Molecular Docking and ADME-Based Prioritization of 20 Quinazolinone Scaffolds for Anticonvulsant Potential

Quinazolinone derivatives have attracted significant attention for their broad pharmacological potential, particularly in the treatment of central nervous system (CNS) disorders such as epilepsy. In the present study, a series of twenty novel quinazolinone derivatives were designed and evaluated for their potential anticonvulsant activity through molecular docking studies. The compounds were docked into the active site of the GABAAreceptor, a wellestablished target for antiepileptic drugs, using its crystallographic structure (PDB ID: 4COF). Molecular docking was carried out using AutoDockVina, and binding affinities were compared to standard antiepileptic agents. Several compounds demonstrated high binding affinity toward the receptor, with key hydrogen bonding and hydrophobic interactions involving critical amino acid residues such as TYR157, THR202, and PHE77. The top-performing derivative exhibited a binding energy of –9.3 kcal/mol, suggesting strong interaction and potential modulation of GABAergic signaling. These results support the potential of quinazolinone scaffolds as promising leads for the development of new anticonvulsant agents, and warrant further in vitro and in vivo validation.