Identification of Xenoestrogens in Food Additives by an Integrated in Silico and in Vitro Approach

被引：61

作者：

Amadasi, Alessio ^{[2
]}

Mozzarelli, Andrea ^{[1
,2
]}

Meda, Clara ^{[4
]}

Maggi, Adriana ^{[4
]}

Cozzini, Pietro ^{[1
,3
]}

机构：

[1] Natl Inst Biostruct & Biosyst, I-00136 Rome, Italy

[2] Univ Parma, Dept Biochem & Mol Biol, I-43100 Parma, Italy

[3] Univ Parma, Dept Gen & Inorgan Chem, I-43100 Parma, Italy

[4] Univ Milan, Ctr Excellence Neurodegenerat Dis, I-20133 Milan, Italy

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2009年 / 22卷 / 01期

关键词：

ESTROGEN-RECEPTOR-BETA; EFFICIENT MOLECULAR DOCKING; SUBTYPE-SELECTIVE LIGANDS; PROTEIN FLEXIBILITY; FREE-ENERGY; BINDING-AFFINITY; INTUITIVE CALCULATIONS; AUTOMATED DOCKING; STRUCTURAL BASIS; WATER-MOLECULES;

D O I：

10.1021/tx800048m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the search for xenoestrogens within food additives, we have analyzed the Joint FAO-WHO expert committee database, containing 1500 compounds, using an integrated in silico and in vitro approach. This analysis identified 31 potential estrogen receptor a ligands that were reduced to 13 upon applying a stringent filter based on ligand volume and binding mode. Among the 13 potential xenoestrogens, four were already known to exhibit an estrogenic activity, and the other nine were assayed in vitro, determining the binding affinity to the receptor and biological effects. Propyl gallate was found to act as an antagonist, and 4-hexylresorcinol was found to act as a potent transactivator; both ligands were active at nanomolar concentrations, as predicted by the in silico analysis. Some caution should be issued for the use of propyl gallate and 4-hexylresorcinol as food additives.

引用

页码：52 / 63

页数：12

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