Open AccessSchiff-Based Metal Complexes of Lamotrigine: Design, Synthesis, Characterization, and Biological Evaluation
Author(s) -
Saima Najm,
Humaira Naureen,
Kishwar Sultana,
Fareeha Anwar,
Muhammad Mubbashir Khan,
Humaira Nadeem,
Muhammad Saeed
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.1c00027
Subject(s) - dihydrofolate reductase , protein data bank (rcsb pdb) , chemistry , schiff base , stereochemistry , lamotrigine , neurotoxicity , benzimidazole , lead compound , docking (animal) , combinatorial chemistry , enzyme , in vitro , biochemistry , organic chemistry , biology , toxicity , medicine , nursing , neuroscience , epilepsy
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 in vitro anticancer activity. The complexes 6b and 6c displayed the most potent antiproliferative activity against MCF-7 cell lines with an IC 50 value of 11.9 ± 0.27 and 12.0 ± 0.14 μM, respectively, as compared with the standard doxorubicin with an IC 50 value of 0.90 ± 0.14 μM. In vivo 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 6c 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., 6c ) were found to possess the most potent anticancer, anticonvulsant, and neurotoxic potential than lamotrigine alone.