Unconventional chalcogen-containing azolylidene metal complexes as potential anticancer therapeutics

Abstract

Organometallic compounds with N-heterocyclic carbene (NHC) ligands have been studied for their anticancer and antimicrobial properties, with imidazole and benzimidazole derivatives being the predominant scaffolds for potential NHC-containing drugs. In contrast, chalcogen-containing azolylidene ligands, (N,Y)HCs (Y = S, O, Se), remain largely unexplored in both medicinal inorganic chemistry and, more generally, in inorganic chemistry. Consequently, classical (N,N)HC complexes of platinum, gold and ruthenium were selected due to their previously reported biological activity and their proposed mechanisms of action. To study the effect of the incorporation of a chalcogen atom in the ligand, (N,Y)HC analogues bearing (benz)oxazole, (benzo)thiazole or benzoselenazole ligands, were synthesised. The electronic and steric properties of the ligands and complexes were explored and their biological activity was evaluated. The introduction of a chalcogen atom within the heterocyclic scaffold of the ligands was found to modulate their interaction with biomolecules and regulate the cytotoxicity of the metal complexes towards ovarian cancer cells.