Evaluation of Anticancer Potency of Copper(II) Complexes of 7-Hydroxycoumarin N(3)-Substituted Thiosemicarbazones
TL;DR
Molecular docking analyses revealed that ligands HL1-HL4 and their copper(II) complexes were particularly effective in inhibiting the epidermal growth factor receptor (EGFR) protein.
Abstract
Anticancer activity of the 7-hydroxycoumarin N(3)-substituted thiosemicarbazones was evaluated against the human prostate cancer (DU145) and human embryonic kidney‑derived HEK293 cell lines. The cytotoxicity of the free ligands (HL1-HL4) along with the copper complexes [Cu(L1)Cl]-[Cu(L4)Cl] were checked using 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide (MTT) assay. The most potent compound, [Cu(L1)Cl], induced cell death of 56.25 ± 1.17, 73.30 ± 0.71, and 82.33 ± 0.47% at concentrations of 10, 50 and 100 μM, respectively. Cell viability assays revealed that [Cu(L1)Cl] suppressed cancer cell proliferation in a dose-dependent manner with minimal cytotoxic toward HEK293 cells. Acridine Orange/Ethidium Bromide (AO/EB) staining of the compound [Cu(L1)Cl] demonstrated apoptotic morphological changes in DU145 cells, including nuclear shrinkage and chromatin condensation. The intracellular reactive oxygen species (ROS) generation induced by the compound [Cu(L1)Cl] in DU145 cells was evaluated using the 2’,7’-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe. The results showed a significant elevation in ROS levels compared with the untreated control group, with ROS production increasing in a concentrationdependent manner. Additionally, molecular docking analyses revealed that ligands HL1-HL4 and their copper(II) complexes were particularly effective in inhibiting the epidermal growth factor receptor (EGFR) protein.