Molecular Docking and Virtual Screening of Natural Compounds as Potential Anti-Glioblastoma Drugs

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. Fibroblast growth factor 2 (FGF2) is essential in normal neurodevelopment and promotes glioma growth and vascularization. This study aims to identify the binding sites of FGF2 protein receptors using molecular docking and virtual screening with natural compounds, and to determine the free binding energy between FGF2 protein and herbal active compounds from Indonesian plants. This research includes virtual screening with molecular docking using Vina on 1496 Indonesian herbal compounds, docking with Autodock4.2.6, and analysis of the Autodock4.2.6 docking results using Ligplot+. The amino acids derived from the FGF2 protein bind well to each of the FGFR 1-4 receptors. In the virtual screening, the synthetic compound Temozolomide had docking scores in the range (-4.4) to (-5.0), while compounds from Indonesian herbal plants had docking scores in the range (-6.8) to (-8.1). Hydrogen and hydrophobic interactions occur between the FGF2 receptor and selected herbal compounds. This shows the interaction is stable. These natural compounds will inhibit FGF2 binding to other receptors, thereby inducing apoptosis in FGF2. The results of blind docking show that the binding sites are similar, indicating good accuracy. In summary, Pyranoamentoflavone compounds found in nyamplung (Calophyllum Inophyllum), 5,3',5'-Trihydroxy-6,7,4'-trimethoxyflavone in kemuning (Murura Paniculata), and Sotetsuflavone in jamb antidote (Cycas Revoluta) have good potential as an FGF2 inhibitor as an anti-cancer drug for Glioblastoma.