Molecular design and docking analysis of the inhibitory activities of some α_substituted acetamido-N-benzylacetamide as anticonvulsant agents

Abstract

The concentrations of Gama aminobutyric acid (GABA) in the brain have been shown to be a major factor in the determinations of convulsions. Computational molecular docking study was carried out on the α_substituted acetamido-N-benzylacetamide (anticonvulsant agents) to complement our previous QSAR work with the help of Autodock vina version 4.0 of Pyrx software. Docking analysis revealed that all the compounds have better binding scores (with the highest binding score of − 13.8 kcal/mol) than the commercially sold antiepileptic drug vigabatrin (− 4.4 kcal/mol) but with the exception of ligands 2-acetamido-N-benzyl-2-hydroxyacetamide and 2-acetamido-N-benzyl-N-methyl-2-(pyrimidin-2-yl)acetamide which were revealed to have unpromising binding affinities. The most potent derivatives of α_substituted acetamido-N-benzylacetamide (2-acetamido-2-((3-aminophenyl)amino)-N-benzyl-N-methylacetamide with the experimental activity (pED50) of 1.99) from our previous QSAR research was in agreement with this present work as the same compound was revealed to be having the highest binding affinity (− 13.8 kcal/mol). Moreover, three anticonvulsant compounds were designed and one of the compounds (2-acetamido-2-((3-amino-4-vinylphenyl)amino)-N-benzyl-N-methylacetamide) with best binding score of − 14.15 kcal/mol was found to have excellently docked with GABAAT enzyme through amino acid residues of Lys203, Pro347, Arg430, Thr353, Arg192 and Ala346 than the commercially sold vigabatrin (− 4.4 kcal/mol). This study provides a valuable approach for pharmaceutical as well as medicinal chemists to synthesis these newly designed anticonvulsant drugs from α_substituted acetamido-N-benzylacetamide that will be more efficient in managing convulsion.