Investigation of the diastereomerism of dihydrobenzoxathiin SERMs for ER alpha by molecular modeling.

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Zhuang S, Zhang J, Zhang F, Zhang Z, Wen Y, Liu W

Investigation of the diastereomerism of dihydrobenzoxathiin SERMs for ER alpha by molecular modeling.

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7298-305. doi: 10.1016/j.bmcl.2011.10.036. Epub 2011 Oct 19.

PubMed ID

22061644 [ View in PubMed

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Abstract

Molecular dynamics simulations were performed to investigate the distinct uterine activity of ten dihydrobenzoxathiin diastereomers against human estrogen receptor (ER) alpha. These diastereomers share similar binding mode to ER alpha ligand binding domain (LBD). Dihydrobenzoxathiin diastereomers with full antagonistic activity form more stable hydrogen bonds with Glu353 and His524 of ER alpha LBD than corresponding diastereomers. The molecular mechanics based generalized born surface area (MM-GBSA) analysis revealed that van der Waals interactions are predominant to the binding of dihydrobenzoxathiin diastereomers to ER alpha LBD. The per-residue free energy decomposition analysis revealed that the uterine activity difference is contributed mainly by electrostatic interactions. Our study provides mechanistic insights into the difference of uterine activity for dihydrobenzoxathiin diastereomers.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Compound 18	Estrogen receptor alpha	IC 50 (nM)	1.7	N/A	N/A	Details
Compound 18	Estrogen receptor alpha	IC 50 (nM)	1.3	N/A	N/A	Details