Synthesis and biological evaluation of Cu(II) Aroyl-Hydrazone Schiff Base complexes with anticancer activity against breast cancer cells.

Two novel Cu(II) Schiff base complexes were synthesized using aroyl-hydrazone ligands containing pyrrole (Complex 1) and furan (Complex 2) moieties and characterized through FTIR, UV-Vis, EPR, ESI-MS, and NMR spectroscopy, supported by DFT calculations. Spectroscopic and computational analyses confirmed square-planar geometry with coordination via azomethine nitrogen and phenolic oxygen atoms. Binding interactions with bovine serum albumin (BSA) and calf thymus DNA (CT-DNA) were investigated using UV-Vis and fluorescence spectroscopy, revealing stronger affinity for Complex 1 (Kb = 8.52 × 105 M-1) compared to Complex 2 (Kb = 1.06 × 104 M-1). Molecular docking and 100 ns molecular dynamics simulations indicating the stable binding conformations. Cytotoxicity studies against human breast cancer cell lines (MDA-MB-231 and MCF-7) showed that Complex 2 exhibited higher potency (IC₅₀ = 26.91 μM and 41.30 μM, respectively) than Complex 1. ROS and DAPI staining assays demonstrated apoptosis induction by Complex 2 through redox modulation and sub-G1 cell cycle arrest, suggesting a ligand-driven, partially DNA-independent mechanism. This suggests a non-canonical behaviour of action where ligand-driven redox modulation, rather than DNA intercalation, triggers cell death. These findings highlight the significant role of heterocyclic substitution (pyrrole vs. furan) in modulating the biological activity of Cu(II) Schiff base complexes and underscore their potential as redox-active anticancer agents.