Exploring therapeutic potentials of Tridax procumbens for Glioma: An in-silico approach employed network pharmacology, molecular docking, and molecular dynamics simulation

Glioma is a frequent type of malignant brain tumor, originating from glial cells. Despite advances in understanding the molecular biology and genetics of gliomas, the treatment of high-grade gliomas remains challenging. This study focuses on the identification of potentially active compounds from the medicinal plant Tridax procumbens for the treatment of glioma. Using computational approaches such as virtual screening, ADMET profiling, network pharmacology, molecular docking, and molecular dynamics, ten potential phytocompounds were identified from a total of 106 compounds. Further analysis revealed a network of 170 common genes between the phytochemicals and disease genes, comprising 161 nodes and 2083 edges. Molecular docking experiments demonstrated that luteolin, quercetin, and 6-Hydroxyluteolin 6,3′-dimethyl ether 5-rhamnoside exhibited potential inhibitory activities against two targeted proteins, HSP90 and SRC. Luteolin with HSP90 protein and Quercetin with SRC protein complexes were found to be the highest in docking performance with the least binding affinities −10 kcal mol⁻¹ and −9.3 kcal mol⁻¹ respectively. Molecular dynamics simulations explored Quercetin-SRC and Luteolin-HSP90 interactions over 300 nanoseconds. Quercetin-SRC binding showed dynamic and flexible behavior with an RMSD, RMSF, and radius of gyration of 0.22 nm, 0.35 nm, and 2.12 nm, respectively, whereas Luteolin-HSP90 binding was more stable and less flexible, with an RMSD of 0.14 nm, RMSF of 0.14 nm, a radius of gyration of 1.74 nm, and maintained consistent strong interactions with specific solvent accessibility. The analysis of free binding energy in Quercetin-SRC and Luteolin-HSP90 complexes indicated highly favorable formation driven by altered interactions, with delta total values of −33.74 and −29.26 kcal/mol, respectively. Both phytochemical luteolin and quercetin showed strong inhibitory potential against HSP90 and SRC proteins, indicating their potential as effective therapeutic agent for glioma treatment. This integrated approach emphasizes the significance of these compounds in advancing treatment strategies for glioma. However, pre-clinical and clinical experimentations are required to establish the potential of T. procumbens as a treatment for glioma.