In Silico Molecular Docking of Murraya koenigii (L.) Spreng. Metabolites against the Androgen Receptor

Abstract

Prostate cancer is strongly driven by androgen receptor (AR) signaling, making the AR ligand-binding domain an important therapeutic target. Murraya koenigii (L.) Spreng. contains diverse secondary metabolites with reported pharmacological activities, but their interaction with AR remains insufficiently characterized. This study evaluated 20 secondary metabolites of M. koenigii using molecular docking with AutoDock4, using SARM C-23 as the reference ligand. The docking protocol was validated by redocking the native ligand, yielding an RMSD of 0.77 Å. Nine metabolites showed more favorable predicted binding energies and lower inhibition constants than SARM C-23: mahanine, mahanimbine, isomahanine, pyrayafoline D, murrayazoline, O-methylmurrayamine, mahanimbinine, murrayacinine, and mahanimboline. Their predicted binding energies ranged from −10.03 to −11.48 kcal/mol, with Ki values of 3.84–44.60 nM. Interaction analysis indicated that these compounds occupied the AR binding site through predominantly hydrophobic and hydrogen-bond interactions. SwissADME analysis identified O-methylmurrayamine as having the most favorable overall predicted oral drug-likeness profile, although several high-affinity compounds showed excessive lipophilicity and/or poor predicted solubility. These findings identify promising AR-binding candidates from M. koenigii, particularly O-methylmurrayamine, which warrants further biochemical, cellular, pharmacokinetic, and in vivo validation.