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The anti-herpetic activity of fluorine-containing compounds based on β-D-glucopyranose
* 1 , 1 , 1 , 2 , 1
1  Institute of Microbiology and Virology, National Academy of Sciences of Ukraine
2  Institute of Organic Chemistry, National Academy of Sciences of Ukraine

Published: 30 October 2019 by MDPI in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Introduction: The diseases caused by Herpes Simplex Virus 1 (HSV-1) are widely spread. The shortage of antiviral compounds due to their high toxicity and emergence of resistant viruses is a major problem in the treatment of patients. This work is related to the determination of the antiviral activity of new fluorine containing derivatives against HSV-1.

Methodology: Cytotoxicity and anti-herpetic activity of compounds 10S-25 ((1-S-thio-(1- methylsulfonyl-2-difluoromethyl-vinyl)-2,3,4,6,-tetra-O-acetyl-β-D-glucopyranose) and 10S-27 1-(β-D-glucopyranosyl)-4-(hexafluoropropyl)-5-tosyl-1H-1,2,3-triazole) were studied using MTT assay. To sort the compounds, four experimental procedures were used: co-incubation of compounds and HSV-1, addition of compounds during virus adsorption and penetration, addition of compounds post-infection. The antiviral activity was assessed using real-time PCR and virus yield reduction assay.

Results: Compounds 10S-25 and 10S-27 demonstrated high toxicity for cells and their IC50 values were 13 and 250 µg/ml, respectively. It was determined, that only 10S-27 inhibited the formation CPE of the HSV-1 (EC50 value is 48 µg/ml). The absence of virucidal activity and prevention of the adsorption and penetration of HSV-1 into cells were shown for this compound. But in the presence of 10S-27 in higher concentration, HSV-1 DNA replication was inhibited and the viral DNA copy number was reduced to 38 %. Moreover, it was found that 10s-27 in concentrations 4 - 150 μg/ml reduced the titer of the virus obtained de novo by 39 - 98%.

Conclusion: Taken together, our results showed that 10S-27 possesses an anti-HSV-1 activity at non-toxic concentrations with multiple mechanisms, but further investigation is needed to explore this action in detail.

Keywords: fluorine-containing compound, herpes simplex virus 1 and antiviral activity