In this review, we present a timeline that shows the origin of mixed chelate copper (II) complexes, registered as Mark Title Casiopeínas^®, as the first copper (II) compounds proposed as anticancer drugs in 1988 and 1992. In the late twentieth century, the use of essential metals as anticancer agents was not even considered, except for their antifungal or antibacterial effects; also, copper, as gold salts, was used for arthritis problems. The use of essential metals as anticancer drugs to diminish the secondary toxic effects of Cisplatin was our driving force: to find less toxic and even more economical compounds under the rational design of metal chelate complexes. Due to their chemical properties, copper compounds were the choice to continue anticancer drug development. In this order of ideas, the rational designs of mixed chelate–copper (II) complexes (Casiopeínas, (Cas) homoleptic or heteroleptic, depending on the nature of the secondary ligand) were synthesized and fully characterized. In the search for new, more effective, and less toxic drugs, Casiopeína^® (Cas) emerged as a family of approximately 100 compounds synthesized from coordinated Cu(II) complexes with proven antineoplastic potential through cytotoxic action. The Cas have the general formula [Cu(N–N)(N–O)]NO₃ and [Cu(N–N)(O–O)]NO₃, where N–N is an aromatic substituted diimine (1,10-phenanthroline or 2,2′-bipyridine), and the oxygen donor (O–O) is acetylacetonate or salicylaldehyde. Lately, some similar compounds have been developed by other research groups considering a similar hypothesis after Casiopeína’s discoveries had been published, as described herein. As an example of translational medicine criteria, we have covered each step of the established normative process for drug development, and consequently, one of the molecules (Casiopeína III ia (CasIIIia)) has reached the clinical phase I. For these copper compounds, other activities, such as antibacterial, antiparasitic and antiviral, have been discovered.

Metal-based compounds, known as metallodrugs, offer promising alternatives for cancers with limited treatment options, such as triple-negative breast cancer (TNBC). Casiopeinas^®, a family of copper-based compounds, have shown anticancer and antiproliferative effects both in vitro and in vivo. However, their long-term effects, particularly on metabolic pathways related to invasion and metastasis, remain unknown. This study addresses the sustained impact of Casiopeina IIIia (CasIIIia) and Casiopeina IIgly (CasIIgly) on TNBC cell metabolism, as well as their relationship with intra- and extracellular copper concentrations associated with these compounds. Our results revealed effects on several pathways, including those related to amino acid, lipid, and carbohydrate metabolism and energy production, all of which are involved in epithelial–mesenchymal transition (EMT), invasion, and metastasis. These metabolic changes were accompanied by progressive intracellular accumulation of Casiopeinas^®, suggesting a relationship between the concentration and their metabolic effects. These findings suggest that Casiopeinas^® could be a promising therapeutic option for TNBC treatment.