2. Academic Validation
  3. New type of anti-influenza agents based on benzo[d][1,3]dithiol core

New type of anti-influenza agents based on benzo[d][1,3]dithiol core

  • Bioorg Med Chem Lett. 2020 Dec 15;30(24):127653. doi: 10.1016/j.bmcl.2020.127653.
Tatyana M Khomenko 1,  Vladimir V Zarubaev 2,  Marina V Kireeva 3,  Alexandrina S Volobueva 4,  Alexander V Slita 4,  Sophia S Borisevich 5,  Dina V Korchagina 1,  Nina I Komarova 1,  Konstantin P Volcho 1,  Nariman F Salakhutdinov 1
Affiliations

Affiliations

  • 1 Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
  • 2 Department of Virology, Pasteur Institute of Epidemiology and Microbiology, 14 Mira St., 197101, St. Petersburg, Russia. Electronic address: zarubaev@gmail.com.
  • 3 Saint Petersburg State University, 7/9 Universitetskaya nab.,199034, St. Petersburg, Russia.
  • 4 Department of Virology, Pasteur Institute of Epidemiology and Microbiology, 14 Mira St., 197101, St. Petersburg, Russia.
  • 5 Ufa Institute of Chemistry Ufa Federal Research Center RAS, pr. Oktyabrya, 71, 450054 Ufa, Russia.
PMID: 33129992 DOI: 10.1016/j.bmcl.2020.127653
Abstract

We synthesized a series of amides with a benzo[d][1,3]dithiol core. The chemical library of compounds was tested for their cytotoxicity and inhibiting activity against Influenza Virus A/California/07/09 (H1N1)pdm09 in MDCK cells. For each compound, values of CC50, IC50 and selectivity index (SI) were determined. Compounds of this structure type were for the first time found to exhibit anti-influenza activity. The structure of an amide substituent in the tested compounds was demonstrated to have a significant effect on their activity against the H1N1 Influenza Virus and cytotoxicity. Compound 4d has a high selectivity index of about 30. 4d was shown to be most potent at early stages of viral cycle. In direct fusogenic assay it demonstrated dose-dependent activity against fusogenic activity of hemagglutinin of Influenza Virus. Based on molecular docking and regression analysis data, viral hemagglutinin was suggested as possible target for these new Antiviral agents.

Keywords

Antiviral activity; Benzodithiols; H1N1 influenza virus; Hemagglutinin; Heterocyclic compounds; M2 channel.

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