Anti-influenza activity of monoterpene-containing substituted coumarins

Tatyana M Khomenko; Vladimir V Zarubaev; Iana R Orshanskaya; Renata A Kadyrova; Victoria A Sannikova; Dina V Korchagina; Konstantin P Volcho; Nariman F Salakhutdinov

doi:10.1016/j.bmcl.2017.04.091

Anti-influenza activity of monoterpene-containing substituted coumarins

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2920-2925. doi: 10.1016/j.bmcl.2017.04.091. Epub 2017 Apr 29.

Authors

Tatyana M Khomenko¹, Vladimir V Zarubaev², Iana R Orshanskaya³, Renata A Kadyrova³, Victoria A Sannikova¹, Dina V Korchagina⁴, Konstantin P Volcho¹, Nariman F Salakhutdinov¹

Affiliations

¹ Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
² Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. Electronic address: zarubaev@gmail.com.
³ Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
⁴ Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.

PMID: 28501512
DOI: 10.1016/j.bmcl.2017.04.091

Abstract

Compounds simultaneously carrying the monoterpene and coumarin moieties have been tested for cytotoxicity and inhibition of activity against influenza virus A/California/07/09 (H1N1)pdm09. The structure of substituents in the coumarin framework, as well as the structure and the absolute configuration of the monoterpenoid moiety, are shown to significantly influence the anti-influenza activity and cytotoxicity of the compounds under study. The compounds with a bicyclic pinane framework exhibit the highest selectivity indices (the ratios between the cytotoxicity and the active dose). The derivative of (-)-myrtenol 15c, which is characterized by promising activity, low cytotoxicity, and synthetic accessibility, has the greatest potential among this group of compounds. It exhibited the highest activity when added to the infected cell culture at early stages of viral reproduction.

Keywords: Anti-influenza activity; Antivirals; Aurapten; Coumarin; Cytotoxicity; Influenza A virus; Myrtenal; Terpene.

Publication types

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

MeSH terms

Animals
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cell Death / drug effects
Cells, Cultured
Coumarins / chemical synthesis
Coumarins / chemistry
Coumarins / pharmacology*
Dogs
Dose-Response Relationship, Drug
Influenza A Virus, H1N1 Subtype / drug effects*
Madin Darby Canine Kidney Cells / drug effects*
Madin Darby Canine Kidney Cells / virology
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Monoterpenes / chemistry
Monoterpenes / pharmacology*
Structure-Activity Relationship
Virus Replication / drug effects

Substances

Antiviral Agents
Coumarins
Monoterpenes
coumarin