Репозиторий Университета

Probing chemical space of tick-borne encephalitis virus reproduction inhibitors with organoselenium compounds


  • Orlov A.
  • Eletskaya A.
  • Frolov K.
  • Golinets A.
  • Palyulin V.
  • Krivokolysko S.
  • Kozlovskaya L.
  • Dotsenko V.
  • Osolodkin D.
Дата публикации:01.06.2018
Журнал: Archiv der Pharmazie
БД: Scopus
Ссылка: Scopus
Индекс цитирования: 5

Аннтотация

© 2018 Deutsche Pharmazeutische Gesellschaft Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is the leading cause of arboviral neuroinfections in Europe. Only a few classes of the nucleoside and non-nucleoside inhibitors were investigated against TBEV reproduction. Paving the way to previously unexplored areas of anti-TBEV chemical space, we assessed the inhibition of TBEV reproduction in the plaque reduction assay by various compounds derived from cyanothioacetamide and cyanoselenoacetamide. Compounds from seven classes, including 4-(alkylthio)-2-aryl-3-azaspiro[5.5]undec-4-ene-1,1,5-tricarbonitriles, 3-arylamino-2-(selenazol-2-yl)acrylonitriles, ethyl 6-(alkylseleno)-5-cyano-2-oxo-1,2-dihydropyridine-3-carboxylates, 6-(alkylseleno)-2-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles, 2-(alkylseleno)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles, 8-selenoxo-3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec-2-ene-1,9-dicarbonitriles, and selenolo[2,3-b]quinolines, inhibited TBEV reproduction with EC50 values in the micromolar range while showing moderate cytotoxicity and no inhibition of enterovirus reproduction. Thus, new scaffolds with promising anti-TBEV activity were found.


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