IDENTIFICATION OF NATURAL EGFR TYROSINE KINASE INHIBITORS FROM CHENOPODIUM QUINOA WILLD. VIA COMBINATORIAL IN SILICO AND PHARMACOLOGICAL SCREENING

Abstract

Chenopodium quinoa Willd. seeds are recognized for their nutritional value and therapeutic potential, largely attributed to their rich content of bioactive compounds such as phenolic acids and flavonoids, which exhibit antioxidant and anticancer properties. This study investigates the potential of C. quinoa secondary metabolites to inhibit the epidermal growth factor receptor (EGFR) tyrosine kinase using integrated computational approaches, including molecular docking,  and MM-PBSA binding free energy calculations. Molecular docking results revealed that a key bioactive compound from C. quinoa binds strongly to the active site of the EGFR tyrosine kinase domain (PDB ID: 1M17), achieving a docking score of –10.215 kcal/mol, which compares favorably with the standard inhibitor erlotinib. In silico ADMET prediction confirmed the drug-likeness of the identified compound, indicating no significant toxicity (e.g., hERG inhibition, hepatotoxicity, or skin sensitization), non-mutagenic properties, and a favorable blood-brain barrier permeability profile. The BOILED-Egg model further suggested high gastrointestinal absorption and oral bioavailability, along with efflux from the central nervous system. The computational findings demonstrate that C. quinoa contains compounds with high binding affinity for EGFR, surpassing that of erlotinib, suggesting its potential as a source of novel EGFR inhibitors. Consequently, C. quinoa represents a promising candidate for anticancer drug development, warranting further in vitro and in vivo validation to confirm its therapeutic efficacy.

Keywords: 

Chenopodium Quinoa, Antidiabetic, Antioxidant, EGFR Activation, Molecular Docking, ADMET, Phenolic acids, Functional Food, In Silico Toxicology