2. Academic Validation
  3. Anti-influenza activity of diazaadamantanes combined with monoterpene moieties

Anti-influenza activity of diazaadamantanes combined with monoterpene moieties

  • Bioorg Med Chem Lett. 2017 Oct 1;27(19):4531-4535. doi: 10.1016/j.bmcl.2017.08.062.
Evgeniy Suslov 1,  Vladimir V Zarubaev 2,  Alexander V Slita 3,  Konstantin Ponomarev 1,  Dina Korchagina 1,  Daniel M Ayine-Tora 4,  Jóhannes Reynisson 4,  Konstantin Volcho 5,  Nariman Salakhutdinov 5
Affiliations

Affiliations

  • 1 Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
  • 2 Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russia. Electronic address: zarubaev@gmail.com.
  • 3 Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russia.
  • 4 School of Chemical Sciences, University of Auckland, New Zealand.
  • 5 Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation.
PMID: 28886889 DOI: 10.1016/j.bmcl.2017.08.062
Abstract

The Antiviral activity of several diaza-adamantanes containing monoterpenoid moieties against a rimantadine-resistant strain of the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. Hetero-adamantanes containing monoterpene moieties at the aminal position of the heterocycle were found to exhibit lower activity compared to compounds with a diaza-adamantane fragment and a monoterpene moiety linked via an amino group at the 6-position of the hetero-adamantane ring. The highest selectivity index (a ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration) out of 30 was observed for compound 8d, which contains a citronellal monoterpenoid moiety. Diaza-adamantane 8d was superior to its adamantane-containing analog 5 both in its anti-influenza activity and selectivity. Furthermore, 8d has more balanced physicochemical properties than 5, making the former a more promising drug candidate. Modelling these compounds against an Influenza Virus M2 ion channel predicted plausible binding modes to both the wild-type and the mutant (S31N).

Keywords

Antivirals; Citronellal; Diaza-adamantane; Influenza; Myrtenal; Terpene.

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