Multi-Target Interaction of Cymbopogon citratus Stapf and Cassia auriculata Linn Phytoconstituents in Epilepsy: An Integrated Molecular Docking, Dynamics, and MM/GBSA Study

Abstract

Background: Epilepsy is a complex neurological disorder characterised by dysregulated neuronal signalling, oxidative stress and neuroinflammation. The current AEDs have some limitations, such as drug resistance and side-effects, and thus the search for novel multi-target therapeutic agents is obligatory. The phytoconstituents of Cymbopogon citratus Stapf viz citral, neral, linalool and Cassia auriculata Linn viz apigenin, kaemferol, rutin, quercetin was evaluated in this study as possible antiepileptic modulators by integrated computational analyses.
Methods: Molecular docking was carried out with the epilepsy-related targets glycine receptor (PDB ID: 6UBS) and GABAA receptor (PDB ID: 4COF). The lead compounds linalool and apigenin were then further studied using 100 ns molecular dynamics simulation, binding free energy using MM/GBSA, energy decomposition analysis, and ADMET profiling.
Results: Docking scores for selected phytoconstituents were found to be ranging from −1.12 to −5.52 kcal/mol that showed favourable binding affinity of linalool and apigenin with both the targets. To assess the stability of the protein–ligand interactions, the molecular dynamics simulations were performed for 100 ns showing stable RMSD and RMSF profiles. The stability of these bindings was obtained from MM/GBSA analysis and was found to be high in both cases with ΔG bind of −40.66 and −40.53 kcal/mol in the cases of 4COF and 6UBS, respectively.
Conclusion: The results suggest that phytoconstituents of Cymbopogon citratus Stapf and Cassia auriculata linn are potential candidates for epilepsy therapeutic applications and are shown to exhibit favourable ADMET properties while interacting with a number of receptors.