Anticancer drugs based on metal complexes of 2-imine-8-hydroxyquinolines

Cancer treatment remains a public health challenge, requiring, more than ever, the development of effective and selective therapeutic drugs. Metal complexes of 8-hydroxyquinoline (8HQ) have long been recognized to exhibit significant potential in this field due to its potent chelating properties, stability, and broad spectrum of bioactivity. When coordinated to a metal center with potential therapeutic properties, synergistic or additive effects can be achieved. This mini-review summarizes the synthesis, characterization, and biological evaluation of metal complexes (Zn, Cu, V, Ni, Fe and Ru) of 8-hydroxyquinoline derived ligands, which were recently developed in our group. The focus was on 8HQ ligands substituted at position 2 by an imine, with particular attention given to the challenges of selectivity and solubility. Malignant melanoma, colon, lung and triple-negative breast cancers were selected for the in vitro screening of the complexes’ anticancer properties. Cellular assays revealed that the mechanisms of action involve reactive oxygen species (ROS) generation and apoptotic cell death. A nanoliposomal encapsulation strategy was employed to deliver the drugs passively and overcome selectivity and aqueous solubility issues in vivo . The key findings demonstrate the potential of these complexes in both in vitro and in vivo settings, supporting their application as next-generation anticancer therapies.