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Biotransformation reactions of five-membered aromatic heterocyclic rings.
(R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver cytochrome P450 2A6.
- S. Khojasteh-Bakht, L. Koenigs, R. Peter, W. Trager, S. Nelson
- Biology, ChemistryDrug metabolism and disposition: the biological…
- 1 July 1998
Addition of various nucleophiles, a chelator of iron, or scavengers of reactive oxygen species or extensive dialysis failed to protect CYP2A6 from inactivation, and menthofuran caused a time- and concentration-dependent loss of CYP 2A6 activity.
Pennyroyal Toxicity: Measurement of Toxic Metabolite Levels in Two Cases and Review of the Literature
Four recent cases of pennyroyal toxicity are reported, two of which had laboratory confirmation of pulegone or its major toxic metabolite menthofuran, and these cases are placed in the context of reported signs and symptoms of toxicity.
Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: evidence for formation of a furan epoxide.
- S. Khojasteh-Bakht, W. Chen, L. Koenigs, R. Peter, S. Nelson
- Chemistry, BiologyDrug metabolism and disposition: the biological…
- 1 May 1999
Two P-450s were found to oxidize menthofuran to a newly identified metabolite, 2-hydroxymenthofuran, which is an intermediate in the formation of the known metabolites mintlactone and isomintlact one.
( R )-( 1 )-MENTHOFURAN IS A POTENT , MECHANISM-BASED INACTIVATOR OF HUMAN LIVER CYTOCHROME P 450 2 A 6
Menthofuran is a potent, mechanism-based inactivator of human liver cytochrome P450 (CYP or P450) 2A6 and appears to be the major proximate toxin, based on toxicokinetic studies.
Glutathione S-transferase catalyzes the isomerization of (R)-2-hydroxymenthofuran to mintlactones.
- S. Khojasteh-Bakht, S. Nelson, W. Atkins
- Chemistry, BiologyArchives of biochemistry and biophysics
- 1 October 1999
It is demonstrated that glutathione S-transferase (GST) catalyzes the tautomerization of 2-hydroxymenthofuran to mintlact one and isomintlactone, apparently without the formation of stable glutathion (GSH) conjugates.
Formation of a quinoneimine intermediate of 4-fluoro-N-methylaniline by FMO1: carbon oxidation plus defluorination.
The identification of N-acetylcysteine adducts by LC-MS/MS and NMR further supports the formation of a quinoneimine intermediate, and it is proposed that a labile 1-fluoro-4-(methylimino)cyclohexa-2,5-dienol intermediate was formed leading to an electrophilic quin oneimine Intermediate.
Inhibitory properties of trapping agents: glutathione, potassium cyanide, and methoxylamine, against major human cytochrome p450 isoforms.
The capability of commonly used trapping agents to reversibly inhibit major cytochrome P450 (CYP) isoforms was assessed and Glutathione and cyanide did not inhibit the enzymes at concentrations up to 10 mM; however methoxylamine did show inhibition.
Metabolic stability screen for drug discovery using cassette analysis and column switching.
- J. Halladay, Susan D. Wong, Sharmin M Jaffer, A. K. Sinhababu, S. Khojasteh-Bakht
- BiologyDrug metabolism letters
Improved the metabolic stability assay using the cassette analysis method, column switching, and incorporated time saving techniques in method development to yield a robust method which reduces data turnaround time, increases compound throughput, and maximizes mass spectrometer usage.
METABOLISM, PHARMACOKINETICS, TISSUE DISTRIBUTION, AND EXCRETION OF [14C]CP-424391 IN RATS
- S. Khojasteh-Bakht, J. O'Donnell, H. Fouda, M. Potchoiba
- Biology, ChemistryDrug Metabolism and Disposition
- 1 January 2005
The metabolic fate and disposition of radiolabeled CP-424391 in rats was investigated: fecal and urinary metabolic profiles were consistent in both genders, and radioactivity was widely distributed in all tissues except for the central nervous system.