title: Experimental verification, and domain definition, of structural alerts for protein binding: epoxides, lactones, nitroso, nitros, aldehydes and ketones.
abstract: This study outlines how a combination of in chemico and Tetrahymena pyriformis data can be used to define the applicability domain of selected structural alerts within the profilers of the OECD QSAR Toolbox. Thirty-three chemicals were profiled using the OECD and OASIS profilers, enabling the applicability domain of six structural alerts to be defined, the alerts being: epoxides, lactones, nitrosos, nitros, aldehydes and ketones. Analysis of the experimental data showed the applicability domains for the epoxide, nitroso, aldehyde and ketone structural alerts to be well defined. In contrast, the data showed the applicability domains for the lactone and nitro structural alerts needed modifying. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in the chemical category in predictive and regulatory toxicology. This study highlights the importance of utilizing multiple profilers in category formation.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Nelms
authors.forename: M T D
authors.initials: MT
authors.lastname: Cronin
authors.forename: T W
authors.initials: TW
authors.lastname: Schultz
authors.forename: S J
authors.initials: SJ
authors.lastname: Enoch
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D007659:Ketones / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D007783:Lactones / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009602:Nitrosamines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009930:Organic Chemicals / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000254:growth & development*; D014116:Toxicology / Q000379:methods*
chemical_list: D000447:Aldehydes; D004852:Epoxy Compounds; D007659:Ketones; D007783:Lactones; D009602:Nitrosamines; D009603:Nitroso Compounds; D009930:Organic Chemicals; D015800:Protozoan Proteins; D005978:Glutathione