Influenza antiviral activity of F- and OH-containing isopulegol-derived octahydro-2H-chromenes

Irina V Ilyina; Oksana S Patrusheva; Vladimir V Zarubaev; Maria A Misiurina; Alexander V Slita; Iana L Esaulkova; Dina V Korchagina; Yuri V Gatilov; Sophia S Borisevich; Konstantin P Volcho; Nariman F Salakhutdinov

doi:10.1016/j.bmcl.2020.127677

Influenza antiviral activity of F- and OH-containing isopulegol-derived octahydro-2H-chromenes

Bioorg Med Chem Lett. 2021 Jan 1:31:127677. doi: 10.1016/j.bmcl.2020.127677. Epub 2020 Nov 7.

Affiliations

¹ Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev av.9, 630090 Novosibirsk, Russia.
² Pasteur Institute of Epidemiology and Microbiology, 14 Mira str., 197101 St. Petersburg, Russia.
³ Laboratory of Chemical Physics, Ufa Chemistry Institute of the Ufa Federal Research Center, 71 Octyabrya pr., 450054 Ufa, Russia.
⁴ Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev av.9, 630090 Novosibirsk, Russia. Electronic address: volcho@nioch.nsc.ru.

PMID: 33171219
DOI: 10.1016/j.bmcl.2020.127677

Abstract

We synthesized fluoro- and hydroxy-containing octahydro-2H-chromenes by the Prins reaction starting from a monoterpenoid (-)-isopulegol and a wide range of aromatic aldehydes in the presence of the BF₃∙Et₂O/H₂O system acting as both an acid catalyst and a fluorine source. Activity of the produced compounds against the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. The highest activity was demonstrated by fluoro- (11i) and hydroxy-containing (10i) derivatives of 2,4,6-trimethoxybenzaldehyde. The most pronounced virus-inhibiting effect of compounds 10i and 11i was observed at an early stage of infection. These compounds were supposed to be capable of binding to viral hemagglutinin, which is an agreement with data on the effect of compounds 10i and 11i on the viral fusogenic activity as well as by molecular docking studies.

Keywords: Antiviral; Chromene; Fluorine; Influenza; Monoterpene.

Publication types

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

MeSH terms

Animals
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Benzopyrans / chemical synthesis
Benzopyrans / chemistry
Benzopyrans / pharmacology*
Caco-2 Cells
Cell Death / drug effects
Cyclohexane Monoterpenes / chemical synthesis
Cyclohexane Monoterpenes / chemistry
Cyclohexane Monoterpenes / pharmacology*
Dogs
Dose-Response Relationship, Drug
Humans
Influenza A virus / drug effects*
Madin Darby Canine Kidney Cells / drug effects
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship

Substances

Antiviral Agents
Benzopyrans
Cyclohexane Monoterpenes
isopulegol