Novel Synthetic Chalcones Display Potent Anti-Leishmania (Viannia) braziliensis Profile and Inhibit Proteolytic Activities

The variable efficacy and toxicity of pentavalent antimonials underscore the urgent need for new therapeutic candidates. Among the compounds currently explored, chalcones have emerged as promising bioactive scaffolds, exhibiting antiparasitic activity and the potential to inhibit key proteases, which are essential enzymes to virulence and pathogenesis of the parasite.

In this study, chalcone derivatives obtained via a novel synthetic approach were evaluated for their antileishmanial activity against L.(V.)braziliensis. Their drug-likeness properties were initially assessed in silico, and the inhibitory activity against proteases was subsequently evaluated using promastigote protein extracts. In Tris–HCl buffer, compound <b>3j</b> exhibited the most pronounced inhibitory effect, 36% residual activity, followed by compounds <b>3d</b> and 2′,4′,6′-trimethoxy-chalcone (<b>TMC</b>), which showed 47% residual activity.