score = 30.0, 04-10-2018, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 04-10-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.861 (2) - 2016=2.988 (5)
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