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In vitro Activity of the Novel Pyrimidines and Their Condensed Derivatives Against Poliovirus

Author(s):

Volodymyr Brovarets*, Roman Solomyannyi, Sergii Slivchuk, Viktor Zhirnov, Eduard Rusanov, Donald Smee and Jung-ae Choi   Pages 1 - 9 ( 9 )

Abstract:


Background: Substituted pyrimidine derivatives (non-nucleoside) are found to be associated with various biological activities. The various substituted pyrimidines are also having significant in vitro activity against different DNA and RNA viruses. The present study focuses on the anti-PV activity of new pyrimidines and their condensed derivatives. Methods: A series of novel pyrimidines and their condensed derivatives were synthesized and their structures were confirmed by spectral data. Their antiviral activities against poliovirus type 3 (PV-3) were evaluated in vitro. In cell culture, morphological changes observed in cells infected with polioviruses, including cell rounding and detachment from the substrate, are generally termed cytopathic effects (CPE). The effects of synthetic pyrimidines on PV amplification in a culture of the heteroploid cell line, Vero 76 (African green monkey kidney cells) were investigated. Results: Bioassays in vitro showed that one of seven synthesized compounds, 7-(Benzenesulfonyl)-5- benzyl-N-(prop-2-en-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine, has potent antiviral activity against PV-3 (EC50 = 0.75 μM). The selectivity index of this compound is similar to that of pirodavir. Conclusion: The need for antiviral agents to treat PV-associated diseases remains great, but few options currently exist. Here we show that substituted pyrimidine derivatives are a promising structure class of chemical compounds for the development of antiviral drugs against PV infections.

Keywords:

Antiviral discovery, pyrimidine derivatives, poliovirus, Vero cells

Affiliation:

Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences, Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine - Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases Kyiv, Kyiv, Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine - Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases Kyiv, Kyiv, Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine - Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases Kyiv, Kyiv, Institute of Organic Chemistry and Petrochemistry, NAS of Ukraine Kyiv, Kyiv, Institute for Antiviral Research, Utah State University Logan, UT, Institute for Antiviral Research, Utah State University Logan, UT



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