Enzymology of the reduction of the novel fused pyrazine mono-N-oxide bioreductive drug, RB90740 roles for P450 reductase and cytochrome b5 reductase

Biochemical Pharmacology

Volumn 51, Issue 6, 1996, Pages 829-837

  Barham, Helen M ^a   Stratford, Ian J ^a  

^a MEDICAL RESEARCH COUNCIL   (United Kingdom)

Author keywords

bioreductive drug; cytochrome b5 reductase; hypoxia; P450 reductase; pyrazine mono N oxide; tumour

Indexed keywords

1,2 DIHYDRO 8 (4 METHYL 1 PIPERAZINYL) 4 PHENYLIMIDAZO[1,2 A]PYRIDO[3,2 E]PYRAZINE; 1,2 DIHYDRO 8 (4 METHYL 1 PIPERAZINYL) 4 PHENYLIMIDAZO[1,2 A]PYRIDO[3,2 E]PYRAZINE 5 OXIDE; 5 PROPYL 2 THIOURACIL; ADENOSINE PHOSPHATE; ANTINEOPLASTIC AGENT; CARBON MONOXIDE; CYTOCHROME B5; CYTOCHROME B5 REDUCTASE; CYTOCHROME B5 REDUCTASE INHIBITOR; CYTOCHROME P450 ISOENZYME; CYTOCHROME P450 REDUCTASE; CYTOCHROME P450 REDUCTASE INHIBITOR; DIPHENYLENEIODONIUM CHLORIDE; DRUG METABOLITE; ENZYME INHIBITOR; HYDROXYMERCURIBENZOIC ACID; METYRAPONE; PYRAZINE N OXIDE; RB 90740; RB 92815; RB 92816; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; REDUCING AGENT; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYMOLOGY; FEMALE; HYPOXIA; LIVER MICROSOME METABOLISM; METABOLIC ACTIVATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REDUCTION;

EID: 0029865395     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/0006-2952(95)02257-0     Document Type: Article

References (49)

1. Jenkins TC, Naylor MA, O'Neill P, Threadgill MD, Cole S, Stratford IJ, Adams GE, Fielden EM, Suto MJ and Stier MA, Synthesis and evaluation of 1-(3-(2-haloethylamino)propyl)-2-nitroimidazoles as pro-drugs of RSU 1069 and its analogs, which are radiosensitizers and bioreductively activated cycotoxins. J Med Chem 33: 2603-2610, 1990.
2. Sartorelli AC, The role of mitomycin antibiotics in the chemotherapy of solid tumours. Biochem Pharmacol 35: 67-69, 1986.
3. Rockwell S, Keyes SR and Sartorelli AC, Preclinical studies of porfiromycin as an adjunct to radiotherapy. Radiat Res 116: 100-113, 1988.
4. Hendricks HR, Pizao PE, Berger DP, Kooistra KL, Bibby MC, Boven E, Dreef-van der Neulen HC, Henrar REC, Fiebig HH, Double JA, Hornstra HW, Pinedo HM, Workman P and Schwartsmann G, EO9: A novel bioreductive alkylating indoloquinone with preferential solid tumour activity and lack of bone marrow toxicity in preclinical models. Eur J Cancer 29A: 897-906, 1993.
5. Zeman EM, Brown JM, Lemmon MJ, Hirst VK and Lee WW, SR 4233: A new bioreductive agent with high selective toxicity for hypoxic mammalian cells. Int J Radiat Oncol Biol Phys 12: 1239-1242, 1986.
6. Patterson LH, Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: A new class of bioreductive drug. Cancer Metastasis Rev 12: 119-134, 1993.
7. Zeman EM, Baker MA, Lemmon MJ, Pearson CI, Adams JA, Brown JM, Lee WE and Tracy M, Structure-activity relationships for benzotriazene-di-N-oxides. Int J Radiat Oncol Biol Phys 16: 977-982, 1989.
8. Minchington AI, Lemmon MJ, Tracy M, Pollart DJ, Martinez AP, Tosto LM and Brown JM, Second-generation 1,2,4-benzotriazine 1,4-di-N-oxide bioreductive anti-tumour agents: pharmacology and activity in vitro and in vivo. Int J Radiat Oncol Biol Phys 22: 701-706, 1992.
9. Lloyd RV, Dulling DR, Rumyantseva GV, Mason RP and Bridson PK, Microsomal reduction of 3-amino-1, 2, 4-benzotriazine 1, 4-dioxide to a free radical. Mol Pharmacol 40: 440-445, 1991.
10. Laderoute K, Wardman P and Rauth AM, Molecular mechanisms for the hypoxia-dependent activation of 3-amino-1, 2, 4-benzotriazine-1, 4-Dioxide (SR 4233). Biochem Pharmacol 37: 1487-1495, 1988.
11. Fitzsimmons SA, Lewis AD, Riley RJ and Workman P, Reduction of 3-amino-1, 2, 4-benzotriazine-1, 4-di-N-oxide (tirapazamine, WIN 59075, SR 4233) to a DNA-damaging species: a direct role for NADPH: cytochrome P450 oxidoreductase. Carcinogenesis 15: 1503-1510, 1994.
12. Patterson AV, Barham H, Chinje E, Adams GE, Harris AL and Stratford IJ, Importance of P450 reductase activity in breast tumour cells for determining sensitivity to the bioreductive drug, tirapazamine (SR 4233). Br J Cancer 72: 1144-1150, 1995.
13. Walton MI, Wolf CR and Workman P, The role of cytochrome P450 and cytochrome P450 reductase in the reductive bioactivation of the novel benzotriazine DI-N-Oxide hypoxic cytotoxin 3-amino-1, 2, 4-benzotriazine-1, 4-dioxide (SR 4233, WIN 59075) by mouse liver. Biochem Pharmacol 44: 251-259, 1992.
14. Cahill A and White INH, Reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) and the induction of unscheduled DNA synthesis in rat and human derived cell lines. Carcinogenesis 11: 1407-1411, 1990.
15. Riley RJ and Workman P, Enzymology of the reduction of the potent benzotriazine-di-N-oxide hypoxic cell cytotoxic SR 4233 (WIN 59075) by NAD(P)H: (quinone acceptor) oxidoreductase (EC 1.6.99.2) purified from Walker 256 rat tumor cells. Biochem Pharmacol 43: 167-174, 1992.
16. Patterson AV, Robertson N, Houlbrook S, Stephens MA, Adams GE, Harris AL and Stratford IJ, The role of DT-diaphorase in determining the sensitivity of human tumour cells to tirapazamine (SR4233). Int J Radiat Oncol Biol Phys 29: 369-372, 1994.
17. Naylor MA, Stratford IJ, Stephens MA, Nolan J, Sutton B, Fielden EM and Adams GE, 8-alkylamino-substituted phenylimidazo[2,2-a]quinoxaline mono-N-oxides with potential applications in bioreductive anti-cancer therapy. Anti-Cancer Drug Design 8: 439-461, 1993.
18. Naylor MA, Adams GE, Haigh A, Cole S, Jenner T, Robertson N, Siemann D, Stephens MA and Stratford IJ, Fused pyrazine mono-N-oxides as bioreductive drugs III. Characterization of RB 90740 in vitro and in vivo. Anti Cancer Drugs 6: 259-269, 1995.
19. Adams GE and Stratford IJ, Bioreductive drugs for cancer therapy: The search for tumour specificity. Int J Radiat Oncol Biol Phys 29: 231-238, 1994.
20. Hoban PR, Walton MI, Robson CN, Godden J, Stratford IJ, Harris AL and Hickson ID, Decreased NADPH: Cytochrome P-450 reductase activity and impaired drug activation in a mammalian cell line resistant to mitomycin C under aerobic but not hypoxic conditions. Cancer Res 50: 4692-4697, 1990.
21. Shaw L, Lennard MS, Tucker GT, Bax NDS and Woods HF, Irreversible binding and metabolism of propranolol by human liver microsomes - relationship to polymorphic oxidation. Biochem Pharmacol 36: 2283-2288, 1987.
22. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Groeke NM, Olson BJ and Klenk DC, Measurement of protein using bicinchoninic acid. Anal Biochem 150: 76-85, 1985.
23. Sutton BM, Reeves NJ, Naylor MA, Fielden EM, Cole S, Adams GE and Stratford IJ, Pharmacokinetics, metabolism and distribution of RB90740 in C3H mice. Int J Radiat Oncol Biol Phys 29: 339-344, 1994.
24. Robertson N, Haigh A, Adams GE and Stratford IJ, Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia. Eur J Cancer 30A: 1013-1019, 1994.
25. 5 reductase in human tumour cells. Br J Cancer, submitted for publication.
26. Phillips AH and Langdon RG, Hepatic triphosphopyridine nucleotide-cytochrome c reductase: Isolation, characterization and kinetic studies. J Biol Chem 237: 2652-2660, 1962.
27. 5 in cytochrome P450 catalysis. Cytochrome P450: Structure, Mechanism and Biochemistry (Ed. Oritz de Montellano RP), pp. 89-119. Plenum, New York, 1986.
28. Segura-Aguiler J, Cortes-Vizcaino V, Llombart-Bosch A, Ernster L, Monsalve E and Romero FJ, The levels of quinone reductases, superoxide dismutase and glutathione-related enzymatic activities in diethylstitestrol-induced carcinogenesis in the kidney of male Syrian golden hamsters. Carcinogenesis 11: 1727-1732, 1990.
29. Tew DG, Inhibition of cytochrone P450 reductase by the diphenyldiiodonium cation. Kinetic analysis and covalent modifications. Biochemistry 32: 10209-10215, 1993.
30. O'Donnell VB, Smith GCM and Jones OTG, Involvement of phenyl radicals in iodonium compound inhibition of flavoenzymes. Mol Pharmacol 46: 778-785, 1994.
31. 5 reductase from rabbit liver cytosol: partial purification and characterization. Biochem Biophys Acta 526: 42-51, 1978.
32. Lee E and Kariya K, Propythiouracil, a selective inhibitor of NADH-cytochrome b, reductase. FEBS 209: 49-51, 1986.
33. Workman P and Walton MI, Enzyme-directed bioreductive drug development. Selective activation of drugs by redox processes (Eds. G Adams et al.), pp. 89-112. Plenum, New York, 1986.
34. Workman P and Stratford IJ, The experimental development of bioreductive drugs and their role in cancer therapy. Cancer Metastasis Reviews 12: 73-82, 1993.
35. Plumb JA, Gerritsen M and Workman P, DT-diaphorase protects cells from the hypoxic cytotoxicity of indoloquinone EO9. Br J Cancer 70: 1136-1143, 1994.
36. Baker MA, Zeman EM, Hirst VK and Brown JM, Metabolism of SR 4233 by Chinese hamster ovary cells: Basis of selective hypoxic cytotoxicity. Cancer Res 48: 5947-5952, 1988.
37. Keyes SR, Fracasso PM, Heimbrook DC, Rockwell S, Sligar SG and Sartorelli AC, Role of NAD(P)H: Cytochrome c reductase and DT-diaphorase in the biotransformation of mytomycin-c. Cancer Res 44: 5638-5643, 1984.
38. Vromans RM, van der Straat R, Groeneveld M and Vermeulen NPE, One-electron reduction of mitomycin c by rat liver: role of cytochrome P450 and NADPH-cytochrome P450 reductase. Xenobiotica 20: 967-978, 1990.
39. Bailey SM, Lewis AD and Workman P, Involvement of NADPH: Cytochrome P450 in activation of EO9 to a DNA damaging species. Br J Cancer 69 (Suppl. XXI): 57, 1994.
40. Walton MI, Wolf CR and Workman P, Molecular enzymology of the reductive bioactivation of hypoxic cell cytotoxins. Int J Radiat Oncol Biol Phys 16: 983-986, 1989.
41. 5 reductase from sheep lung and its electrophoretic, spectral and some other properties. Int J Biochem 22: 1029-1035, 1990.
42. Porter TD and Coon MJ, Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 266: 13469-13472, 1990.
43. 5 reductase. Cancer Res 53: 4907-4912, 1993.
44. 5 reductase. Cancer Letters 84: 149-154, 1994.
45. 5. Mol Pharmacol 34: 578-583, 1988.
46. Walton MI and Workman P, Enzymology of the reductive bioactivation of SR 4233: A novel benzotriazine di-N-oxide hypoxic cell cytotoxin. Biochem Pharmacol 39: 1735-1742, 1990.
47. 2 tension measurements. Cancer Res 51: 3316-3322, 1991.
48. Testa J and Jenner P, Inhibitors of cytochrome P-450s and their mechanism of action. Drug Metab Rev 12: 1-117, 1981.
49. Goeptar AR, Scheerens H and Vermuelen NPE, Oxygen and zenobiotic reductase activities of cytochrome P450. Crit Rev Toxicol 25: 25-65, 1995.