Cancer is characterized by non-normal cell differentiation in or on a part of the body, leading to uncontrolled growth, metastasis, and the rapid spread of cells beyond their usual boundaries. Glioblastoma (GBM) is the most common and aggressive type of astrocytic tumor. It is associated with a poor prognosis and a high mortality rate. Current treatment options are limited and provide only modest anticancer effects, underscoring the urgent need for the development of more effective therapies for GBM [1].

DNA is regarded as the primary target of platinum-based drugs when they are used as chemotherapeutics. The significant therapeutic potential of these compounds against solid tumors has highlighted the inherent advantages of metal-based drugs in cancer treatment. Transition metals like iron and zinc, which are abundant and essential in living systems, have been studied for their potential in cancer chemotherapy [[2], [3], [4], [5]]. The choice and modifications in the organic structure of the ligands, in the metal geometry, or even in the second coordination sphere with uncoordinated moieties, can interfere in the activity and selectivity of the complexes.

Multidentate phenolate-based ligands have been extensively studied with different metal centers, exhibiting diverse catalytic and biological activities [[6], [7], [8], [9], [10], [11]]. Substitutions in these organic ligands can enhance the catalytic activities of the metallic compounds and increase the specificity of the compounds in the studied substrate [[12], [13], [14], [15]]. The corresponding ligands mostly contain nitrogenated and oxygenated substituents, such as amines, amides, alcohols, and phenols, and only a few examples with sulfur portions as a thioether are reported in this class of compounds. The lack of examples is intriguing, given the importance of sulfur compounds in various biological reactions, where amino acids like methionine, cysteine, and taurine, as well as glutathione play crucial roles [16]. Metallic compounds with bioinspired sulfur-containing ligands can mimic essential interactions and potentially lead to significant improvements in catalytic and biological activities.

Herein, we describe the synthesis of complexes containing the sulfur ligand: 2-((bis(2-(phenylthio)ethyl)amino)methyl)-6-((bis(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (HL). This new ligand is phenol-based and is an N3O donor containing two thioether pendant arms. The complexes [Zn(L)(OAc)]ClO4 (1), a mononuclear zinc(II) compound, and [Fe2(L)(μ-OAc)(μ-O)](ClO4)2 (2), a dinuclear iron(III), are shown in Scheme 1. Different instrumental techniques like elemental analysis, IR, UV–Vis, and ESI-MS spectrometry were used to successfully characterize the complexes, and X-ray crystallography analysis was used to determine the molecular structures. The DNA cleavage and interaction of 1 and 2 were evaluated, showing significant DNase activity. Lastly, the cytotoxicity activities of the complexes were studied against glioblastoma cancer cell lines. Overall, this study effectively outlined the significance of the new phenol-based ligand and the potential of these respective complexes to have effective DNA binding and cleavage and cytotoxicity activities.