Schiff-Based Metal Complexes of Lamotrigine: Design, Synthesis, Characterization, and Biological Evaluation.

In the current study, a series of Schiff base derivatives of lamotrigine are complexed with zinc, copper, silver, and tin and characterized by spectroscopic techniques and biological assays. Docking analyses revealed six complexes with favorable binding interactions, which were further subjected to anticancer activity. The complexes and displayed the most potent antiproliferative activity against MCF-7 cell lines with an IC value of 11.9 ± 0.27 and 12.0 ± 0.14 μM, respectively, as compared with the standard doxorubicin with an IC value of 0.90 ± 0.14 μM. anticonvulsant activities of the compounds were evaluated by the subcutaneous pentylenetetrazole model and neurotoxic activities by the minimal motor impairment model. The neurotoxicity of targeted compounds was measured using the rotating rod (ROT) method. Computational studies were carried out using the reported crystal structures of multidrug-resistant protein (PDB-ID: 2KAV) and dihydrofolate reductase (PDB-ID: 3GHW), indicating that the compound showed significant interactions at the voltage-gated sodium ion channel in the brain and at dihydrofolate reductase enzyme in the breast. Certain metal complexes of Schiff base ligands (e.g., ) were found to possess the most potent anticancer, anticonvulsant, and neurotoxic potential than lamotrigine alone.