scholarly journals Cytochrome P450 Can Epoxidize an Oxepin to a Reactive 2,3-Epoxyoxepin Intermediate: Potential Insights into Metabolic Ring-Opening of Benzene

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4542
Author(s):  
Holly M. Weaver-Guevara ◽  
Ryan W. Fitzgerald ◽  
Noah A. Cote ◽  
Arthur Greenberg
Keyword(s):  
Cytochrome P450 ◽  
Ammonium Nitrate ◽  
Ring Opening ◽  
Human Liver ◽  
Liver Microsomes ◽  
Major Product ◽  
Major Pathway ◽  
Cytochrome P450 Isoforms ◽  
Stable Product ◽  
Cerium Iv Ammonium Nitrate

Dimethyldioxirane epoxidizes 4,5-benzoxepin to form the reactive 2,3-epoxyoxepin intermediate followed by very rapid ring-opening to an o-xylylene that immediately isomerizes to the stable product 1H-2-benzopyran-1-carboxaldehyde. The present study demonstrates that separate incubations of 4,5-benzoxepin with three cytochrome P450 isoforms (2E1, 1A2, and 3A4) as well as pooled human liver microsomes (pHLM) also produce 1H-2-benzopyran-1-carboxaldehyde as the major product, likely via the 2,3-epoxyoxepin. The reaction of 4,5-benzoxepin with cerium (IV) ammonium nitrate (CAN) yields a dimeric oxidized molecule that is also a lesser product of the P450 oxidation of 4,5-benzoxepin. The observation that P450 enzymes epoxidize 4,5-benzoxepin suggests that the 2,3-epoxidation of oxepin is a major pathway for the ring-opening metabolism of benzene to muconaldehyde.

STEREOSELECTIVE METABOLISM OF ENDOSULFAN BY HUMAN LIVER MICROSOMES AND HUMAN CYTOCHROME P450 ISOFORMS

2006 ◽  
Vol 34 (7) ◽  
pp. 1090-1095 ◽  
Author(s):  
Hwa-Kyung Lee ◽  
Joon-Kwan Moon ◽  
Chul-Hee Chang ◽  
Hoon Choi ◽  
Hee-Won Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Stereoselective Metabolism ◽  
Human Cytochrome ◽  
Cytochrome P450 Isoforms

In VitroInhibition of Huanglian [Rhizoma coptidis(L.)] and its Six Active Alkaloids on Six Cytochrome P450 Isoforms in Human Liver Microsomes

2011 ◽  
Vol 25 (11) ◽  
pp. 1660-1665 ◽  
Author(s):  
Yong-Long Han ◽  
Hong-Liang Yu ◽  
Dan Li ◽  
Xiang-Le Meng ◽  
Zhi-Yong Zhou ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Rhizoma Coptidis ◽  
Cytochrome P450 Isoforms

scholarly journals Chloramphenicol Is a Potent Inhibitor of Cytochrome P450 Isoforms CYP2C19 and CYP3A4 in Human Liver Microsomes

2003 ◽  
Vol 47 (11) ◽  
pp. 3464-3469 ◽  
Author(s):  
Ji-Young Park ◽  
Kyoung-Ah Kim ◽  
Su-Lyun Kim
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Human Liver ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Human Liver Microsomes ◽  
Human Cytochrome ◽  
Cytochrome P450 Isoforms ◽  
Potent Inhibitory Effect ◽  
Cyp Isoforms

ABSTRACT The inhibitory effect of chloramphenicol on human cytochrome P450 (CYP) isoforms was evaluated with human liver microsomes and cDNA-expressed CYPs. Chloramphenicol had a potent inhibitory effect on CYP2C19-catalyzed S-mephytoin 4′-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation, with apparent 50% inhibitory concentrations (inhibitory constant [Ki ] values are shown in parentheses) of 32.0 (7.7) and 48.1 (10.6) μM, respectively. Chloramphenicol also weakly inhibited CYP2D6, with an apparent 50% inhibitory concentration (Ki ) of 375.9 (75.8) μM. The mechanism of the drug interaction reported between chloramphenicol and phenytoin, which results in the elevation of plasma phenytoin concentrations, is clinically assumed to result from the inhibition of CYP2C9 by chloramphenicol. However, using human liver microsomes and cDNA-expressed CYPs, we showed this interaction arises from the inhibition of CYP2C19- not CYP2C9-catalyzed phenytoin metabolism. In conclusion, inhibition of CYP2C19 and CYP3A4 is the probable mechanism by which chloramphenicol decreases the clearance of coadministered drugs, which manifests as a drug interaction with chloramphenicol.

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