Screening for xenobiotic electrophilic metabolites using pulsed ultrafiltration-mass spectrometry

Combinatorial Chemistry and High Throughput Screening

Volumn 2, Issue 3, 1999, Pages 165-175

  Nikolic, Dejan ^a   Fan, Peter W ^a   Bolton, Judy L ^a   Van Breemen, Richard B ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 TERT BUTYL 4,6 DIMETHYLPHENOL; CHEMICAL COMPOUND; CYPROHEPTADINE; CYTOCHROME P450; EPOXIDE; GLUTATHIONE; GLUTATHIONE DERIVATIVE; GLUTATHIONE TRANSFERASE; HYDROXYCHAVICOL; IMINE; LIVER ENZYME; QUINONE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SKATOLE; UNCLASSIFIED DRUG; XENOBIOTIC AGENT;

ANIMAL TISSUE; ARTICLE; CONJUGATE; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME SUBSTRATE; FEMALE; FLOW INJECTION ANALYSIS; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; METABOLITE; NONHUMAN; PRIORITY JOURNAL; RAT; SCREENING; ULTRAFILTRATION; XENOBIOTIC METABOLISM;

ANIMALS; FEMALE; MASS SPECTROMETRY; MICROSOMES, LIVER; RATS; RATS, SPRAGUE-DAWLEY; ULTRAFILTRATION; XENOBIOTICS;

EID: 0032977774     PISSN: 13862073     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (28)

1. Thompson L.A. and Ellman J.A. Synthesis and applications of small molecule libraries. Chem. Rev. 1996, 29, 132-143.
2. Rodrigues AD Preclinical drug metabolism in the age of high-throughput screening: An industrial perspective. Pharmaceut. Res. 1997, 14, 1504-1510.
3. van Breemen R.B., Nikolic D., Bolton J.L. Metabolic screening using on-line ultrafiltration mass spectrometry. Drug Metab. Dispos. 1998, 26, 85-90
4. van Breemen R.B., Huang C.R., Nikolic D., Woodbury C.P. and Venton D.L. Pulsed ultrafiltration mass spectrometry: A new method for screening combinatorial libraries. Anal. Chem. 1997, 69, 2159-2164.
5. Zhao Y.Z., van Breemen R.B., Nikolic D., Huang C.R., Woodbury C.P., Schilling A. and Venton D.L. Screening solution-phase combinatorial libraries using pulsed ultrafiltration/electrospray mass spectrometry. J. Med. Chem. 1997, 40, 4006-4012.
6. Nikolic D. and van Breemen R.B. Screening for inhibitors of dihydrofolate reductase using pulsed ultrafiltration mass spectrometry. Combin. Chem. High Through. Screen 1998, 1, 47-55.
7. Peter M.G. Chemical modifications of biopolymers by quinones and quinone methides. Angew. Chem. Int. Ed. Engl. 1989, 28, 555.
8. Thompson D.C., Thompson J.A., Sugumaran M. and Moldeus P. Biological and toxicological consequences of quinone methide formation. Chem-Biol. Interact. 1993, 86, 129-162.
9. Chatterjee M. and Rokita S.E. The role of a quinone methide in the sequence specific alkylation of DNA. J. Am. Chem. Soc. 1994, 116, 1690-1697.
10. Lewis, M.A., Yoerg-Graff D., Bolton J.L. and Thompson J.A. Alkylation of 2'-deoxynucleosides and DNA by quinone methides derived from 2,6-di-tert-butyl-4-methylphenol. Chem. Res. Toxicol. 1996, 9, 1368-1374.
11. Bolton J.L., Turnipseed S.B. and Thompson J.A. Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins: studies utilizing amino acid and peptide models. Chem-Biol Interact. 1997, 107, 185-200.
12. Bolton J.L., Valerio L.G. and Thompson J.A. The enzymatic formation and chemical reactivity of quinone methides correlate with alkylphenol-induced toxicity in rat hepatocytes. Chem. Res. Toxicol. 1992, 5, 816-22.
13. Stone C.A., Wenger H.C., Ludden C.T., Stavorski J.M. and Ross C.A. Antiserotonin-antihistaminic properties of cyproheptadine. J. Pharmacol. Exp. Ther. 1961, 131, 73.
14. Hucker H.B., Balletto A.J., Stauffer S.C., Zacchei A.G. and Arison B.H. Physiological disposition and urinary metabolites of cyproheptadine in the dog, rat and cat. Drug Metab. Dispos. 1974, 2, 406.
15. Wold J.S. and Fisher L.J. The tissue distribution of cyproheptadine and its metabolites in rats and mice. J Pharmacol Exp Ther. 1972, 183, 188.
16. Frigerio A., Sossi N., Belvedere G., Pantarotto C. and Garaattini S. Identification of desmethylcyproheptadine-10,11-epoxide and other cyproheptadine metabolites isolated from rat urine. Pharm Sci. 1974, 63, 1536.
17. Klaassen C.D. "Casarett & Doull's toxicology, the basic science of poisons." 1996, ed. 5, p. 177-183, McGraw-Hill, New York.
18. Yost G.S., Buckpitt A.R., Roth R.A. and McLemore T.L. Contemporary issues in toxicology: Mechanisms of lung injury by systemically administered chemicals. Tox. Appl. Pharm. 1989, 101, 179-195.
19. Skiles G.L. and Yost G.S. Mechanistic studies on the cytochrome P450-catalyzed dehydrogenation 3-methylindole. Chem. Res. Toxicol. 1996, 8, 291-297.
20. Skordos K.W., Skiles G.L., Laycock J.D., Lanza D.L and Yost G.S. Evidence supporting the formation of 2,3-epoxy-3methylindole: a reactive intermediate of the pneumotoxin 3-methylindole. Chem. Res. Toxicol. 1998, 11, 741-749.
21. Fennell T.R., Miller J.A. and Miller E.C. Characterization of the biliary and urinary glutathione and N-acetylcysteine metabolites of the hepatic carcinogen 1'-hydroxysafrole and its 1'-oxo metabolite in rats and mice. Cancer Res. 1984, 44, 3231-3240.
22. Crampton R.F., Gray T.J.B., Grasso P. and Parke D.V. Long-term studies on chemically induced liver enlargement in rat II. Transient induction of microsomal enzymes leading to liver damage and nodular hyperplasia produced by safrole and ponceau MX. Toxicology 1977, 7, 307-326.
23. Benedetti MS, Malnoe A and Broillet AL Absorption, metabolism and excretion of safrole in the rat and man. Toxicology 1977, 7, 69-83.
24. Bolton J.L, Acay NM and Vukomanovic V Evidence that 4-allylortho-quinones spontaneously rearrange to their more electrophilic quinone methides: Potential bioactivation mechanism for the hepatocarcinogen safrole. Chem. Res. Toxicol. 1994, 7, 443-450.
25. McCracken P.G., Bolton J.L. and Thatcher G.R.J. Covalent modification of proteins and peptides by the quinone methide from 2-tert-butyl-4,6-dimethylphenol: selectivity and reactivity with respect to competitive hydration. J. Org. Chem. 1997, 62, 1820-1825.
26. Thompson J.A., Malkinson A.M., Wand M.D., Mastovich S.L., Mead E.W., Schullek K.M. and Laudenschlager W.G. Oxidative metabolism of butylated hydroxytoluene by hepatic and pulmonary microsomes from rats and mice. Drug Metab. Dispos. 1987, 15, 833-840.
27. O'Brien, P. J. Molecular mechanisms of quinone cytotoxicity. Chem.-Biol. Interact. 1991, 86, 1-14.
28. Ramanathan R., Cao K., Cavalieri E. and Gross M.L. Mass spectrometric methods for distinguishing structural isomers of glutathione conjugates of estrone and estradiol. J. Am. Soc. Mass Spectrom. 1998, 9, 612-619.