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 = 2216 mu M). Derivatives of camphor, therefore, can be considered as prospective antiinfluenza compounds active against influenza viruses resistant to adamantane-based drugs. (C) 2014 Elsevier Ltd. All rights reserved.

Cite: Sokolova A.S. , Yarovaya O.I. , Korchagina D.V. , Zarubaev V.V. , Tretiak T.S. , Anfimov P.M. , Kiselev O.I. , Salakhutdinov N.F.
Camphor-based symmetric diimines as inhibitors of influenza virus reproduction
Bioorganic and Medicinal Chemistry. 2014. V.22. N7. P.2141-2148. DOI: 10.1016/j.bmc.2014.02.038 WOS Scopus РИНЦ

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Apr 1, 2014

Identifiers:

Web of science	WOS:000334337800014
Scopus	2-s2.0-84897438413
Elibrary	21870078
OpenAlex	W2007597464

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