Synthesis and antiviral properties of novel indole-based thiosemicarbazides and 4-thiazolidinones

Bioorg Med Chem. 2016 Jan 15;24(2):240-6. doi: 10.1016/j.bmc.2015.12.008. Epub 2015 Dec 8.

Abstract

A novel series of indolylthiosemicarbazides (6a-6g) and their cyclization products, 4-thiazolidinones (7a-7g), have been designed, synthesized and evaluated, in vitro, for their antiviral activity against a wide range of DNA and RNA viruses. Compounds 6a, 6b, 6c and 6d exhibited notable antiviral activity against Coxsackie B4 virus, at EC50 values ranging from 0.4 to 2.1 μg/mL. The selectivity index (ratio of cytotoxic to antivirally effective concentration) values of these compounds were between 9 and 56. Besides, 6b, 6c and 6d also inhibited the replication of two other RNA viruses, Sindbis virus and respiratory syncytial virus, although these EC50 values were higher compared to those noted for Coxsackie B4 virus. The SAR analysis indicated that keeping the free thiosemicarbazide moiety is crucial to obtain this antiviral activity, since the cyclization products (7a-7g) did not produce any antiviral effect.

Keywords: 4-Thiazolidinone; Antiviral activity; Coxsackie B4 virus; Indole; Thiosemicarbazide.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cats
  • Cells, Cultured
  • Chlorocebus aethiops
  • DNA Viruses / drug effects*
  • Dogs
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Madin Darby Canine Kidney Cells
  • Microbial Sensitivity Tests
  • Molecular Structure
  • RNA Viruses / drug effects*
  • Semicarbazides / chemical synthesis
  • Semicarbazides / chemistry
  • Semicarbazides / pharmacology*
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Indoles
  • Semicarbazides
  • Thiazolidines
  • thiosemicarbazide
  • indole