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

被引：51

作者：

Torres, Enrique ^{[1
]}

Moreno-Viguri, Elsa ^{[1
,2
]}

Galiano, Silvia ^{[1
]}

Devarapally, Goutham ^{[3
]}

Crawford, Philip W. ^{[3
]}

Azqueta, Amaia ^{[4
]}

Arbillaga, Leire ^{[4
]}

Varela, Javier ^{[5
]}

Birriel, Estefania ^{[5
]}

Di Maio, Rossanna ^{[5
]}

Cerecetto, Hugo ^{[5
]}

Gonzalez, Mercedes ^{[5
]}

Aldana, Ignacio ^{[1
]}

Monge, Antonio ^{[1
]}

Perez-Silanes, Silvia ^{[1
,2
]}

机构：

[1] Univ Navarra, Ctr Appl Pharmacobiol Res, Drug R&D Unit, Neglected Dis Sect, Pamplona 31008, Spain

[2] CIMA, Inst Salud Trop, Pharmacotherapy Lab, Pamplona 31008, Spain

[3] SE Missouri State Univ, Dept Chem, Cape Girardeau, MO 63701 USA

[4] Univ Navarra, Dept Pharmacol & Toxocol, Pamplona 31008, Spain

[5] Univ Republica, Fac Quim, Fac Ciencias, Grp Quim Med,Lab Quim Organ, Montevideo 11400, Uruguay

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 66卷

关键词：

Chagas disease; Trypanosoma cruzi; Quinoxaline 1,4-di-N-oxide; Mutagenicity; Cytotoxicity; Reduction potential; DI-N-OXIDES; TRYPANOSOMA-CRUZI GROWTH; CHAGAS-DISEASE; BIOLOGICAL EVALUATION; DRUG DISCOVERY; MEDICINAL CHEMISTRY; CYCLIC VOLTAMMETRY; NONAQUEOUS SOLVENTS; MUTAGENICITY TEST; IMPACT;

D O I：

10.1016/j.ejmech.2013.04.065

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：324 / 334

页数：11

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