In Silico Study of Bioactive Compounds from Faloak Stem Bark (Sterculia quadrifida R. Br.) Against Estrogen Receptor Alpha as Potential Breast Anticancer Agents

Abstract

Estrogen receptor alpha (ERα) is an important therapeutic target in hormone-dependent breast cancer, prompting the investigation of natural compounds with potential receptor-binding activity. This study aimed to evaluate the binding affinities and molecular interaction profiles of six bioactive compounds reported in Faloak (Sterculia quadrifida R. Br.) stem bark against ERα. Ligand structures were retrieved from PubChem, while the three-dimensional structure of ERα was obtained from the Protein Data Bank (PDB ID: 3ERT). Molecular docking was performed using PyRx version 0.8, and selected binding poses were analyzed using BIOVIA Discovery Studio Visualizer. The co-crystallized ligand, 4-hydroxytamoxifen, was used as the reference ligand. The docking scores of the tested compounds ranged from −7.1 to −8.6 kcal/mol, compared with −9.5 kcal/mol for 4-hydroxytamoxifen. Catechin-4-ol 3-O-α-L-rhamnopyranoside exhibited the most favorable docking score among the tested compounds and formed interactions with Glu353, Leu387, Met343, Leu525, Met421, Phe404, and Leu391. The observed hydrogen-bonding and hydrophobic interactions showed similarities to the interaction profile of the reference ligand, supporting the prioritization of this compound for further investigation. These findings identify catechin-4-ol 3-O-α-L-rhamnopyranoside as a promising computational candidate for further ERα-targeted research. However, molecular docking alone cannot establish receptor antagonistic activity or anticancer efficacy. Further molecular dynamics simulations and experimental studies are required to evaluate binding stability, biological activity, safety, and potential therapeutic relevance in breast cancer.