Quantitative structure-activity relationships for estimating the aryl hydrocarbon receptor binding affinities of resveratrol derivatives and the antioxidant activities of hydroxystilbenes

摘要

Quantitative structure-activity relationships (QSARs) were developed for the aryl hydrocarbon receptor (AhR) binding affinity of non-fluorinated and fluorinated cis and trans 3,4',5-substituted resveratrol derivatives. Lower quality QSAR fits were found when all compounds were modeled together, in contrast to strong correlations with Hammett substituent constants and atomic charges for separate non-fluorinated/fluorinated and cisltrans groupings. The collective findings suggest little promise in developing new resveratrol derivatives with significantly higher AhR binding affinity beyond the range already mapped by the available experimental data sets. The results also suggest that future QSAR searches for AhR binding affinity among resveratrol derivatives will likely need to proceed in a more constrained class-by-class fashion owing to the potentially different mechanistic implications from changes in the types/positions of aromatic substitution and the cisltrans geometrical isomerism. The antioxidant activity of hydroxystilbenes can be accurately modeled using high-quality empirical univariate relationships with various molecular descriptors. In comparison, correlations between theoretical bond dissociation enthalpies and ionization energies of the molecular and dissociated forms yielded lower quality QSAR fits with the antioxidant behavior.