In vitro antiviral activity of four isothiazole derivatives against poliovirus type 1.
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.
Pinizzotto
M R
MR
Institute of Microbiology, University of Catania, Italy.
Garozzo
A
A
Guerrera
F
F
Castro
A
A
La Rosa
M G
MG
Furneri
P M
PM
Geremia
E
E
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
D000998:Antiviral Agents; D012367:RNA, Viral; D013844:Thiazoles