A mononuclear PdII complex with Naphcon; crystal structure, experimental and computational studies of the interaction with DNA/BSA and evaluation of anticancer activity

Ramezanpour, A., Karami, K., Kharaziha, M., Zakariazadeh, M., Lipkowski, J., Shahpiri, A., Azizi, N. and Namazian, M., 2021. A mononuclear PdII complex with Naphcon; crystal structure, experimental and computational studies of the interaction with DNA/BSA and evaluation of anticancer activity. Polyhedron, 206, p.115333.

 

Throughout this study, a new palladium (II) complex, trans-[Pd(Naph)₂Cl₂], with naphazoline hydrochloride (Naphcon) as an imidazole derivative, 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole;hydrochloride, was synthesized and characterized by elemental analysis, spectroscopic methods (UV–Vis, IR, and ¹H NMR) and single crystal X-ray structure analysis. The cytotoxicity of Naphcon and the Pd^II complex were investigated in vitro against human breast (MCF-7) and cervical epithelial carcinoma (HeLa) cancer cells. The results revealed the higher anticancer activity of complex rather that of Naphcon against MCF-7 cell line. The findings of in vitro studies including fluorescence and UV–Vis spectroscopy, circular dichroism (CD), thermal denaturation and viscosity measurement indicated the interaction of the Pd^II complex with calf-thymus DNA (CT-DNA) via a combination of covalent and non-covalent interactions, whereas the free Naphcon interacted with CT-DNA mainly through the groove binding mode. Moreover, the ability of Naphcon and the Pd^II complex to cleave pUC57 plasmid DNA was investigated. In addition, the interaction of both Naphcon and its Pd^II complex was explored with bovine serum albumin (BSA) by means of absorption and fluorescence spectroscopy. The binding constant (K_b) could be calculated for compounds through these spectroscopic methods. Based on the competitive binding studies using Eosin, Ibuprofen and Digoxin as site markers, the binding site of the Pd^II complex and Naphcon was found to be located on site-III and I of BSA, respectively. Furthermore, protease activity of compounds was examined under physiological conditions. Finally, to validate all data obtained from biophysical studies, the molecular docking simulation was employed as a computational method.