Synthesis, Characterization, and Bioactivity of a Dioxime-Based Copper(II) Complex: SOD/Catalase Mimicry, DNA/HSA Binding, and In Silico Evaluation for Cuproptosis-Mediated Anticancer Activity

Cisplatin’s chemotherapy is hindered by drug resistance and toxicity, making copper complexes a potential alternative. A novel copper(II) complex, CuLBr, was synthesized from a tetradentate vicinal dioxime ligand (H2L) and characterized. CuLBr features a distorted square pyramidal geometry with a CuN4Br chromophore. DFT calculations showed a narrowed HOMO-LUMO gap and increased electrophilicity, enhancing its chemical reactivity. CuLBr exhibited potent biomimetic catalytic activity, functioning as an efficient superoxide dismutase mimic and catalase mimic. Biophysical studies (UV-Vis, fluorescence, and viscosity) demonstrated a strong, spontaneous affinity of CuLBr for calf thymus DNA and Human Serum Albumin, suggesting groove-binding and static quenching mechanisms. In vitro assays revealed superior anticancer activity against HepG-2, HCT-116, and MDA-MB-231 cell lines, with greater selectivity than the free ligand and doxorubicin. Molecular docking studies reveal a high binding affinity of CuLBr with key proteins, including ferredoxin-1 and VEGF. This may suggest potential dual mechanisms of action, involving the induction of cuproptosis and the inhibition of tumor angiogenesis. These findings position CuLBr as an effective multi-metal-based anticancer agent with advantageous selectivity.