Hypoxia-selective antitumor agents. 13. Effects of acridine substitution on the hypoxia-selective cytotoxicity and metabolic reduction of the bis-bioreductive agent nitracrine N-oxide

Journal of Medicinal Chemistry

Volumn 39, Issue 13, 1996, Pages 2508-2517

  Lee, Ho H ^a   Wilson, William R ^a   Ferry, Dianne M ^a   Van Zijl, Pierre ^a   Pullen, Susan M ^a   Denny, William A ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

ACRIDINE DERIVATIVE; NITRACRINE; NITRACRINE N OXIDE; UNCLASSIFIED DRUG;

ALKYLATION; AMINO ACID SUBSTITUTION; ANTINEOPLASTIC ACTIVITY; ARTICLE; CYTOTOXICITY; DIFFUSION COEFFICIENT; DNA ALKYLATION; DNA BINDING; DRUG EFFECT; DRUG TRANSPORT; HYPOXIA; METABOLIC REGULATION; NONHUMAN; REACTION ANALYSIS;

ACRIDINES; ANIMALS; ANTINEOPLASTIC AGENTS; CELL DIVISION; CELL HYPOXIA; CELL LINE; CELL SURVIVAL; CRICETINAE; CRICETULUS; CULTURE MEDIA; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE; MICE, INBRED C3H; MOLECULAR STRUCTURE; NITRACRINE; OXIDATION-REDUCTION; TUMOR CELLS, CULTURED;

EID: 0029952167     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9600104     Document Type: Article

References (36)

1. Ledochowski, A.; Stefanska. B. Research on tumour-inhibiting compounds. XXIX. Some N-9 derivatives of 1-, 2-, 3- and 4-nitro-9-aminoacridine. Ann. Soc. Chim. Polonorum 1966, 40, 301-306.
2. Kwasniewska-Rokicinska, C.; Swiecki, J.; Wieczorkiewicz, A. Therapeutic efficacy of compounds C-283 in patients with mammary carcinoma. Arch. Immunol. Ther. Exp. 1973, 21, 863-869.
3. Roberts, P. B.; Anderson, R. F.; Wilson, W. R. Hypoxia-selective radiosensitization of mammalian cells by nitracrine, an elecron-affmic DNA intercalator. Int. J. Radiat. Biol. 1987, 51, 641-654.
4. Roberts, P. B.; Denny, W. A.; Wakelin, L. P. G.; Anderson, R. F.; Wilson, W. R. Radiosensitization of mammalian cells in vitro by nitroacridines. Radiat. Res. 1990, 123, 153-164.
5. Wilson, W. R.; Denny, W. A.; Twigden, S. J.; Baguley, B. C.; Probert, J. C. Selective toxicity of nitracrine to hypoxic mammalian cells. Br. J. Cancer 1984, 49, 215-223.
6. Wilson, W. R.; Anderson, R. F.; Denny, W. A. Hypoxia-selective antitumor agents. 1. Relationship between structure, redox properties and hypoxia-selective cytotoxicity for 4-substituted derivatives of nitracrine. J. Med. Chem. 1989, 32, 23-30.
7. Wilson, W. R.; van Zijl, P.; Denny, W. A. Bis-bioreductive agents as hypoxia-selective cytotoxins : N-oxides of nitracrine. Int. J. Radiat. Oncol. Biol. Phys. 1992, 22, 693-697.
8. Wilson, W. R.; Denny, W. A. DNA-binding nitroheterocycles as hypoxia-selective cytotoxins. In Radiation Research, a Twentieth-Century Perspective; Dewey, W. C., Edington, M., Fry, R. J. M., Hall, E. J., Whitmore, G. F., Eds.; Academic Press: Toronto, 1992; Vol. 2, pp 796-801.
9. Wilson, W. R.; Denny, W. A.; Stewart, G. M.; Fenn, A.; Probert, J. C. Reductive metabolism and hypoxia-selective cytotoxicity of nitracrine. Int. J. Radiat. Oncol. Biol. Phys. 1986, 12, 1235-1238.
10. Bickel, M. H. The pharmacology and biochemistry of N-oxides. Pharmacol. Rev. 1969, 21, 325-355.
11. Woynarowski, J. M.; Bartoszek, A. A.; Konopa, J. DNA damage in HeLa S3 cells by an antitumor drug ledakrin and other antitumor1-nitro-9-aminoacridines. Chem.-Biol. Int. 1984, 49, 311-328.
12. Denny, W. A.; Wilson, W. R.; Atwell, G. J.; Anderson, R. F. Hypoxia-selective Antitumor Agents. 4. Relationships between hypoxia-selective cytotoxicity and structure for sidechain derivatives of nitracrine: the 'imidoacridan hypothesis'. J. Med. Chem. 1990, 33, 1288-1295.
13. Wilson, W. R. Tumour hypoxia; challenges for cancer chemotherapy. In Cancer Biology and Medicine; Waring, M. J., Ponder, B. A. J., Eds.; Kluwer: Lancaster, 1992; Vol. 3, pp 87-131.
14. Patterson, L. H. Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent. Cancer Metastatis Rev. 1993, 12, 119-134.
15. Wilson, W. R.; Denny, W. A.; Pullen, S. M.; Thompson, K. M.; Li, A. E.; Patterson, L. H.; Lee, H. H. Tertiary amine N-oxides as bioreductive drugs: DACA N-oxide, nitracrine N-oxide and AQ4N. Br. J. Cancer 1996, in press.
16. Cole, S.; Patterson, L. H.; Williams, C. A.; Bowler, J. D.; Raleigh, S.; Stratford, I. J. The activity of AQ4N, a novel, bioreductively-activated cytotoxin against KHT, RIF-1 and SCCVII murine tumours in vivo. Br. J. Cancer 1996, in press.
17. Wilson, W. R.; Thompson, L. H.; Anderson, R. F.; Denny, W. A. Hypoxia-selective antitumor agents. 2. Electronic effects of 4-substituents on the mechanisms of cytotoxicity and metabolic stability of nitracrine analogues. J. Med. Chem. 1989, 32, 31-38.
18. O'Connor, C. J.; McLennan, D. J.; Sutton, B. M.; Denny, W. A.; Wilson, W. R. Effect of reduction potential on the rate of reduction of nitroacridines by xanthine oxidase and by dihydroflavin mononucleotide. J. Chem. Soc., Perkin Trans. II 1991, 951-954.
19. Skonieczny, S. Reactions at C-9 of acridine derivatives. Part XXV. Heterocycles 1980, 14, 985-1032.
20. Denny, W. A.; Atwell, G. J.; Roberts, P. B.; Anderson, R. F.; Boyd, M.; Lock, C. J .L.; Wilson, W. R. Hypoxia-selective antitumor agents. 6. 4-Alkylaminonitroquinolines, a new class of hypoxia-selective cytotoxic agents. J. Med. Chem. 1992, 35, 4832-4841.
21. Staab, H. A. Syntheses using heterocyclic amides (azolides). Angew. Chem., Int. Ed. Engl. 1962, 1, 351-367.
22. Rewcastle, G. W.; Denny, W. A. The synthesis of substituted 9-oxoacridan-4-carboxylic acids; Part 3. The reaction of methyl anthranilates with diphenyliodonium-2-carboxylates. Synthesis 1985, 220-222.
23. Dictionary of Organic Compounds; Chapman and Hall: New York, 1982; Vol. 1, p 284, entry A-02269.
24. Davis, F. A.; Stringer, O. D. Chemistry of oxaziridines. 2. Improved synthesis of 2-sulfonyloxaziridines. J. Org. Chem. 1982, 47, 1774-1777.
25. Stefanska, B.; Ledochowski, A. Research on tumour-inhibiting compounds. Part XLVI. Derivatives of 1- and 3-nitro-9-aminoacridine N-oxides. Rocz. Chem. 1968, 42, 1973-1980.
26. Denny, W. A.; Atwell, G. J.; Rewcastle, G. W.; Baguley, B. C. Potential Antitumor Agents. 49. 5-Substituted derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide with in vivo solid tumor activity. J. Med. Chem. 1987, 30, 658-663.
27. Siim, B. G.; Wilson, W. R. Efficient redox cycling of nitroquinoline bioreductive drugs due to aerobic nitroreduction in Chinese hamster cells. Biochem. Pharmacol. 1995, 50, 75-82.
28. Hoy, C. A.; Thompson, L. H.; Mooney, C. L.; Salazar, E. P. Defective DNA crosslink removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents. Cancer Res. 1985, 45, 1737-1747.
29. Powis, G.; DeGraw, C. L. N-Oxide reduction by hemoglobin, cytochrome C and ferrous ions. Res. Commun. Chem. Pathol. Pharmacol. 1980, 30, 143-150.
30. Finlay, G. J.; Baguley, B. C.; Wilson, W. R. A semiautomated microculture method for investigating growth inhibitory effects of cytotoxic compounds on exponentially growing carcinoma cells. Anal. Biochem. 1984, 139, 272-277.
31. Bunnett, J. F.; Rauhut, M. M. 2-Bromo-3-methylbenzoic Acid. Organic Syntheses; Wiley: New York, 1963; Collective Vol. 4, pp 114-116.
32. Cholody, W.; Ledochowski, A. Research on tumour-inhibiting compounds. Part LXXI. Synthesis of 2-methoxy-9-aminoacridine nitro derivatives. Nitration of 2-methoxyacridone. Pol. J. Chem. 1983, 57, 285-290.
33. M acidity function in methanol-dimethyl sulphoxide. J. Chem. Soc., Perkin Trans. II 1972, 1178-1182.
34. Siim, B. G.; Atwell, G. J.; Wilson, W. R. Oxygen dependence of the cytotoxicity and metabolic activation of 4-alkylamino-5-nitroquinoline bioreductive drugs. Br. J. Cancer 1994, 70, 596-603.
35. Hay, M. P.; Wilson, W. R.; Moselen, J. W.; Palmer, B. D.; Denny, W. A. Hypoxia-selective antitumor agents. 8. Bis(nitroimidazolyl)alkanecarboxamides: a new class of hypoxia-selective cytotoxins and hypoxic cell radiosensitizers. J. Med. Chem. 1994, 37, 381-391.
36. Cain, B. F.; Atwell, G. J.; Denny, W. A. Potential Antitumor Agents. Part 16. 4′-(Acridin-9-ylamino)methanesulfonanilides. J. Med. Chem. 1975, 18, 1110-1117.