In vitro metabolism of N-(5-chloro-2-methylphenyl)-N'-(2- methylpropyl)thiourea: Species comparison and identification of a novel thiocarbamide-glutathione adduct

Chemical Research in Toxicology

Volumn 10, Issue 7, 1997, Pages 733-741

  Stevens, Gregory J ^a   Hitchcock, Karen ^a   Karen Wang, Y ^a   Coppola, Gary M ^a   Versace, Richard W ^a   Chin, Jefferson A ^a   Shapiro, Michael ^a   Suwanrumpha, Somchai ^a   Mangold, Bonnie L K ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

1 (5 CHLORO 2 METHYLPHENYL) 3 (2 METHYLPROPYL)THIOUREA; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; THIOUREA DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOG; DRUG GLUCURONIDATION; DRUG HYDROXYLATION; HUMAN; HUMAN TISSUE; LIVER MICROSOME; LIVER MICROSOME METABOLISM; MONKEY; NONHUMAN; RAT; TOXICOKINETICS;

ANIMALS; ANTILIPEMIC AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOGS; FEMALE; GLUTATHIONE; HUMANS; LIVER; MACACA FASCICULARIS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; MICROSOMES, LIVER; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; THIOUREA;

ANIMALIA; CANIS FAMILIARIS;

EID: 0030745713     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx9700230     Document Type: Article

References (30)

1. Neal, R. A., and Halpert, J. (1982) Toxicology of thiono-sulfur compounds. Annu. Rev. Pharmacol. Toxicol. 22, 321-339.
2. Ziegler, D. M. (1982) Functional groups bearing sulfur. In Metabolism of Functional Groups (Jakoby, W. B., Bend, J. R., and Caldwell, J., Eds.) pp 171-184, Academic Press, New York.
3. Ziegler, D. M. (1988) Flavin-Containing monooxygenases: catalytic mechanism and substrate specificities. Drug Metab. Rev. 19, 1-32.
4. Poulsen, L. L., Hyslop, R. M., and Ziegler, D. M. (1979) S-Oxygenation of N-substituted thioureas catalyzed by the pig liver microsomal FAD-containing monooxygenase. Arch. Biochem. Biophys. 198, 78-88.
5. Cashman, J. R., and Hanzlik, R. P. (1981) Microsomal oxidation of thiobenzamide, a photometric assay for the flavin-containing monooxygenase. Biochem. Biophys. Res. Commun. 98, 147-153.
6. Cashman, J. R. (1995) Structural and catalytic properties of the mammalian flavin-containing monooxygenase. Chem. Res. Toxicol. 8, 165-181.
7. Hunter, A. L., and Neal, R. A. (1975) Inhibition of hepatic mixed-function oxidase activity in vitro and in vivo by various thionosulfur-containing compounds. Biochem. Pharmacol. 24, 2199-2205.
8. 35S-labeled thiocarbamides in rat hepatic microsomes. Biochem. Pharmacol. 43, 881-888.
9. Decker, C. J., and Doerge, D. R. (1991) Rat hepatic microsomal metabolism of ethylenethiourea. Contributions of the flavin-containing monooxygenase and cytochrome P450 isozymes. Chem. Res. Toxicol. 4, 482-489.
10. Krieter, P. A., Ziegler, D. M., Hill, K. E., and Burk, R. F. (1984) Increased biliary GSSG efflux from rat livers perfused with thiocarbamide substrates for the flavin-containing monooxygenase. Mol. Pharmacol. 26, 122-127.
11. Omura, T., and Sato, R. (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 239, 2370-2378.
12. Bradford, M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254.
13. Smith, P. F., Fisher, R., Shubat, P. J., Gandolfi, A. J., Krumdieck, C. L., and Brendel, K. (1987) In vitro cytotoxicity of allyl alcohol and bromobenzene in a novel organ culture system. Toxicol. Appl. Pharmacol. 87, 509-522.
14. Cashman, J. R., and Hanzlik, R. P. (1981) Microsomal oxidation of thiobenzamide. A photometric assay for the flavin-containing monooxygenase. Biochem. Biophys. Res. Commun. 98, 147-153.
15. Walter, W., and Randau, G. (1969) Thioharnstoff-S-monoxide. Leibigs Ann. Chem. 722, 52-79.
16. Ortiz de Montellano, P. R., and Mathews, J. M. (1981) Autocatalytic alkylation of the cytochrome P450 prosthetic haem group by 1-aminobenzotriazole. Biochem. J. 195, 761-764.
17. Mathews, J. M., and Bend, J. R. (1986) N-Alkylaminobenzotriazoles as isozyme-selective suicide inhibitors of rabbit pulmonary microsomal cytochrome P450. Mol. Pharmacol. 30, 25-32.
18. Barr, J., Weir, A. J., Brendel, K., and Sipes, I. G. (1991) Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism. Xenobiotica 21, 331-339.
19. Barr, J., Weir, A. J., Brendel, K., and Sipes, I. G. (1991) Liver slices in dynamic organ culture. II. An in vitro cellular technique for the study of integrated drug metabolism using human tissue. Xenobiotica 21, 331-339.
20. Vickers, A. E. M., Fischer, V., Connors, S., Fisher, R. L., Baldeck, J. P., Maurer, G., and Brendel, K. (1992) Cyclosporin A metabolism in human liver, kidney, and intestine slices: comparison to rat and dog slices and human cell lines. Drug Metab. Dispos. 20, 802-809.
21. Vickers, A. E. M. (1994) Use of human organ slices to evaluate the biotransformation and drug-induced side-effects of pharmaceuticals. Cell Biol. Toxicol. 10, 407-414.
22. Waldhauser, L., and Uetrecht, J. (1991) Oxidation of propylthiouracil to reactive metabolites by activated neutrophils: Implication for agranulocytosis. Drug Metab. Dispos. 19, 354-359.
23. Sterling, C. J. M. (1971) The sulfinic acids and their derivatives. Int. J. Sulfur Chem. 64, 277-320.
24. Dyroff, M. C., and Neal, R. A. (1981) Identification of the major protein adduct formed in rat liver after thioacetamide administration. Cancer Res. 41, 3430-3435.
25. Kedderis, G. L., and Rickert, D. E. (1985) Loss of rat liver microsomal P-450 during methimazole metabolism; role of flavin-containing monooxygenase. Drug Metab. Dispos. 13, 58-61.
26. Decker, C. J., Cashman, J. R., Sugiyama, K., Maltby, D., and Correia, M. A. (1991) Formation of glutathionyl-spironolactone disulfide by rat liver cytochromes P450 or hog liver flavin-containing monooxygenases: a functional probe of two-electron oxidation of the thiosteroid. Chem. Res. Toxicol. 4, 669-677.
27. Lee, P. W., and Neal, R. A. (1978) Metabolism of methimazole by rat liver cytochrome P450-containing monooxygenases. Drug Metab. Dispos. 6, 591-600.
28. Mugford, C. A., Mortillo, M., Mico, B. A., and Tarlogg, J. B. (1992) 1-Aminobenzotriazole-induced destruction of hepatic and renal cytochromes P450 in male Sprague-Dawley rats. Fund. Appl. Toxicol. 19, 43-49.
29. Town, C., Henderson, L., Chang, D., Mortillo, M., and Garland, W. (1993) Distribution of 1-aminobenzotriazole in male rats after administration of an oral dose. Xenobiotica 23, 383-390.
30. Maryanoff, C. A., Stanzione, R. C., and Plampin, J. N. (1986) Reactions of oxidized thioureas with amine nucleophiles. Phosphorus Sulfur 27, 221-232.