In vitro antiviral activity of some uridine derivatives of 2-deoxy sugars against classical swine fever virus

Król, Ewelina; Wandzik, Ilona; Szeja, W.; Grynkiewicz, Grzegorz; Szewczyk, Bogusław

doi:10.1016/j.antiviral.2010.02.314

Cited by 20 publications

(22 citation statements)

References 53 publications

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“…This significant antiviral activity of tunicamycin encouraged us to synthesize compounds mimicking the tunicamycin structure and to check their antiviral activity. In our previous studies, we have demonstrated that two compounds belonging to tunicamycin derivatives—uridine derivatives of 2-deoxy sugars (named IW3 and IW7)—possess significant antiviral activity against classical swine fever virus [ 49 ]. We have shown that these two compounds affect protein glycosylation similarly to tunicamycin, but they are significantly less toxic.…”

Section: Discussionmentioning

confidence: 99%

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

Król

Wandzik

Krejmer-Rabalska

et al. 2017

IJMS

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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 (IC50) 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.

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Section: Discussionmentioning

confidence: 99%

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

Król

Wandzik

Krejmer-Rabalska

et al. 2017

IJMS

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“…As an example, tunicamycin, a nucleoside antibiotic containing uridine and 11-carbon disaccharide tunicamine in its structure inhibits N-glycosylation in eukaryotes. Inspired by tunicamycin activity we have recently synthesized a small library of uridine derivatives of 2-deoxy sugars containing hydrophobic motifs in their structures (compounds 1 – 9 , IW3 , IW7 , Figure 1 ) [ 24 , 25 , 26 ]. Lipophilic moieties were included because the common approach in antiviral prodrug design is to increase passive permeability and several antiviral drugs, e.g., sofosbuvir or oseltamivir are administered in the form of more lipophilic prodrugs in order to increase permeability.…”

Section: Introductionmentioning

confidence: 99%

“…Lipophilic moieties were included because the common approach in antiviral prodrug design is to increase passive permeability and several antiviral drugs, e.g., sofosbuvir or oseltamivir are administered in the form of more lipophilic prodrugs in order to increase permeability. Uridine derivatives synthesized by us turned out to be active in vitro against classical swine fever virus (CSFV), a member of the family Flaviviridae [ 24 ], and influenza virus, belonging to the Orthomyxoviridae [ 25 ]. The observed antiviral potency was attributed to impaired maturation of viral proteins caused by the inhibition of N-glycosylation process in cis-Golgi or very early in medial-Golgi compartments.…”

Section: Introductionmentioning

confidence: 99%

Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars

et al. 2018

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Hepatitis C virus (HCV), the etiological agent of the most common and dangerous diseases of the liver, is a major health problem worldwide. Despite many attempts, there is still no vaccine available. Although many drugs have been approved for use mostly in combination regimen, their high costs make them out of reach in less developed regions. Previously, we have synthesized a series of compounds belonging to uridine derivatives of 2-deoxy sugars and have proved that some of them possess antiviral activity against influenza A virus associated with N-glycosylation inhibition. Here, we analyze the antiviral properties of these compounds against HCV. Using cell culture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and replicon cell lines, we have shown high anti-HCV activity of two compounds. Our results indicated that compounds 2 and 4 significantly reduced HCVcc propagation with IC50 values in low μM range. Further experiments using the HCVpp system confirmed that both compounds significantly impaired the infectivity of produced HCVpp due to the inhibition of the correct maturation of viral glycoproteins. Overall, our results suggest that inhibiting the glycosylation process might be a good target for new therapeutics not only against HCV, but other important viral pathogens which contain envelopes with highly glycosylated proteins.

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“…Zidovudine (3′-azido-3′-deoxythymidine) is the first approved drug for the treatment of HIV 1 , marketed under the brand name Retrovir. Over the past few years, several derivatives of the nucleosides are known to possess antimicrobial 2 , anticancer 3 , anti-inflammatory 4 and antiviral activities [5][6][7][8] .…”

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confidence: 99%

An efficient approach to the synthesis of thymidine derivatives containing various acyl groups: characterization and antibacterial activities

Arifuzzaman¹,

Islam²,

Rahman³

et al. 2018

actapharm

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INTRODUCTION Nucleosides are key compounds involved in major biological processes, such as nucleic acids and proteins synthesis, cell signaling, enzyme regulation, and metabolism. Nucleoside and their derivatives have emerged as molecules with ABSTRACT In search of new leads toward potent antibacterial agents; therefore, a series of thymidine analogues were synthesized by direct acylation method and furnished the 5´-O-acyl thymidine derivatives in good yield. A number of acyl derivatives were prepared in order to obtain a series of newer components for antibacterial screening experiments. The synthesized compounds were characterized by their FTIR, 1 HNMR spectral data and elemental analysis. These thymidine derivatives were evaluated for in vitro antibacterial screening studies against a number of human pathogenic microorganisms by disc diffusion method. The study revealed that most of the tested chemicals exhibited moderate to good antibacterial activities. It was also observed that the test chemical 2-bromobenzoyl derivative 11 very significantly inhibited the growth of all Gram-positive and Gram-negative bacterial strains used. For comparative studies, antibacterial activity of standard antibiotics, Azithromycin was also carried out against these microorganisms. Hence, these thymidine derivatives can be used to discover antibacterial agents that may serve as leads in the development of new pharmaceuticals research activities.

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In vitro antiviral activity of some uridine derivatives of 2-deoxy sugars against classical swine fever virus

Cited by 20 publications

References 53 publications

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

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

Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars

An efficient approach to the synthesis of thymidine derivatives containing various acyl groups: characterization and antibacterial activities

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