Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2,3-dione 3-thiosemicarbazones

Abstract

In this work, novel 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-[4-(substituted phenyl)-thiosemicarbazones] 6a-n and 7a-n were synthesized. The antiviral effects of the compounds were tested against HSV-1 (KOS), HSV-2 (G) HSV-1 TK^- KOS ACV^r and VV in HEL cell cultures using acyclovir and ganciclovir as standards, and Coxsackie B4 virus in Vero cell cultures using ribavirin and mycophenolic acid as standards. R₂ ethyl substituted 7 derivatives were found effective against viruses tested. R₁ 4-CF₃ substituted 7d, R₁ 4-OCH₃ substituted 7 g and R₁ 3-Cl substituted 7 l showed activity against HSV-1 (KOS), HSV-2 (G) HSV-1 TK^- KOS ACV^r and VV. Whereas only R₁ 4-Br substituted 7n has selective activity against coxsackie B4 virus. Molecular modelingstudies of 7d and 7l were performed to determine binding side on HSV-1 glycoprotein B and D, HSV-2 glycoprotein B structures.

Keywords: 5-Fluoro-1H-indole-2,3-diones; Antiviral activity; Molecular modeling; Synthesis; Thiosemicarbazones.