Hypoxia-activated prodrugs: Substituent effects on the properties of nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (nitroCBI) prodrugs of DNA minor groove alkylating agents

Journal of Medicinal Chemistry

Volumn 52, Issue 22, 2009, Pages 7258-7272

  Tercel, Moana ^a   Atwell, Graham J ^a   Yang, Shangjin ^a   Stevenson, Ralph J ^a   Botting, K Jane ^a   Boyd, Maruta ^a   Smith, Eileen ^a   Anderson, Robert F ^a,b   Denny, William A ^a   Wilson, William R ^a   Pruijn, Frederik B ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

7 SULFONAMIDE; ALKYLATING AGENT; AMIDE; ANTINEOPLASTIC AGENT; DNA; NITRO DERIVATIVE; NITRO SECO 1,2,9,9A TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL 4 ONE; PRODRUG; SULFONAMIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL CULTURE; CONTROLLED STUDY; CYTOTOXICITY; DNA MINOR GROOVE; DNA STRUCTURE; DRUG METABOLISM; ELECTRON; FEMALE; HUMAN; HUMAN CELL; HYPOXIA; HYPOXIC CELL; MALE; MOUSE; NONHUMAN; REDUCTION; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; CELL HYPOXIA; CELL LINE, TUMOR; CELL SURVIVAL; CELL TRANSFORMATION, NEOPLASTIC; DNA; FEMALE; HUMANS; INDOLES; MICE; MICE, NUDE; OXIDATION-REDUCTION; PRODRUGS; SPHEROIDS, CELLULAR; TUMOR STEM CELL ASSAY;

EID: 70949091047     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm901202b     Document Type: Article

References (46)

1. Lunt, S. J.; Chaudary, N.; Hill, R. P. The tumor microenvironment and metastatic disease. Clin. Exp. Metastasis 2009, 26, 19-34.
2. Bertout, J. A.; Patel, S. A.; Simon, M. C. The impact of O2 availability on human cancer. Nat. Rev. Cancer 2008, 8, 967-975.
3. Brown, J. M.; Wilson, W. R. Exploiting tumor hypoxia in cancer treatment. Nat. Rev. Cancer 2004, 4, 437-447.
4. McKeown, S. R.; Cowen, R. L.; Williams, K. J. Bioreductive drugs: from concept to clinic. J. Clin. Oncol. 2007, 19, 427-442.
5. Chen, Y.; Hu, L. Design of anticancer prodrugs for reductive activation. Med. Res. Rev. 2008, 29, 29-64.
6. Stratford, I. J.; Workman, P. Bioreductive drugs into the next millennium. Anti-Cancer Drug Des. 1998, 13, 519-528.
7. Hicks, K. O.; Pruijn, F. B.; Secomb, T. W.; Hay, M. P.; Hsu, R.; Brown, J. M.; Denny, W. A.; Dewhirst,M. W.; Wilson, W. R. Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugs. J. Natl. Cancer Inst. 2006, 98, 1118-1128.
8. Wilson, W. R.; Hicks, K. O.; Pullen, S. M.; Ferry, D. M.; Helsby, N. A.; Patterson, A. V. Bystander effects of bioreductive drugs: potential for exploiting pathological tumor hypoxia with dinitrobenzamide mustards. Radiat. Res. 2007, 167, 625-636.
9. Marcu, L.; Olver, I. Tirapazamine: from bench to clinical trials. Curr. Clin. Pharmacol. 2006, 1, 71-79.
10. Rischin, D.; Peters, L.; Fisher, R.; Macann, A.; Denham, J.; Poulsen, M.; Jackson, M.; Kenny, L.; Penniment, M.; Corry, J.; Lamb, D.; McClure, B. Tirapazamine, cisplatin, and radiation versus fluorouracil, cisplatin, and radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02). J. Clin. Oncol. 2005, 23, 79-87. (Pubitemid 41702625)
11. Albertella, M. R.; Loadman, P. M.; Jones, P. H.; Phillips, R. M.; Rampling, R.; Burnet, N.; Alcock, C.; Anthoney, A.; Vjaters, E.; Dunk, C. R.; Harris, P. A.; Wong, A.; Lalani, A. S.; Twelves, C. J. Hypoxia-selective targeting by the bioreductive prodrug AQ4N in patients with solid tumors: results of a phase I study. Clin. Cancer Res. 2008, 14, 1096-1104.
12. Patterson, L. H. Bioreductively activated antitumor N-oxides: the case of AQ4N, a unique approach to hypoxia-activated cancer chemotherapy. Drug Metab. Rev. 2002, 34, 581-592.
13. Patterson, A. V.; Ferry, D. M.; Edmunds, S. J.; Gu, Y.; Singleton, R. S.; Patel, K.; Pullen, S. M.; Syddall, S. P.; Atwell, G. J.; Yang, S.; Denny, W. A.; Wilson, W. R. Mechanism of action and preclinical antitumor activity of the novel hypoxia-activated DNA crosslinking agent PR-104. Clin. Cancer Res. 2007, 13, 3922-3932.
14. Duan, J. X.; Jiao, H.; Kaizerman, J.; Stanton, T.; Evans, J. W.; Lan, L.; Lorente, G.; Banica, M.; Jung, D.; Wang, J.; Ma, H.; Li, X.; Yang, Z.; Hoffman, R. M.; Ammons, W. S.; Hart, C. P.; Matteucci, M. Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs. J. Med. Chem. 2008, 51, 2412-2420.
15. Boger, D. L.; Johnson, D. S. CC-1065 and the duocarmycins: understanding their biological function through mechanistic studies. Angew. Chem., Int. Ed. Engl. 1996, 35, 1438-1474. (Pubitemid 26310030)
16. Tichenor, M. S.; Boger, D. L. Yatakemycin: total synthesis, DNA alkylation, and biological properties. Nat. Prod. Rep. 2008, 25, 220-226.
17. Li, L. H.; DeKoning, T. F.; Kelly, R. C.; Krueger, W. C.; McGovren, J. P.; Padbury, G. E.; Petzold, G. L.; Wallace, T. L.; Ouding, R. J.; Prairie, M. D. Cytotoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue. Cancer Res. 1992, 52, 4904-4913.
18. Kobayashi, E.; Okamoto, A.; Asada, M.; Okabe, M.; Nagamura, S.; Asai, A.; Saito, H.; Gomi, K.; Hirata, T. Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors. Cancer Res. 1994, 54, 2404-2410. (Pubitemid 24138732)
19. Pavlidis, N.; Aamdal, S.; Awada, A.; Calvert, H.; Fumoleau, P.; Sorio, R.; Punt, C.; Verweij, J.; van Oosterom, A.; Morant, R.; Wanders, J.; Hanauske, A. R. Carzelesin phase II study in advanced breast, ovarian, colorectal, gastric, head and neck cancer, non-Hodgkin's lymphoma and malignant melanoma: a study of the EORTC early clinical studies group (ECSG). Cancer Chemother. Pharmacol. 2000, 46, 167-171.
20. Markovic, S. N.; Suman, V. J.; Vukov, A. M.; Fitch, T. R.; Hillman, D. W.; Adjei, A. A.; Alberts, S. R.; Kaur, J. S.; Braich, T. A.; Leitch, J. M.; Creagan, E. T. Phase II trial of KW2189 in patients with advanced malignant melanoma. Am. J. Clin. Oncol. 2002, 25, 308-312.
21. Jeffrey, S. C.; Torgov, M. Y.; Andreyka, J. B.; Boddington, L.; Cerveny, C. G.; Denny,W.A.; Gordon, K. A.; Gustin, D.; Haugen, J.; Kline, T.; Nguyen, M. T.; Senter, P. D. Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates. J. Med. Chem. 2005, 48, 1344-1358.
22. Tietze, L. F.; Major, F.; Schuberth, I.; Spiegl, D. A.; Krewer, B.; Maksimenka, K.; Bringmann, G.; Magull, J. Selective treatment of cancer: synthesis, biological evaluation and structural elucidation of novel analogues of the antibiotic CC-1065 and the duocarmycins. Chem. - Eur. J. 2007, 13, 4396-4409.
23. Ahn, G. O.; Botting, K. J.; Patterson, A. V.; Ware, D. C.; Tercel, M.; Wilson, W. R. Radiolytic and cellular reduction of a novel hypoxia-activated cobalt(III) prodrug of a chloromethylbenzindoline DNA minor groove alkylator. Biochem. Pharmacol. 2006, 71, 1683-1694.
24. Tercel, M.; Denny, W. A. Synthesis of nitrogen and sulfur analogues of the seco-CI alkylating agent. J. Chem. Soc., Perkin Trans. 1 1998, 509-519.
25. Atwell, G. J.; Tercel, M.; Boyd, M.; Wilson, W. R.; Denny, W. A. Synthesis and cytotoxicity of 5-amino-1-(chloromethyl)-3-[(5,6,7- trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz[e]indole (aminoseco- CBI-TMI) and related 5-alkylamino analogues: new DNA minor groove alkylating agents. J. Org. Chem. 1998, 63, 9414-9420.
26. Tercel, M.; Gieseg, M. A.; Denny, W. A.; Wilson, W. R. Synthesis and cytotoxicity of amino-seco-DSA: an amino analogue of the DNA alkylating agent duocarmycin SA. J. Org. Chem. 1999, 64, 5946-5953.
27. Tercel, M.; Gieseg, M. A.; Milbank, J. B.; Boyd, M.; Fan, J. Y.; Tan, L. K.; Wilson, W. R.; Denny, W. A. Cytotoxicity and DNA interaction of the enantiomers of 6-amino-3-(chloromethyl)- 1-[(5,6,7-trimethoxyindol-2-yl) carbonyl]indoline (amino-seco-CITMI). Chem. Res. Toxicol. 1999, 12, 700-706.
28. Gieseg, M. A.; Matejovic, J.; Denny, W. A. Comparison of the patterns of DNA alkylation by phenol and amino seco-CBI-TMI compounds: use of a PCR method for the facile preparation of single end-labelled double-stranded DNA. Anti-Cancer Drug Des. 1999, 14, 77-84.
29. Hay, M. P.; Anderson, R. F.; Ferry, D. M.; Wilson, W. R.; Denny, W. A. Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy. J. Med. Chem. 2003, 46, 5533-5545.
30. Tercel, M.; Denny, W. A.; Wilson, W. R. Anovel nitro-substituted seco-CI: application as a reductively activated ADEPT prodrug. Bioorg. Med. Chem. Lett. 1996, 6, 2741-2744.
31. Wilson, W. R.; Stribbling, S. M.; Pruijn, F. B.; Syddall, S. P.; Patterson, A. V.; Liyanage, H. D. S.; Smith, E.; Botting, K. J.; Tercel, M. Nitro-chloromethylbenzindolines: hypoxia-activated prodrugs of potent adenine N3 DNA minor groove alkylators. Mol. Cancer Ther. 2009, 8, 2903-2913.
32. Patel, V. F.; Andis, S. L.; Enkema, J. K.; Johnson, D. A.; Kennedy, J. H.; Mohamadi, F.; Schultz, R. M.; Soose, D. J.; Spees, M. M. Total synthesis of seco (+)- and ent-(-)-oxaduocarmycin SA: construction of the (chloromethyl)indoline alkylating subunit by a novel intramolecular aryl radical cyclization onto a vinyl chloride. J. Org. Chem. 1997, 62, 8868-8874.
33. Note for substituent numbering that an n-substituted naphthoic acid 53 becomes (n + 1)-substituted as a benzindoline 57 or 58.
34. Searcey, M.; Patterson, L. H. Preparation of Benzindole and Benzoquinoline Derivatives as Prodrugs for Tumor Treatment. Patent WO02067930A1, 2002.
35. Jin, W.; Trzupek, J. D.; Rayl, T. J.; Broward, M. A.; Vielhauer, G. A.; Weir, S. J.; Hwang, I.; Boger, D. L. A unique class of duocarmycin and CC-1065 analogues subject to reductive activation. J. Am. Chem. Soc. 2007, 129, 15391-15397.
36. 6 (13 examples).
37. Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Nikaitani, D.; Lien, E. J. "Aromatic" substituent constants for structure-activity correlations. J. Med. Chem. 1973, 16, 1207-1216.
38. m, with the estimated E(1) only varying by 0-14 mV compared to the values given in Table 2.
39. Wardman, P. Electron transfer and oxidative stress as key factors in the design of drugs selectively active in hypoxia. Curr. Med. Chem. 2001, 8, 739-761.
40. Denny, W. A.; Wilson, W. R. Considerations for the design of nitrophenyl mustards as agents with selective toxicity for hypoxic tumor cells. J. Med. Chem. 1986, 29, 879-887.
41. Palmer, B. D.; Wilson, W. R.; Pullen, S. M.; Denny, W. A. Hypoxia-selective antitumor agents. 3. Relationships between structure and cytotoxicity against cultured tumor cells for substituted N, N-bis(2-chloroethyl)anilines. J. Med. Chem. 1990, 33, 112-121.
42. Palmer, B. D.; Wilson, W. R.; Cliffe, S.; Denny, W. A. Hypoxiaselective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells. J. Med. Chem. 1992, 35, 3214-3222.
43. Anderson, R. F.; Denny, W. A.; Li, W.; Packer, J. E.; Tercel, M.; Wilson, W. R. Pulse radiolysis studies on the fragmentation of arylmethyl quaternary nitrogen mustards by one-electron reduction in aqueous solution. J. Phys. Chem. 1997, 101, 9704-9709.
44. Hay, M. P.; Gamage, S. A.; Kovacs, M. S.; Pruijn, F. B.; Anderson, R. F.; Patterson,A. V.; Wilson, W. R.; Brown, J. M.; Denny, W. A. Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine. J. Med. Chem. 2003, 46, 169-182.
45. Lee, H. H.; Wilson, W. R.; Ferry, D. M.; van Zijl, P.; Pullen, S. M.; Denny, W. A. 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. J. Med. Chem. 1996, 39, 2508-2517.
46. Wilson, W. R.; Pullen, S. M.; Hogg, A.; Hobbs, S. M.; Pruijn, F. B.; Hicks, K. O. In Vitro and in Vivo Models for Evaluation of GDEPT: Quantifying Bystander Killing in Cell Cultures and Tumors. In Suicide Gene Therapy: Methods and Reviews; Springer, C. J., Ed.; Humana Press: Totowa, NJ, 2003; pp 403-432.