CONTEXT: 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. MATERIALS AND 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. DISCUSSION AND CONCLUSION: 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.
CONTEXT: 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. MATERIALS AND 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. DISCUSSION AND CONCLUSION: 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: Mohammed A Baghdadi; Fahad A Al-Abbasi; Ali M El-Halawany; Ali H Aseeri; Ahmed M Al-Abd Journal: Molecules Date: 2018-04-26 Impact factor: 4.411