Camphor-based symmetric diimines as inhibitors of influenza virus reproduction

  • Bioorg Med Chem. 2014 Apr 1;22(7):2141-8. doi: 10.1016/j.bmc.2014.02.038.
Anastasiya S Sokolova  1 ,  O Cyrilliclga I Yarovaya  2 ,  Dina V Korchagina  3 ,  Vladimir V Zarubaev  4 ,  Tatiana S Tretiak  5 ,  Pavel M Anfimov  5 ,  Oleg I Kiselev  5 ,  Nariman F Salakhutdinov  3
Affiliations
  • 1. Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia.
  • 2. Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia. Electronic address: [email protected].
  • 3. Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia.
  • 4. Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. Electronic address: [email protected].
  • 5. Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
PMID: 24631360 DOI: 10.1016/j.bmc.2014.02.038
Abstract

Influenza is a continuing world-wide public health problem that causes significant morbidity and mortality during seasonal epidemics and sporadic pandemics. The purpose of the study was synthesis and investigation of Antiviral activity of camphor-based symmetric diimines and diamines. A set of C2-symmetric nitrogen-containing camphor derivatives have been synthesized. The Antiviral activity of these compounds was studied against rimantadine- and amantadine-resistant Influenza Virus A/California/7/09 (H1N1)pdm09 in MDCK cells. The highest efficacy in virus inhibiting was shown for compounds 2a-e with cage moieties bound by aliphatic linkers. The therapeutic index (selectivity index) for 2b exceeded that for reference compounds amantadine, deitiforin and rimantadine almost 10-fold. As shown by structure-activity analysis, the length of the linker has a dramatic effect on the toxicity of compounds. Compound 2e with -C12H24- linker exhibited the lowest toxicity (CTD50=2216μM). Derivatives of camphor, therefore, can be considered as prospective antiinfluenza compounds active against influenza viruses resistant to adamantane-based drugs.

Keywords
Antivirals; Camphor; Diimine derivatives; Influenza.