Benzimidazole-Quinazoline Fused Derivativesvia In-Silico Study Approach Targeting GABA A Receptor for PET-based Brain Imaging

Epilepsy is a neurological disorder that originates from an electrical imbalance in the brain. According to the data, approximately. ~50 millionpeople are affected by this disease. Exploring the epileptic region of the brain using positron emission tomography/computed tomography (PET/CT) is beneficial to medical research and can lead to accurate treatment. Many radiopharmaceuticals are used to explore the brain using PET scans, which are verycost-effective. This article aims to design potent scaffolds based on a benzimidazole-quinazoline fused skeleton and systematically screen them through a multi-parameter in silico approach involving DFT calculations, ADMET profiling, target prediction, molecular docking, and molecular dynamics simulation. The GABA _A receptor is a crucial molecular target in epileptic conditions, and this study reveals that fluorine-substituted ligands have substantial binding affinities. In this study, it was observed that the fluorine (-F) atoms improved binding through hydrogen bonding and π-π interactions. The potent scaffolds can be radiolabeled with [ ¹⁸ F] fluorine atom to make suitable candidates for PET brain imaging. After screening the most promising scaffolds BEN01, BEN05, BEN07, BEN08, and BEN15, are shows the best physicochemical and pharmacokinetic characteristics. According to this study fluorinated benzimidazole–quinazoline fused ligands have the potential to be employed as radiopharmaceutical scaffolds for PET-based imaging of epileptic brain areas and other neurological disorders.