Identification of Medicinal Plant–Derived Active Compounds Targeting Glutathione S-Transferase (GST) in Fruit Fly

Glutathione S-transferase (GST) is a crucial enzyme in insects, involved in detoxifying plant-derived compounds and insecticides, thereby enhancing insect resistance. This study employed a bioinformatics approach to evaluate the inhibitory effects of phytochemicals from 14 medicinal plants on GST (PDB ID: 5F0G) using molecular docking. A total of 741 phytochemical compounds from plants including Artemisia absinthium, Achillea millefolium, Ferula assa-foetida, Datura stramonium, Estragon, Glycyrrhiza glabra, Nicotiana tabacum, Nerium oleander, Chrysanthemum spp., Rosmarinus officinalis, Juniperus spp., Urtica dioica, Salvia officinalis, and Allium sativum, along with two synthetic pesticides, diazinon and malathion, were analyzed. Compound structures were obtained from PubChem, and the GST active site was identified via CASTp and PyMOL. Docking simulations were performed using AutoDock Vina, with interactions visualized in LigPlot+ and Discovery Studio. Physicochemical and toxicological properties were predicted using pkCSM. Results indicated that phytochemical compounds such as Chamazulene, β-Acoradiene, Selin-4,7(11)-diene, and Digitoxigenine exhibited the strongest GST inhibition, while Dimethyl trisulfide showed the weakest activity. Overall, a total of 13 compounds showed binding energies stronger than –7 kcal/mol. β-Acoradiene from Achillea millefolium demonstrated the highest binding affinity, and ADMET profiling revealed favorable pharmacokinetic properties for most natural compounds, in contrast to higher toxicity of synthetic pesticides. These findings highlight the potential of specific phytochemical compounds as natural insecticide candidates targeting GST, offering an eco-friendly alternative to synthetic chemicals.