0000000000313692

AUTHOR

Daniel Mansuy

showing 2 related works from this author

REDUCTION OF NILUTAMIDE BY NO SYNTHASES : IMPLICATIONS FOR THE ADVERSE EFFECTS OF THIS NITROAROMATIC ANTIANDROGEN DRUG

2003

Nitric oxide synthases (NOSs) are flavohemeproteins that catalyze the oxidation of l-arginine to l-citrulline with formation of the widespread signal molecule NO. Beside their fundamental role in NO biosynthesis, these enzymes are also involved in the formation of reactive oxygen species and in the interactions with some xenobiotic compounds. Nilutamide is a nonsteroidal antiandrogen that behaves as a competitive antagonist of the androgen receptors and is proposed in the treatment of metastatic prostatic carcinoma. However, therapeutic effects of nilutamide are overshadowed by the occurrence of several adverse reactions mediated by toxic mechanism(s), which remain(s) poorly investigated. H…

Time FactorsFree RadicalsNitric Oxide Synthase Type IIImedicine.drug_class[CHIM.THER] Chemical Sciences/Medicinal ChemistryNitric Oxide Synthase Type IINitric Oxide Synthase Type I[CHIM.THER]Chemical Sciences/Medicinal ChemistryToxicologyAntiandrogenImidazolidinesNitric oxide03 medical and health scienceschemistry.chemical_compoundMice0302 clinical medicineHydroxylaminemedicineAnimalsAnaerobiosisAmines030304 developmental biologychemistry.chemical_classification0303 health sciencesReactive oxygen speciesElectron Spin Resonance SpectroscopyImidazolesAndrogen AntagonistsGeneral MedicineRecombinant Proteins3. Good healthRatsAndrogen receptorEnzymechemistryBiochemistryCompetitive antagonist030220 oncology & carcinogenesisNilutamideCattleNitric Oxide SynthaseOxidation-ReductionNADPmedicine.drug
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Oxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18 and 2C19. Evidence that this drug is a mechanism-based inhibitor…

1996

Oxidation of tienilic acid by human cytochromes P-450 (CYP) 2C9, 2C18, 2C8 and 2C19 was studied using recombinant enzymes expressed in yeast. CYP 2C9 was the best catalyst for 5-hydroxylation of tienilic acid (K(m) = 5 +/- 1 microM, kcat = 1.7 +/- 0.2 min-1), 30-fold more potent in terms of kcat/K(m) than CYP 2C18 (K(m) = 150 +/- 15 microM, kcat = 1.8 +/- 0.2 min-1) and 300-fold more potent than CYP 2C8 (K(m) = 145 +/- 15 microM, kcat = 0.2 +/- 0.1 min-1). CYP 2C19 was unable to catalyze this hydroxylation under our experimental conditions. During this study, a marked effect of the ionic strength on the activities (hydroxylations of tienilic acid and tolbutamide) of these cytochromes P-450 …

MaleCytochromeTolbutamideTicrynafenSaccharomyces cerevisiaeurologic and male genital diseasesHydroxylationBiochemistryMixed Function OxygenasesHydroxylationchemistry.chemical_compoundCytochrome P-450 Enzyme SystemMicrosomesmedicineCytochrome P-450 Enzyme InhibitorsHumansheterocyclic compoundsEnzyme InhibitorsCytochrome P-450 Enzyme Inhibitorschemistry.chemical_classificationbiologyChemistryorganic chemicalsMembrane ProteinsGlutathionerespiratory systemRecombinant ProteinsIsoenzymesenzymes and coenzymes (carbohydrates)EnzymeBiochemistrySteroid 16-alpha-HydroxylaseTienilic acidSuicide inhibitionbiology.proteinMicrosomeMicrosomes LiverAryl Hydrocarbon HydroxylasesOxidation-Reductionmedicine.drugEuropean journal of biochemistry
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