Effect of N(4)-Phenyl Substitution in 2-Oxo-1,2-dihydroquinoline-3-carbaldehyde Semicarbazones on the Structure, DNA/Protein Interaction, and Antioxidative and Cytotoxic Activity of Cu(II) Complexes

Abstract

A new ligand, 2-oxo-1,2-dihydroquinoline-3-carbaldehyde semicarbazone (OQsc-H) (<b>1</b>);, its N(4)-phenyl derivative (OQsc-Ph) (<b>2</b>); and their corresponding copper­(II) complexes [CuCl₂(OQsc-H)]·H₂O·CH₃OH (<b>3</b>), [CuCl₂(OQsc-Ph)­(H₂O)]·CH₃OH (<b>4</b>), and [CuNO₃(OQsc-Ph)­(H₂O)]­NO₃·H₂O·C₂H₅OH (<b>5</b>) have been synthesized and characterized by structural, analytical, and spectral methods, in order to investigate the influence of N(4)-phenyl substitution on structure and pharmacological properties. In all of the complexes, the ligands coordinated to the Cu­(II) ion in a neutral fashion via ONO donor atoms. The single-crystal X-ray structures of neutral complex (<b>3</b>) and cationic complex (<b>5</b>) exhibit a slightly distorted square-pyramidal structure, while neutral complex (<b>4</b>) revealed an octahedral structure. The interaction of the compounds with calf thymus DNA (CT-DNA) has been explored by absorption and emission titration methods, which revealed that compounds <b>1</b>–<b>5</b> could interact with CT-DNA through intercalation. A gel electrophoresis pictogram demonstrated the ability of the complexes (<b>3</b>–<b>5</b>) to cleave the pBR322 plasmid DNA through a hydrolytic process. The interactions of the compounds with bovine serum albumin (BSA) were also investigated using UV–visible, fluorescence, and synchronous fluorescence spectroscopic methods. The results indicated that all of the compounds could quench the intrinsic fluorescence of BSA in a static quenching process. Investigations of antioxidative properties showed that all of the compounds have strong radical scavenging potencies against hydroxyl radicals, 2,2-diphenyl-1-picrylhydrazyl radicals, nitric oxide, and superoxide anion radicals. Further, the cytotoxic effect of the compounds examined on cancerous cell lines such as human cervical cancer cells (HeLa), human laryngeal epithelial carcinoma cells (HEp-2), human liver carcinoma cells (Hep G2), human skin cancer cells (A431), and noncancerous NIH 3T3 mouse embryonic fibroblasts cell lines showed that all three complexes exhibited substantial cytotoxic activity. Further, all of the pharmacological investigations support the fact that there exists a strong influence of N(4)-phenyl substitution in semicarbazone