Selective treatment of hypoxic tumor cells in vivo: Phosphate pre-prodrugs of nitro analogues of the duocarmycins

Angewandte Chemie - International Edition

Volumn 50, Issue 11, 2011, Pages 2606-2609

  Tercel, Moana ^a   Atwell, Graham J ^a   Yang, Shangjin ^a   Ashoorzadeh, Amir ^a   Stevenson, Ralph J ^a   Botting, K Jane ^a   Gu, Yongchuan ^a   Mehta, Sunali Y ^a   Denny, William A ^a   Wilson, William R ^a   Pruijn, Frederik B ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

antitumor agents; duocarmycins; hypoxia; phosphates; prodrugs

Indexed keywords

ALKYLATING AGENTS; ANTI-TUMOR AGENTS; ANTITUMOR COMPOUNDS; DUOCARMYCINS; HYPOXIA; IN-VIVO; PRODRUGS; SELECTIVE TREATMENT; TUMOR CELLS;

PHOSPHATES;

TUMORS;

2 PYRROLIDONE DERIVATIVE; AMINE; ANTINEOPLASTIC AGENT; DUOCARMYCIN A; INDOLE DERIVATIVE; PRODRUG;

ANIMAL; ANOXIA; ARTICLE; CELL SURVIVAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECT; HUMAN; MOUSE; TUMOR CELL LINE;

AMINES; ANIMALS; ANOXIA; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL SURVIVAL; HUMANS; INDOLES; MICE; MOLECULAR STRUCTURE; PRODRUGS; PYRROLIDINONES;

EID: 79952253984     PISSN: 14337851     EISSN: 15213773     Source Type: Journal    
DOI: 10.1002/anie.201004456     Document Type: Article

References (21)

1. D. L. Boger, D. S. Johnson, Angew. Chem. 1996, 108, 1542
2. Angew. Chem. Int. Ed. Engl. 1996, 35, 1438.
3. L. H. Li, et al., Cancer Res. 1992, 52, 4904
4. E. Kobayashi, A. Okamoto, M. Asada, M. Okabe, S. Nagamura, A. Asai, H. Saito, K. Gomi, T. Hirata, Cancer Res. 1994, 54, 2404.
5. N. Pavlidis, et al., Cancer Chemother. Pharmacol. 2000, 46, 167
6. S. N. Markovic, et al., Am. J. Clin. Oncol. 2002, 25, 308.
7. L. Ducry, B. Stump, Bioconjugate Chem. 2010, 21, 5.
8. L. F. Tietze, F. Major, I. Schuberth, Angew. Chem. 2006, 118, 6724
9. Angew. Chem. Int. Ed. 2006, 45, 6574
10. L. F. Tietze, T. Feuerstein, A. Fecher, F. Haunert, O. Panknin, U. Borchers, I. Schuberth, F. Alves, Angew. Chem. 2002, 114, 785
11. Angew. Chem. Int. Ed. 2002, 41, 759.
12. G. J. Atwell, M. Tercel, M. Boyd, W. R. Wilson, W. A. Denny, J. Org. Chem. 1998, 63, 9414
13. M. A. Gieseg, J. Matejovic, W. A. Denny, Anti-Cancer Drug Des. 1999, 14, 77.
14. W. R. Wilson, S. M. Stribbling, F. B. Pruijn, S. P. Syddall, A. V. Patterson, H. D. S. Liyanage, E. Smith, K. J. Botting, M. Tercel, Mol. Cancer Ther. 2009, 8, 2903
15. M. Tercel, et al., J. Med. Chem. 2009, 52, 7258.
16. J. A. Bertout, S. A. Patel, M. C. Simon, Nat. Rev. Cancer 2008, 8, 967.
17. Y. Chen, L. Hu, Med. Res. Rev. 2008, 29, 29
18. J. M. Brown, W. R. Wilson, Nat. Rev. Cancer 2004, 4, 437.
19. M. Tercel, S. Yang, G. J. Atwell, E. Smith, Y. Gu, R. F. Anderson, W. A. Denny, W. R. Wilson, F. B. Pruijn, Bioorg. Med. Chem. 2010, 18, 4997.
20. See Supporting Information.
21. Some activity was noted when phosphates were administered without radiotherapy. This may represent killing of the hypoxic fraction, or killing of oxic cells, either directly or by diffusion of aminoCBI from hypoxic zones.