Promising Silver(I), Gold(I), and Gold(III)-NHC Chemotypes to Tackle Leishmaniasis

Leishmaniasis, a neglected tropical disease, is an epidemic and a public health concern in at least 98 countries. The currently available treatments impose several limitations, including high toxicity, reduced activity, and drug resistance, demanding a quest for novel and effective therapeutics. Since silver and gold-NHC complexes generally display promising biological applications evading drug resistance, in this research work, we have reported the synthesis, structures, structural characterizations, and in vitro antileishmanial activities of a novel series of Ag(I), Au(I), and Au(III) complexes of quinoxaline-wingtip N-heterocyclic carbene (NHC) ligands. The proligands and metal complexes were synthesized and fully characterized by using different spectroscopic techniques and solid-state single-crystal XRD analysis. All the synthesized complexes are investigated for their in vitro antileishmanial potential against intracellular amastigotes of different Leishmania species. Surprisingly, only Au(I) and Au(III)-NHC complexes are effective and display promising antileishmanial activity with IC50 values varying between 0.3 and 17.5 μM. Structure–activity and toxicity relationships demonstrate the dicationic Au(III)-NHC complex encompassing the phenanthroline ligand as the lead candidate, exhibiting both a high activity and an excellent selectivity index (SI = 157), especially against L. amazonenis. These findings highlight the promising potential of these compounds as alternative therapeutic candidates for the treatment of leishmaniases.