QSAR, molecular docking, and molecular designs of some anti-epilepsy compounds

Abstract

Epilepsy is a non-communicable central nervous system (CNS) disease that accounts for approximately 0.8–1.2 % of the global population at any time. The hyper-activities of gamma butyric acid aminotransferase (GABAAT) enzyme have been confirmed to be largely responsible for seizure/epilepsy. Because of this special function, the GABAAT enzyme has been the main target of many anti-epilepsy drugs (AEDs). To date, many discovered AEDs have not eradicated this neurological disease. Since experimental determinations of modern drugs are usually costly and sometimes non-eco-friendly, in-silco quantitative structure–activity relationship (QSAR)-machine learning, docking and pharmacokinetics (PMK) techniques were used to design and test the oral bio-availabilities of all the designed AEDs. QSAR models were generated, and the predictive properties of R2int = 0.9827, R2ext = 0.9407, and R2adj of 0.9667 indicate the evidence that the developed model was not by chance. Six (6) new AEDs were newly designed, and they were found to have better anti-epileptic activities values of 2.146799, 2.224866, 2.31479, 2.450313, 2.301474, and 2.618303 than the standard AED, Vigabatrin (0.40672). Also, the docked new compounds shows excellent binding energies of −127.001, −129.071, −130.515, −126.881, −130.771, and −126.974 kcal/mol compared to the referenced AED (−76.9173 kcal/mol). The PMK and absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations also revealed that all the designed compounds were found to be bio-available for human administration. 'Therefore, the newly designed analogues (AEDs) could be considered as potential drug candidates for the treatment of epilepsy.