Camphor-based symmetric diimines as inhibitors of influenza virus reproduction

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-sy...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2014-04, Vol.22 (7), p.2141-2148
Main Authors: Sokolova, Anastasiya S., Yarovaya, Оlga I., Korchagina, Dina V., Zarubaev, Vladimir V., Tretiak, Tatiana S., Anfimov, Pavel M., Kiselev, Oleg I., Salakhutdinov, Nariman F.
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Antivirals
Camphor
Camphor - chemistry
Diimine derivatives
Dogs
Dose-Response Relationship, Drug
Imines - chemical synthesis
Imines - chemistry
Imines - pharmacology
Influenza
Influenza A virus
Influenza A virus - drug effects
Influenza virus
Madin Darby Canine Kidney Cells
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Virus Replication - drug effects
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Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2014.02.038