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

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• 作者：Enrique Torres ; Elsa Moreno-Viguri ; Silvia Galiano ; Goutham Devarapally ; Philip W. Crawford ; Amaia Azqueta ; Leire Arbillaga ; Javier Varela ; Estefan¨ªa Birriel ; Rossanna Di Maio ; Hugo Cerecetto ; Mercedes Gonz¨¢lez ; Ignacio Aldana ; Antonio Monge ; Silvia P¨¦rez-Silanes
• 关键词：Chagas disease ; Trypanosoma cruzi ; Quinoxaline 1 ; 4-di-N-oxide ; Mutagenicity ; Cytotoxicity ; Reduction potential
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：66
• 期：Complete
• 页码：324-334
• 全文大小：720 K

文摘

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.