Synthesis, characterization and biological evaluation of three novel copper (II) clonixinate complexes with methylpyridines: Insights into structure, DNA and BSA binding properties and anticancer activity

Three novel mononuclear copper(II) complexes 1-3 with clonixinate anion (clon) derived from clonixin (Hclon) and alpha-, beta-, or gamma-methylpyridine (alpha-, beta-, or gamma-pic) were synthesised. The compounds were characterised by IR, UV-Vis and EPR spectroscopy and elemental analysis. The redox properties of the prepared complexes were studied by square wave voltammetry. The structure of the complexes [Cu(clon)2(alpha-pic)2] (1), [Cu(clon)2(beta-pic)2] (2), [Cu(clon)2(gamma-pic)2] (3) was determined by single-crystal X-ray analysis and the intermolecular interactions were studied by Hirshfeld surface analysis. The interaction of the studied complexes with calf thymus DNA was investigated by UV-Vis absorption titration and further investigation of the possible intercalative mechanism of action was carried out by fluorescence quenching studies with ethidium bromide-DNA adduct monitored via fluorescence emission spectroscopy. Interactions with bovine serum albumin were also evaluated by fluorescence emission spectroscopy. The cytotoxicity and selectivity of 1-3 were studied in vitro on a human breast cancer cell line (MCF-7), a lung cancer cell line (A549), a human glioblastoma cell line (U-118MG) and healthy human fetal lung fibroblast cells (MRC-5). All three complexes showed low to moderate ability to interact with calf thymus DNA, probably through partial intercalation, high and reversible binding to serum albumin and promising cytotoxic effects on the MCF-7 cancer cell line with reasonable selectivity for complexes 1 and 2. Finally, the mitochondrial respiratory capacity of MCF-7 tumour cells was also studied and showed a reduced activity after the addition of the studied complexes.