Half-Sandwich Ruthenium Arene Complexes Bearing Clinically Approved Drugs as Ligands: The Importance of Metal-Drug Synergism in Metallodrug Design

A novel strategy in metallodrug discovery today is incorporating clinically approved drugs into metal complexes as coordinating ligands. Using this strategy, various drugs have been repurposed to prepare organometallic complexes to overcome the resistance of drugs and to design promising alternatives to currently available metal-based drugs. Notably, the combination of organoruthenium moiety and clinical drug in a single molecule has been shown, in some instances, to enhance pharmacological activity and reduce toxicity in comparison to the parent drug. Thus, for the past two decades, there has been increasing interest in exploiting metal-drug synergism to develop multifunctional organoruthenium drug candidates. Herein, we summarized the recent reports of rationally designed half-sandwich Ru(arene) complexes containing different FDA-approved drugs. This review also focuses on the mode of coordination of drugs, ligand-exchange kinetics, mechanism of action, and structure-activity relationship of organoruthenated complexes containing drugs. We hope this discussion may serve to shed light on future developments in rutheniumbased metallopharmaceuticals.