A Study on the Molecular Docking of Quinazolin-4(3H)-One Derivatives against GABAa Receptor: A Novel Approach to Epilepsy Treatment

Antiepileptic drugs are neither preventive nor curative and are employed solely as a means of controlling symptoms. Nowadays, many new active substances such as antiepileptic agents have been developed with the aim of inhibiting the protein targets of antiepileptic agents, which are selective gamma-aminobutyric acid (GABA). Selective GABA is the regulator of central nervous system (CNS) activity. Although the exact mechanisms of action of quinazolinones remain unknown, a study in epilepsy indicated that quinazolinones can enhance the action of GABA. In this study, diazepam and quinazolinone derivatives were used to simulate interactions through the selective GABA activation mechanism of the protein (PDB ID: 4COF), using the docking method with Autodock Vina ver.1.1.2. The role of the new drug development is (i) determining the lead compound, (ii) manipulating the substituent of the lead compound, and (iii) determine the list of new substituents. The results showed that the interaction potential of quinazolinone derivatives with the key residues at the active binding site of the protein could be enhanced by substituting functional groups at position-3 of quinazolinone, as indicated by the docking scores of quinazolinone derivatives ranging from -7.1 to -9.3 kcal/mol, which is higher than that of diazepam. It means they have higher binding energy interaction with the target receptor. Derivative Q-18 had higher binding energy than other quinazolinone derivatives because it has the smallest docking score. All new quinazolinone derivatives are feasible to synthesize and perform their in vitro evaluation. For further investigation, synthesis and in vitro evaluation are required to get antiepileptic activity.