In silico discovery of EGFR and HER2 inhibitors from Galium odoratum phytochemicals for bladder Cancer therapy

Bladder cancer is the most prevalent malignant neoplasm of the urinary system in both men and women, following prostate cancer, and constitutes 2% of all malignancies. Galium odoratum (L.) Scop have distinct anti-cancer capabilities attributed to its antioxidative components, including coumarins and flavonoids found in its leaves. This study seeks to analyze the inhibitory efficacy of EGFR and HER2 in the components of Galium odoratum (L.) Scop and to evaluate its nutraceutical and pharmaceutical potential for bladder cancer. The molecular docking technique was employed to examine the interactions between EGFR and ERBB2 receptors and the phytochemicals derived from the Galium odoratum (L.). Structural similarities of compounds with binding scores below −7 kcal/mol for EGFR were analyzed. The binding affinity of twelve phytochemical compounds from Galium odoratum (L.) Scop . with the EGFR receptor was determined to be < −6.5 kcal/mol. β-caryophyllene and β-selinene had the greatest binding affinity to EGFR. Structural comparison of the β-caryophyllene molecule with β-selinene and intermedeol revealed that they possess the same maximum common substructure (MCS). The MCS technique offers a more viable and adaptable option for forecasting bioactive chemicals. Molecular dynamics simulations further confirmed the structural stability of the β-caryophyllene–EGFR complex under dynamic conditions. By combining molecular docking, structural similarity assessment, and toxicity profiling, this work provides a rational framework for identifying structurally conserved bioactive scaffolds that may guide future drug development strategies. Experimental investigation of β-caryophyllene would clarify their suitability for medicinal applications.