Bioactive Pyrrolo[2,1-<i>f</i>][1,2,4]triazines: Synthesis, Molecular Docking, In Vitro Cytotoxicity Assay and Antiviral Studies
Nataliya N. Mochulskaya,
Svetlana K. Kotovskaya,
Ilya I. Butorin,
Mikhail V. Varaksin,
Valery N. Charushin,
Vladimir L. Rusinov,
Yana L. Esaulkova,
Alexander V. Slita,
Polina A. Ilyina,
Vladimir V. Zarubaev
Affiliations
Nataliya N. Mochulskaya
Department of Organic and Biomolecular Chemistry, Ural Federal University Named after the First President of Russia B.N. Yeltsin, Mira Street, 19, Yekaterinburg 620002, Russia
Svetlana K. Kotovskaya
Department of Organic and Biomolecular Chemistry, Ural Federal University Named after the First President of Russia B.N. Yeltsin, Mira Street, 19, Yekaterinburg 620002, Russia
Ilya I. Butorin
Department of Organic and Biomolecular Chemistry, Ural Federal University Named after the First President of Russia B.N. Yeltsin, Mira Street, 19, Yekaterinburg 620002, Russia
Mikhail V. Varaksin
Department of Organic and Biomolecular Chemistry, Ural Federal University Named after the First President of Russia B.N. Yeltsin, Mira Street, 19, Yekaterinburg 620002, Russia
Valery N. Charushin
Department of Organic and Biomolecular Chemistry, Ural Federal University Named after the First President of Russia B.N. Yeltsin, Mira Street, 19, Yekaterinburg 620002, Russia
Vladimir L. Rusinov
Department of Organic and Biomolecular Chemistry, Ural Federal University Named after the First President of Russia B.N. Yeltsin, Mira Street, 19, Yekaterinburg 620002, Russia
Yana L. Esaulkova
Saint-Petersburg Pasteur Institute, Mira Street, 14, Saint Petersburg 197101, Russia
Alexander V. Slita
Saint-Petersburg Pasteur Institute, Mira Street, 14, Saint Petersburg 197101, Russia
Polina A. Ilyina
Saint-Petersburg Pasteur Institute, Mira Street, 14, Saint Petersburg 197101, Russia
Vladimir V. Zarubaev
Saint-Petersburg Pasteur Institute, Mira Street, 14, Saint Petersburg 197101, Russia
A series of 2,4-disubstituted pyrrolo[2,1-f][1,2,4]triazines containing both aryl and thienyl substituents were synthesized by exploiting the 1,3-cycloaddition reaction of N(1)-ethyl-1,2,4-triazinium tetrafluoroborates with dimethyl acetylenedicarboxylate. The antiviral activity of the synthesized compounds against influenza virus strain A/Puerto Rico/8/34 (H1N1) was studied in experiments on Madin-Darby canine kidney (MDCK) cell culture. Among the pyrrolo[2,1-f][1,2,4]triazine derivatives, compounds with low toxicity and high antiviral activity were identified. Dimethyl 4-(4-methoxyphenyl)-7-methyl-2-p-tolylpyrrolo[2,1-f][1,2,4]triazine-5,6-dicarboxylate was found to demonstrate the best antiviral activity (IC50 4 µg/mL and selectivity index 188). Based on the results of in vitro tests and molecular docking studies performed, a plausible mechanism of action for these compounds was suggested to involve inhibition of neuraminidase.
