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Metal complexes with oxindole- or benzimidazole-based ligands have been extensively studied regarding their antiproliferative activities. Herein, some copper(II) and analogous zinc(II) complexes with imine ligands containing both oxindole- and benzimidazolescaffolds had their toxicity toward cancerous cells evaluated. These compounds are derived from an endogenous oxindole (isatin), through a condensation reaction with 2-aminomethylbenzimidazole, and their structural and spectroscopic characterization were carried out by using different techniques, including elemental analyses, UV/Vis, FTIR, EPR and Raman spectroscopies, in addition to ESI-MS. The main goal was to verify how different scaffolds (oxindole- and benzimidazole-) could influence the activity of metal complexes. Investigations of these copper compounds interactions with DNA indicated that they bind preferentially at the double-strand grooves, causing oxidative damage by simple- or double-strand cleavages. This damage occurs through the generation of reactive oxygen species (ROS), mostly singlet oxygen, hydrogen peroxide, and superoxide ions, which were also able to damage human albumin (HSA), observed by SDS-PAGE gel, and to cause lipid peroxidation in phosphatidylcholine liposomes, verified by fluorescence measurements. Further, for analogous heteroleptic compounds Cu(isambz)(phenClO 4 4 and Zn(isambz)(phen)ClO 4 5 , containing also 1,10-phenantroline (phen) as secondary ligand, results signaled the radical hydroxyl as the most important ROS formed. The cytotoxicity of these metal complexes was then verified by assays of cell viability, using the reagent MTT, toward malignant cells (cervical HeLa and melanoma SK-Mel), compared to non-tumor cells (fibroblasts). Corresponding IC 50 values were determined for both cancerous cell lines in the range of a few μM, attesting their remarkable reactivity. Therefore, the herein focused metal compounds, exhibiting diverse targets, could be promising alternatives for metallodrugs against cancer.
Zaballa et al. (Thu,) studied this question.