New quaternary ammonium camphor derivatives and their antiviral activity, genotoxic effects and cytotoxicity

Anastasiya S Sokolova; Capital O Cyrilliclga I Yarovaya; Capital A Cyrillicndrey V Shernyukov; Capital Em Cyrillicichail A Pokrovsky; Capital A Cyrillicndrey G Pokrovsky; Valentina A Lavrinenko; Vladimir V Zarubaev; Tatiana S Tretiak; Pavel M Anfimov; Oleg I Kiselev; Anatoly B Beklemishev; Nariman F Salakhutdinov

doi:10.1016/j.bmc.2013.08.014

New quaternary ammonium camphor derivatives and their antiviral activity, genotoxic effects and cytotoxicity

Bioorg Med Chem. 2013 Nov 1;21(21):6690-8. doi: 10.1016/j.bmc.2013.08.014. Epub 2013 Aug 12.

Authors

Anastasiya S Sokolova¹, Capital O Cyrilliclga I Yarovaya, Capital A Cyrillicndrey V Shernyukov, Capital Em Cyrillicichail A Pokrovsky, Capital A Cyrillicndrey G Pokrovsky, Valentina A Lavrinenko, Vladimir V Zarubaev, Tatiana S Tretiak, Pavel M Anfimov, Oleg I Kiselev, Anatoly B Beklemishev, Nariman F Salakhutdinov

Affiliation

¹ N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia.

Abstract

The synthesis and biological evaluation of a novel series of dimeric camphor derivatives are described. The resulting compounds were studied for their antiviral activity, cyto- and genotoxicity. Compounds 3a and 3d in which the quaternary nitrogen atoms are separated by the C5H10 and С9H18 aliphatic chain, exhibited the highest efficiency as an agent inhibiting the reproduction of the influenza virus A(H1N1)pdm09. The cytotoxicity data of compounds 3 and 4 revealed their moderate activity against malignant cell lines; compound 3f had the highest activity for the CEM-13 cells. These results show close agreement with the data of independent studies on toxicity of these compounds, in particular that the toxicity of compounds strongly depends on spacer length.

Keywords: Antivirals; Camphor; Cytotoxicity; Genotoxicity; Imine derivatives; Influenza.

MeSH terms

Animals
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry*
Antiviral Agents / toxicity
Binding Sites
Bridged Bicyclo Compounds / chemical synthesis
Bridged Bicyclo Compounds / chemistry*
Bridged Bicyclo Compounds / toxicity
Camphor / analogs & derivatives*
Camphor / chemical synthesis
Camphor / toxicity
Cell Line, Tumor
Cell Survival / drug effects
Dogs
Escherichia coli / drug effects
Escherichia coli / genetics
Humans
Influenza A Virus, H1N1 Subtype / drug effects
Influenza A Virus, H1N1 Subtype / metabolism
Madin Darby Canine Kidney Cells
Molecular Docking Simulation
Mutagenicity Tests
Protein Structure, Tertiary
Quaternary Ammonium Compounds / chemical synthesis
Quaternary Ammonium Compounds / chemistry*
Quaternary Ammonium Compounds / toxicity
Viral Matrix Proteins / chemistry
Viral Matrix Proteins / metabolism

Substances

Antiviral Agents
Bridged Bicyclo Compounds
M2 protein, Influenza A virus
N1,N1,N12,N12-tetraethyl-N1,N12-bis(2-((1,7,7-trimethylbicyclo(2.2.1)heptan-2-ylidene)amino)ethyl)dodecane-1,12-diaminium
Quaternary Ammonium Compounds
Viral Matrix Proteins
Camphor