Synthesis of 1,4-di-N-oxide quinoxalines designed against Leishmaniasis

Abstract

According to the World Health Organization, leishmaniasis are neglected diseases that affects 12 million people worldwide and puts at risk 350 million people. The current therapy has a number of limitations and drawbacks justifying the search for new drugs more effective and safe. Recently, studies have shown that N-oxides compounds are active against amastigote forms of Leishmania amazonensis (EC50 = 2.1¼M) and Leishmania donovani (EC50 = 3.1¼M), presenting selectivity indexes above 60. In animals, the N-oxides compounds reduced the parasite burden of the spleen and liver to values greater than 50%, and did not induce toxicity during chronic treatment. Thus, using molecular modification tools to optimize the leishmanicidal activity of these promising prototypes, we propose in this project the synthesis of new derivatives of quinoxalines 1,4-di-N-oxides designed against leishmaniasis. (AU)