title: Inhibitory effect of thiosemicarbazone derivatives on Junin virus replication in vitro.
abstract: The inhibitory effect of several thiosemicarbazones (TSCs), synthesized from aromatic ketones and terpenones, and their heterocyclic thiadiazoline (TDZ) derivatives, was investigated against Junin virus (JUNV), an arenavirus agent of Argentine haemorrhagic fever. From the 25 compounds tested, six compounds belonging to the TSC group were found to be selective inhibitors of JUNV, with EC50 values determined by a virus yield inhibition assay in the range 3.4-12.5 microM, and selectivity indices greater than 10. By contrast, most of the TDZs obtained by heterocyclization of the TSCs were not active against JUNV. No conclusive structure-activity relationships could be established but systematically higher activity was associated to TSCs derived from aromatic ketones. The mode of action of one of the most active compound, the 3,4-dihydronaphtalen-1(2H)one thiosemicarbazone (tetralone thiosemicarbazone), was studied further. This TSC lacked virucidal effects on JUNV virions. Results from time of addition experiments and viral protein expression assays suggest that tetralone thiosemicarbazone inhibited a late stage in the replicative cycle of JUNV.
authors.affiliation: Laboratorio de Virologia, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria, Buenos Aires, Argentina.
authors.forename: Cybele C
authors.initials: CC
authors.lastname: García
authors.forename: Beatriz N
authors.initials: BN
authors.lastname: Brousse
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Carlucci
authors.forename: Albertina G
authors.initials: AG
authors.lastname: Moglioni
authors.forename: Miriam
authors.initials: M
authors.lastname: Martins Alho
authors.forename: Graciela Y
authors.initials: GY
authors.lastname: Moltrasio
authors.forename: Norma B
authors.initials: NB
authors.lastname: D'Accorso
authors.forename: Elsa B
authors.initials: EB
authors.lastname: Damonte
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018051:Junin virus / Q000187:drug effects* / Q000254:growth & development; D008956:Models, Chemical; D015394:Molecular Structure; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology*; D013997:Time Factors; D014709:Vero Cells / Q000187:drug effects / Q000821:virology
chemical_list: D000998:Antiviral Agents; D013882:Thiosemicarbazones