Abstract

The development of hybrid compounds containing limonene- and recognized anti-T. cruzi-heterocycleframeworks is described. The six new compounds displayed broad antitrypanosomal activities having 5-nitrofuran and 5- nitroindazole derivatives, the best profiles. In addition, a 5-nitroindazole derivative evaluated against a panel of fungi exhibited relevant activities. Knowing that free-radical-production operates as one of the mechanisms of action on these heterocycles, we studied a potential extra-mechanism, membrane-sterols changes. Non-relevant T. cruzi squalene accumulation was observed for any of the tested hybrid-limonene derivatives.

Keywords: Limonene derivatives, Anti-T. cruzi agents, Antifungal, Lipinski rule, 5-nitrofuran, 5-nitroindazole