title: In vitro antiviral activity of four isothiazole derivatives against poliovirus type 1.
abstract: The in vitro effects of four isothiazoles [5,5'-diphenyl-3,3'-diisothiazole disulfide, 5-phenyl-3-mercapto-isothiazole, 5,5'-(4-chlorophenyl)-3,3'- diisothiazole disulfide, and 5-(4-chlorophenyl)-3-mercapto-isothiazole] on poliovirus type 1 were studied. The derivatives tested demonstrated remarkable viral inhibition, with a higher selectivity index than the previously studied iminodithiole precursors. Under one-step growth conditions, all the isothiazole derivatives caused the greatest activity if added during or after (within 1 h) poliovirus adsorption. These data suggest interference with early events of viral replication. [5-3H]Uridine incorporation into RNA showed that the compounds tested reduced poliovirus RNA synthesis, which was completely shut off after 2 h of incubation and reduced by 50-60% after 4 h. Also, pretreatment of the cell cultures with the compounds for 24 h caused a substantial inhibition of viral replication. The data suggest that the four isothiazole derivatives may have a multi-step antiviral mode of action different from their iminodithiole precursors.
authors.affiliation: Institute of Microbiology, University of Catania, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Pinizzotto
authors.forename: A
authors.initials: A
authors.lastname: Garozzo
authors.forename: F
authors.initials: F
authors.lastname: Guerrera
authors.forename: A
authors.initials: A
authors.lastname: Castro
authors.forename: M G
authors.initials: MG
authors.lastname: La Rosa
authors.forename: P M
authors.initials: PM
authors.lastname: Furneri
authors.forename: E
authors.initials: E
authors.lastname: Geremia
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006801:Humans; D017955:Poliovirus / Q000187:drug effects* / Q000502:physiology; D012367:RNA, Viral / Q000096:biosynthesis; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D013844:Thiazoles