Synthesis and biological evaluation of 6-nitro-1,2,4-triazoloazines containing polyphenol fragments possessing antioxidant and antiviral activity

Bioorg Med Chem Lett. 2020 Jul 1;30(13):127216. doi: 10.1016/j.bmcl.2020.127216.

E N Ulomskiy ¹, A V Ivanova ², E B Gorbunov ³, I L Esaulkova ⁴, A V Slita ⁴, E O Sinegubova ⁴, E K Voinkov ⁵, R A Drokin ⁵, I I Butorin ⁵, E R Gazizullina ², E L Gerasimova ², V V Zarubaev ⁶, V L Rusinov ¹

Affiliations

1 Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation; Institute of Organic Synthesis, Ural Division of RAS, 620990, 22/20 S. Kovalevskoy st./Akademicheskaya st., Yekaterinburg, Russian Federation.
2 Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Analytical Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation.
3 Institute of Organic Synthesis, Ural Division of RAS, 620990, 22/20 S. Kovalevskoy st./Akademicheskaya st., Yekaterinburg, Russian Federation.
4 Pasteur Institute for Epidemiology and Microbiology, 197101, 14 Mira st., Saint Petersburg, Russian Federation.
5 Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation.
6 Pasteur Institute for Epidemiology and Microbiology, 197101, 14 Mira st., Saint Petersburg, Russian Federation. Electronic address: [email protected].

PMID: 32360104 DOI: 10.1016/j.bmcl.2020.127216

Abstract

Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different Polyphenols were synthesized and their antioxidant and Antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.

Keywords

Anti-viral activity; Antioxidant activity; Azolo-azines; Influenza virus; Polyphenols.

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