Copper(II) complexes with 4-(diethylamino)salicylaldehyde and α-diimines: Anticancer, antioxidant, antigenotoxic effects and interaction with DNA and albumins

• Published in: Journal of inorganic biochemistry 2022-10, Vol.235, p.111942, Article 111942
• Main Authors: Vitomirov, Teodora, Dimiza, Filitsa, Matić, Ivana Z., Stanojković, Tatjana, Pirković, Andrea, Živković, Lada, Spremo-Potparević, Biljana, Novaković, Irena, Anđelković, Katarina, Milčić, Miloš, Psomas, George, Ristović, Maja Šumar
• Format: Article
• Language: English
• Subjects: Albumins; Aldehydes; Antineoplastic Agents - pharmacology; Antioxidants - pharmacology; Coordination Complexes - pharmacology; Copper - pharmacology; Cu(II) complexes; Cytotoxicity; DNA - metabolism; Genotoxicity; HeLa Cells; Humans; Hydrogen Peroxide; Interaction with biomolecules; Molecular Docking Simulation; Phenanthrolines - pharmacology; Salicylaldehyde derivative
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2022.111942

In this article, cytotoxicity, the mechanisms of cytotoxic activity, genotoxicity, and interaction with DNA and proteins, of two Cu(II) complexes with a salicylaldehyde derivative (4-(diethylamino)salicylaldehyde) and α-diimine (2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen)) are reported. Both Cu(II) complexes performed cytotoxic effects against all tested malignant cell lines. Complexes exerted highest cytotoxicity against HeLa and A375 malignant cell lines. The cytotoxic activity of Cu(II) complex with phen as a α-diimine co-ligand was significantly higher in comparison with cytotoxic activity of Cu(II) complex with bipy. Pretreatment with specific inhibitors of caspase-3, caspase-8 or caspase-9, in order to clear up the mode of cell death triggered by two Cu(II) complexes in HeLa cells, indicated the ability of these complexes to induce apoptosis through activation of target caspases. Cu(II)-phen complex exhibited significant antioxidant activity compared with Cu(II)-bipy complex, and showed a better effect on reducing intracellular ROS levels in HeLa cells. Tested complexes did not display genotoxic potential in human peripheral blood leucocytes, but exhibited an antigenotoxic effect in post-treatment, after H2O2 exposure. The study of the in vitro biological properties regarding their affinity towards CT (calf-thymus) DNA and serum albumins showed that the compounds can intercalate to CT DNA, and bind reversibly and tightly to the albumins. Molecular docking studies of the ability of compounds to bind to biomacromolecules are consistent with in vitro studies. [Display omitted] •Cu(II) complexes with 4-(diethylamino)salicylaldehyde and α-diimines were studied.•Cytotoxic, antioxidant, antigenotoxic study and interaction with DNA and proteins.•The complexes showed good cytotoxic and antioxidant activity.•The complexes exhibited an antigenotoxic effect in post-treatment.•The binding to DNA is via intercalation, and to the albumins is reversibly.