Molecular Docking, Drug-Likeness, and Toxicity Profiling of Taraxacum Officinale-derived Phytochemicals Against Estrogen Receptor Alpha (ERα) in Breast Cancer

Public interest in the anticancer potential of dandelion ( Taraxacum officinale ) root has grown following reports that its extract can induce cell death in cancer cell lines, but whether individual T. officinale phytochemicals directly engage estrogen receptor alpha (ERα), the principal target in hormone receptor-positive breast cancer, has not been characterised. This study computationally evaluated eight bioactive phytochemicals reported from T. officinale root (taraxasterol, lupeol, β-sitosterol, chlorogenic acid, caffeic acid, chicoric acid, luteolin, and quercetin) as potential ERα inhibitors, benchmarked against tamoxifen. Molecular docking was performed using AutoDock Vina against the ERα ligand-binding domain (PDB: 3ERT), with docking protocol validity confirmed by redocking the native ligand and calculating the root-mean-square deviation (RMSD). Drug-likeness was assessed using SwissADME (Lipinski's Rule of Five), and pharmacokinetic and toxicity behaviour were predicted using pkCSM. Redocking reproduced the native ligand pose with an RMSD of 0.260 Å. Binding scores ranged from -4.5 (lupeol) to -8.5 kcal/mol (luteolin), versus -9.8 kcal/mol for tamoxifen. Luteolin, quercetin, chicoric acid, β-sitosterol, and chlorogenic acid showed the most favourable docking energies; luteolin and quercetin reproduced key hydrogen bonds seen for the native ligand, though none reproduced tamoxifen's Asp351 salt bridge. Chlorogenic acid, caffeic acid, luteolin, and quercetin showed zero Lipinski violations, and all eight phytochemicals were hepatotoxicity-inactive in silico, unlike tamoxifen. These findings offer a receptor-level perspective on dandelion's reported anticancer activity and identify candidates warranting experimental validation.