In the present article the 1,4-dioxane derivative 1, a potent noncompetitive NMDA receptor antagonist, showed cytotoxic activity in the MCF7 breast cancer cell line significantly higher than those of the functionally related compounds (S)-(+)-ketamine and MK-801. Encouraged by this result and considering that copper complexes have been highlighted to be promising anticancer agents, the NMDA receptor ligand 1 was linked to the bifunctionalizable species 2 and 3, affording the conjugated derivatives 4 and 5 that were used for the preparation of the stable Cu(II) complexes 6 and 7. All the compounds were evaluated against a panel of human cancer cell lines derived from solid tumors. Complex 7 showed the best antitumor activity in all the studied cell lines. This result suggests that 7 might act through synergistic mechanisms of action due to the presence of the NMDA ligand 1 and copper(II) in the same chemical entity. Furthermore, the cellular mechanisms affected by complex 7 were assessed through cytofluorimetric and western blot analyses. Data suggested the induction of cell death through paraptosis mediated by endoplasmic reticulum (ER) stress.