New N6-substituted adenine derivatives with high antiviral activity against RNA-containing viruses

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Resumo

In this work, two new compounds, N6-(4,5-dimethoxyphenyl)adenine and N6-(3,5-di-trifluoromethylphenyl)adenine, with a broad spectrum of antiviral activity against RNA viruses, were identified. We showed that these compounds exhibit pronounced antiviral activity against human poliovirus types 1, 2 and 3, belonging to enterovirus C species. Both compounds also demonstrated pronounced antiviral activity against Coxsackie viruses B3, B5 and B6, belonging to enterovirus B species. In addition, the compounds demonstrated antiviral activity against Newcastle disease virus, which belongs to the paramyxovirus genus. The compounds discovered in this work can subsequently serve as prototypes for the development of new antiviral drugs against epidemiologically significant human RNA viruses.

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Sobre autores

A. Zenchenko

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vladimiroslovsky@gmail.com
Rússia, Moscow

Yu. Semenova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vladimiroslovsky@gmail.com
Rússia, Moscow

E. Naberezhnaya

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vladimiroslovsky@gmail.com
Rússia, Moscow

Ya. Gumennaya

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vladimiroslovsky@gmail.com
Rússia, Moscow

A. Lipatova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: vladimiroslovsky@gmail.com
Rússia, Moscow

V. Oslovsky

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Autor responsável pela correspondência
Email: vladimiroslovsky@gmail.com
Rússia, Moscow

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2. Fig. 1. Synthesis of N6-(4,5-dimethoxyphenyl)adenine (2a) and N6-(3,5-di-trifluoromethylphenyl)adenine (2b). Reagents and conditions: i. R-NH2, DIPEA, n-BuOH, 90°C, 8 h, yield 75% for 2a and 68% for 2b.

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3. Fig. 2. Antiviral properties of compounds 2a,b. EC50 – concentration of substances (µM) providing 50% inhibition of virus-induced cytopathic effect of various RNA-containing viruses on HEK293T cells 48 hours after infection. All data represent the mean ± standard error of the mean (SEM) for at least 3 biological replicates. * – p-value<0.05, ** – p-value<0.01.

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