Molecular Docking and ADMET Properties of Six Selected Cytotoxic Compounds From Citrus Aurantium And Commiphora africana Against Human Protein Tyrosine Kinase (PTK6) And Human Androgen Receptor (HAR)

Cancer is a life-threatening disease affecting both the young and the aged populations globally. A computational approach is a fast and robust method used in the virtual screening of compounds against target protein diseases such as cancer. This technique gives insight into selecting a candidate drug for design and development. The present study investigated six selected previously reported cytotoxic compounds using in silico studies for their potential use as anticancer inhibitors. Four acridone alkaloids (5-hydroxynoracronycine, citracridone-I, citracridone-III, and citrusinine-I) from Citrus aurantium and two resveratrol compounds (3-hydroxy-5-methoxybenzoic acid and pinostilbene) from Commiphora africana were selected as ligands. Target proteins: human protein tyrosine kinase (PTK6) and human androgen receptor (HAR) were retrieved from the RCSB Protein Data Bank (PDB) web server with ID 1E3G and 6CZ4, respectively. Ligand-protein interactions were modeled using molecular docking. The pharmacokinetic properties of compounds were established via SwissADME and ADMET web servers. Pinostilbene and 5-hydroxynoracronycine revealed the highest binding affinity scores of -8.8 and -9.6 kcal/mol against target proteins-1E3G and 6CZ4, respectively. The docking scores of reference drugs- cyclophosphamide and 5-fluorouracil were -5.4 and -5.2 Kcal/mol, respectively, for 1E3G, while 6CZ4 showed -5.7 and -5.1 Kcal/mol scores, respectively. All the studied compounds, including the reference drugs, revealed high gastrointestinal absorption with water solubility ranging from moderately soluble to very soluble and complied with Lipinski’s Rule of 5 without any violation. The present investigation suggests pinostilbene and 5-hydroxynoracronycine as potential inhibitors against cancer proliferation.