Targeting GABAA receptor-associated protein using bioactive phytochemicals from Semecarpus anacardium for treatment of epilepsy

Abstract

Epilepsy is one of the most prevalent neurological illnesses, defined by a persistent susceptibility to epileptic seizures. Seizures cause aberrant impulses that disrupt electrical functioning in the brain, resulting in unannounced brain activity. Plant-derived medications have recently received increased attention due to their great efficacy with low toxicity and adverse effects, particularly in the treatment of neurodegenerative diseases. The work focusses on in silico molecular modeling to find novel and more potent antiepileptic phytocompounds from Semecarpus anacardium for the therapeutic management of epilepsy. Sixteen bioactive phytocompounds were identified using a data bank, and their frameworks were obtained from the PubChem directory. GABA_A receptor-associated protein (GABARAP) was utilized as a potent target for screening of antiepileptic agent. For further investigation, a very effective phytochemical based on binding energy was selected according to docking assessment. Molecular docking analysis identified amentoflavone (AME) as the most potent bioactive chemical against the GABARAP (-8.1 kcal/mol). A computational molecular dynamics inquiry confirmed the stability of the GABARAP+AME complex via normal mode analysis. The reactive spots and the structural steadiness of AME was assessed through density functional theory calculation. Further, to authorize drug-likeness belongings of top scored phytocompound AME, in silico pharmacokinetic and toxicity prediction was carried out. The intermolecular interaction measured by dynamic circumstances provided the path for the discovery of the bioactive chemical amentoflavone, which has effective anti-epileptic properties.