Synthesis, Characterization, and Biological Evaluation of Novel Bioactive Schiff Base Metal Complexes and their Molecular Docking Studies

A series of bioactive cobalt(II) and copper(II) complexes were synthesized using novel thiol-containing aromatic amine Schiff base ligands and evaluated for their biological activities. We elucidated the type of bonding between Schiff base ligand and metal ions in the newly synthesized complexes using a variety of spectroscopic and analytical methods. The Schiff base ligand functions as a bidentate, coordinating with the metal ions via the azomethine nitrogen (N) and thiol sulfur (S), resulting in octahedral or tetrahedral geometries. These complexes demonstrated strong DNA binding interactions, with binding constants ranging from 102–104 M−1. Further, the ethidium bromide displacement assays indicated intercalative and groove-binding modes, supported by in-silico molecular studies. All these complexes also showed potent antioxidant activity, achieving up to 85 % inhibition in free radical scavenging assays. Further, the antimicrobial studies demonstrated potent efficacy against gram-positive (Vancomycin-resistant Enterococcus, Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, with minimum inhibitory concentrations range between 4 and 8 µg/mL. The In-vitro cytotoxicity assays against human breast cancer and hepatocellular carcinoma cell lines revealed significant anticancer potential, with IC50 found as low as 39.91 µM for complex 6. Morphological assessments confirmed apoptosis induction via oxidative stress-mediated pathways. Furthermore, density functional theory calculations validated the reliability of the synthesized complexes structural parameters and provided insights into their electronic properties. These results suggest that the synthesized cobalt(II) and copper(II) complexes hold significant promise as candidates for antimicrobial, antioxidant, and anticancer therapies, paving the way for potential pharmaceutical applications.