Heteroscorpionate copper complexes functionalized with memantine: as novel antiglioblastoma agents

Over the years, copper coordination compounds have attracted considerable attention in the field of medicinal inorganic chemistry due to their rich redox behavior, variable coordination environments, and potential for therapeutic applications. Herein, as part of our ongoing research into the antitumor properties of Cu complexes of ligands conjugated to biologically active molecules, we present the synthesis and preliminary biological evaluation of new Cu(I) and Cu(II) complexes incorporating memantine ring-conjugated bis(pyrazolyl)acetate ligands. As coordinating agents, the bis(pyrazolyl)- and bis(3,5-dimethylpyrazolyl)-acetic acids were chosen thanks to their κ3N,N’,O coordination mode and presence of a carboxylic group suitable for the coupling with the primary amine group of memantine drug yielding the new ligands LMem and L2Mem (Figure 1). All the complexes were fully characterized both in solid state and in solution and their electronic and molecular structures were investigated by XPS, NEXAFS and, XAS. In addition, X-ray diffraction analysis was carried out on the ligands LMem and L2Mem, along with complexes [(PPh3)Cu(L2Mem)]PF6 and [Cu(L2Mem)2Cl2]. The cytotoxicity of the ligands and their corresponding Cu(I) and Cu(II) complexes was investigated against glioblastoma cell lines.