Oral Presentation 21st International Conference on Biological Inorganic Chemistry 2025

DNA cleavage and antitumoral activity of zinc(II) and iron(III) complexes with a new phenol-based ligand containing uncoordinated thioether moieties (122185)

Rosely Peralta 1 , Daniele Durigon 1
  1. Federal University of Santa Catarina, Florianópolis, SANTA CATARINA, Brazil

Cancer is characterized by abnormal cell growth, metastasis, and the rapid spread of cells beyond their usual boundaries. Glioblastoma (GBM) is the most common and aggressive form of astrocytic tumor (1). Metals, like iron and zinc, which are abundant and essential in living systems, have been studied for their potential in cancer chemotherapy (2–5). 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. 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 a phenol-based N3O donor containing two thioether pendant arms and twocomplexes [Zn(L)(µ-OAc)]ClO4 (1), and [Fe2(L)(µ-OAc)(µ-O)](ClO4)2 (2) were synthesized and characterized.The DNA cleavage and interaction of 1 and 2 were evaluated, showing significant DNase activity. Complex 1 exhibits better activity than complex 2 at lower concentrations and with a faster rate of action. Both compounds appear to interact with DNA primarily through electrostatic interactions, showing a preference for the minor groove. The zinc compound cleaves DNA via a hydrolytic mechanism, while the iron complex operates through a mixed mechanism and ROS scavengers can partially inhibit the reaction. Lastly, the cytotoxicity activities of the complexes were studied against glioblastoma cancer cell lines. The cytotoxicity studies demonstrated a clear reduction in cell viability when exposed to the complexes, with distinct responses between primary GBM and C6 cells. The zinc complex 1 significantly reduced cell viability in GBM cells even at low concentrations but required higher concentrations for gliotypic C6 rat cells. In contrast, the iron complex was effective only in the highly tumorigenic primary GBM cells.

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