Copper(ii) complexes based on quinoline-derived Schiff-base ligands: synthesis, characterization, HSA/DNA binding...

Area of Science:

• Coordination Chemistry
• Medicinal Inorganic Chemistry
• Biophysical Chemistry

Background:

• Development of novel metal complexes for therapeutic applications.
• Understanding metal-ligand interactions with biological macromolecules like DNA and proteins.
• Schiff base ligands derived from quinoline offer versatile coordination properties.

Purpose of the Study:

• To synthesize and characterize novel copper(II) complexes with quinoline-derived Schiff base ligands.
• To investigate the binding interactions of these complexes with human serum albumin (HSA) and calf thymus DNA (CT-DNA).
• To evaluate the cytotoxic potential and mechanism of action of the synthesized copper(II) complexes against cancer cell lines.

Main Methods:

• Synthesis and characterization of copper(II) complexes ([Cu(L1)(NO3)2] (C1), [Cu(L2)Cl2] (C2), and [Cu(L2)SO4]2·H2O (C3)).
• Spectroscopic analysis (fluorescence quenching) and molecular docking to study HSA and CT-DNA binding.
• Cytotoxicity assays (MTT) against HeLa, HL-7702, Hep-G2, NCI-H460, and MGC80-3 cell lines.
• Cell cycle analysis and reactive oxygen species (ROS) detection to elucidate the mechanism of action.

Main Results:

• Copper(II) complexes (C1-C3) effectively bind to HSA via static quenching and hydrophobic interactions, and to CT-DNA through intercalation.
• The binding affinities of the copper(II) complexes with HSA and CT-DNA are superior to their parent ligands.
• Complexes C1-C3 exhibit significant cytotoxicity against HeLa cells, with C3 being 1.9-3.5 times more potent than cisplatin.
• Cell cycle arrest at the G0/G1 phase and ROS-mediated mitochondrial apoptosis were observed in tumor cells treated with these complexes.

Conclusions:

• Novel copper(II) Schiff base complexes demonstrate efficient binding to HSA and CT-DNA.
• These complexes possess promising anticancer properties, showing selective cytotoxicity against cancer cells and inducing apoptosis.
• The findings highlight the therapeutic potential of these copper(II) complexes as anticancer agents.