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Probing chemical space of tick‐borne encephalitis virus reproduction inhibitors with organoselenium compounds
Author(s) -
Orlov Alexey A.,
Eletskaya Anastasia A.,
Frolov Konstantin A.,
Golinets Anastasia D.,
Palyulin Vladimir A.,
Krivokolysko Sergey G.,
Kozlovskaya Liubov I.,
Dotsenko Victor V.,
Osolodkin Dmitry I.
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700353
Subject(s) - tick borne encephalitis virus , flavivirus , chemistry , virus , encephalitis , nucleoside , stereochemistry , reproduction , virology , biology , ecology
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[7.3.1.0 2,7 ]tridec‐2‐ene‐1,9‐dicarbonitriles, and selenolo[2,3‐ b ]quinolines, inhibited TBEV reproduction with EC 50 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.