Molecular Docking, ADME and Toxicity Study of Dibenzo-α-pyrone derivatives for GABA and NMDA receptors for their antiepileptic activity

Abstract

The twelve most effective dibenzo-α-pyrone derivatives as anticonvulsant chemicals have been chosen from our earlier study, and their 2D structures have been determined. Using Spartan'14 version 1.1.2, the compounds' 3D structures were generated, optimized, and transferred in PDB format. Molecular docking investigations of effective anticonvulsant drugs utilized the Toshiba Satellite, Dual-core CPU, Windows 8 operating system, and the AutoDockVina of PyRx virtual screening program. PyRx was activated with the flexible docking option to dock the GABAAT enzyme, NMDA, and dibenzo-α-pyrone derivatives (Ligands) into the X, Y, and Z coordinate systems. Some Dibenzo- α -pyrone compounds were studied for their antiepileptic efficacy by molecular docking, absorption, distribution, metabolism, and toxicity. Docking analysis revealed that all the compounds have good binding scores, and SS9 derivative has the highest binding score compared to others in both the targets selected. ADME results revealed that most parameters are within limits, and toxicity analysis suggested that the designed compounds are low in toxicity. This research on molecular docking gives a valued insight for medicinal and pharmaceutical chemists to synthesize more derivatives of designed Dibenzo-α-pyrone compounds as lead for antiepileptic drugs, which would be more effective for managing convulsions.