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

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.

• Authors: Enrique Torres, 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
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 66 Pg. 324-34 (Aug 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23811257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antiprotozoal Agents
• Oxides
• Quinoxalines

Topics

• Animals
• Antiprotozoal Agents (chemistry, pharmacology, therapeutic use, toxicity)
• Cell Line
• Chagas Disease (drug therapy)
• Electrochemistry
• Mice
• Mutagenesis (drug effects)
• Oxides (chemistry)
• Quinoxalines (chemistry, pharmacology, therapeutic use, toxicity)
• Trypanosoma cruzi (drug effects)