Highly potent activity of isopulegol-derived substituted octahydro-2H-chromen-4-ols against influenza A and B viruses

  • Bioorg Med Chem Lett. 2018 Jun 15;28(11):2061-2067. doi: 10.1016/j.bmcl.2018.04.057.
Irina V Ilyina  1 ,  Vladimir V Zarubaev  2 ,  Irina N Lavrentieva  2 ,  Anna A Shtro  3 ,  Iana L Esaulkova  4 ,  Dina V Korchagina  5 ,  Sophia S Borisevich  6 ,  Konstantin P Volcho  7 ,  Nariman F Salakhutdinov  1
Affiliations
  • 1. Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev av.9, 630090 Novosibirsk, Russian Federation; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation.
  • 2. Pasteur Institute of Epidemiology and Microbiology, 14 Mira str., 197101 St. Petersburg, Russian Federation.
  • 3. Department of Pre-clinical trials, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russian Federation.
  • 4. Saint Petersburg State University, 7/9 Universitetskaya nab., 199034 St. Petersburg, Russian Federation.
  • 5. Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev av.9, 630090 Novosibirsk, Russian Federation.
  • 6. Laboratory of chemical physics, Ufa Chemistry Institute of the Ufa Federal Research Center, 71 Octyabrya pr., 450054 Ufa, Russian Federation.
  • 7. Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev av.9, 630090 Novosibirsk, Russian Federation; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
PMID: 29716780 DOI: 10.1016/j.bmcl.2018.04.057
Abstract

A set of (-)-isopulegol derived octahydro-2H-chromen-4-ols was synthesized and evaluated in vitro for Antiviral activity against panel of reference Influenza Virus strains differing in subtype, origin (human or avian) and drug resistance. Compound (4R)-11a produced via one-pot synthesis by interaction between (-)-isopulegol and acetone was found to exhibit an outstanding activity against a number of H1N1 and H2N2 Influenza Virus strains with selectivity index more than 1500. (4R)-11a was shown to be most potent at early stages of viral cycle. Good correlation between anti-viral activity and calculated binding energy to hemagglutinin TBHQ active site was demonstrated.

Keywords
Antiviral; Chromene; Influenza; Monoterpene; Montmorillonite K10.
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