Synthesis of Gold(I) and Palladium(II) Complexes Bearing <i>N</i>‐Heterocyclic Carbene Thioglucosides with Selective Cytotoxicity Towards Ovarian Cancer Cells

Abstract We report the development of an efficient and versatile synthetic protocol for the preparation of gold(I) and palladium(II) complexes bearing N‐heterocyclic carbene (NHC) thioglucosides and their azolium precursors. Gold(I) and Nolan‐type palladium(II)‐allyl complexes were synthesized under mild aerobic conditions using potassium carbonate as a base. Additionally, allyl palladate complexes were prepared via a straightforward solvent‐free method. In vitro assays on three ovarian cancer cell lines (OVCAR‐5, A2780, and its cisplatin‐resistant clone A2780cis) revealed interesting structure‐activity relationships (SARs). Gold(I) complexes with saturated NHC ligands showed enhanced activity, while Nolan‐type palladium(II)‐allyl complexes with unsaturated NHC ligands exhibited higher efficacy. Allyl palladates demonstrated similar activity regardless of whether the ligand was saturated or not. The most promising compounds display high selectivity for cancer cells, with cytotoxicity comparable to cisplatin on A2780 and OVCAR‐5 lines and superior activity against the A2780cis line. Notably, these compounds showed minimal toxicity towards non‐cancerous MRC‐5 cells. This selective anticancer activity is likely due to the presence of glucoside units, suggesting their role as targeting agents.