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

• Published in: Bioorganic & medicinal chemistry letters 2018-06, Vol.28 (11), p.2061-2067
• Main Authors: Ilyina, Irina V., Zarubaev, Vladimir V., Lavrentieva, Irina N., Shtro, Anna A., Esaulkova, Iana L., Korchagina, Dina V., Borisevich, Sophia S., Volcho, Konstantin P., Salakhutdinov, Nariman F.
• Format: Article
• Language: English
• Subjects: Antiviral; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Chromene; Dose-Response Relationship, Drug; Influenza; Influenza A virus - drug effects; Influenza B virus - drug effects; Microbial Sensitivity Tests; Molecular Structure; Monoterpene; Montmorillonite K10; Structure-Activity Relationship; Terpenes - chemical synthesis; Terpenes - chemistry; Terpenes - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.04.057

[Display omitted] •A set of chiral octahydro-2H-chromen-4-ols was synthesized from isopulegol.•Some compound demonstrated high antiviral activity against flu viruses.•Compound (R)-11a exhibits an outstanding antiviral activity with SI up to 1500.•Hemagglutinin was assumed to be a target for (R)-11a. 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.