Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

  • Eur J Med Chem. 2013 Aug:66:324-34. doi: 10.1016/j.ejmech.2013.04.065.
Enrique Torres  1 ,  Elsa Moreno-Viguri ,  Silvia Galiano ,  Goutham Devarapally ,  Philip W Crawford ,  Amaia Azqueta ,  Leire Arbillaga ,  Javier Varela ,  Estefanía Birriel ,  Rossanna Di Maio ,  Hugo Cerecetto ,  Mercedes González ,  Ignacio Aldana ,  Antonio Monge ,  Silvia Pérez-Silanes
Affiliations
  • 1. Neglected Diseases Section, Drug R&D Unit, Center for Applied Pharmacobiology Research, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain.
PMID: 23811257 DOI: 10.1016/j.ejmech.2013.04.065
Abstract

As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with fluoro groups at the 6- and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups, possessed a greater ease of reduction of the N-oxide groups.

Keywords
2-aminofluorene; 4-NPD; 4-nitro-o-phenylendiamine; AF; BFX; Bnz; Chagas disease; Cytotoxicity; Fc; GM; IC(50); Mutagenicity; NR; Nfx; Nifurtimox; PGI; Quinoxaline 1,4-di-N-oxide; Reduction potential; SI; T. cruzi; TBAP; Trypanosoma cruzi; benznidazole; benzofuroxan; concentration for 50% growth inhibition; ferrocene; glucose minimal; number of revertants; percentage of growth inhibition; selectivity index; tetrabutylammonium perchlorate.