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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>A series of reduced Schiff base ligands derived from salicylaldehyde (1) and methoxybenzylamines (2a\u2013c) were prepared and used to prepare three copper(II) complexes, 5a (2-methoxyderivative), 5b (3-methoxyderivative), and 5c (4-methoxyderivative). They were characterized by spectral methods and X-ray crystallography. The complexes showed DNA cleavage activity, with 30% cleavage at 3 \u00d7 10\u22123 M and up to 94.5% at 5 \u00d7 10\u22123 M. Absorption titration studies with ct-DNA and EB-DNA displacement methods revealed strong binding of the prepared complexes, with complexes 5b and 5c favored. Viscosity measurements and thermal degradation of DNA studies indicate DNA groove binding. All complexes exhibit a moderately strong binding affinity to serum albumin. The complexes performed very well in the resazurin assay monitoring mitochondrial activity, with significant cytotoxic effects (around 95% already at 1 \u00d7 10\u22124 M). The MTT assay confirmed the complexes\u2019 cytotoxicity against cancer cell lines (A549, HepG2) compared with HEL fibroblasts. All complexes showed remarkable selectivity for HepG2 cells, with selectivity indices (HEL vs. HepG2) up to 3.05 for complex 5a, and complex 5b achieved the lowest IC50 (33.0 \u00b1 5.3 \u03bcM) against HepG2 cells. From a regioisomerism perspective, complex 5a outperformed the others in DNA cleavage; complex 5b, with the 3-methoxy group, showed the most interesting cytotoxicity results, and both complexes 5b and 5c showed good DNA-binding properties.<\/jats:p>","DOI":"10.3390\/ijms27198650","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"8650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Schiff Base Copper(II) Complexes Derived from 2-, 3-, and 4-Methoxybenzylamine: DNA Binding and Cleavage, BSA Binding, Cytotoxic and SOD Mimetic Properties"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1442-9951","authenticated-orcid":false,"given":"Lucia","family":"Lintnerov\u00e1","sequence":"first","affiliation":[{"name":"Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Peter","family":"Herich","sequence":"additional","affiliation":[{"name":"Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"},{"name":"Department of Physical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinsk\u00e9ho 9, 812 37 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jana","family":"Korec","sequence":"additional","affiliation":[{"name":"Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Barbora","family":"Svitkov\u00e1","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3508-5265","authenticated-orcid":false,"given":"Fl\u00f3ra","family":"Jozef\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"},{"name":"Department of Inorganic Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinsk\u00e9ho 9, 812 37 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Karol","family":"Lu\u0161pai","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, 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