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

• New quinoxaline 1,4-di-N-oxide derivatives as promising antichagasic agents.
• New quinoxaline derivatives with excellent activity and selectivity against T. cruzi.
• Electron-withdrawing substituents in the quinoxaline enhanced anti-T. cruzi activity.
• Lower negative reduction potential values enhanced efficacy against the parasites.

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.

Eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized and they have shown excellent in vitro biological activity against Trypanosoma cruzi, identifying one of the compounds as the most active and selective in the cytotoxicity assay.Figure optionsDownload as PowerPoint slide