Ferrocene-Based Hybrids as Anticancer Agents: Recent Advances and Structure–Activity Insights

Cancer remains one of the most challenging diseases worldwide, second only to cardiovascular disorders in incidence and mortality. The increasing prevalence of drug resistance and the inadequate selectivity of conventional chemotherapeutics necessitate the exploration of alternative molecular frameworks with improved efficacy and reduced systemic toxicity. Organometallic compounds have recently emerged as promising candidates in this regard, owing to their well-defined coordination geometries, tunable redox potentials, and capability to interact with vital biomolecular targets. Among them, ferrocene, an iron(II) sandwich complex composed of two cyclopentadienyl rings, represents a versatile pharmacophore for the development of novel anticancer agents. Its reversible Fe(II)/Fe(III) redox cycle facilitates the controlled generation of reactive oxygen species (ROS), leading to oxidative stress and apoptosis in malignant cells. A notable example is ferrocifen, which is a ferrocene-modified derivative of the breast cancer drug tamoxifen. Furthermore, these tamoxifen hybrids showed strong antiproliferative effects against not only hormone-dependent but also hormone-independent cancer cell lines. This review systematically discusses recent progress in ferrocene-based hybrid molecules as potent anticancer agents. Special emphasis is placed on how electronic effects, linker modification, and substituent patterning influence biological activity. This review article highlights the key insights that support the rational design of selective, redox-active ferrocene-derived anticancer agents with the potential to overcome multidrug resistance.