Synthesis of substituted phenyl diaziridines and characterization as mechanism-based inactivators of human cytochrome P450 2B6

Drug Metabolism and Disposition

Volumn 34, Issue 11, 2006, Pages 1849-1855

  Sridar, Chitra ^a   Kobayashi, Yoshimasa ^a   Brevig, Holly ^a   Kent, Ute M ^a   Puppali, Satish G ^b   Rimoldi, John M ^b   Hollenberg, Paul F ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (3 METHYL 4 METHOXYPHENYL) 3 TRIFLUOROMETHYLDIAZIRIDINE; 3 (3,4 DIMETHOXYPHENYL) 3 TRIFLUOROMETHYLDIAZIRIDINE; 3 (3,4,5 TRIMETHOXYPHENYL) 3 TRIFLUOROMETHYLDIAZIRIDINE; 3 (4 ETHOXYPHENYL) 3 TRIFLUOROMETHYLDIAZIRIDINE; 3 (4 METHOXYPHENYL) 3 TRIFLUOROMETHYLDIAZIRIDINE; 3 (4 METHYLTHIOPHENYL) 3 TRIFLUOROMETHYLDIAZIRIDINE; 7 BENZYLOXY 4 TRIFLUOROMETHYLCOUMARIN; 7 ETHOXY 4 (TRIFLUOROMETHYL)COUMARIN; AZIRIDINE DERIVATIVE; COUMARIN DERIVATIVE; CYTOCHROME P450 2B6; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 2E1; HEME; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DEBENZYLATION; DIALYSIS; DRUG ACTIVITY; DRUG INHIBITION; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INACTIVATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE;

ARYL HYDROCARBON HYDROXYLASES; AZIRIDINES; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HUMANS; MOLECULAR STRUCTURE; NADP; OXIDOREDUCTASES, N-DEMETHYLATING; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS;

EID: 33751092846     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.106.010082     Document Type: Article

References (25)

1. Battioni P, Mahy JP, Delaforge M, and Mansuy D (1983) Reaction of monosubstituted hydrazines and diazenes with rat-liver cytochrome P450. Formation of ferrous-diazene and ferric sigma-alkyl complexes. Eur J Biochem 134:241-248.
2. Blobaum AL, Kent UM, Alworth WL, and Hollenberg PF (2002) Mechanism-based inactivation of cytochromes P450 2E1 and 2E1 T303A by tert-butyl acetylenes: characterization of reactive intermediate adducts to the heme and apoprotein. Chem Res Toxicol 15:1561-1571.
3. Coon MJ (2005) Cytochrome P450: nature's most versatile biological catalyst. Annu Rev Pharmacol Toxicol 45:1-25.
4. Findlay BC, Fishwick CWG, and Kersey ID aWP (1995) A simple and efficient preparation of 3-Aryl-3-trifluoromethyl-3H-diazirinyl sulfoxides and sulfones. Synthesis 553-556.
5. Gillam EM, Baba T, Kim BR, Ohmori S, and Guengerich FP (1993) Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch Biochem Biophys 305:123-131.
6. Gonzalez FJ (1988) The molecular biology of cytochrome P450s. Pharmacol Rev 40:243-288.
7. Hanna IH, Reed JR, Guengerich FP, and Hollenberg PF (2000) Expression of human cytochrome P450 2B6 in Escherichia coli: characterization of catalytic activity and expression levels in human liver. Arch Biochem Biophys 376:206-216.
8. Hanna IH, Teiber JF, Kokones KL, and Hollenberg PF (1998) Role of the alanine at position 363 of cytochrome P450 2B2 in influencing the NADPH- and hydroperoxide-supported activities. Arch Biochem Biophys 350:324-332.
9. Hartmann RW, Hector M, Wachall BG, Palusczak A, Palzer M, Huch V, and Veith M (2000) Synthesis and evaluation of 17-aliphatic heterocycle-substituted steroidal inhibitors of 17alpha-hydroxylase/C17-20-lyase (P450 17). J Med Chem 43:4437-4445.
10. Hata Y and Watanabe M (1982) A new metabolic reaction of diaziridines by rat liver microsomes. Biochem Biophys Res Commun 106:526-532.
11. Hatanaka Y, Hashimoto M, Kurihara H, and Nakayama H, and Kanaoka Y (1994) A novel family of aromatic diazirines for photoaffinity labeling. J Org Chem 59:383-387.
12. Kent UM, Juschyshyn MI, and Hollenberg PF (2001) Mechanism-based inactivators as probes of cytochrome P450 structure and function. Curr Drug Metab 2:215-243.
13. Lindeke B (1982) The non- and postenzymatic chemistry of N-oxygenated molecules. Drug Metab Rev 13:71-121.
14. Maples KR, Jordan SJ, and Mason RP (1988) In vivo rat hemoglobin thiyl free radical formation following administration of phenylhydrazine and hydrazine-based drugs. Drug Metab Dispos 16:799-803.
15. Muakkassah SF and Yang WC (1981) Mechanism of the inhibitory action of phenelzine on microsomal drug metabolism. J Pharmacol Exp Ther 219:147-155.
16. Ortiz de Montellano PR, Beilan HS, Kunze KL, and Mico BA (1981) Destruction of cytochrome P-450 by ethylene. Structure of the resulting prosthetic heme adduct. J Biol Chem 256:4395-4399.
17. Porter TD and Coon MJ (1991) Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 266:13469-13472.
18. Post AJ and Morrison H (1996) Generation of Carbenes via the Photosensitization of Spirodiaziridines with Ketones(1). J Org Chem 61:1560-1561.
19. Raag R, Swanson BA, Poulos TL, and Ortiz de Montellano PR (1990) Formation, crystal structure, and rearrangement of a cytochrome P-450cam iron-phenyl complex. Biochemistry 29:8119-8126.
20. Shimada T, Wunsch RM, Hanna IH, Sutter TR, Guengerich FP, and Gillam EM (1998) Recombinant human cytochrome P450 1B1 expression in Escherichia coli. Arch Biochem Biophys 357:111-120.
21. Silverman RB (1995) Mechanism-Based Enzyme Inactivators. Methods Enzymol 249:240-283.
22. Starke DW, Blisard KS, and Mieyal JJ (1984) Substrate specificity of the monooxygenase activity of hemoglobin. Mol Pharmacol 25:467-475.
23. Swanson BA, Dutton DR, Lunetta JM, Yang CS, and Ortiz de Montellano PR (1991) The active sites of cytochromes P450 IA1, IIB1, IIB2, and IIE1. Topological analysis by in situ rearrangement of phenyl-iron complexes. J Biol Chem 266:19258-19264.
24. Tuck SF and Ortiz de Montellano PR (1992) Topological mapping of the active sites of cytochromes P4502B1 and P4502B2 by in situ rearrangement of aryl-iron complexes. Biochemistry 31:6911-6916.
25. Yamaguchi Y, Khan KK, He YA, He YQ, and Halpert JR (2004) Topological changes in the CYP3A4 active site probed with phenyldiazene: effect of interaction with NADPH-cytochrome P450 reductase and cytochrome b5 and of site-directed mutagenesis. Drug Metab Dispos 32:155-161.