Indolequinone inhibitors of NRH:Quinone oxidoreductase 2. Characterization of the mechanism of inhibition in both cell-free and cellular systems

Biochemistry

Volumn 50, Issue 31, 2011, Pages 6678-6688

  Yan, Chao ^a   Dufour, Marine ^b   Siegel, David ^a   Reigan, Philip ^a   Gomez, Joe ^a   Shieh, Biehuoy ^a   Moody, Christopher J ^b   Ross, David ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE SITE; AMINE NITROGEN; BIOCHEMICAL TESTING; CELL-FREE; CELL-FREE SYSTEM; CELLULAR SYSTEM; ELECTROPHILES; IMINIUM; K562 CELLS; LEAVING GROUPS; MOLECULAR MODELING SIMULATIONS; NANOMOLAR CONCENTRATION; OXIDOREDUCTASES; PARTITION RATIOS; SIDE-CHAINS; STRUCTURAL PARAMETER; SUBSTITUTED PHENOL;

CELL CULTURE; CELLS; CELLULAR ARRAYS; CELLULAR TELEPHONE SYSTEMS; HYDROGEN BONDS; MASS SPECTROMETRY; PHENOLS;

ENZYME INHIBITION;

5 (3 AMINOPROPYL)AMINO 1,2 DIMETHYL 3 [(2,4,6 TRIFLUOROPHENOXY)METHYL]INDOLE 4,7 DIONE; 5 (3 DIMETHYLAMINO)PROPYLAMINO 1,2 DIMETHYL 3 (HYDROXYMETHYL) INDOLE 4,7 DIONE; 5 (3 DIMETHYLAMINO)PROPYLAMINO 1,2 DIMETHYL 3 (PHENOXYMETHYL)INDOLE 4,7 DIONE; 5 (3 DIMETHYLAMINO)PROPYLAMINO 1,2 DIMETHYL 3 [(2,4,6 TRIFLUOROPHENOXY)METHYL]INDOLE 4,7 DIONE; 5 (3 DIMETHYLAMINO)PROPYLMETHYLAMINO 1,2 DIMETHYL 3 [(2,4,6 TRIFLUOROPHENOXY)METHYL]INDOLE 4,7 DIONE; 5 (4 AMINOBUTYL)AMINO 1,2 DIMETHYL 3 [(2,4,6 TRIFLUOROPHENOXY)METHYL]INDOLE 4,7 DIONE; 5 (4 AMINOBUTYL)AMINO 1,2 DIMETHYL 3 [(4 NITROPHENOXY)METHYL]INDOLE 4,7 DIONE; 6 (3 DIMETHYLAMINO)PROPYLAMINO 1,2 DIMETHYL 3 [(2,4,6 TRIFLUOROPHENOXY)METHYL]INDOLE 4,7 DIONE; 6 (4 AMINOBUTYL)AMINO 1,2 DIMETHYL 3 [(2,4,6 TRIFLUOROPHENOXY)METHYL]INDOLE 4,7 DIONE; ANTINEOPLASTIC AGENT; ELECTROPHILE; HYDROGEN; INDOLE DERIVATIVE; NITROGEN; NRH:QUINONE OXIDOREDUCTASE 2; OXIDOREDUCTASE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CHEMICAL PARAMETERS; CHEMICAL STRUCTURE; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; HYDROGEN BOND; KINETICS; LEUKEMIA CELL LINE; MASS SPECTROMETRY; MOLECULAR DYNAMICS; PRIORITY JOURNAL;

ALKYLATION; AMINATION; BINDING, COMPETITIVE; CATALYTIC DOMAIN; CELL-FREE SYSTEM; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CRYSTALLOGRAPHY, X-RAY; HUMANS; INDOLEQUINONES; K562 CELLS; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; NAD(P)H DEHYDROGENASE (QUINONE); QUINONE REDUCTASES; RECOMBINANT PROTEINS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 79961052684     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi2002967     Document Type: Article

References (43)

1. Ernster, L. and Navazio, F. (1958) Soluble diaphorase in animal tissues Acta Chem. Scand. 12, 595-602
2. Ernster, L., Ljunggren, M., and Danielson, L. (1960) Purification and some properties of a highly dicumarol-sensitive liver diaphorase Biochem. Biophys. Res. Commun. 2, 88-92
3. Martius, C. (1954) [The place of vitamin K1 in respiratory chain; preliminary report.] Biochem. Z. 326, 26-27
4. Ernster, L. (1987) DT-diaphorase: A historical review Chem. Scr. 27A, 1-13
5. Jaiswal, A. K., Burnett, P., Adesnik, M., and McBride, O. W. (1990) Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H:quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6 Biochemistry 29, 1899-1906 (Pubitemid 20074738)
6. Zhao, Q., Yang, X. L., Holtzclaw, W. D., and Talalay, P. (1997) Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase) Proc. Natl. Acad. Sci. U.S.A. 94, 1669-1674 (Pubitemid 27113893)
7. Liao, S., Dulaney, J. T., and Williams-Ashman, H. G. (1962) Purification and properties of a flavoprotein catalyzing the oxidation of reduced ribosyl nicotinamide J. Biol. Chem. 237, 2981-2987
8. Bianchet, M. A., Faig, M., and Amzel, L. M. (2004) Structure and mechanism of NAD[P]H:quinone acceptor oxidoreductases (NQO) Methods Enzymol. 382, 144-174 (Pubitemid 38240789)
9. Vella, F., Ferry, G., Delagrange, P., and Boutin, J. A. (2005) NRH:quinone reductase 2: An enzyme of surprises and mysteries Biochem. Pharmacol. 71, 1-12 (Pubitemid 41715231)
10. Siegel, D. and Ross, D. (2000) Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues Free Radical Biol. Med. 29, 246-253
11. Graves, P. R., Kwiek, J. J., Fadden, P., Ray, R., Hardeman, K., Coley, A. M., Foley, M., and Haystead, T. A. (2002) Discovery of novel targets of quinoline drugs in the human purine binding proteome Mol. Pharmacol. 62, 1364-1372 (Pubitemid 35403831)
12. Bantscheff, M., Eberhard, D., Abraham, Y., Bastuck, S., Boesche, M., Hobson, S., Mathieson, T., Perrin, J., Raida, M., Rau, C., Reader, V., Sweetman, G., Bauer, A., Bouwmeester, T., Hopf, C., Kruse, U., Neubauer, G., Ramsden, N., Rick, J., Kuster, B., and Drewes, G. (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors Nat. Biotechnol. 25, 1035-1044 (Pubitemid 47517638)
13. Fu, Y., Buryanovskyy, L., and Zhang, Z. (2008) Quinone reductase 2 is a catechol quinone reductase J. Biol. Chem. 283, 23829-23835
14. Gaikwad, N. W., Yang, L., Rogan, E. G., and Cavalieri, E. L. (2009) Evidence for NQO2-mediated reduction of the carcinogenic estrogen ortho-quinones Free Radical Biol. Med. 46, 253-262
15. Jamieson, D., Tung, A. T., Knox, R. J., and Boddy, A. V. (2006) Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor Br. J. Cancer 95, 1229-1233 (Pubitemid 44658487)
16. Yan, C., Kepa, J. K., Siegel, D., Stratford, I. J., and Ross, D. (2008) Dissecting the role of multiple reductases in bioactivation and cytotoxicity of the antitumor agent 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone (RH1) Mol. Pharmacol. 74, 1657-1665
17. Siegel, D., Reigan, P., Guo, W., and Ross, D. (2007) The metabolism of antitumor quinones by NRH:quinone oxidoreductase 2 (NQO2). In Proceedings of the American Association for Cancer Research, American Association for Cancer Research, Los Angeles.
18. Knox, R. J., Jenkins, T. C., Hobbs, S. M., Chen, S., Melton, R. G., and Burke, P. J. (2000) Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: A novel co-substrate-mediated antitumor prodrug therapy Cancer Res. 60, 4179-4186 (Pubitemid 30636602)
19. Hollander, P. M. and Ernster, L. (1975) Studies on the reaction mechanism of DT diaphorase. Action of dead-end inhibitors and effects of phospholipids Arch. Biochem. Biophys. 169, 560-567
20. Winski, S. L., Faig, M., Bianchet, M. A., Siegel, D., Swann, E., Fung, K., Duncan, M. W., Moody, C. J., Amzel, L. M., and Ross, D. (2001) Characterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches Biochemistry 40, 15135-15142 (Pubitemid 33151928)
21. Buryanovskyy, L., Fu, Y., Boyd, M., Ma, Y., Hsieh, T. C., Wu, J. M., and Zhang, Z. (2004) Crystal structure of quinone reductase 2 in complex with resveratrol Biochemistry 43, 11417-11426 (Pubitemid 39186963)
22. Wang, Z., Hsieh, T. C., Zhang, Z., Ma, Y., and Wu, J. M. (2004) Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chromatography Biochem. Biophys. Res. Commun. 323, 743-749 (Pubitemid 39243382)
23. Wu, K., Knox, R., Sun, X. Z., Joseph, P., Jaiswal, A. K., Zhang, D., Deng, P. S., and Chen, S. (1997) Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase Arch. Biochem. Biophys. 347, 221-228 (Pubitemid 27492792)
24. Kwiek, J. J., Haystead, T. A., and Rudolph, J. (2004) Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines Biochemistry 43, 4538-4547 (Pubitemid 38500583)
25. Mailliet, F., Ferry, G., Vella, F., Berger, S., Coge, F., Chomarat, P., Mallet, C., Guenin, S. P., Guillaumet, G., Viaud-Massuard, M. C., Yous, S., Delagrange, P., and Boutin, J. A. (2005) Characterization of the melatoninergic MT3 binding site on the NRH:quinone oxidoreductase 2 enzyme Biochem. Pharmacol. 71, 74-88 (Pubitemid 41713529)
26. Winger, J. A., Hantschel, O., Superti-Furga, G., and Kuriyan, J. (2009) The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2) BMC Struct. Biol. 9, 7
27. Dufour, M., Yan, C., Siegel, D., Colucci, M. A., Jenner, M., Oldham, N. J., Gomez, J., Reigan, P., Li, Y., Matteis, C. I. D., Ross, D., and Moody, C. J. (2011) Mechanism-based inhibition of quinone reductase 2 (NQO2). Selectivity for NQO2 over NQO1 and structural basis for flavoprotein inhibition ChemBioChem 12, 1203-1208
28. Beall, H. D., Mulcahy, R. T., Siegel, D., Traver, R. D., Gibson, N. W., and Ross, D. (1994) Metabolism of bioreductive antitumor compounds by purified rat and human DT-diaphorases Cancer Res. 54, 3196-3201 (Pubitemid 24208928)
29. Friedlos, F., Jarman, M., Davies, L. C., Boland, M. P., and Knox, R. J. (1992) Identification of novel reduced pyridinium derivatives as synthetic co-factors for the enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2) Biochem. Pharmacol. 44, 25-31
30. Silverman, R. B. (1988) Mechanism based enzyme inhibition. In Chemistry and Enzymology, pp 3-30, CRC Press, Boca Raton, FL.
31. Kitz, R. and Wilson, I. B. (1962) Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase J. Biol. Chem. 237, 3245-3249
32. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) Protein measurement with the Folin phenol reagent J. Biol. Chem. 193, 265-275
33. Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays J. Immunol. Methods 65, 55-63 (Pubitemid 14203433)
34. Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., and Swaminathan, S. (1983) CHARMM: A program for macromolecular energy, minimization, and dynamics calculations J. Comput. Chem. 4, 187-217
35. Luty, B. A., Wasserman, Z. R., Stouten, P. F. W., Hodge, C. N., Zacharias, M., and McCammon, J. A. (1995) A molecular mechanics/grid method for evaluation of ligand-receptor interactions J. Comput. Chem. 16, 454-464
36. Gilson, M. K. and Honig, B. (1988) Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis Proteins 4, 7-18
37. Reigan, P., Colucci, M. A., Siegel, D., Chilloux, A., Moody, C. J., and Ross, D. (2007) Development of indolequinone mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1): NQO1 inhibition and growth inhibitory activity in human pancreatic MIA PaCa-2 cancer cells Biochemistry 46, 5941-5950 (Pubitemid 46799156)
38. Nolan, K. A., Zhao, H., Faulder, P. F., Frenkel, A. D., Timson, D. J., Siegel, D., Ross, D., Burke, T. R., Jr., Stratford, I. J., and Bryce, R. A. (2007) Coumarin-based inhibitors of human NAD(P)H:quinone oxidoreductase-1. Identification, structure-activity, off-target effects and in vitro human pancreatic cancer toxicity J. Med. Chem. 50, 6316-6325 (Pubitemid 350250419)
39. Cavelier, G. and Amzel, L. M. (2001) Mechanism of NAD(P)H:quinone reductase: Ab initio studies of reduced flavin Proteins 43, 420-432 (Pubitemid 32476438)
40. Zhou, Z., Fisher, D., Spidel, J., Greenfield, J., Patson, B., Fazal, A., Wigal, C., Moe, O. A., and Madura, J. D. (2003) Kinetic and docking studies of the interaction of quinones with the quinone reductase active site Biochemistry 42, 1985-1994 (Pubitemid 36258671)
41. Suleman, A. and Skibo, E. B. (2002) A comprehensive study of the active site residues of DT-diaphorase: Rational design of benzimidazolediones as DT-diaphorase substrates J. Med. Chem. 45, 1211-1220 (Pubitemid 34263558)
42. Maiti, A., Reddy, P. V., Sturdy, M., Marler, L., Pegan, S. D., Mesecar, A. D., Pezzuto, J. M., and Cushman, M. (2009) Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities J. Med. Chem. 52, 1873-1884
43. Colucci, M. A., Reigan, P., Siegel, D., Chilloux, A., Ross, D., and Moody, C. J. (2007) Synthesis and evaluation of 3-aryloxymethyl-1,2- dimethylindole-4,7-diones as mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1) activity J. Med. Chem. 50, 5780-5789 (Pubitemid 350106033)