{ZnII2} and {ZnIIAuI} Metal Complexes with Schiff Base Ligands as Potential Antitumor Agents Against Human Glioblastoma Multiforme Cells

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Abstract
The challenges of glioblastoma multiforme treatment are related to limitations in tumor removal surgery, its high heterogeneity and aggressiveness, development of resistance to standard therapy, the blood–brain barrier, and the side and toxic effects of the conventional antitumor agents used in clinical practice. Although new treatment strategies continue to emerge, progress remains slow and has not resulted in substantial improvements in patient survival. The main goal of research in recent years has been aimed at developing ways to deal with all these challenges. One of the ways to improve the control of glioblastomas is the introduction of effective new antitumor agents. Metal complexes represent a particularly promising class of compounds in this context. This is why the aim of this study was to assess the effects of six homo- and heterometallic coordination compounds bearing Schiff base ligands—[Zn2(Ampy)(µ-OH)(H2O)2](ClO4)2 (ZnAmpy), [Zn2(Dmen)(µ-OH)(H2O)2](ClO4)2 (ZnDmen), 1∞[{Zn2(Ampy)(μ3-OH)}2(H2O){μ-[Au(CN)2]}](ClO4)3·THF·H2O (ZnAmpyAu), [{Zn2(Dmen)(μ-OH)}2{μ-[Au(CN)2]}{[Au(CN)2]2}](ClO4)·H2O (ZnDmenAu), 1∞[Zn(Salampy){μ-Au(CN)2}] (ZnSalampyAu), and 1∞[Zn(Saldmen)(μ-Au(CN)2}] (ZnSaldmenAu)—on the viability and proliferation of 8MGBA and U251MG human glioblastoma multiforme cells (HDmen and HAmpy are bicompartmental Schiff base ligands resulting from the condensation of 2,6-diformyl-p-cresol with N,N-dimethylethylenediamine and 2-(aminomethyl)pyridine, respectively, while HSaldmen and HSalampy are tridentate Schiff base ligands obtained via condensation of salicylaldehyde with N,N-dimethylethylenediamine and 2-(aminomethyl)pyridine, respectively). Among these compounds, ZnSaldmenAu is a new compound and is reported here for the first time. Cytotoxicity of the compounds was evaluated through analysis of cell viability, 2D/3D growth, cytopathological alterations, and induction of cell death. The results obtained by methods with different targets in cells and the associated mechanisms of action revealed that the compounds investigated show promising cytotoxic/potential antitumor activity in treated cells.
Funding Information
  • National Science Fund, Bulgarian Ministry of Education and Science (KП-06-M61/3)

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