Aryl acetylenes as mechanism-based inhibitors of cytochrome P450- dependent monooxygenase enzymes

Chemical Research in Toxicology

Volumn 10, Issue 1, 1997, Pages 91-102

  Foroozesh, Maryam ^a,c   Primrose, Ginny ^a   Guo, Zuyu ^b,d   Bell, L Chastine ^b   Alworth, William L ^a   Guengerich, F Peter ^b  

^a Tulane University   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c XAVIER UNIVERSITY OF LOUISIANA   (United States)

^d Rhone Poulenc Rorer ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLENE DERIVATIVE; BETA NAPHTHOFLAVONE; CYTOCHROME P450; ENZYME INHIBITOR; ISOSAFROLE; PHENOBARBITAL; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RESORUFIN DERIVATIVE; UNSPECIFIC MONOOXYGENASE;

ANIMAL CELL; ARTICLE; DEALKYLATION; ENZYME INACTIVATION; ENZYME INHIBITION; LIVER MICROSOME METABOLISM; NONHUMAN; RAT;

ACETYLENE; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BENZENE DERIVATIVES; BIPHENYL COMPOUNDS; CYTOCHROME P-450 CYP1A1; CYTOCHROME P-450 CYP1A2; CYTOCHROME P-450 CYP2B1; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; MALE; MICROSOMES, LIVER; NAPHTHALENES; PHENANTHRENES; PYRENES; RABBITS; RATS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; STEROID HYDROXYLASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0031021458     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx960064g     Document Type: Article

References (46)

1. Nelson, D. R., Tetsuya, K., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyereiscn, R., Gonzalez, F. J., Coon, M. J., Gunsalus, I. C., Gotoh, O., Okuda, K., and Nebert, D. W. (1993) The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 12, 1-51.
2. Schenkman, J. B., and Greim, H. (1993) (Eds.) in Cytochrome P450, Springer-Verlag, New York.
3. Kadlubar, F. F., and Hammons, G. J. (1987) The role of cytochrome P-450 in the metabolism of chemical carcinogens. In Mammalian Cytochromes P-450 (Guengerich, F. P., Ed.) Vol. II, pp 81-130, CRC Press, Boca Raton, FL.
4. Prough, R. A., and Spearman, M. E. (1987) Endogenous and dietary chemicals: metabolism and interaction with cytochrome P-450. In: Mammalian Cytochromes P-450 (Guengerich, F. P., Ed.) Vol. II, pp 153-172, CRC Press, Boca Raton, FL.
5. Leo, M. A., Lasker, J. M., Raucy, J. L., Kim, C. I., Black, M., and Lieber, C. S. (1989) Metabolism of retinol and retinoic acid by human liver cytochrome P450IIC8. Arch. Biochem. Biophys. 269, 305-312.
6. Guengerich, F. P., and Shimada, T. (1991) Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem. Res. Toxicol. 4, 381-407.
7. Ortiz de Montellano, P. R., and Kunze, K. L. (1980) Self-catalyzed inactivation of hepatic cytochrome P-450 by ethynyl substrates. J. Biol. Chem. 255, 5578-5585.
8. Gan, L.-S. L., Acebo, A. L., and Alworth, W. L. (1984) 1-Ethynylpyrene, a suicide inhibitor of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity in liver microsomes. Biochemistry 23, 3827-3836.
9. Gan, L.-S. L., Lu, J.-Y. L., Hershkowitz, D. M., and Alworth, W. L. (1985) Effects of acetylenic and olefinic pyrenes upon cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity in liver microsomes. Biochem. Biophys. Res. Commun. 129, 591-596.
10. Hammons, G. J., Alworth, W. L., Hopkins, N. E., Guengerich, F. P., and Kadlubar, F. F. (1989) 2-Ethynylnapthalene as a mechanism-based inactivator of the cytochrome P-450 catalyzed N-oxidation of 2-naphthylamine. Chem. Res. Toxicol. 2, 367-374.
11. Hall, M., Parker, D. K., Grover, P. L., Lu, J.-Y. L., Hopkins, N. E., and Alworth, W. L. (1990) Effects of 1-ethynylpyrene and related inhibitors of P450 isozymes upon benzo[a]pyrene metabolism by liver microsomes. Chem.-Biol. Interact. 76, 181-192.
12. Hopkins, N. E., Foroozesh, M. K., and Alworth, W. L. (1992) Suicide inhibitors of cytochrome P450 1A1 and P450 2B1. Biochem. Pharmacol. 44, 787-797.
13. Roberts, E. S., Hopkins, N. E., Alworth, W. L., and Hollenberg, P. F. (1993) Mechanism-based inactivation of cytochrome P450 2B1 by 2-ethynylnaphthalene: identification of an active site peptide. Chem. Res. Toxicol. 6, 470-479.
14. Chan, W. K., Sui, Z., and Ortiz de Montellano, P. R. (1993) Determinants of protein modification versus heme alkylation: inactivation of cytochrome P450 1A1 by 1-ethynylpyrene and phenylacetylene. Chem. Res. Toxicol. 6, 38-45.
15. Alworth, W. L., Viaje, A., Sandoval, A., Warren, B. S., and Slaga, T. J. (1984) Potent inhibitory effects of suicide inhibitors of P450 isozymes on 7,12-dimethylbenzo[a]anthracene and benzo[a]pyrene initiated skin tumors. Carcinogenesis 12, 1209-1215.
16. Alworth, W. L., Young-Sciame, R., and Hecht, S. S. (1991) Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone mouse lung tumorigenesis by arylalkynes, mechanism-based inactivators of cytochrome P450. Carcinogenesis 12, 1209-1215.
17. Ortiz de Montellano, P. R., and Komives, E. A. (1985) Branchpoint for heme alkylation and metabolic formation in the oxidation of arylacetylenes by cytochrome P-450. J. Biol. Chem. 260, 3330-3336.
18. CaJacob, C. A., Chan, W. K., Shephard, E., and Ortiz de Montellano, P. R. (1988) The catalytic site of rat hepatic lauric acid ω-hydroxylase. Protein versus prosthetic heme alkylation fatty acids. J. Biol. Chem. 263, 18640-18649.
19. Yun, C.-H., Hammons, G. J., Jones, G., Martin, M. V., Hopkins, N. E., Alworth, W. L., and Guengerich, F. P. (1992) Modification of cytochrome P450 1A2 enzymes by the mechanistic inactivator 2-ethynylnaphthalene and the photoaffinity label 4-azidobiphenyl. Biochemistry 31, 10556-10563.
20. 3H-labeled 2-ethynylnaphthalene-inactivated P450 2B1 and 2B4 using amino acid sequencing and mass spectrometry. Biochemistry 33, 3766-3771.
21. Roberts, E. S., Hopkins, N. E., Zaluzec, E. J., Cage, D. A., Alworth, W. L., and Hollenberg, P. F. (1995) Mechanism-based inactivation of cytochrome P450 2B1 by 9-ethynylphenanthrene. Arch. Biochem. Biophys. 323, 295-302.
22. Prough, R. A., Burke, M. D., and Mayer, R. T. (1978) Direct fluorometric methods for measuring mixed-function oxidase activity. Methods Enzymol. 52, 372-377.
23. Fu, P. P., Lee, H. M., and Harvey, R. G. (1980) Regioselective catalytic hydrogenation of polycyclic aromatic hydrocarbons under mild conditions. J. Org. Chem. 45, 2797-2803.
24. Harvey, R. G., Schmolka, S., Cortez, C., and Lee, H. (1988) Synthesis of 2-bromopyrene and 2-hydroxypyrene. Synth. Commun. 18, 2207-2209.
25. Neenan, T. X., and Whitesides, G. M. (1988) Synthesis of high carbon materials from acetylenic precursors. Preparation of aromatic monomers bearing multiple ethynyl groups. J. Org. Chem. 53, 2489-2496.
26. Gerasimenko, Y. E., and Shevcbuk, I. N. (1968) Pyrene chemistry VIII. 4-Acylpyrenes and 3H-benz[c,d]pyrene-3-one. J. Org. Chem. USSR 4, 2120-2123.
27. Negishi, E., King, A., and Tours, J. (1985) Conversion of methyl ketones into terminal alkynes. Org. Synth. 64, 44-47.
28. Takahaski, S., Kuroyama, Y., Sonogashira, K., and Hagihara, N. A. (1980) Convenient synthesis of ethynylarenes and diethynylarenes. Synthesis 88, 627-630.
29. Guengerich, F. P. (1994) Analysis and characterization of enzymes. In Principles and Methods of Toxicology (Hayes A. W., Ed.) 3rd ed., pp 1259-1313, Raven Press, New York.
30. Bradford, M. 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.
31. Guengerich, F. P., Dannan, G. A., Wright, T., Martin, M. V., and Kaminsky, L. S. (1982) Purification and characterization of liver microsomal cytochromes P-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated form rats treated with phenobarbital or βnaphthoflavone. Biochemistry 21, 6019-6030.
32. Alterman, M. A., and Dowgii, A. I. (1990) A simple and rapid method for the purification of cytochrome P450 (form LM4). Biomed. Chromatogr. 4, 221-222.
33. Sandhu, P., Guo, Z., Baba, T., Martin, M. V., Tukey, R. H., and Guengerich, F. P. (1994) Expression of modified human cytochrome P450 1A2 in Escherichia coli: effects of 5′ substitution, stabilization, purification, spectral characterization, and catalytic activities of the enzyme. Arch. Biochem. Biophys. 309, 168-177.
34. Guo, Z., Gillam, E. M. J., Ohmori, S., Tukey, R. H., and Guengerich, F. P. (1994) Expression of modified human cytochrome P450 1A1 in Escherichia coli: effects of 5′ substitution, stabilization, purification, spectral characterization, and catalytic properties. Arch. Biochem. Biophys. 312, 436-446.
35. Berthou, F., Flinois, J.-P., Ratanasavanh, D., Beaune, P., Riche, C., and Guillouzo, A. (1991) Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes. Drug Metab. Dispos. 19, 561-567.
36. Lubet, R. A., Mayer, R. T., Cameron, J. W., Nims, R. W., Burke, M. D., Wolff, T., and Guengerich, F. P. (1985) Dealkylation of pentoxyresorufin: A rapid and sensitive assay for measuring the induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat. Arch. Biochem. Biophys. 238, 43-48.
37. Yasukochi, Y., and Master, B. S. S. (1976) Some properties of a detergent-solubilized NADPH-cytochrome c (cytochrome P450) reductase purified by biospecific affinity chromotography. J. Biol. Chem. 251, 5337-5344.
38. Cornish-Bowden, A. (1979) Fundamentals of Enzyme Kinetics, pp 49-51, Butterworth & Co., Boston, MA.
39. Omura, T., and Sato, R. (1964) The carbon monoxide-binding pigment of liver microsomes. Evidence for its hemoprotein nature. J. Biol. Chem. 239, 2370-2378.
40. Kitz, R., and Wilson, I. B. (1962) Esters of methane sulfonic acid as irreversible inhibitors of acetylcholinesterase. J. Biol. Chem. 237, 3245-3249.
41. Silverman, R. B. (1988) In Mechanism-based Enzyme Inactivation: Chemistry and Enzymology, Vol. I, pp 16-20, CRC Press, Boca Raton, FL.
42. Burke, M. D., Thompson, S., Weaver, R. J., Wolf, C. R., and Mayer, R. T. (1994) Cytochrome P450 specificities of alkoxyresorufin O-dealkylation in human and rat liver. Biochem. Pharmacol. 48, 923-936.
43. Roberts, E. S., Ballou, D. P., Hopkins, N. E., Alworth, W. L., and Hollenberg, P. F. (1995) Mechanistic studies of 9-ethynylphenanthrene-inactivated cytochrome P450 2B1. Arch. Biochem. Biophys. 323, 303-312.
44. Poulas, T. L., Cupp-Vickery, J., and Li, H. (1995) Structural studies on prokaryotic cytochromes P450. In Cytochrome P450, Structure, Mechanism, and Biochemistry (Ortiz de Montellano, P. R., Ed.) 2nd ed., pp 135-138, Plenum Press, New York.
45. Hasemann, C. A., Kurumbail, R. G., Boddupalli, S. S., Peterson, J. A., and Deisenhofer, J. (1995) Structure and function of cytochrome P450: a comparative study of three crystal structures. Curr. Biol. 3, 41-62.
46. Roberts, E. S., Pernecky, S. J., Alworth, W. L., and Hollenberg, P. F. (1996) A role for threonine 302 in the mechanism-based inactivation of P450 2B4 by 2-ethynylnaphthalene. Arch. Biochem. Biophys. 331, 170-176.