51. Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents
- Author
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Javier Varela, Antonio Monge, Enrique Torres, Silvia Galiano, Leire Arbillaga, Amaia Azqueta, Estefanía Birriel, Mercedes González, Philip W. Crawford, Goutham Devarapally, Ignacio Aldana, Elsa Moreno-Viguri, Rossanna Di Maio, Silvia Pérez-Silanes, and Hugo Cerecetto
- Subjects
Trypanosoma cruzi ,Oxide ,Antiprotozoal Agents ,Cell Line ,chemistry.chemical_compound ,Mice ,Quinoxaline ,Quinoxalines ,Drug Discovery ,medicine ,Electrochemistry ,Organic chemistry ,Animals ,Chagas Disease ,Nifurtimox ,Cytotoxicity ,Pharmacology ,biology ,Organic Chemistry ,Biological activity ,Oxides ,General Medicine ,biology.organism_classification ,chemistry ,Ferrocene ,Benznidazole ,Mutagenesis ,medicine.drug - 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.
- Published
- 2013