Structure, DNA/proteins binding, docking and cytotoxicity studies of copper(II) complexes with the first quinolone drug nalidixic acid and 2,2'‑dipyridylamine.

This work presents the synthesis, structural characterization and biological affinity of the newly synthesized copper(II) complexes with the first antibacterial quinolone drug nalidixic acid (nal) or N-donor ligand 2,2'‑dipyridylamine (bipyam). [Cu(II)(nal)(bipyam)Cl], (2) reveals a distorted square pyramidal based geometry in Cu(II) atom confirmed by X-ray crystallography technique. The theoretical stabilities and optimized structures of the complex were obtained from DFT calculations. The ability of the complexes to bind with calf thymus DNA (CT DNA) were investigated by electronic absorption, fluorescence, circular dichroism, and viscosity measurements techniques. The experimental results reveal that the complexes strongly interact with CT DNA via intercalative mode but complex 2 exhibits the highest affinity giving K=3.91±0.13×10, M. The fluorescence spectroscopy measurements show that both complexes have the superior ability to the replacement of EtBr from DNA-bound EtBr solution and bind to DNA through intercalative mode. Both complex also shows the superior affinity towards proteins with comparatively high binding constant values which have been further revealed by fluorescence spectroscopy measurements. Molecular docking analysis indicates that the interaction of the complexes and proteins are stabilized by hydrogen bonding and hydrophobic interaction. Furthermore, the results of in vitro cytotoxicity reveal that the complex 2 has excellent cytotoxicity than 1 against human breast cancer cell lines (MCF-7).