Статья

Camphor-based symmetric diimines as inhibitors of influenza virus reproduction

A. Sokolova, O. Yarovaya, D. Korchagina, V. Zarubaev, T. Tretiak, P. Anfimov, O. Kiselev, N. Salakhutdinov,
2021

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 μM). Derivatives of camphor, therefore, can be considered as prospective antiinfluenza compounds active against influenza viruses resistant to adamantane-based drugs. © 2014 Elsevier Ltd. All rights reserved.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • A. Sokolova
    Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russian Federation
  • O. Yarovaya
    Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russian Federation
  • D. Korchagina
    Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St.-Petersburg, Russian Federation
  • V. Zarubaev
  • T. Tretiak
  • P. Anfimov
  • O. Kiselev
  • N. Salakhutdinov
Название журнала
  • Bioorganic and Medicinal Chemistry
Том
  • 22
Выпуск
  • 7
Страницы
  • 2141-2148
Ключевые слова
  • 1,7,7 trimethylbicyclo[2.2.1]heptan; amantadine; amine; antivirus agent; camphor derivative; deitiphorin; diimine derivative; imine; ribavirin; rimantadine; Schiff base; unclassified drug; antivirus agent; camphor; imine; animal cell; antiviral activity; antiviral resistance; article; controlled study; dose response; drug synthesis; Influenza virus A; nonhuman; structure activity relation; virus inhibition; virus replication; animal; chemical structure; chemistry; dog; drug effects; MDCK cell line; microbial sensitivity test; synthesis; virus replication; Dryobalanops; Orthomyxoviridae; Animals; Antiviral Agents; Camphor; Dogs; Dose-Response Relationship, Drug; Imines; Influenza A virus; Madin Darby Canine Kidney Cells; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Structure-Activity Relationship; Virus Replication
Издатель
  • Elsevier Ltd
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus