Biological and Medicinal Chemistry

Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment

Authors

  • JOE ANTHONY MANZANO Laboratory for Organic Reactivity, Discovery, and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015 Philippines & Department of Biological Sciences, College of Science, University of Santo Tomas, España Blvd., Manila 1015 Philippines ,
  • CECIL LAURENCE III CRUZ Laboratory for Organic Reactivity, Discovery, and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015 Philippines & Senior High School Department, University of Santo Tomas, España Blvd., Manila 1015 Philippines ,
  • ALLAN PATRICK MACABEO Laboratory for Organic Reactivity, Discovery, and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015 Philippines

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. Thus, a total of 119 database-derived A. galanga secondary metabolites was molecularly docked onto the catalytic site of human placental aromatase using the UCSF Chimera platforms according to the AutoDock Vina Broyden-Fletcher-Goldfarb-Shanoo (BFGS) algorithm. 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 exhibited druggability with at most one violation of the Lipinski Rule of Five (LRo5). Overall, the study indicates the potential of top A. galanga secondary metabolites as promising drug pharmacophores in developing therapeutics against breast cancer.

Content

Thumbnail image of Manzano et al_Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment_chemrxiv-MS.pdf

Supplementary material

Thumbnail image of Manzano et al_Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment_chemrxiv-Appendices.pdf
APPENDICES Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment
APPENDICES for "Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment"