Cl. Waller et al., USING 3-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS TO EXAMINE ESTROGEN-RECEPTOR BINDING AFFINITIES OF POLYCHLORINATED HYDROXYBIPHENYLS, Environmental health perspectives, 103(7-8), 1995, pp. 702-707
Certain phenyl-substituted hydrocarbons of environmental concern have
the potential to disrupt the endocrine system of animals, apparently i
n association with their estrogenic properties. Competition with natur
al estrogens for the estrogen receptor is a possible mechanism by whic
h such effects could occur. We used comparative molecular field analys
is (CoMFA), a three-dimensional quantitative structure-activity relati
onship (QSAR) paradigm, to examine the underlying structural propertie
s of ortho-chlorinated hydroxybiphenyl analogs known to bind to the es
trogen receptor. The cross-validated and conventional statistical resu
lts indicate a high degree of internal predictability for the molecule
s included in the training data set. in addition to the phenolic (A) r
ing system, conformational restriction of the overall structure appear
s to play an important role in estrogen receptor binding affinity. Hyd
rophobic character as assessed using hydropathic interaction fields al
so contributes in a positive way to binding affinity. The CoMFA-derive
d QSARs may be useful in examining the estrogenic activity of a wider
range of phenyl-substituted hydrocarbons of environmental concern. com
parative molecular field analysis, esrradiol equivalents, estrogen rec
eptor, poiychlorinated biphenyls, quantitative structureactivity reiat
ionships.