Abstract

Abstract Glioblastoma (GBM), an aggressive primary brain tumor originating from glial cells, poses significant treatment challenges due to its rapid growth and invasiveness. The exact mechanisms of GBM's brain damage remain unclear. This study examines primary molecular markers commonly assessed in GBM patients, including brain‐derived neurotrophic factor (BDNF), platelet‐derived growth factor receptor A (PDGFRA), O 6 ‐methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA) using computational approaches. The study revealed significant differences ( p ≤ 0.05) in PDGFRA, EGFR, and VEGFA expression rates, which are particularly interesting. Additionally, MGMT and VEGFA showed higher hazard ratios. Expression levels of MGMT and VEGFA were visualized in immune and malignant cells using single‐cell RNA datasets GSE103224 and GSE148842. From a total of 48 compounds in Gracilaria edulis and 86 in Gracilaria salicornia , we identified 15 compounds capable of crossing the blood‐brain barrier. Notably, 2‐tridecanone (binding affinity [BA] = −4.2 kcal/mol; root mean square deviation [RMSD] = 1.479 Å) and decanoic acid, ethyl ester (BA = −4.2 kcal/mol; RMSD = 1.702 Å) from G. edulis interacted with MGMT via hydrogen bonds. The compound alpha‐terpineol interacted with MGMT (BA = −5.7 kcal/mol; RMSD = 0.501 Å) and VEGFA (BA = −4.7 kcal/mol; RMSD = 2.483 Å). Ethanolic and methanolic extracts from G. edulis and G. salicornia demonstrated mild anti‐cell proliferation properties in the GBM LN‐229 cell line, suggesting potential therapeutic benefits. This study highlights the significance of molecular markers and natural compounds in understanding and potentially treating GBM.