Synthesis and characterization of copper-based anticancer compound; in vitro interaction studies with DNA/HSA, SOD...

A new copper(II) complex derived from the ligand ethylene [O,O'-bis{5-{(1E)-(2 hydroxyphenyl)methylene]amino} - 2-hydroxybenzoic acid] was designed, synthesized and characterized by spectroscopic (IR, UV-Vis, ESI-MS, X-ray diffraction, EPR and elemental analytical methods. In vitro interaction studies were carried out with CT DNA, HSA and SOD targets by employing various biophysical methods viz., UV-Vis, fluorescence, FTIR (in case of HSA only), circular dichroism and gel electrophoresis. Notably, the copper(II) complex exhibited a high propensity for DNA binding via electrostatic mode; The results of fluorescence titration revealed that the copper(II) complex strongly quench the intrinsic fluorescence of HSA through a static quenching procedure. Copper(II) complex cleaves pBR322 DNA via hydrolytic mechanism and strongly binds to the DNA minor groove. Furthermore, Copper(II) complex cleaves pBR322 DNA via hydrolytic pathway. Our results showed that copper(II) complex is capable of inhibiting the growth of MCF7, A2780 and K562 tumor cell lines revealed remarkable cytotoxicity of Cu(II) complex with GI₅₀ values <10 μg mL^-1 for most of the cell lines tested, which accompanied by systemic toxicity as was evident from the slightly significant histopathologic alterations in liver of mice. In addition, Cu(II) complex exhibit excellent superoxide dismutase (SOD) mimetic activity with an IC₅₀ of 0.109 μM. Molecular docking studies of the Cu(II) complex were carried out with DNA, HSA and SOD targets to ascertain the specific binding mode thereby substantiated the spectroscopic results. Communicated by Ramaswamy H. Sarma.