Gold(I)–NHC Complexes Containing Selenium as Promising Antileishmanial Agents

Leishmaniasis is a neglected tropical disease whose current treatments remain limited by toxicity, resistance, and administration challenges, highlighting the need for new therapies. Gold(I)–N-heterocyclic carbene (NHC) complexes, initially designed for anticancer applications, are promising bioinorganic scaffolds. Selenium incorporation is attractive given its role in redox processes, including thioredoxin reductase (TrxR) [1], while Leishmania redox homeostasis relies on trypanothione reductase (TR) as a key target. Au(I)–NHC-Se complexes were synthesized via Ag₂O-mediated transmetalation under inert atmosphere [2], and characterized by spectroscopic, structural, and X-ray diffraction analyses. In vitro biological evaluation included cytotoxicity in THP-1-derived macrophages and anti-amastigote assays against L. braziliensis, L. amazonensis, and L. infantum. Complexes showed low-micromolar activity (<2 µM) with high host-cell selectivity (IC₅₀ = 0.2 µM; SI = 255 against L. amazonensis). GSH/BSA studies confirmed thiol affinity, while DFT and docking supported Au–S interactions, indicating TrxR and TR as potential targets. This novelty led to a patent filing.