Cytotoxic Cu(II) Complexes with a Novel Quinoline Derivative Ligand: Synthesis, Molecular Docking, and Biological Activity Analysis

Abstract

The utilization of metallodrugs as a viable alternative to organic molecules has gained significant attention in modern medicine. We hereby report synthesis of new imine quinoline ligand (<b>IQL</b>)-based Cu(II) complexes and evaluation of their potential biological applications. Syntheses of the ligand and complexes were achieved by condensation of 7-chloro-2-hydroxyquinoline-3-carbaldehyde and 2,2'-thiodianiline, followed by complexation with Cu(II) metal ions. The synthesized ligand and complexes were characterized using UV-vis spectroscopy, TGA/DTA, FTIR spectroscopy, ¹H and ¹³C NMR spectroscopy, and pXRD. The pXRD diffractogram analysis revealed that the synthesized ligand and its complexes were polycrystalline systems, with nanolevel average crystallite sizes of 13.28, 31.47, and 11.57 nm for <b>IQL</b>, <b>CuL</b>, and <b>CuL</b> _<b>2</b> , respectively. The molar conductivity confirmed the nonelectrolyte nature of the Cu(II) complexes. The biological activity of the synthesized ligand and its Cu(II) complexes was evaluated with <i>in vitro</i> assays, to examine anticancer activity against the <i>MCF-7</i> human breast cancer cell line and antibacterial activity against Gram-positive (<i>Staphylococcus aureus</i>) and Gram-negative (<i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>) bacterial strains. The <b>CuL</b> complex had the highest cytotoxic potency against <i>MCF-7</i> breast cancer cells, with an IC₅₀ of 43.82 ± 2.351 μg/mL. At 100 μg/mL, <b>CuL</b> induced the largest reduction of cancer cell proliferation by 97%, whereas <b>IQL</b> reduced cell proliferation by 53% and <b>CuL</b> _<b>2</b> by 28%. The minimum inhibitory concentration for <b>CuL</b> was found to be 12.5 μg/mL against the three tested pathogens. Evaluation of antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl revealed that <b>CuL</b> exhibited the highest antioxidant activity with IC₅₀ of 153.3 ± 1.02 μg/mL. Molecular docking results showed strong binding affinities of <b>CuL</b> to active sites of <i>S. aureus</i>, <i>E. coli</i>, and <i>estrogen receptor alpha</i>, indicating its high biological activity compared to <b>IQL</b> and <b>CuL</b> _<b>2</b> .