Influence of Ligand Functionalization on the Physicochemical and Biological Properties of Cyclometalated Au(III) Complexes

This work investigates the influence of ligand functionalization on the physicochemical properties, thiol reactivity, and antileishmanial activity of phenylpyridine-based cyclometalated Au(III) complexes. Four functionalized derivatives were synthesized and fully characterized, and their lipophilicity, interactions with N-acetylcysteine as a model biological thiol, and activity against Leishmania amazonensis were evaluated. The results demonstrate that ligand functionalization effectively modulates lipophilicity and thiol-binding behavior, leading to distinct biological responses. While the parent and methyl-substituted complexes exhibited comparable antileishmanial activity, the glycine-functionalized derivative showed significantly reduced potency. Overall, these findings highlight ligand functionalization as a valuable strategy for fine-tuning the properties and biological performance of cyclometalated Au(III) complexes, providing insights for the rational design of new metallodrugs against leishmaniasis.