Network Pharmacology and Docking-Based Evaluation of Quercetin as an Inhibitor of PI3K Pathway in Glioblastoma
Year: 2025
Type: article
Abstract: Background: Glioblastoma multiforme (GBM) is a brain tumor that is the most aggressive and treatment-resistant tumor in adults. It has poor survival outcome. The abnormal activation of the PI3K/AKT/mTOR signaling pathway is one of the major mechanisms driving GBM progression. The limited potential and toxic nature of synthetic inhibitors necessitate safer substitutes. Quercetin, a type of flavonoid obtained from plants, shows anticancer capabilities; however, nothing is known about its multi-target potential in GBM via PI3K inhibition. Methods: The approach relied on using systems pharmacology and molecular docking. Using network pharmacology, researchers predicted potential targets of quercetin and compared them with GBM associated genes. Functional enrichment analyses were performed using GO and KEGG. Molecular docking study was performed with PI3Kγ (PDB ID: 4OVU) and SwissADME drug-likeness. Results: Quercetin significantly influences the binding activity associated with receptor tyrosine kinases and regulatory and catalytic activity of PI3K. The docking analysis revealed that quercetin has a stronger binding affinity (-8.6 kcal/mol) with PI3Kγ when compared with idelalisib (-7.6 kcal/mol). Quercetin was found to form hydrogen bonds and electrostatic interactions with amino acids of PI3Kγ like GLU-201, ARG-90, and ARG-209. Quercetin showed good solubility, GI absorption and inhibition profile of CYP. Conclusion: quercetin is highlighted as a possible multi-target inhibitor of the PI3K/AKT/mTOR pathway in GBM in this study. The features that ensure modifications and stability, can create its potential as a natural and safer therapeutic in future drug development for GBM.
Source: Bioinfo Chem
Institution: Galgotias University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: hybrid
Funder: Galgotias University
OpenAlex ID: W7212420448