Determination and prediction of xenoestrogens by recombinant yeast-based assay and QSAR

Estrogenic activities expressed by the logarithm of relative potency (logRP), for 8 xenoestrogens were determined using the recombinant yeast-based assay. The determined logRP values were employed as an independent external data set to validate an estrogenic activity quantitative structure-activity relationship (QSAR) model. The QSAR model was established using partial least squares regression and molecular descriptors derived from DRAGON software. For the training set of the QSAR model that included 25 xenoestrogens, R-2 = 0.889, the leave-one-out cross-validation squared correlation coefficient (Q(LOO)(2)) was 0.897. For the external validation set, the predicted logRP values were consistent with the observed values, with a root mean square error (RMSE) of 0.736 log units and the squared correlation coefficient (Q(EXT)(2)) was 0.775. Six descriptors were included in the QSAR model, which indicated that the logRP value was related to molecular size, shape profiles, symmetry and polarizability. Comparatively, the developed model has good robustness and predictivity. Moreover, the applicability domain of the model was discussed. (c) 2008 Elsevier Ltd. All rights reserved.