Ruthenium-Based Coordination and Heterocyclic Compounds as Promising Next-Generation Metallotherapeutic Agents for Cancer Treatment

Cancer remains a major global health challenge, and the limitations of conventional chemotherapeutic agents, including systemic toxicity, poor selectivity, drug resistance, and inadequate therapeutic responses, have stimulated the development of alternative therapeutic strategies. Ruthenium-based compounds have emerged as promising candidates in medicinal inorganic chemistry because of their distinctive coordination chemistry, variable oxidation states, tunable ligand exchange kinetics, and ability to interact with diverse biological targets. In particular, coordination compounds containing heterocyclic ligands have attracted considerable attention because heterocycles can modulate lipophilicity, cellular uptake, DNA interactions, redox behavior, and molecular recognition. This review summarizes recent advances in ruthenium-based coordination and heterocyclic compounds as potential anticancer agents. Emphasis is placed on their structural characteristics, ligand design, mechanisms of cellular action, interactions with DNA and proteins, reactive oxygen species generation, mitochondrial dysfunction, apoptosis, cell-cycle regulation, and inhibition of cancer-associated signaling pathways. The influence of ligand architecture and ruthenium oxidation state on biological activity is also discussed. Selected ruthenium complexes investigated in preclinical and clinical research are highlighted to illustrate the progression of this field. Current challenges, including selectivity, stability, pharmacokinetics, resistance, toxicity, and translation from in vitro studies to clinical applications, are considered. Finally, emerging strategies involving targeted ligands, nanocarriers, photoactivated ruthenium complexes, and combination therapy are discussed as potential approaches for developing next-generation ruthenium metallotherapeutics.