title: Experimental verification of structural alerts for the protein binding of cyclic compounds acting as Michael acceptors.
abstract: 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.
authors.affiliation: a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK .
authors.forename: N
authors.initials: N
authors.lastname: Rodriguez-Sanchez
authors.forename: T W
authors.initials: TW
authors.lastname: Schultz
authors.forename: M T D
authors.initials: MT
authors.lastname: Cronin
authors.forename: S J
authors.initials: SJ
authors.lastname: Enoch
mesh_terms: D000473:Alkanes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D001665:Binding Sites; D003500:Cyclization; D005062:European Union; D005978:Glutathione / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D007880:Legislation, Drug; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000187:drug effects; D018675:Toxicity Tests; D014116:Toxicology
chemical_list: D000473:Alkanes; D000475:Alkenes; D006571:Heterocyclic Compounds; D007659:Ketones; D009930:Organic Chemicals; D005978:Glutathione