Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
Article Details
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Monostory K, Hazai E, Vereczkey L
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
Chem Biol Interact. 2004 Apr 15;147(3):331-40. doi: 10.1016/j.cbi.2004.03.003.
- PubMed ID
- 15135088 [ View in PubMed]
- Abstract
p-Nitrophenol hydroxylation is widely used as a probe for microsomal CYP2E1. Several drugs are known as CYP2E1 inhibitors because of their capability to inhibit p-nitrophenol hydroxylation. Our results suggest further participation of CYP2A6 and CYP2C19 enzymes in p-nitrophenol hydroxylation. Moreover, CYP2A6 and CYP2C19 may be considered as the primary catalysts, whereas CYP2E1 can also contribute to the hydroxylation of p-nitrophenol. Further aim of our study was to evaluate the selectivity of p-nitrophenol hydroxylase inhibitors towards cytochrome P450 enzymes. The effects of antifungals: bifonazole, econazole, clotrimazole, ketoconazole, miconazole; CNS-active drugs: chlorpromazine, desipramine, fluphenazine, thioridazine; and the non-steroidal anti-inflammatory drug: diclofenac were investigated on the enzyme activities selective for CYP2A6, CYP2C9, CYP2C19, CYP2E1 and CYP3A4. None of the drugs could be considered as a potent inhibitor of CYP2E1. Strong inhibition was observed for CYP3A4 by antifungals with IC(50) values in submicromolar range. However, ketoconazole was the only imidazole derivative that could be considered as a selective inhibitor of CYP3A4. The CNS-active drugs investigated were found to be weak inhibitors of CYP2A6, CYP2C9, CYP2C19, CYP2E1 and CYP3A4. Diclofenac efficiently inhibited CYP2C9 and to a less extent CYP3A4 enzyme.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Bifonazole Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Bifonazole Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Chlorpromazine Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Clotrimazole Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Clotrimazole Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails Desipramine Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Econazole Cytochrome P450 3A4 Protein Humans NoInhibitorDetails Miconazole Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Miconazole Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Miconazole Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Thioridazine Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails