Comparative Molecular Field Analysis of Polyhalogenated Dibenzo-p-dioxins, Dibenzofurans, and Biphenyls

摘要

Comparative molecular field analysis was performed on polyhalogenated dibenzo-p-dioxins, dibenzofurans, and biphenyls for Arly hydrocarbon (Ah) receptor binding and enzyme inducing activities determined by others using in vitro assays. Since various members of all three classes of compounds have been shown to produce qualitatively similar toxicities, a separate Comparative Molecular Field Analysis (CoMFA) was performed on each class of compounds and on combinations of the different classes for each bioactivity. For the Ah receptor binding, the CoMFA-derived Quantitative Structure-Activity Relationships (QSARs) for all three classes of compounds and combinations thereof showed strong cross-validated correlations indicating that they are highly predictive. For enzyme induction, the QSARs were highly predictive for the furans, partially successful for the dioxins, and clearly unpredictive for the biphenyls.