Biomaterial Database

Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxybiphenyls. 1995

C L Waller, and D L Minor, and J D McKinney

Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

Certain phenyl-substituted hydrocarbons of environmental concern have the potential to disrupt the endocrine system of animals, apparently in association with their estrogenic properties. Competition with natural estrogens for the estrogen receptor is a possible mechanism by which such effects could occur. We used comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (QSAR) paradigm, to examine the underlying structural properties of ortho-chlorinated hydroxybiphenyl analogs known to bind to the estrogen receptor. The cross-validated and conventional statistical results indicate a high degree of internal predictability for the molecules included in the training data set. In addition to the phenolic (A) ring system, conformational restriction of the overall structure appears to play an important role in estrogen receptor binding affinity. Hydrophobic character as assessed using hydropathic interaction fields also contributes in a positive way to binding affinity. The CoMFA-derived QSARs may be useful in examining the estrogenic activity of a wider range of phenyl-substituted hydrocarbons of environmental concern.

UI	MeSH Term	Description	Entries
D011078	Polychlorinated Biphenyls	Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.	PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D011960	Receptors, Estrogen	Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.	Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular