Synthesis, characterization, DNA/HSA interactions and in vitro cytotoxic activities of two novel water-soluble copper(II) complexes with 1,3,5-triazine derivative ligand and amino acids

Two water-soluble copper(II) complexes of 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine (pzta) and amino acids, [Cu(pzta)(L-ArgH)(H2O)](ClO4)(2) (1) and [Cu(pzta)(L-Met)(H2O)]ClO4 center dot 3H(2)O (2) (L-ArgH: protonated L-Argininate; L-Met: L-Methioninate), were synthesized and characterized. The determined X-ray crystallographic structures of 1 and 2 exhibited distorted square-pyramidal coordination geometries. Their binding properties toward calf thymus DNA (CT-DNA) and human serum protein (HSA) were measured by spectroscopic (UV-Vis, fluorescence, circular dichroism (CD)), calorimetric (isothermal titration calorimetry (ITC)) and molecular docking technology. DNA binding experiments showed that the complexes bound to DNA through a groove binding mode, the positive Delta H and Delta S values indicated that the hydrophobic interaction was the main force in the binding between the complexes and DNA. Besides, the complexes caused the fluorescence quenching of HSA through a static quenching procedure, changed the secondary structure and microenvironment of the Trp-214 residue, and preferably bound to subdomain IIA of HSA driven by hydrophobic and hydrogen-bond interactions. These results were further verified by the molecular docking technology. Furthermore, the in vitro cytotoxicities of the complexes against three human carcinoma cell lines (A549, PC-3 and HeLa) were evaluated, which confirmed that the complexation improved the anticancer activity of the pzta ligand significantly.