Quinoxaline derivatives as new inhibitors of coxsackievirus B5

Eur J Med Chem. 2018 Feb 10;145:559-569. doi: 10.1016/j.ejmech.2017.12.083. Epub 2017 Dec 27.


Enteroviruses are among the most common and important human pathogens for which there are no specific antiviral agents approved by the US Food and Drug Administration so far. Particularly, coxsackievirus infections have a worldwide distribution and can cause many important diseases. We here report the synthesis of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses. Promisingly, three compounds showed a very potent and selective antiviral activity against coxsackievirus B5, with EC50 in the sub-micromolar range (0.3-0.06 μM). A combination of experimental techniques (i.e. virucidal activity, time of drug addition and adsorption assays) and in silico modeling studies were further performed, aiming to understand the mode of action of the most active, selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6-yl)methylthio]benzoate (6).

Keywords: Antiviral activity; Enteroviruses; Viral protein VP1; in silico modeling.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cattle
  • Cell Line
  • Cell Survival / drug effects
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Enterovirus B, Human / drug effects*
  • Haplorhini
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Structure-Activity Relationship


  • Antiviral Agents
  • Quinoxalines