QSAR models to predict mutagenicity of acrylates, methacrylates and αα α , ββ 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 <SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='α’>αα
α
, <SPAN role=presentation tabIndex=0 id=MathJax-Element-4-Frame class=MathJax style="POSITION: relative" data-mathml='β’>ββ
β
-unsaturated carbonyl moiety using two endpoints for this activity – Ames test and mammalian cell gene mutation test – and also to gather information about the molecular features that most contribute to eliminate the mutagenic effects of these chemicals.

Methods

Two data sets were used for modeling the two mutagenicity endpoints: (1) Ames test and (2) mammalian cells mutagenesis. The first one comprised 220 molecules, while the second one 48 substances, ranging from acrylates, methacrylates to <SPAN role=presentation tabIndex=0 id=MathJax-Element-5-Frame class=MathJax style="POSITION: relative" data-mathml='α’>αα
α
, <SPAN role=presentation tabIndex=0 id=MathJax-Element-6-Frame class=MathJax style="POSITION: relative" data-mathml='β’>ββ
β
-unsaturated carbonyl compounds. 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% confidentiality by combining the three models for the Ames test mutagenicity. We have also identified several structural alerts to assist the design of new monomers.

Significance

These individual models and especially their combination are attractive from the point of view of molecular modeling and could be used for the prediction and design of new monomers that do not pose a human health risk.

Introduction

A matrix resin made of acrylate or methacrylate based monomers that are photo and/or chemically polymerizable is used usually for dental resin filling materials and adhesives. These dental restorative materials are prepared in situ and, as the polymerization is often not ideal, some unreacted monomers will dribble from the restoration over time . Any unpolymerized monomer in the composite has a potential biological liability if it leaches from the composite toward the pulp of the tooth . Among other substances, triethylene glycol dimethacrylate (TEGDMA)( Fig. 1 ) causes DNA deletions in mammalian cells .

Nov 30, 2017 | Posted by in Dental Materials | Comments Off on QSAR models to predict mutagenicity of acrylates, methacrylates and αα α , ββ β -unsaturated carbonyl compounds
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