Esters and amides of benzofuroxan-1-N–oxide derivatives as trypanocidal and leishmanicidal agents

American trypanosomiasis and leishmaniasis are worldwide health problems that warrant attention given the current ineffective treatment options. In this study, 6-ester-, and 6-benzamide- benzofuroxan-1-N-oxide derivatives were evaluated against trypomastigotes of the NINOA of Trypanosoma cruzi (T. cruzi), and promastigotes of QEPS strain of Leisnmania mexicana (L. mexicana). Compounds BFX-9, and BFX-10 had the best trypanocidal activity with values of half-maximal inhibitory concentration (IC50) of 16.25, and 0.5 µM, respectively, over 9-fold more active than both benznidazole and nifurtimox. Also, BFX-10 had the best selectivity index (SI) value of 77.16 toward trypomastigotes of T. cruzi over macrophages J774.2. Compounds BFX-3, BFX-5, and BFX-8 had the best leishmanicidal activity, better than glucantime, and miltefosine, with IC50 values 9.75, 7.03, and 9.57 µM, and SI values of 3.91, 3.92, and 4.64, respectively, toward L. mexicana promastigotes over macrophages. This study shows that new modifications at 6-position on the benzofuroxan scaffold allowed obtain potent anti-Trypanosoma cruzi and anti-leishmania agents.