Biological Evaluation of Uridine Derivatives of 2-Deoxy Sugars as Potential Antiviral Compounds against Influenza A Virus.

Autor: Krol E; Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland. ewelina@biotech.ug.gda.pl., Wandzik I; Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland. Ilona.Wandzik@polsl.pl., Krejmer-Rabalska M; Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland. martyna.krejmer@biotech.ug.edu.pl., Szewczyk B; Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland. szewczyk@biotech.ug.gda.pl.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2017 Aug 04; Vol. 18 (8). Date of Electronic Publication: 2017 Aug 04.
DOI: 10.3390/ijms18081700
Abstrakt: Influenza virus infection is a major cause of morbidity and mortality worldwide. Due to the limited ability of currently available treatments, there is an urgent need for new anti-influenza drugs with broad spectrum protection. We have previously shown that two 2-deoxy sugar derivatives of uridine (designated IW3 and IW7) targeting the glycan processing steps during maturation of viral glycoproteins show good anti-influenza virus activity and may be a promising alternative approach for the development of new anti-influenza therapy. In this study, a number of IW3 and IW7 analogues with different structural modifications in 2-deoxy sugar or uridine parts were synthesized and evaluated for their ability to inhibit influenza A virus infection in vitro. Using the cytopathic effect (CPE) inhibition assay and viral plaque reduction assay in vitro, we showed that compounds 2 , 3 , and 4 exerted the most inhibitory effect on influenza virus A/ostrich/Denmark/725/96 (H5N2) infection in Madin-Darby canine kidney (MDCK) cells, with 50% inhibitory concentrations ( IC 50 ) for virus growth ranging from 82 to 100 (μM) without significant toxicity for the cells. The most active compound ( 2 ) showed activity of 82 μM with a selectivity index value of 5.27 against type A (H5N2) virus. Additionally, compound 2 reduced the formation of HA glycoprotein in a dose-dependent manner. Moreover, an analysis of physicochemical properties of studied compounds demonstrated a significant linear correlation between lipophilicity and antiviral activity. Therefore, inhibition of influenza A virus infection by conjugates of uridine and 2-deoxy sugars is a new promising approach for the development of new derivatives with anti-influenza activities.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
Externí odkaz: