Antitumor activity of Ruthenium-Areno complexes: Evidence and prospects for biomedical applications

Ruthenium-arene complexes are organometallic compounds being investigated as antitumor agents due to their structural diversity and the possibility of modulating their properties through the arene and the coordinating ligands. Accordingly, this literature review aimed to compile the structural characteristics, mechanisms of action, and biological responses of these ruthenium-arene complexes, as well as their applications in terms of structure, antitumor activity, and sensitivity in different tumor lines. The reviewed studies describe effects on multiple targets, such as DNA and nuclear targets, mitochondria, lysosomes, and immune pathways, as well as selectivity mechanisms related to transport, activation in the tumor microenvironment, and cellular localization. In vitro activity varied depending on the complex’s structure and the tumor line, with responses that were superior to, comparable to, or inferior to those of the reference drugs, and, in some cases, no cytotoxicity. Modifications to the arene, ligands, substituents, charge, and nuclearity influenced physicochemical properties, cellular uptake, and antitumor activity, without indicating a structural feature, ligand family, or tumor type consistently associated with higher activity. These structure-activity relationships provide insights for the optimization of ruthenium-arene complexes. However, the predominance of in vitro studies, the scarcity of in vivo data, and the lack of clinical evidence for this class prevent the establishment of its clinical potential, although they support further investigation of these compounds as candidates for future antitumor strategies.