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

Irina V Ilyina; Vladimir V Zarubaev; Irina N Lavrentieva; Anna A Shtro; Iana L Esaulkova; Dina V Korchagina; Sophia S Borisevich; Konstantin P Volcho; Nariman F Salakhutdinov

doi:10.1016/j.bmcl.2018.04.057

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. Epub 2018 Apr 24.

Authors

Irina V Ilyina¹, Vladimir V Zarubaev², Irina N Lavrentieva², Anna A Shtro³, Iana L Esaulkova⁴, Dina V Korchagina⁵, Sophia S Borisevich⁶, Konstantin P Volcho⁷, Nariman F Salakhutdinov¹

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: volcho@nioch.nsc.ru.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cyclohexane Monoterpenes
Dose-Response Relationship, Drug
Influenza A virus / drug effects*
Influenza B virus / drug effects*
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship
Terpenes / chemical synthesis
Terpenes / chemistry
Terpenes / pharmacology*

Substances

Antiviral Agents
Cyclohexane Monoterpenes
Terpenes
isopulegol