Identification of reactive toxicants: structure-activity relationships for amides.
Cell Biol Toxicol
; 22(5): 339-49, 2006 Sep.
Article
de En
| MEDLINE
| ID: mdl-16845611
ABSTRACT
A diverse series of amides were evaluated for aquatic toxicity (IGC(50)) assessed in the Tetrahymena pyriformis population growth impairment assay and for reactivity (EC(50)) with the model soft nucleophile thiol in the form of the cysteine residue of the tripeptide glutathione. All alkylamides along with some halo-substituted amides are well predicted by the simple hydrophobicity (log K (ow))-electrophilicity (E (lumo)) response-surface model [log(IGC(-1) (50)) = 0.45(log K (ow)) - 0.342(E (lumo)) - 1.11]. However, 2-halo amides with the halogen at the end of the molecule and alpha,beta-unsaturated primary amides are among those derivatives identified as being more toxic than predicted by the model. Amides, which exhibit excess toxicity, were capable of forming covalent bonds through an S(N)2 displacement or a Michael addition. Moreover, only those amides exhibiting excess toxicity were reactive with thiol, suggesting that the reactivity with model nucleophiles such as the thiol group may provide a means of accurately defining reactive toxicants.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tetrahymena pyriformis
/
Amides
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Cell Biol Toxicol
Sujet du journal:
TOXICOLOGIA
Année:
2006
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique