Exploring substituent effects in gold(I) N-heterocyclic carbene complexes: the role of selenoethers in antiproliferative activity.

A family of gold(I) complexes bearing N-heterocyclic carbene (NHC) ligands functionalized with a selenoether moiety is reported herein. By combining selenium-containing groups with gold NHC scaffolds, we aimed to develop multifunctional anticancer agents with enhanced efficacy through the simultaneous modulation of multiple biological pathways. All new compounds were subjected to comprehensive spectroscopic characterization, with X-ray crystallographic analysis performed on representative samples. The gold(I) complexes exhibited antiproliferative activity against a wide panel of human cancer cell lines, in both 2D and 3D models, with IC50 values comparable to those displayed by cisplatin. However, the complexes bearing the selenoether moiety showed anticancer activity comparable to that of their non-functionalized counterparts. Mechanistic investigations suggest that the antiproliferative effects are primarily associated with thioredoxin reductase inhibition.