Zn(ii)/Au(i) and Zn(ii)/Ag(i) Complexes With Salen Schiff Base Express Promising Cytotoxic Activity in Human Cancer Cells

Abstract

Objective: The aim of our study was to evaluate the influence of two complexes of Zn(II)/Au(I) and Zn(II)/Ag(I) with Schiff base ligand (H2Salen) obtained from the condensation reaction between salicylaldehyde and ethylenediamine (abbreviated ZnSalenAu, ZnSalenAg) on viability and proliferation of cultured human cancer cells.Methods: The following cell lines were used as model systems: Human cervical carcinoma (cervical carcinoma), A549 (non-small cell lung cancer [NSCLC]), glioblastoma multiforme (8MGBA), and A431 (squamous cell carcinoma) and its multidrug-resistant (MDR) clones A431-MDR, A431-MRP, and A431-ABCG2 that express mdr1, mrp1, or abcg2 gene, respectively. The investigations were performed by thiazolyl blue tetrazolium bromide test, neutral red uptake cytotoxicity assay, crystal violet staining, hematoxylin and eosin staining, double staining with acridine orange, and propidium iodide in short-term experiments (12–72 h, with monolayer cell cultures) as well as colony-forming method in long-term experiments (25 days, with three dimensional cancer cell colonies).Results: The results obtained revealed that ZnSalenAu and ZnSalenAg decreased significantly viability and proliferation of the treated cells in a time- and concentration-dependent manner being more active as compared to the free ligand H2Salen.Conclusion: The present study demonstrates for the 1st time the ability of two heterometallic complexes ZnSalenAu and ZnSalenAg to decrease significantly viability and proliferation of cultured cell lines established from some of the most common and aggressive human cancers (NSCLC, carcinoma of uterine cancer, 8MGBA, and squamous cell carcinoma) as well as MDR cancer cells.

Homo- and heterometallic complexes of Zn(ii), {Zn(ii)Au(i)}, and {Zn(ii)Ag(i)} with pentadentate Schiff base ligands as promising anticancer agents

“…In our previous studies, important information has been obtained regarding the biological activity (cytotoxic, antitumor effect) of other metal complexes with Schiff base ligands, including {Zn(II)Au(I)} and {Zn(II)Ag(I)} complexes with Salen 2− Schiff base, and Cu(II) and Co(II) complexes with o-vanillin amino acids Schiff bases. 38,39 Analysis of data regarding the structure and biological activity of these complexes and similar compounds will facilitate the development of future antitumor agents with improved properties in the desired direction.…”

“…37 It has also been found in our previous investi-gations that {Zn(II)Au(I)} complexes with Salen 2− Schiff bases as well as Cu(II) complexes with o-vanillin amino acids Schiff bases reduce the survival and 2D/3D growth of human cervical carcinoma HeLa cells. 38,39 The search for new, highly effective antitumor drugs with good biological tolerance is one of the major challenges facing modern biomedical science. In this context, the aim of our study was to develop a series of homo-and heterometallic complexes of Zn(II), Au(I), and Ag(I) bearing Schiff base ligands obtained by condensation of 2,6-diformyl-p-cresol with various amines (N,N-dimethyl-ethylenediamine, 2-aminomethyl-pyridine, and 2-aminoethyl-pyridine) and to evaluate their antitumor effect on cultured tumor cell lines MCF-7, MDA-MB-231, HeLa and Lep-3 non-tumor embryonal fibroblastoid cells.…”