Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes.

@article{Dansette1990OxidativeAO,
  title={Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes.},
  author={Patrick M. Dansette and Claudine Amar and C J Smith and Catherine Pons and Daniel Mansuy},
  journal={Biochemical pharmacology},
  year={1990},
  volume={39 5},
  pages={
          911-8
        }
}
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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.
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.
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.
Involvement of cytochrome P450-mediated metabolism in tienilic acid hepatotoxicity in rats.
First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives.
Novel Metabolic Bioactivation Mechanism for a Series of Anti-Inflammatory Agents (2,5-Diaminothiophene Derivatives) Mediated by Cytochrome P450 Enzymes
TLDR
The disruption of formation of the 2,5-diimine reactive intermediate resulted in the elimination of glutathione conjugate formation both in vitro and in vivo and provided a rational approach to mitigating potential safety risks associated with this class of thiophenes in drug research and development.
Cytochrome P450 oxidation of the thiophene-containing anticancer drug 3-[(quinolin-4-ylmethyl)-amino]-thiophene-2-carboxylic acid (4-trifluoromethoxy-phenyl)-amide to an electrophilic intermediate.
TLDR
Multiple features determine any consequence of a BRI, with these complexities determining why one BRI is benign while another is not, as demonstrated by mass spectral characterization of several thioether conjugates of the presumed thiophene S-oxide.
Evidence for thiophene-S-oxide as a primary reactive metabolite of thiophene in vivo: formation of a dihydrothiophene sulfoxide mercapturic acid.
Inactivation of Cytochrome P 450 ( P 450 ) 3 A 4 but not P 450 3 A 5 by OSI-930 , a Thiophene-Containing Anticancer Drug
TLDR
Results showed that OSI-930 inactivated purified, recombinant cytochrome P450 (P450) 3A4 in the reconstituted system in a mechanism-based manner and suggested that clinical drug interactions of OSi-930 via this pathway are not likely.
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References

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TLDR
The monooxygenase activities, the sensitivity to in vitro alpha-naphthoflavone and metyrapone, the results of steroid metabolism, and slab gel electrophoresis are strong indications for multiplicity of human liver cytochrome P-450.
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The urinary metabolites of 2-(4-(2-thienylcarbonyl)phenyl)propionic acid (suprofen, S) in rats were analyzed by radio-GC, GC/MS, or 1H NMR technique. Radio-GC analysis of trimethylsilylated materials…
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TLDR
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TLDR
The time-course of the inhibitory effect of tiquizium bromide on stomach contraction correlated well with the plasma levels of unchanged drug after intraduodenal administration.
Synthese d'un diuretique marque au carbone 14: Acide dichloro‐2,3 [thenoyl‐2 (14C = 0)]‐4 phenoxy acetique (D.C.I. acide tiénilique)
2-Thenoic acid (14C = 0) 1 is prepared in 75 % radioactive yield by carbonation with 14CO2 of 2-thienyL-magnesium bromide. Boiling of 1 with oxalyl chloride gives rise to 2-thenoylchloride (14CO)…
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