Oleanolic acid purified from the stem bark of <i>Olax subscorpioidea</i> Oliv. inhibits the function and catalysis of human 17 <i>β</i> -hydroxysteroid dehydrogenase 1

Abstract

Cancer is a leading cause of global death. Medicinal plants have gained increasing attention in cancer drug discovery. In this study, the stem bark extract of <i>Olax subscorpioidea</i>, which is used in ethnomedicine to treat cancer, was subjected to phytochemical investigation leading to the isolation of oleanolic acid (OA). The structure was elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic (NMR) data, and by comparing its data with previously reported data. Molecular docking was used to investigate the interactions of OA with nine selected cancer-related protein targets. OA docked well with human 17<i>β</i>-hydroxysteroid dehydrogenase type-1 (17<i>β</i>HSD1), caspase-3, and epidermal growth factor receptor tyrosine kinase (binding affinities: -9.8, -9.3, and -9.1 kcal/mol, respectively). OA is a triterpenoid compound with structural similarity to steroids. This similarity with the substrates of 17<i>β</i>HSD1 gives the inhibitor candidate an excellent opportunity to bind to 17<i>β</i>HSD1. The structural and functional dynamics of OA-17<i>β</i>HSD1 were investigated by molecular dynamics simulations at 240 ns. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (-52.76, and -63.56 kcal/mol, respectively). The average C-α root mean square of deviation (RMSD) value of OA (1.69 Å) compared with the unbound protein (2.01 Å) indicated its high stability at the protein's active site. The binding energy and stability at the active site of 17<i>β</i>HSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.