tetano
Editor, Senior Moderator
Bioorg Med Chem. 2014 Mar 1. pii: S0968-0896(14)00144-8. doi: 10.1016/j.bmc.2014.02.038. [Epub ahead of print]
Camphor-based symmetric diimines as inhibitors of influenza virus reproduction.
Sokolova AS1, Yarovaya CO2, Korchagina DV3, Zarubaev VV4, Tretiak TS5, Anfimov PM5, Kiselev OI5, Salakhutdinov NF3.
Author information
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.
Copyright ? 2014 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antivirals, Camphor, Diimine derivatives, Influenza
PMID:
24631360
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24631360
Camphor-based symmetric diimines as inhibitors of influenza virus reproduction.
Sokolova AS1, Yarovaya CO2, Korchagina DV3, Zarubaev VV4, Tretiak TS5, Anfimov PM5, Kiselev OI5, Salakhutdinov NF3.
Author information
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.
Copyright ? 2014 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antivirals, Camphor, Diimine derivatives, Influenza
PMID:
24631360
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24631360