Metabolism-dependent mutagenicity of a compound containing a piperazinyl indazole motif: Role of a novel P450-mediated metabolic reaction involving a putative oxaziridine intermediate

Chemical Research in Toxicology

Volumn 19, Issue 10, 2006, Pages 1341-1350

  Chen, Hao ^a   Murray, Joel ^a   Kornberg, Brian ^a   Dethloff, Lloyd ^a   Rock, David ^a   Nikam, Sham ^a   Mutlib, Abdul E ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 INDAZOLONE; 6 CHLORO 3,3 DIMETHYL 5 (3 PIPERAZIN 1 YL PROPYL) 1,3 DIHYDROINDOL 2 ONE; 6 CHLORO 5 [3 [4 (1H INDAZOL 3 YL)PIPERAZIN 1 YL]PROPYL] 3,3 DIMETHYL 1,3 DIHYDROINDOL 2 ONE; 6 CHLORO 5 [3 [4 (1H INDAZOL 3 YL)PIPERIDIN 1 YL PROPYL] 3,3 DIMETHYL 1,3 DIHYDROINDOL 2 ONE; CYTOCHROME P450; CYTOCHROME P450 3A; INDAZOLE DERIVATIVE; MUTAGENIC AGENT; OXAZIRIDINE DERIVATIVE; PIPERAZINYL INDAZOLE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; CELLULAR DISTRIBUTION; CONFERENCE PAPER; CONTROLLED STUDY; DEINDAZOLIZATION; DRUG METABOLISM; DRUG STRUCTURE; ELIMINATION REACTION; ENZYME INACTIVATION; HYDROLYSIS; LIVER MICROSOME; METABOLIC REGULATION; MUTAGENICITY; NONHUMAN; PROTEIN MOTIF; RAT; REACTION ANALYSIS; SALMONELLA TYPHIMURIUM;

ANIMALS; AZIRIDINES; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME ACTIVATION; INDAZOLES; KINETICS; LIVER; MICROSOMES; MOLECULAR STRUCTURE; MUTAGENESIS; OXIDATION-REDUCTION; PIPERAZINES; RATS; SALMONELLA TYPHIMURIUM; STRUCTURE-ACTIVITY RELATIONSHIP; TESTOSTERONE;

SALMONELLA TYPHIMURIUM;

EID: 33750206490     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx050354+     Document Type: Conference Paper

References (24)

1. Ames, B. N., McCann, J., and Yamasaki, E. (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsomes mutagenicity test. Mutat. Res. 31, 347-364.
2. Maron, D. M., and Ames, B. N. (1983) Revised method for the Salmonella mutagenicity test. Mutat. Res. 3113, 173-215.
3. Vance, W. A., Okamoto, H. S., and Wang, Y. Y. (1986) Structure-activity relationships of nitro and methyl-nitro derivatives of indoline, indole, indazole and benzimidazole in Salmonella tvphimurium. Mutat. Res. 173, 169-176.
4. Chen, H., Murray, J., Andreana, T., Dethloff, L., and Mutlib, A. E. (2004) Metabolism-dependent mutagenicity of Compound A: role of a novel N-dearylation pathway via a possible reactive oxaziridine intermediate. Drug Metab. Rev. 36, 197.
5. Ames, B. N., McCann, J., and Yamasaki, E. (1975) Methods for detecting carcinogen and mutagens with the Salmonella/mammalian mutagenicity test. Mutat. Res. 31, 347-364.
6. Claxton, L. D., Allen, J., Auletta, A., Mortelmans, K., Nestmann, E., and Zeiger, E. (1987) Guide for the Salmonella typhimurium/mammalian microsomes tests for bacterial mutagenicity. Mutat. Res. 189, 83-91.
7. Gatehouse, D., Haworth, S., Cebula, T., Gocke, E., Kier, L., Matsushima, T., Melcion, C., Nohmi, T., Ohta, T., Venitt, S., and Zeiger, E. (1994) Recommendations for the performance of bacterial mutation assays. Mutat. Res. 312, 217-233.
8. Majeska, J. B., and Mayo, J. K. (2000) The Ames Salmonella Assay: State of the Art, Presented at the 31st Annual Meeting of the Environmental Mutagen Society, New Orleans, LA.
9. Hutzler, M. J., and Tracy, T. (2002) Atypical kinetic profiles in drug metabolism reactions. Drug Metab. Dispos. 30, 355-362.
10. Tracy, T. S., Hutzler, M. J., Haining, R. L., Rettie, A. E., Hummel, M. A., and Dickmann, L. J. (2003) Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: Effect on atypical kinetic metabolism profiles. Drug Metab. Dispos. 30, 385-390.
11. Abe-Onishi, Y., Yomota, C., Sugimoto, N., Kubota, H., and Tanamoto, K. (2004) Determination of benzoyl peroxide and benzoic acid in wheat flour by high-performance liquid chromatography and its identification by high-performance liquid chromatography-mass spectrometry. J. Chromatogr., A. 1040, 209-214.
12. Magnusson, M. O., and Sandstrom, R. (2004) Quantitative analysis of eight testosterone metabolites using column switching and liquid chromatography/ tandem mass spectrometry. Rapid Commun. Mass Spectrom. 18, 1089-1094.
13. Chang, T., Levine, M., and Vellward, G. D. (1992) Selective inhibition of rat hepatic microsomal cytochrome P450. Effect of the in vitro administration of cimetidine. Drug Metab. Dispos. 260, 1450-1455.
14. Nedelcheva, D., and Gut, I. (1994) P450 in the rat and man: methods of investigation, substrate specificities and relevance to cancer. Xenobiotica 24, 1151-1175.
15. Guengerich, F. P., Dannan, G. A., Wright, S. T., Martin, M. V., and Kaminski, L. S. (1982) Purification and characterization of liver microsomal cytochrome P450: electrophoretic, spectral, catalytic and immunochemical properties and inducibility of eight isoeymes isolated from rats treated with Phenobarbital and alpha-naphthoflavone. Biochem. 21, 6019-6031.
16. Cooper, K. O., Reik, L. M., Jayyosi, Z., Bandiera, S., Kelley, M., Ryan, D. E., Daniel, R., McCluskey, S. A., Levin, W., and Thomas, P. E. (1993) Regulation of two members of the steroid-inducible cytochrome P450 subfamily (3A) in rats. Arch. Biochem. Biophys. 301, 345-354.
17. Silverman, R. B. (1996) Mechanism-Based Enzyme Inactivators. In Contemporary Enzyme Kinetics and Mechanisms (Purich, D. L., Ed.) pp 291-335, Academic Press, San Diego, CA.
18. Tschirret-Guth, R., and Wood, H. B. (2003) Substituent effect on the reductive N-dearylation of 3-(indol-1-yl)-1,2-benzisoxazoles by rat liver microsomes. Drug Metab. Dispos. 31, 999-1004.
19. Prakash, C., Kamel, A., and Cui, D. (1997) Characterization of the novel benzisothiazole ring-cleaved products of the antipsychotic drug ziprasidone. Drug Metab. Dispos. 25, 897-901.
20. Ullman, E. F., and Bartkus, E. A. (1962) 3-Indazolone, a proposed intermediate in the von Richter reaction. Chem. Ind. (London). 40, 93-94.
21. Davis, F. A., and Sheppard, A. C. (1989) Applications of oxaziridines in organic synthesis. Tetrahedron 45, 5703-5742.
22. Guengerich, P. F. (1990) Mechanism-based inactivation of human liver microsomal cytochrome P450 IIIA4 by gestodone. Chem. Res. Toxicol. 3, 363-371.
23. Chen, Q., Ngui, J. S., Doss, G. A., Wang, R. W., Cai, X., DiNinno, F. P., Blizzard, T. A., Hammond, M. L., Sterns, R. A., Evans, D. C., Ballie, T. A., and Tang, W. (2002) Cytochrome P450 3A4-mediated bioactivation of raloxifene: Irrversible enzyme inhibition and thiol adduct formation. Chem. Res. Toxicol. 15, 907-914.
24. Daniels, J. S., Chatterji, T., MacGillivray, L. R., and Gates, K. S. (1998) Photochemical DNA cleavage by the antitumor agent 3-amino-1,2,4- benzotriazine-1,4-dioxide. J. Org. Chem. 63, 10027-10030.