Investigation of Hydantoin‐Based Drugs Used in the Treatment of Epilepsy Using Quantum Chemical Calculations, Molecular Docking, Molecular Dynamics, <scp>ADMET</scp>, In Vitro, and Spectroscopic Methods

ABSTRACT Present investigation deals with the structural and pharmacokinetic properties of hydantoin‐based drug molecules such as phenytoin, mephenytoin, and ethotoin. Hydantoin‐based drugs are widely used as anticonvulsants in the treatment of epilepsy. In this study, optimized structures, and theoretical vibrational wavenumbers of phenytoin, mephenytoin, and ethotoin molecules were determined using Gaussian 09 program with density functional theory (DFT) and B3LYP/6‐311++G(d,p) basis set, vibration mode assignments were performed with the GAR2PED program, and the theoretical results were supported by FTIR and Raman spectroscopy. In addition, thermodynamic parameters, Mulliken charge values, HOMO‐LUMO, natural bond orbital, MEP, hyperpolarizability analyzes of hydantoin‐based molecules were performed. Docking analysis of all molecules with the GABA‐AT receptor, which has an important place in epilepsy studies, were also carried out. Then, the molecular dynamic (MD) simulations of the hydantoin‐based drugs‐GABA‐AT complexes were realized for 50 ns. ADMET profiles of all molecules were determined and presented by parameters of toxicity and drug‐likeness. Additionally, to determine the effects of hydantoin‐based drugs on glioblastoma cells, cytotoxic effects of phenytoin, mephenytoin, and ethotoin were evaluated on U‐87 Human glioblastoma cell line.