Journal ArticleDOI
Structure-activity relationships for reactivity of carbonyl-containing compounds with glutathione
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TLDR
A rapid and inexpensive spectrophotometric assay for determining the reactive to glutathione (GSH) was developed and used to determine GSH reactivity data for 21 aliphatic derivatives of esters, ketones and aldehydes.Abstract:
For toxicological-based structure-activity relationships to advance, will require a better understanding of molecular reactivity. A rapid and inexpensive spectrophotometric assay for determining the reactive to glutathione (GSH) was developed and used to determine GSH reactivity (reactGSH) data for 21 aliphatic derivatives of esters, ketones and aldehydes. From these data, a series of structure-activity relationships were evaluated. The structure feature associated with reactGSH was an acetylenic or olefinic moiety conjugated to a carbonyl group (i.e. polarized alpha,beta-unsaturation). This structure conveys the capacity to undergo a covalent interaction with the thiol group of cysteine (i.e. Michael- addition). Quantitatively reactGSH of the alpha,beta-unsaturated carbonyl compounds is reliant upon the specific molecular structure with several tendencies observed. Specifically, it was noted that for alpha,beta-unsaturated carbonyl compounds: (1) the acetylenic-substituted derivatives were more reactive than the corresponding olefinic-substituted ones; (2) terminal vinyl-substituted derivatives was more reactive than the internal vinylene-substituted ones; (3) methyl substitution on the vinyl carbon atoms diminishes reactivity and methyl-substitution on the carbon atom farthest from the carbonyl group causes a larger reduction; (4) derivatives with carbon-carbon double bond on the end of the molecule (i.e. vinyl ketone) were more reactive than one with the carbon-oxygen bond at the end of the molecule (i.e. aldehyde) and (5) the ester with an additional unsaturated vinyl groups were more reactive than the derivative having an unsaturated ethyl group.read more
Citations
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Alternative (non-animal) methods for cosmetics testing: current status and future prospects—2010
Sarah Adler,David A. Basketter,Stuart Creton,Olavi Pelkonen,Jan van Benthem,Valérie Zuang,Klaus Ejner Andersen,Alexandre Angers-Loustau,Aynur O. Aptula,Anna Bal-Price,Emilio Benfenati,Ulrike Bernauer,J.G.M. Bessems,Frédéric Y. Bois,Alan R. Boobis,Esther Brandon,Susanne Bremer,Thomas H. Broschard,Silvia Casati,Sandra Coecke,Raffaella Corvi,Mark T. D. Cronin,George P. Daston,Wolfgang Dekant,Susan P. Felter,Elise Grignard,Ursula Gundert-Remy,Tuula Heinonen,Ian Kimber,Jos C. S. Kleinjans,Hannu Komulainen,Reinhard Kreiling,Joachim Kreysa,Sofia B. Leite,George Loizou,Gavin Maxwell,Paolo Mazzatorta,Sharon Munn,Stefan Pfuhler,Pascal Phrakonkham,Aldert H. Piersma,Albrecht Poth,Pilar Prieto,Guillermo Repetto,Vera Rogiers,Greet Schoeters,Michael Schwarz,Rositsa Serafimova,Hanna Tähti,Emanuela Testai,Joost H.M. van Delft,Henk Van Loveren,Mathieu Vinken,Andrew Worth,Jose-Manuel Zaldivar +54 more
TL;DR: In this paper, Adler et al. present a survey of the authors' work in the field of bioinformatics, including the following authors:Sarah AdlerDavid BasketterStuart CretonOlavi PelkonenJan van BenthemValerie Zuang • Klaus Ejner AndersenAlexandre Angers-LoustauAynur AptulaAnna Bal-PriceEmilio Benfenati • Ulrike BernauerJos BessemsFrederic Y. BoisAlan BoobisEsther BrandonSusanne Bremer • Thomas
Journal ArticleDOI
Measurement and estimation of electrophilic reactivity for predictive toxicology.
Johannes A.H. Schwöbel,Yana K. Koleva,Steven J. Enoch,Fania Bajot,Mark Hewitt,Judith C. Madden,David W. Roberts,Terry W Schultz,Mark T. D. Cronin +8 more
TL;DR: Measurement and Estimation of Electrophilic Reactivity for Predictive Toxicology Johannes A. H. Schw€obel, Yana K. Koleva, Steven J. Enoch, Fania Bajot, Mark Hewitt, Judith C.Madden, and Mark T. Schultz.
Journal ArticleDOI
A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity.
TL;DR: The literature defining the structural alerts associated with covalent protein binding and the associated electrophilic reaction chemistry are reviewed and incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.
Journal ArticleDOI
LC-MS-based characterization of the peptide reactivity of chemicals to improve the in vitro prediction of the skin sensitization potential.
Andreas Natsch,Hans Gfeller +1 more
TL;DR: A modified assay based on both liquid chromatography-mass spectrometry (LC-MS) analysis and detection of free thiol groups allows simultaneous determination of peptide depletion, peptide oxidation, adduct formation, and thiol reactivity and generates a more detailed characterization of the reactivity of a molecule.
Journal ArticleDOI
Investigation of peptide reactivity of pro-hapten skin sensitizers using a peroxidase-peroxide oxidation system.
G. Frank Gerberick,John A. Troutman,Leslie M. Foertsch,Jeffrey D. Vassallo,Mike Quijano,Roy L. M. Dobson,Carsten Goebel,Jean-Pierre Lepoittevin +7 more
TL;DR: Preliminary work shows the potential to incorporate an enzyme-mediated activation step for pro-haptens into an in chemico skin sensitization assay that results in the detection of all types of sensitizers.
References
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Book
Advanced Organic Chemistry: Reactions, Mechanisms, and Structure
TL;DR: Localized Chemical bonding Delocalized Chemical Bonding Bonding Weaker than Covalent Stereochemistry Carbocations, Carbanions, Free Radicals, Carbenes and Nitrenes Mechanisms and Methods of Determining them Photochemistry Acids and Bases Effects of Structure on Reactivity Aliphatic Nucleophilic Substitution Aromatic Electrophilic Substitutes Aliphatically Electrophilic Substitution Free-Radical Substitution Addition to Carbon-Carbon Multiple Bonds Adding to Carbon Hetero Multiple Bonds Eliminations Rearrangements Ox
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Medical Defense Against Mustard Gas: Toxic Mechanisms and Pharmacological Implications
TL;DR: Books and internet are the recommended media to help you improving your quality and performance.
Journal ArticleDOI
Reaction of Glutathione with Conjugated Carbonyls
TL;DR: Comparing biological activities of con jugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered and the equilibrium constants as well as the rate constants for forward and reverse reaction show an extreme variation depending on the carbonyl structure.
Journal ArticleDOI
Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing, alpha,beta-unsaturated chemicals.
TL;DR: It is suggested that substitution on the carbon-carbon double bond in the methacrylates and vinylene unsaturated esters does not enhance toxicity over that of baseline, and the modeling of the toxicity of the alpha,beta-unsaturated carbonyl domain is currently limited to models for narrow subdomains.
Journal ArticleDOI
Quantitative correlation studies between the acute lethal toxicity of 15 organic halides to the guppy (Poecillah Reticulata) and chemical reactivity towards 4‐nitrobenzylpyridine
TL;DR: In this article, the authors determined the acute mortality of reactive organic halides to the guppy (Poecilia reticulata) of 15 compounds and found that these compounds were significantly more toxic than non-reactive organic chemicals with unspecific toxicity.