QSAR models to predict mutagenicity of acrylates, methacrylates and , α,β-unsaturated carbonyl compounds

Abstract

Objective. The purpose of this study is to develop a quantitative structure-activity relationship(QSAR) model that can distinguish mutagenic from non-mutagenic species with,-unsaturated carbonyl moiety using two endpoints for this activity - Ames test and mammaliancell genemutation test - and also to gather information about the molecular featuresthat most contribute to eliminate the mutagenic effects of these chemicals.Methods. Two data setswere used for modeling the twomutagenicity endpoints: (1) Ames testand (2) mammalian cellsmutagenesis. The first one comprised 220 molecules, while the secondone 48 substances, ranging from acrylates, methacrylates to ,-unsaturated carbonylcompounds. The QSAR models were developed by applying linear discriminant analysis(LDA) along with different sets of descriptors computed using the DRAGON software.Results. For both endpoints, there was a concordance of 89% in the prediction and 97% confidentialityby combining the three models for the Ames test mutagenicity. We have alsoidentified several structural alerts to assist the design of new monomers.Significance. These individual models and especially their combination are attractive fromthe point of view of molecular modeling and could be used for the prediction and design ofnew monomers that do not pose a human health risk.