In Silico Potentials of Alpinia galanga Constituents against Human Placental Aromatase Vital in Postmenopausal Estrogen-dependent Breast Cancer Pathogenesis

Abstract

Breast cancer is the leading cause of cancer-related deaths among women. With the clinical success of several synthetic aromatase inhibitors (AIs) as therapeutic agents in post-menopausal estrogen receptor-positive breast cancer, natural products have been tapped in search of chemically diverse compounds with potential better effectiveness against aromatase while conferring reduced adverse effects. Alpinia galanga is among the Philippine native medicinal plants with extensive studies on its phytopharmacological properties, yet reports on its human placental aromatase inhibitory activity remain rudimentary. To determine the aromatase inhibitory activity of A. galanga in silico, a total of 119 database-derived A. galanga secondary metabolites were evaluated molecularly docked onto the catalytic site of human placental aromatase using the UCSF Chimera platforms according to the AutoDock Vina BFGS algorithm. To assess binding stability, molecular dynamics (MD) simulations using the GROMACS software package were carried out. Drug-likeness was assessed in silico using SwissADME. Of the screened compounds, galanolactone (1), 4-(3,4-dimethoxy-trans-cinnamoyl)-trans-cinnamic acid (2), isocoronarin D (3), quercetin (4), β-sitosterol (5), (E)-8ß,17-epoxylabd-12-ene-15,16-dial (6), galangin (7), labda- 8(17),12-diene-15,16-dial (8), 7-(4-Hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (9), and 3,5,7-trihydroxy-4-methoxyflavanone (10) conferred highest binding affinities against aromatase ranging from binding energies of –8.7 to –8.0 kcal/mol with notable formed hydrogen bonds and interactions against key amino acid residues. Top-ranked compounds were predicted to have good druggability, whereas MD simulations demonstrated the stability of the ligands inside the complex. Overall, the study indicates the potential of top A. galanga secondary metabolites as promising drug pharmacophores in developing therapeutics against breast cancer.