In silico Evaluation of Paroxysmal Neurological Disorders Using Molecular Docking Analysis of Hydantoin-Based Compounds Targeting Protein 1XBL for Anticonvulsant Activity

Introduction: Paroxysm is a chronic neurological disorder characterized by recurrent seizures resulting from abnormal neuronal activity, necessitating the development of safer and more effective anticonvulsant agents. In the present study, a series of hydantoin-based derivatives (RT-1 to RT-9) were evaluated using an integrated in silico approach combining molecular docking and ADMET analysis. Materials and Methods: The target protein (PDB ID: 1XBL) was employed to investigate ligand-protein interactions and binding affinity. Results: Molecular docking results revealed that all compounds exhibited moderate to strong binding affinity, with docking scores ranging from -6.9 to -7.9 kcal/mol. Among them, RT-3, RT-4, and RT-5 demonstrated the highest binding affinity, supported by multiple stabilizing interactions, including hydrogen bonding, hydrophobic contacts, and electrostatic interactions with key amino acid residues such as ASN197, GLU193, and ARG587. ADMET analysis indicated that RT-5 exhibited the highest LD₅₀ value, suggesting low acute toxicity, while RT-9 showed a balanced toxicity profile with minimal hepatotoxicity. Discussion: Pharmacokinetic evaluation revealed that selected compounds (RT-2, RT-5, RT-7, and RT-9) possess high gastrointestinal absorption, indicating good oral bioavailability. Drug-likeness assessment further identified RT-7 and RT-9 as favorable candidates with minimal rule violations. Conclusion: In this research paper; the study highlights RT-3, RT-5, and RT-9 as promising lead compounds for anticonvulsant drug development. However, further structural optimization and experimental validation are required to confirm their therapeutic potential. The findings demonstrate the effectiveness of combining molecular docking and ADMET profiling in accelerating drug discovery.