Scaffold-Driven Antileishmanial Activity in Ester-Functionalized NHCs and Au(I) Complexes

Leishmaniasis remains a neglected tropical disease that urgently requires new therapeutic alternatives. Gold(I) N-heterocyclic carbene (NHC) complexes have emerged as promising antiparasitic candidates, although the influence of the heterocyclic scaffold and metal coordination on biological activity remains poorly understood. In this study, ester-functionalized benzimidazole- and imidazole-derived NHC proligands and their corresponding Au(I) complexes were evaluated against Leishmania amazonensis promastigotes to establish structure–activity relationships. A clear scaffold-dependent behavior was observed. Benzimidazole-derived proligands exhibited antileishmanial activity, whereas their Au(I) complexes were inactive. Conversely, in the imidazole series, only the Au(I) complexes displayed biological activity, while the free ligands were inactive. These contrasting profiles demonstrate that the biological effect of Au(I) coordination is strongly dependent on the ligand framework and substitution pattern. Ongoing studies are investigating the relationship between antileishmanial activity, solution stability, lipophilicity, and interactions with biologically relevant molecules to guide the rational design of more effective Au(I)-based antileishmanial agents.