In Silico Investigation of Aristolochia longa Anticancer Potential against the Epidermal Growth Factor Receptor (EGFR) in the Tyrosine Kinase Domain

Abstract

This study employed in silico methods to identify potential therapeutic targets for the inactive EGFR tyrosine kinase domain in complex with Erlotinib (PDB: 4HJO) which is known to cause cancer, using natural extracts from Aristolochia longa root. A library comprising five natural compounds (Luteolin, 4-hydroxycinnamic acid, Kaempferol, ferulic acid, citric acid, and quinic acid) and the standard Erlotinib (control) were subjected to Lipinski's rule of five, ADMET parameter analyses, molecular docking and molecular dynamics simulation. Results revealed comparable pharmacological responses between the five compounds and the standard drug, demonstrating promising outcomes without limitations. Notably, Luteolin, Kaempferol, and quinic acid exhibited higher binding energies than the reference molecule, with binding affinities of -9.083 kcal/mol, -8.260 kcal/mol, and -5.857 kcal/mol, respectively. Molecular dynamics simulations confirmed the stability of the most effective EGFR protein-ligand, displaying consistent interaction profiles, favorable molecular properties, and a stable trajectory (RMSD, RMSF). Overall, these in silico analyses highlight the potential of aromatic and medicinal plant-derived compounds to inhibit EGFR protein associated with cancer development, emphasizing the need for further in vitro and in vivo investigations to explore their therapeutic applications in cancer patients.