title: Anti-estrogenic activity of mansonone G and mansorin A derivatives.
abstract: BACKGROUND
  Mansonone G and mansorin A are major bioactive constituents from Mansonia gagei Drumm (Sterculiaceae) wood, and their mild anti-estrogenic activity was reported previously by the authors.
  
  
  OBJECTIVE
  In order to increase the potency of their anti-estrogenic effect and to clarify their binding way to estrogen receptor on a molecular level, several derivatives of both compounds will be prepared and a docking study of the original compounds and their derivatives on estrogen receptor alpha (ERα) was carried out.
  
  
  METHODS
  The original compounds were isolated from the heartwood of M. gagei. Nine alkyl derivatives were prepared by acetylation, methylation, or adding a basic side chain to the free hydroxyl group of both compounds. The estrogenic/anti-estrogenic activities of the derivatives compared to the original compounds were carried out using ERα competitive binding screen and yeast two-hybrid assay expressing ERα and ERβ using concentrations ranging from 10 to 100 μM.
  
  
  RESULTS
  Acetyl mansonone G showed a 10-fold increase in its binding ability to ERα compared to mansonone G with an IC₅₀ 630 μM. Similarly, methyl mansonone G and acetyl mansonone G showed 50% and 35% inhibition of 17β-estradiol-induced β-galactosidase activity at 10 μM in the yeast expressing ERα, and 42% and 30%, respectively, at 10 μM in the yeast expressing ERβ. Virtual docking of acetyl mansonone G to ERα showed that it binds, with its acetyl oxygen, in a similar way to the 17β-OH of estradiol.
  
  
  CONCLUSIONS
  The phenolic hydroxyl group in mansonones and mansorins was not essential for binding to estrogen receptors. In addition, acetyl mansonone G could represent a promising starting material for the synthesis of anti-estrogenic agents.
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. ahalawany2003@yahoo.com
authors.forename: Ali M
authors.initials: AM
authors.lastname: El-Halawany
authors.forename: Riham
authors.initials: R
authors.lastname: Salah El Dine
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
mesh_terms: D003374:Coumarins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D020128:Inhibitory Concentration 50; D019660:Malvaceae / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009285:Naphthoquinones / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000187:drug effects / Q000378:metabolism
chemical_list: C586322:3,8-dimethyl-5-isopropyl-6-methoxycoumarin; D003374:Coumarins; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009285:Naphthoquinones; C586321:mansonone G; D004958:Estradiol; D001616:beta-Galactosidase