Gold–NHC complexes: from synthetic aspects to anti-cancer activity

Abstract

Recent advancements in Au(I)–N-heterocyclic carbene (NHC) complexes have demonstrated significant potential for developing novel anticancer agents. These complexes exhibit unique properties, such as a strong affinity for thiol and selenol-containing biomolecules, which enable the selective targeting of cancer cells while minimising effects on healthy tissues. Recent studies have explored various structural modifications to enhance the anticancer efficacy of Au(I)–NHC complexes, including ligand substitution, incorporation of bioactive moieties, and hybridisation with other metal complexes. Mechanistic investigations have revealed that these complexes induce apoptosis through multiple pathways, such as inhibition of thioredoxin reductase (TrxR), disruption of mitochondrial function, and generation of reactive oxygen species (ROS). The introduction of NHC ligands is particularly advantageous, as they provide stability and tunability to the Au(I) centre, allowing for the optimisation of pharmacokinetic and pharmacodynamic properties. Moreover, the emergence of Au(I)–NHC complexes with dual-action mechanisms, combining anticancer activity with antiangiogenic or anti-inflammatory properties, has further broadened their therapeutic potential. This review article highlights the most recent breakthroughs in the design, synthesis, and biological evaluation of Au(I)–NHC complexes, emphasizing their promise as a new class of targeted anticancer therapeutics. While primarily focused on Au(I) complexes, it also includes a brief discussion of selected Au(III) complexes for comparison.