Abstract
Epilepsy stands out as one of the prevalent and severe brain disorders. Traditional medicinal plants have been used as remedies for epilepsy in various cultures. By utilizing natural lead compounds identified through virtual screening and pharmacokinetic prediction, it becomes feasible to develop effective lead molecules for the management of epilepsy. The primary aim of this study is therefore to conduct an in-silico investigation on the bioactive compounds present in medicinal plants traditionally used for treating epilepsy.
The study utilized computational tools including the Maestro 12.8 software on the Windows 10 platform. Ligand preparation involved obtaining SDF format files from the PubChem database and using the ligprep panel. Protein preparation included downloading protein structures from RCSB directory and utilizing the protein preparation wizard, followed by receptor grid generation to define active sites for docking. Molecular docking was performed using HTVS, and ADMET predictions were conducted using in-silico integrative models such as Swiss ADME to assess pharmacokinetic and toxicity properties of test compounds.
Results from the study revealed that 8 phytoconstituents from C. bonduc had higher binding affinity than the standard molecule diazepam against the GABA receptor protein, up to 45 exhibited higher binding affinity than tiagabine against the GAT receptor while 4 compounds were seen to have higher affinity than bumetanide against the Human NKCC receptor. 20 phytoconstituents from O. majorana were observed to have higher binding affinity than the standard against GAT, 22 compounds had higher binding affinity than diazepam against the GABA receptor while 4 compounds had higher score than Human NKCC standard. 8 phytoconstituents from A. squamosa had higher binding affinity than the standard molecule diazepam, 6 compounds had higher binding affinity than tiagabine while 4 compounds with comparative docking affinities as the standard against Human NKCC were selected together with the other compounds from the other target proteins for further screening. ADMET analysis revealed favorable pharmacokinetic and toxicity properties while post docking analysis showed the molecular interactions of ligands with the receptors.
In conclusion, in-silico studies of the various plant phytoconstituents provided considerable leads for further drug development and lead optimization.
