1 H-Indole-2,3-dione 3-thiosemicarbazones Carrying a 4-sulfamoylphenyl Moiety with Selective Antiviral Activity Reovirus-1

Abstract

1 H -Indole-2,3-dione 3-[4-(4-sulfamoylphenyl)thiosemicarbazones] 6a - j were evaluated against para-influenza-3, reovirus-1, sindbis, coxsackie B4, and Punto Toro viruses. New 1-methyl-1 H -indole-2,3-dione 3-[4-(4-sulfamoylphenyl) thiosemicarbazones] 7a - c were synthesized to evaluate the contribution of methyl substitution at position 1 of the indole ring to antiviral activity. The test results showed that 5-trifluoromethoxy substituted compound 6c (EC 50 2-9 mu M) and 5-bromo substituted 6f (EC 50 2-3 mu M) have non-toxic selective antiviral activity, while not all standards are active against reovirus-1. Molecular docking studies of 6c and 6f were carried out to determine the possible binding positions with reovirus-1. Trifluoromethoxy and bromine substitutions at position 5 of the indole ring provided selective antiviral activity, while methyl substitution at position 1 of the indole ring significantly decreased the activity against reovirus-1 and increased toxicity.