Computational discovery of glioblastoma multiforme inhibitors from medicinal fungi: An integrated approach combining virtual screening, DFT, and toxicity profiling

Glioblastoma multiforme (GBM) is one of the deadliest brain cancers, notorious for its resistance to current treatments. To explore new therapeutic options, we turned to nature’s pharmacy - medicinal fungi. Using a comprehensive in silico pipeline, we screened 1,830 fungal metabolites from the MEFSAT database against a key GBM target protein (PDB ID: 5HJB). Promising candidates were refined through molecular docking, MM-GBSA energy profiling, and Density Functional Theory (DFT) calculations. Further analysis using QTAIM, SwissADME, and ProTox 3.0 helped predict stability, drug-likeness, and safety. Gallicynoic acid F (Ligand A3) stood out for its strong binding, low predicted toxicity, and favorable pharmacokinetics, making it a compelling lead for further exploration. Our findings suggest that fungal metabolites hold real potential as future GBM therapeutics.