Fluorination of amino-quinones enhances anti-Trypanosoma cruzi activity.

Quinones are well-established antiparasitic agents. Despite the widespread use of fluorine to modulate biological activity and physicochemical properties in drug design, its systematic incorporation into quinoidal frameworks remains underexplored. Here, we report a mild and operationally simple direct electrophilic fluorination of a wide scope of amino-substituted 1,4-naphthoquinones. The fluorinated quinones were evaluated in vitro against Trypanosoma cruzi (T. cruzi), revealing a consistent and pronounced enhancement in trypanocidal activity upon fluorine incorporation compared with their non-fluorinated aminoquinone precursors. Notably, several fluorinated aminoquinone exhibited higher trypanocidal activity than benznidazole, the drug currently used in the clinical treatment of Chagas disease. This work highlights the potential of fluorine to beneficially influence the properties and biological activity of quinoidal systems.