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

Abstract

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.