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

Abstract

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 ]tridec-2-ene-1,9-dicarbonitriles, and selenolo[2,3-b]quinolines, inhibited TBEV reproduction with EC 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.

Examination of molecular space and feasible structures of bioactive components of humic substances by FTICR MS data mining in ChEMBL database

“… [a] ND — not determined. [b] 3-amino-7,7-dimethyl-2-(4methylbenzoyl)-5H,6H,7H,8H-selenopheno[2,3- b ]quinolin-5-one 5 .All values are in μg/mL.…”

“…Four-fold dilutions of the HS samples were preincubated with the virus (20–40 PFU) (EC 50_pre ) or added to the PEK cells monolayer simultaneously with the virus (EC 50_sim ) in 24-well plates. The same sequential concentrations of KOH and previously investigated compound 3-amino-7,7-dimethyl-2-(4-methylbenzoyl)-5H,6H,7H,8H-selenopheno[2,3- b ]quinolin-5-one 5 were used as a negative and positive controls, respectively. The plates were incubated for 1 h and overlaid with 1.26% methylcellulose.…”

Getting to Know the Neighbours with GTM: The Case of Antiviral Compounds

“…For instance, a series of close analogs of compound 9 was shown to inhibit flavivirus reproduction through the prevention of the capsid protein C dimerisation (Supplementary Figure S4) . In addition, we have recently discovered two selenolo[2,3‐ b ]quinolines, similar in shape to 9 and potently inhibiting TBEV reproduction (Supplementary Figure S4) …”

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

“…Previously, we found that aminomethylation of isostructural analogs of compound 11, 1,4-dihydropyridine-2-thiolates and -selenolates 14, under the action of an excess of HCHO and primary amines leads to the formation of new tricyclic system derivatives, namely 3,5,7,11-tetraazatricyclo[7.3.1.0 2.7 ]tridec-2-ene 15 [33,34]. Some of compounds 15 showed antiviral activity against tick-borne encephalitis virus [35]. At the same time, the Mannich reaction involving 2-(dicyanomethylene)pyridine 2 under similar conditions [4] non-2-ene system.…”