Hydroxylation of the thiophene ring by hepatic monooxygenases. Evidence for 5-hydroxylation of 2-aroylthiophenes as a general metabolic pathway using a simple UV-visible assay.

@article{Neau1990HydroxylationOT,
  title={Hydroxylation of the thiophene ring by hepatic monooxygenases. Evidence for 5-hydroxylation of 2-aroylthiophenes as a general metabolic pathway using a simple UV-visible assay.},
  author={Evelyne Neau and Patrick M. Dansette and V I Andronik and Daniel Mansuy},
  journal={Biochemical pharmacology},
  year={1990},
  volume={39 6},
  pages={
          1101-7
        }
}
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26 Citations
Methods Citations
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26 Citations

Hydroxylation and formation of electrophilic metabolites of tienilic acid and its isomer by human liver microsomes. Catalysis by a cytochrome P450 IIC different from that responsible for mephenytoin hydroxylation.
First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives.
Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid.
TLDR
TA exhibited all of the characteristics of a mechanism-based inactivator for P 450 2C9 and 2C10 enzymes and could be a starting point for the appearance of anti-P450 2C antibodies detected in patients treated with TA and suffering from immunoallergic hepatitis.
In vitro metabolism of isaxonine phosphate: formation of two metabolites, 5-hydroxyisaxonine and 2-aminopyrimidine, and covalent binding to microsomal proteins.
New biological reactive intermediates: metabolic activation of thiophene derivatives.
TLDR
This work has shown that the major oxidized metabolites of severaI2-aroylthiophenes, such as tienilic acid, were derived from 5-hydroxylation of their thiophene ring (Neau et ai., 1990).
Differential oxidation of two thiophene-containing regioisomers to reactive metabolites by cytochrome P450 2C9.
TLDR
The goal of the work presented in this article was to identify the reactive metabolites of TA and TAI by the characterization of products derived from P450 2C9-mediated oxidation and found that TAI was oxidized to two different types of reactive intermediates that ultimately lead to two types of products, a pair of hydroxythiophene/thiolactone tautomers and an S-oxide dimer.
Human-liver cytochromes P-450 expressed in yeast as tools for reactive-metabolite formation studies. Oxidative activation of tienilic acid by cytochromes P-450 2C9 and 2C10.
TLDR
The results suggest the important role of P450 2C9 in the oxidative metabolism of tienilic acid in human liver and indicate that the 5-hydroxylation reaction could be a useful marker for P450 1C9 activity and underline the interest of human liver P450s expressed in yeast as tools for studying the formation of reactive metabolites.
Substrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid.
New Biological Reactive Intermediates
TLDR
It has been shown that the major oxidized metabolites of several 2-aroylthiophenes, such as tienilic acid (Mansuy et al., 1984) were derived from 5-hydroxylation of their thiophene ring.
Interaction of new sulfaphenazole derivatives with human liver cytochrome p450 2Cs: structural determinants required for selective recognition by CYP 2C9 and for inhibition of human CYP 2Cs.
TLDR
A series of new derivatives of sulfaphenazole (SPA) were synthesized in order to further explore CYP 2C9 active site and to determine the structural factors explaining the selectivity of SPA for CYP2C9 within the human P450 2C subfamily.
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Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug.
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