Indolequinone antitumor agents: Reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia- selective cytotoxicity in vitro

Journal of Medicinal Chemistry

Volumn 41, Issue 15, 1998, Pages 2720-2731

  Naylor, Matthew A ^a   Swann, Elizabeth ^c   Everett, Steven A ^a   Jaffar, Mohammed ^b   Nolan, John ^a   Robertson, Naomi ^b   Lockyer, Stacey D ^b   Patel, Kantilal B ^a   Dennis, Madeleine F ^a   Stratford, Michael R L ^a   Wardman, Peter ^a   Adams, Gerald E ^a   Moody, Christopher J ^c   Stratford, Ian J ^b  

^a MOUNT VERNON HOSPITAL   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c UNIVERSITY OF EXETER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 (1 AZIRIDINYL) 3 HYDROXYMETHYL 2 (3 HYDROXY 1 PROPENYL) 1 METHYL 4,7 INDOLEDIONE; ANTINEOPLASTIC AGENT; INDOLE DERIVATIVE; QUINONE DERIVATIVE;

ANIMAL CELL; ARTICLE; CELL HYPOXIA; CONTROLLED STUDY; DRUG ACTIVATION; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STABILITY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NONHUMAN; RADIOLYSIS; REDUCTION; STRUCTURE ACTIVITY RELATION;

EID: 15144357021     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970744w     Document Type: Article

References (52)

1. Cotterill, A. S.; Moody, C. J.; Mortimer, R. J.; Norton, C. L.; O'Sullivan, N.; Stephens, M. A.; Stradiotto, N. R.; Swann, E.; Stratford, I. J. Cyclopropamitosenes, novel bioreductive anti-cancer agents. Synthesis, electrochemistry, and biological activity of 7-substituted Cyclopropamitosenes and related indolequinones. J. Med. Chem. 1994, 37, 3834-3843.
2. Cotterill, A. S.; Hartopp, P.; Jones, G. B.; Moody, C. J.; Norton, C. L.; O'Sullivan, N.; Swann, E. Cyclopropamitosenes, novel bioreductive anticancer agents. Synthesis of 7-methoxycyclopropamitosene and related indolequinones. Tetrahedron 1994, 50, 7657-7674.
3. Maliepaard, M.; de Mol, N. J.; Janssen, L. H. M.; Hoogvliet, J. C.; van der Neut, W.; Verboom, W.; Reinhoudt, D. N. Reductive activation of potential antitumor mitosene compounds. J. Med. Chem. 1993, 36, 2091-2097.
4. Maliepaard, M. Ph.D. Thesis, Utrecht, 1994.
5. Moody, C. J.; O'Sullivan, N.; Stratford, I. J.; Stephens, M. A.; Workman, P.; Bailey, S. M.; Lewis, A. Cyclopropamitosenes: novel bioreductive anticancer agents - mechanism of action and enzymic reduction. Anti-Cancer Drugs 1994, 5, 367-372.
6. Naylor, M. A.; Jaffar, M.; Nolan, J.; Stephens, M. A.; Butler, S.; Patel, K. B.; Everett, S. A.; Adams, G. E.; Stratford, I. J. 2-Cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: structure-activity in vitro and efficacy in vivo. J. Med. Chem. 1997, 40, 2335-2346.
7. Oostveen, E. A.; Speckamp, W. N. Mitomycin analogues I. Indoloquinones as (potential) bisalkylating compounds. Tetrahedron 1987, 43, 255-262.
8. Speckamp, W. N.; Oostveen, E. A. Indoloquinone compounds. Int. Patent WO 87/06227, 1987.
9. Dirix, L. Y.; Tonnesen, F.; Cassidy, J.; Epelbaum, R.; ten Bokkel Huinink, W. W.; Pavlidis, N.; Sorio, R.; Gamucci, T.; Wolff, I.; Te Velde, A.; Lan, J.; Verweij, J. EO9 Phase II Study in Advanced Breast, Gastric, Pancreatic and Colorectal Carcinoma by the EORTC Early Clinical Studies Group. Eur. J. Cancer 1996, 32A, 2019-2022.
10. Verboom, W.; Reinhoudt, D. N.; Lammerink, B. H. M.; Orlemans, E. O. M.; van Veggel, F. C. J. M.; Lelieveld, P. Novel bioreductive mitosene and mitosane analogues of mitomycin c. Anti-Cancer Drug Des. 1987, 2, 271-277.
11. Orlemans, E. O. M.; Verboom, W.; Scheltinga, M. W.; Reinhoudt, D. N.; Lelieveld, P.; Fiebig, H. H.; Winterhalter, B. R.; Double, J. A.; Bibby, M. C. Synthesis, mechanism of action, and biological evaluation of mitosenes. J. Med. Chem. 1989, 32, 1612-1620.
12. Franck, R. W.; Tomasz, M. In Chemistry of Antitumor Agents; Wilman, D. E. V., Ed.; Blackie and Son Ltd.: Glasgow, 1990; pp 379-393.
13. Carter, S. K.; Crooke, S. T. Mitomycin C; Current Status and New Developments; Academic Press: New York, 1979.
14. Remers, W. A; Dorr, R. T. In Alkaloids: Chemical and Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1988; Vol. 6, pp 1-74.
15. Danishefsky, S. J.; Schkeryantz, J. M. Chemical explorations driven by an enchantment with mitomycinoids - a twenty year account. Synlett 1995, 475-490.
16. Casner, M. L.; Remers, W. A.; Bradner, W. T. Synthesis and biological activity of 6-substituted mitosene analogues of the mitomycins. J. Med. Chem. 1985, 28, 921-926.
17. Hodges, J. C.; Remers, W. A. Synthesis and antineoplastic activity of mitosene analogues of the mitomycins. J. Med. Chem. 1981, 24, 1184-1191.
18. Iyengar, B. S.; Remers, W. A.; Bradner, W. T. Preparation and antitumor activity of 7-substituted 1,2-aziridinomitosenes. J. Med. Chem. 1986, 29, 1864-1868.
19. Kunz, K. R.; Iyengar, B. S.; Dorr, R. T.; Alberts, D. S.; Remers, W. A. Structure-activity relationships for mitomycin c and mitomycin a analogues. J. Med. Chem. 1991, 34, 2281-2286.
20. Leadbetter, G.; Frost, D. L.; Ekwuribe, N. N.; Remers, W. A. Mitomycin antibiotics. Synthesis of 1-substituted 7-methoxymitosenes. J. Org. Chem. 1974, 39, 3580-3583.
21. Kennedy, K. A. Hypoxie cells as specific drug targets for chemotherapy. Anti-Cancer Drug Des. 1987, 2, 181-194.
22. Coleman, C. N. Hypoxia in tumors: A paradigm for the approach to biochemical and physiological heterogeneity. J. Natl. Cancer Inst. 1988, 80, 310-317.
23. Workman, P.; Walton, M. I. In Selective Activation of Drugs by Redox Processes; Adams, G. E., Ed.; Plenum Press: New York, 1990; pp 173-191.
24. Robertson, N.; Stratford, I. J.; Houlbrook, S.; Carmichael, J.; Adams, G. E. The sensitivity of human tumor cells to quinone bioreductive drugs - what role for DT-diaphorase. Biochem. Pharmacol. 1992, 44, 409-412.
25. Walton, M. I.; Suggett, N.; Workman, P. The role of human and rodent DT-diaphorase in the reductive metabolism of hypoxic cell cytotoxins. Int. J. Radiat. Oncol. Biol. Phys. 1992, 22, 643-647.
26. Workman, P. In New Applications in Cancer Pharmacology: Drug Design and Development; Workman, P., Ed.; Springer-Verlag: New York, 1992; pp 63-74.
27. Bailey, S. M.; Suggett, N.; Walton, M. I.; Workman, P. Structure-activity relationships for DT-diaphorase reduction of hypoxic cell directed agents-indoloquinones and diaziridinyl benzoquinones. Int. J. Radiat. Oncol. Biol. Phys. 1992, 22, 649-653.
28. Workman, P.; Stratford, I. J. The experimental development of bioreductive drugs and their role in cancer therapy. Cancer Metastasis Rev. 1993, 12, 73-82.
29. Li, V. S.; Choi, D.; Wang, Z.; Jimenez, L. S.; Tang, M.; Kohn, H. The role of the C-10 substituent in mitomycin C-1 DNA bonding. J. Am. Chem. Soc. 1996, 118, 2326-2331.
30. Jones, G. B.; Moody, C. J. Structurally modified antitumour agents. Part 2. Total synthesis of a cyclopropamitosene. J. Chem. Soc., Perkin Trans, 1 1989, 2455-2462.
31. Sundberg, R. J. The Chemistry of Indoles; Academic Press: New York, 1970.
32. 4 for the reductive activation of mitomycin c. J. Am. Chem. Soc. 1993, 115, 10497-10509.
33. Hong, Y. P.; Kohn, H. Studies on the use of chromium(II) perchlorate for the reductive activation of mitomycin c. J. Am. Chem. Soc. 1991, 113, 4634-4644.
34. Swallow, A. J. In Function of Quinones in Energy Conserving Systems; Trumpower, B., Ed.; Academic Press: London, 1982; pp 59-72.
35. Butler, J.; Spanswick, V. J.; Cummings, J. The autoxidation of the reduced forms of EO9. Free Radical Res. 1996, 25, 141-148.
36. Wilson, I.; Wardman, P.; Lin, T.; Sartorelli, A. One-electron reduction of 2-and 6-methyl-1,4-naphthoquinone bioreductive alkylating agents. J. Med. Chem. 1986, 29, 1381-1384.
37. Bays, J. P.; Blumer, S. T.; Baral-Tosh, S.; Behar, D.; Neta, P. Intramolecular electron transfer and dehalogenation of nitroaromatic anion radicals. J. Am. Chem. Soc. 1983, 105, 320-324.
38. Adams, G. E.; Willson, R. L. Pulse radiolysis studies on the oxidation of organic radicals in aqueous solution. Trans. Faraday Soc. 1969, 65, 2981-2987.
39. Hoey, B. M.; Butler, J.; Swallow, A. J. Reductive activation of mitomycin C. Biochemistry 1988, 27, 2608-2614.
40. Jaffar, M.; Naylor, M. A.; Lockyer, S. D.; Phillips, R. M.; Everett, S. A.; Adams, G. E.; Stratford, I. J. 5-Substituted analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2-[1H-indole-4,7-dione]-prop-2-en-1-ol (EO9, NSC 382459) and their regioisomers as hypoxia-selective agents: structure-cytotoxicity in vitro. Anti-Cancer Drug Des. 1997, 13, 105-123.
41. Denny, W. A.; Wilson, W. R. Bioreducible mustards - a paradigm for hypoxia-selective prodrugs of diffusible cytotoxins (HPDCs). Cancer Metastasis Rev. 1993, 12, 135-151.
42. Tercel, M. T.; Wilson, W. R.; Anderson, R. F.; Denny, W. A. Hypoxia-selective antitumor agents. 12. Nitrobenzyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine. J. Med. Chem. 1996, 39, 1084-1094.
43. Denny, W. A.; Wilson, W. R.; Hay, M. P. Recent developments in the design of bioreductive drugs. Br. J. Cancer 1996, 74 (Suppl. XXVII), S32-S38.
44. Stratford, I. J.; Stephens, M. A. The differential hypoxic cytotoxicity of bioreductive agents determined in vitro by the MTT assay. Int. J. Radiat. Oncol. Biol. Phys. 1989, 16, 973-976.
45. Naylor, M. A.; Stephens, M. A.; Stratford, I. J.; Keohane, A.; O'Neill, P.; Threadgill, M. D.; Webb, P.; Fielden, E. M.; Adams, G. E. Aziridinyl nitropyrroles and nitropyrazoles as hypoxia-selective cytotoxins and radiosensitizers. Anti-Cancer Drug Des. 1991, 6, 151-167.
46. Naylor, M. A.; Adams, G. E.; Haigh, A.; Cole, S.; Jenner, T.; Robertson, N.; Siemann, D.; Stephens, M. A.; Stratford, I. J. Fused pyrazine mono-N-oxides as bioreductive drugs III. Characterization of RB 90740 in vitro and in vivo. Anti-Cancer Drugs 1995, 6, 259-269.
47. Patel, K. B.; Willson, R. L. Semiquinone free radicals and oxygen. J. Chem. Soc., Faraday Trans, 1 1973, 69, 814-825.
48. Candeias, L. P.; Folkes, L. K.; Porssa, M.; Parrick, J.; Wardman, P. Rates of reaction of indoleacetic acids with horseradish peroxidase compound I and their dependence on the redox potentials. Biochemistry 1996, 35, 102-108.
49. Wardman, P. Reduction potentials of one-electron couples involving free radicals in aqueous solution. J. Phys. Chem. Ref. Data 1989, 18, 1637-1755.
50. Wardman, P.; Clarke, E. D. Redox properties and rate constants in free-radical mediated damage. Br. J. Cancer 1987, 55 (Suppl. VIII), 172-177.
51. Tokunaga, J. Solubilities of oxygen, nitrogen and carbon dioxide in aqueous alcohol solutions. J. Chem. Eng. Data 1975, 20, 41-46.
52. + from hydrogen peroxide formation in pulse-irradiated oxygenated water. J. Phys. Chem. 1968, 72, 626-631.