Antiviral and apoptosis modulating potential of fluorinated derivatives of uracil

Authors

  • Krystyna Naumenko D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0003-4635-0690
  • Anna Golovan D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0001-7283-5435
  • Lubov Zelena D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0002-5148-1030
  • Yuriy Shermolovich Institute of organic chemistry of National Academy of Sciences of Ukraine Murmanska str., 5, Kyiv, Ukraine, 02660, Ukraine https://orcid.org/0000-0003-2242-873X
  • Gudz Ganna Institute of organic chemistry of National Academy of Sciences of Ukraine Murmanska str., 5, Kyiv, Ukraine, 02660, Ukraine https://orcid.org/0000-0002-5245-4712
  • Svіtlana Zagorodnya D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0002-0892-772X

DOI:

https://doi.org/10.15587/2519-8025.2018.124689

Keywords:

Epstein-Barr virus, a fluorinated nucleoside analog, apoptosis, in silico and in vitro

Abstract

The Epstein-Barr virus (EBV) is the first virus that has been classified as a human oncology virus. The ability of EBV to immortalize the cells of the human body is the highest among all known transforming viruses. Fluorine-containing nucleoside analogs represent a significant class of the chemotherapeutics widely used in the treatment for a lot of diseases. They have been playing a major role in treating tumor and virus either as selective inhibitors of enzymes for cancer or viral replication or as nucleic acid chain terminators which interrupt the replication of cancer cells or a virus.

Aim. The purpose of this study was to analyze the potential antiviral and apoptosis modulating activity of fluorinated derivatives of uracil by using in silico and in vitro methods.

Materials and methods. Two analogs (compound G26 and G27) on the base of 5-(p-tolilsulfonil)-6(polyfluoroalkyl)uracil were used in the study. The studies were conducted on cultures of Raji (latent infected EBV) and B95-8 (chronically producing virus) B-lymphoma cells. Trypan blue assay, MTT-method, neutral red uptake assay, PCR, flow cytometry, and web-servers PASS, PharmMapper were used.

Results. According to PASS prediction, all compounds may possess the antiviral activity and anticancer activity. The in vitro study let to reveal the low level of cytotoxicity of these uracil derivatives. Anti-EBV activity was observed for all compounds and EC50 values were 75 and 65 µg/ml. Using PharmMapper, it has been shown that the targets are enzymes necessary for the replication of viral DNA (protease, kinase) and proteins that provide an apoptotic cascade (MAPK, cytochrome). For compound G27, several peaks on the histogram were observed, which may be evidence of changes in the cell cycle of lymphoblastoid cultures.

Conclusions. In this way, the results of the present research shown an antiviral and apoptosis modulating activity of derivatives based on uracil. The data assumed by in silico methods can be used to model the relationship between the structure and activity of substance and predict possible targets of studied chemical compounds. These results can be applied to the further creation of new high-level antiviral agents

Author Biographies

Krystyna Naumenko, D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143

Junior Researcher

Department of Reproduction of Viruses

Anna Golovan, D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143

PhD, Junior Researcher

Department of Reproduction of Viruses

Lubov Zelena, D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143

PhD, Senior Researcher

Department of Physiology of Industrial Microorganisms

Yuriy Shermolovich, Institute of organic chemistry of National Academy of Sciences of Ukraine Murmanska str., 5, Kyiv, Ukraine, 02660

Doctor of Chemical Sciences, Professor, Head of Department

Department of Chemistry of Organic Sulfur Compounds

Gudz Ganna, Institute of organic chemistry of National Academy of Sciences of Ukraine Murmanska str., 5, Kyiv, Ukraine, 02660

PhD, Senior Researcher 

Department of Chemistry of Organic Sulfur Compounds

Svіtlana Zagorodnya, D. K. Zabolotny Institute of Microbiology and Virology of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 154, Kyiv, Ukraine, 03143

PhD, Head of Department

Department of Reproduction of Viruses 

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Published

2018-02-27

How to Cite

Naumenko, K., Golovan, A., Zelena, L., Shermolovich, Y., Ganna, G., & Zagorodnya, S. (2018). Antiviral and apoptosis modulating potential of fluorinated derivatives of uracil. ScienceRise: Biological Science, (1 (10), 31–38. https://doi.org/10.15587/2519-8025.2018.124689

Issue

No. 1 (10) (2018)

Section

Biological Sciences

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Copyright (c) 2018 Krystyna Naumenko, Anna Golovan, Lubov Zelena, Yuriy Shermolovich, Gudz Ganna, Svіtlana Zagorodnya

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