Hydroxypyranone–metal complexes in anticancer therapy: from structural design to mechanistic insights

Abstract

Hydroxypyranone ligands, in particular maltol and kojic acid, have proven to be promising building blocks in the development of transition metal-based anticancer agents. Their ability to chelate biologically relevant metal ions such as vanadium, copper, zinc and ruthenium enables the formation of stable coordination complexes with significant cytotoxic and pro-apoptotic activity. This review highlights the structural characteristics of hydroxypyranone ligands and their influence on the pharmacological properties of metal complexes. Notable systems, including bis(maltolato)oxovanadium(IV) (BMOV), VO–phen complex(Metvan) and Ru(II)–maltol complexes, have shown higher selectivity and lower systemic toxicity compared to classical chemotherapeutic agents such as cisplatin. The most important mechanisms of action include interaction with DNA, the formation of reactive oxygen species (ROS), mitochondrial dysfunction and the inhibition of enzymes. This review highlights the antitumor activity of copper(II), vanadium(IV/V), and ruthenium(II) complexes against hepatocellular and colorectal cancer cell lines. The review highlights the importance of rational ligand design, redox activity and metal ion selection for optimizing the therapeutic index of metallopharmaceuticals. Future perspectives point to the integration of these compounds into advanced drug delivery platforms and their evaluation in preclinical and clinical settings. This review emphasises the therapeutic importance of hydroxypyranone–metal complexes as selective and less toxic alternatives to platinum drugs. It provides new insights into their structure–activity relationships and supports their development as promising candidates for targeted cancer therapy.