Exploring the Pharmacodynamic and Molecular Interactions of Diosgenin as a Multitarget Therapeutic Agent in Breast and Ovarian Cancer Pathways

Diosgenin, a naturally occurring steroidal sapogenin, has emerged as a promising multi‐target anticancer candidate, particularly against hormone‐dependent and chemoresistant breast and ovarian cancers. This study comprehensively investigates its pharmacokinetic, toxicity, molecular docking, and dynamics profiles across six pivotal molecular targets: Serine/Threonine Kinase 11 (STK11), RAC‐Alpha Serine/Threonine‐Protein Kinase (AKT1), Epidermal Growth Factor Receptor (EGFR), Receptor Tyrosine‐Protein Kinase erbB‐2 (ERBB2), Estrogen Receptor Alpha (ESR1), and Cyclin D1 (CCND1). Pharmacokinetic profiling indicates high gastrointestinal absorption, favorable physicochemical characteristics, and low risk for CYP‐mediated interactions. Toxicity analyses confirmed diosgenin's safety, with an LD₅₀ above 8000 mg/kg. Molecular docking revealed high binding affinities with STK11 (−12.1 kcal/mol) and AKT1 (−10.8 kcal/mol), surpassing those of Paclitaxel, a clinically used control. Notably, diosgenin showed comparable or enhanced binding with EGFR and ERBB2, suggesting broader oncogenic pathway modulation. Molecular dynamics simulations (200 ns) validated the stability of the diosgenin–STK11 complex with RMSD stabilizing around 0.6–0.7 nm, Radius of Gyration ~1.89 nm, and robust hydrogen bonding patterns. MMPBSA analysis yielded a total binding free energy of −76.5 kJ/mol, driven predominantly by van der Waals interactions (−233.9 kJ/mol). A comparative dynamics study with Paclitaxel–STK11 revealed that while the control compound exhibited tighter RMSD (0.25–0.3 nm) and compactness (Rg ~1.47 nm), diosgenin maintained more adaptive but energetically stable interactions, supported by higher intra‐protein hydrogen bonding and favorable solvent exposure. These differences underscore diosgenin's potential to act via regulatory or allosteric mechanisms distinct from classical chemotherapeutics. Together, this computational evidence underscores diosgenin's potential as a safe, stable, and efficacious multi‐target anticancer scaffold, warranting subsequent in vitro and in vivo validation for translation into therapeutic applications.