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

09 February 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

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.

Keywords

Alpinia galanga
aromatase inhibitors
breast cancer
molecular docking
human placental aromatase

Supplementary materials

Title
Description
Actions
Title
APPENDICES Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment
Description
APPENDICES for "Molecular docking studies of Alpinia galanga metabolites against human placental aromatase for estrogen-dependent breast cancer treatment"
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.