Evidence supporting the formation of 2,3-epoxy-3-methylindoline: A reactive intermediate of the pneumotoxin 3-methylindole

Chemical Research in Toxicology

Volumn 11, Issue 7, 1998, Pages 741-749

  Skordos, Konstantine W ^a   Skiles, Gary L ^a,b   Laycock, John D ^a,c   Lanza, Diane L ^a   Yost, Garold S ^a  

^a UNIVERSITY OF UTAH   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c Performance Bioanalytical   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; SKATOLE;

ARTICLE; BIOTRANSFORMATION; DETOXIFICATION; ENZYME ACTIVITY; EPOXIDATION; MICROSOME; OXIDATION REDUCTION REACTION; REACTION ANALYSIS;

ALDEHYDE OXIDASE; ALDEHYDE OXIDOREDUCTASES; ANIMALS; CHROMATOGRAPHY, LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; EPOXY COMPOUNDS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GOATS; INDOLES; MALE; MICE; MICROSOMES; OXYGEN RADIOISOTOPES; RABBITS; RATS; SKATOLE;

EID: 0031854435     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx9702087     Document Type: Article

References (22)

1. Bray, T. M., and Carlson, J. R. (1979) Role of mixed-function oxidase in 3-methylindole induced acute pulmonary edema in goats. Am. J. Vet. Res. 40, 1268-1272.
2. Carlson, J. R., and Yost, G. S. (1989) 3-Methylindole-induced acute lung injury resulting from ruminal fermentation of tryptophan. In Toxicants of Plant Origin (Cheeke, P.R., Ed.) Vol. 3, pp 107-123, CRC Press, Boca Raton, FL.
3. Adams, J. D., Laegreid, W. W., Huijzer, J. C., Hayman, C., and Yost, G. S. (1988) Pathology and glutathione status in 3-methylindole-treated rodents. Res. Commun. Chem. Pathol. Pharmacol. 60, 323-335.
4. Ruangyuttikarn, W., Appleton, M. L., and Yost, G. S. (1991) Metabolism of 3-methylindole in human tissues. Drug Metab. Dispos. 19, 977-984.
5. Thornton-Manning, J. R., Appleton, M. L., Gonzalez, F. J., and Yost, G. S. (1996) Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes: correlation of 3-methyleneindolenine formation and protein-binding. J. Pharmacol. Exp. Ther. 276, 21-29.
6. Yokoyama, M. T., and Carlson, J. R. (1974) Dissimilation of tryptophan and related indolic compounds by ruminal microorganisms. Appl. Microbiol. 27, 1540-1548.
7. Nocerini, M. R., Carlson, J. R., and Yost, G. S. (1985) Glutathione adduct formation with microsomally activated metabolites of the pulmonary alkylating and cytotoxic agent, 3-methylindole. Toxicol. Appl. Pharmacol. 81, 75-84.
8. Nocerini, M. R., Yost, G. S., Carlson, J. R., Liberate, D. J., and Breeze, R. G. (1985) Structure of the glutathione adduct of activated 3-methylindole indicates that an imine methide is the electrophilic intermediate. Drug Metab. Dispos. 13, 690-694.
9. Skiles, G. L., and Yost, G. S. (1996) Mechanistic studies on the cytochrome P450-catalyzed dehydrogenation of 3-methylindole. Chem. Res. Toxicol. 9, 291-297.
10. Ruangyuttikarn, W., Skiles, G. L., and Yost, G. S. (1992) Identification of a cysteinyl adduct of oxidized 3-methylindole from goat lung and human liver microsomal proteins. Chem. Res. Toxicol. 5, 713-719.
11. 14C]indole in the rat. Biochem. J. 98, 266-277.
12. Zhang, X., and Foote, C. S. (1993) Dimethyldioxirane oxidation of indole derivatives. Formation of novel indole-2,3-epoxides and a versatile synthetic route to indolinones and indolines. J. Am. Chem. Soc. 115, 8867-8868.
13. Darbyshire, J. F., Iyer, K. R., Grogan, J., Korzekwa, K. R., and Trager, W. F. (1996) Selectively deuterated warfarin. Substrate probe for the mechanism of aromatic hydroxylation catalyzed by cytochrome P450. Drug Metab. Dispos. 24, 1038-1045.
14. Beedham, C. (1987) Molybdenum hydroxylases: biological distribution and substrate-inhibitor specificity. In Progress in Medicinal Chemistry (Ellis, G. P., West, G. B., Eds.) pp 85-127, Elsevier Science, Amsterdam.
15. Smith, D. J., Skiles, G. L., Appleton, M. L., Carlson, J. R., and Yost, G. S. (1993) Metabolic fate of 3-methylindole in goats and mice. Xenobiotica 23, 1025-1044.
16. Skiles, G. L., Adams, J. D., Jr., and Yost, G. S. (1989) Isolation and identification of 3-hydroxy-3-methyloxindole, the major murine metabolite of 3-methylindole. Chem. Res. Toxicol. 2, 254-259.
17. Kohn, M., and Ostersetzer, A. (1911) Einige neue abkommLing desdioxindols. Monatsh. Chem. 32, 905-916.
18. Katritzky, A. R., Akutagawa, K., and Jones, R. A. (1988) Carbon dioxide: a reagent for the protection of nucleophilic centres and the simultaneous activation to electrophilic attack - Part XII. One-pot conversion of 3-methylindole into 2-formyl-3-methyindole. Synth. Commun. 18, 1151-1158.
19. 1-methylnicotinamide oxidase. In Methods of Enzymology (McCormick, D. B., and Wright, L. D., Eds.) pp 216-222, Academic Press, New York.
20. 1 activation in human lung. Toxicol. Appl. Pharmacol. 144, 88-95.
21. Himmelstein, M. W., Acquavella, J. F., Recio, L., Medinsky, M. A., and Bond, J. A. (1997) Toxicology and epidemiology of 1,3-butadiene. Crit. Rev. Toxicol. 27, 1-108.
22. Albright, J. D., and Snyder, H. R. (1959) Reaction of optically active indole mannich bases. J. Am. Chem. Soc. 81, 2239-2245.