Synthesis, structural characterization, and investigation of anti-glioblastoma activity of copper complexes supported by bis(pyrazol-1-yl)acetate ligands functionalized with memantine

ligand. Among all Cu complexes tested, compounds 4 and 5 exhibited potent antiproliferative and cytotoxic effects in U87, T98, and U251 glioma cell lines. These effects were associated with increased reactive oxygen species (ROS) production and mitochondrial dysfunction, as evidenced by mitochondrial depolarization and altered intracellular distribution. Furthermore, the cytotoxic activity of these compounds was shown to be Cu-dependent, as it was effectively inhibited by the Cu chelator tetrathiomolybdate, confirming the essential role of copper in their mechanism of action.