Experimental verification of structural alerts for the protein binding of cyclic compounds acting as Michael acceptors

被引：6

作者：

Rodriguez-Sanchez, N. ^{[1
]}

Schultz, T. W. ^{[2
]}

Cronin, M. T. D. ^{[1
]}

Enoch, S. J. ^{[1
]}

机构：

[1] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 5UX, Merseyside, England

[2] Univ Tennessee, Coll Vet Med, Knoxville, TN USA

来源：

SAR AND QSAR IN ENVIRONMENTAL RESEARCH | 2013年 / 24卷 / 11期

关键词：

in chemico; structural alerts; applicability domain; Michael addition; category formation; OECD QSAR Toolbox; READ-ACROSS; REACTIVITY; PREDICTION; TOXICITY;

D O I：

10.1080/1062936X.2013.820793

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

This study outlines how a combination of and in vitro data can be used to define the applicability domain of selected structural alerts within the protein binding profilers of the Organisation for Economic Co-operation (OECD) Quantitative Structure-Activity Relationship (QSAR) Toolbox. Thirty chemicals containing a cyclic moiety were profiled for reactivity using the OECD and Optimised Approach based on Structural Indices Set (OASIS) protein binding profilers. The profiling results identified 22 of the chemicals as being reactive towards proteins. Analysis of the experimentally data showed 19 of these chemicals to be reactive. Subsequent analysis allowed refinements to be suggested to improve the applicability domain of the structural alerts investigated. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in chemical category in predictive and regulatory toxicology.

引用

页码：963 / 977

页数：15

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