Investigating the Anti-glioblastoma Potential of Alkaloids from the Solanaceae Family: A Multi-Targeted Approach Using Network Pharmacology and Molecular Modeling Approaches
Abdulaziz Alamri, Nasimudeen R. Jabir, Chelapram K. Firoz, Khadeejah Alsolami, Mohd Shahnawaz Khan, Mohammad Hassan Alhashmi, Shams S. M. Tabrez · Journal of Computational Biophysics and Chemistry · 2025
Glioblastoma is a malignant and invasive brain cancer that is difficult to treat and has a short survival rate. This work aims to identify the efficiency of alkaloids from Solanaceae family as anti-glioblastoma drugs employing network pharmacology, molecular docking and molecular dynamics studies. Initially, key alkaloids were identified and screened for drug-likeness, oral bioavailability and molecular weight, resulting in the selection of seven promising compounds: Scopolamine, Atropine, Norhyoscyamine, Solanidine, Vindoline, Duboisine and Homatropine. By analyzing the microarray data, DEGs were obtained related to glioblastoma, and combined with the identified alkaloid targets to establish the compound–target–pathway network. Gene ontology and KEGG pathway analyses identified important biological processes and signaling pathways that contribute to glioblastoma development. Molecular docking analysis indicated the potential of the identified alkaloids to bind effectively with receptors including EGFR, MDM2 and AURKA which are fundamental in glioblastoma development. Molecular dynamics simulations at 100 ns supported the stabilities and interactions of these protein–ligand complexes as well. This thorough review indicates that Solanaceae alkaloids could serve as multifunctional drug candidates for glioblastoma treatment and provide a new direction for the pharmacotherapy of glioblastoma based on natural resources.