Iron-Based Organometallics in Anticancer Therapy: Mechanisms, Metal–Ligand Synergy, and Future Potential

Iron-based organometallic complexes have emerged as a promising class of compounds in anticancer research, offering unique therapeutic mechanisms that are distinct from those of traditional platinum-based agents. This review presents a comprehensive overview of iron-centred organometallics, emphasizing their structural diversity, mechanistic pathways, and synergistic metal–ligand interactions that contribute to their cytotoxic potential. Beginning with an introduction to the biological relevance of iron and its favourable redox properties, the structural frameworks of the iron complexes are explored. These include ferrocenes, iron carbonyls, and NHC-iron derivatives. The core focus is on the mechanisms of action, such as DNA interaction, reactive oxygen species (ROS) generation, enzyme inhibition, and mitochondrial targeting, highlighting how ligand design can fine-tune these effects. Special emphasis is placed on metal–ligand synergy, demonstrating how rational ligand engineering enhances tumor selectivity, bioavailability, and therapeutic efficacy. Recent advances in preclinical studies have shown promising in vitro and in vivo results across diverse cancer models. The review also addresses challenges such as solubility, metabolic stability, and resistance, along with regulatory hurdles impeding clinical translation. Future prospects include nanocarrier-enabled delivery systems, stimuli-responsive formulations, and combination therapies, which can further elevate the clinical potential of iron-based agents. Iron-based organometallics represent a dynamic frontier in medicinal chemistry, with biocompatibility, tunability, and multi-targeted actions, positioning them as next-generation anticancer candidates. This article provides valuable insights into their development, challenges, and transformative potential in precision oncology.

کلیدواژه ها:

Iron-based organometallic complexes ، iron-based anticancer complexes ، ferrocenes ، iron carbonyls ، ferroptosis ، Drug resistance