Integrated Molecular Docking Analysis and Pharmacokinetic Evaluation of Lupeol as Potential Inhibitor of Aurora kinase A (AURKA)

Abstract

Despite the remarkable advancement in the therapeutic strategies for cancer, hepatocellular carcinoma still remains an important cause of morbidity and mortality globally. Aurora kinase A (AURKA) is one of the most promising protein targets for hepatocellular cancer drug research. Natural products continue to provide valuable lead compounds for drug discovery while computational methods enable rapid evaluation of their therapeutic potential before experimental studies. Numerous pharmacological studies have demonstrated that lupeol possesses anti-inflammatory, antioxidant, antimicrobial, hepatoprotective and anticancer activities. However, its molecular interaction with AURKA remains inadequately characterized. This study investigated the binding affinity, molecular interaction, drug-likeness and pharmacokinetic characteristics of lupeol against AURKA using computational tools. Three-dimensional crystal structure of AURKA was retrieved from the Protein Data Bank and prepared by removing water molecules, followed by the addition of polar hydrogen atoms and Gasteiger charges. The three-dimensional structure of lupeol was retrieved from PubChem and docked into the active site of AURKA using AutoDock Vina. Docking validation was carried out by re-docking of the native ligand and root mean square deviation analysis. AURKA-lupeol interactions were analyzed using BIOVIA Discovery Studio Visualizer 2021. Pharmacokinetic properties, drug-likeness, and medicinal chemistry parameters of lupeol were predicted using SwissADME web server. Molecular docking analysis demonstrated that lupeol exhibited a binding affinity of -10.0 kcal/mol toward AURKA, forming alkyl-hydrophobic interaction and van der Waals contacts with amino acid residues within the ATP-binding pocket of AURKA. Lupeol has one Lipinski violation, high lipophilicity and predicted low gastrointestinal absorption but no P-glycoprotein substrate liability. The present study suggests that lupeol exhibits favorable binding interaction with AURKA and suitable pharmacokinetic properties, supporting its potential as a lead compound for further in vitro and in vivo anti hepatocellular cancer evaluation.