Synthesis, Structure, DNA/BSA Binding, DNA Cleaving, Cytotoxic and SOD Mimetic Activities of Copper(II) Complexes Derived from Methoxybenzylamine Schiff Base Ligands

Schiff base ligands prepared from salicylaldehyde and 2-, 3- and 4-methoxybenzylamine were used to prepare copper(II) complexes, characterized by spectral methods, elemental analysis and X-ray crystallography in the case of complex <b>4a</b> derived from 2-methoxybenzylamine. The DNA cleavage activity of the prepared complexes was exceptional, with best activities of over 95% one-strand cleavage for <b>4c</b> at 3 mM and full double-strand cleavage for complex <b>4a</b> at 5 mM. Absorption titration studies with ct-DNA revealed good binding constants (at 10⁵ M^-1) with a decrease of up to 56% light absorption. Meanwhile, the EB-DNA displacement method and viscosity studies revealed groove binding as a possible binding mode. For BSA binding studies, all three complexes showed K_BSA values in the optimal range for reversible BSA binding (10⁴ M^-1). The copper(II) complexes showed significant cytotoxic effects (67-96% at 1 mM) in mitochondrial activity monitoring assays. Cytotoxicity was confirmed against cancer cell lines (A549 and HepG2) and HEL cells. The complexes <b>4a</b> and <b>4c</b> exhibited high activity against HepG2 cancer cells (IC50 < 22 μM), comparable to cisplatin. The radical scavenging activity was determined by the INT method with the best IC50 for <b>4c</b> (189 ± 11 μM). Overall, complexes <b>4a</b> and <b>4c</b> with a methoxy group in the <i>ortho</i> and <i>para</i> positions show high potential in most determined activities, but mainly as DNA cleavers and as cytotoxic agents with selectivity against HepG2 cells.