Doxazolidine, a proposed active metabolite of doxorubicin that cross-links DNA

Journal of Medicinal Chemistry

Volumn 48, Issue 24, 2005, Pages 7648-7657

  Post, Glen C ^a   Barthel, Benjamin L ^a   Burkhart, David J ^a   Hagadorn, John R ^a   Koch, Tad H ^a,b  

^a UNIVERSITY OF COLORADO   (United States)

^b Colorado Cancer Center ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 FORMYL 6,9 DIHYDROXY 14 OXA 1,11 DIAZATETRACYCLO[7.4.1.0 2,7 0 10,12]TETRADECA 2,4,6 TRIEN 8 YLMETHYLCARBAMATE; DAUNORUBICIN; DOXAZOLIDINE; DOXOFORM; DOXORUBICIN; DOXSALIFORM; DRUG METABOLITE; EPIRUBICIN; FORMALDEHYDE; IDARUBICIN; MITOMYCIN C; OXAZOLIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CANCER INHIBITION; CELL STRAIN MCF 7; CROSS LINKING; CRYSTAL STRUCTURE; DNA DRUG COMPLEX; DRUG HALF LIFE; DRUG HYDROLYSIS; DRUG STRUCTURE; HUMAN; HUMAN CELL; MOLECULAR MODEL; RING OPENING;

ANTIBIOTICS, ANTINEOPLASTIC; CELL LINE, TUMOR; CROSS-LINKING REAGENTS; CRYSTALLOGRAPHY, X-RAY; DNA; DOXORUBICIN; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG STABILITY; HUMANS; HYDROLYSIS; MODELS, MOLECULAR; PRODRUGS;

EID: 28144443720     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050678v     Document Type: Article

References (40)

1. DeVita, V. T.; Hellman, S.; Rosenberg, S. A. Cancer: Principles and Practice of Oncology, 6th ed.; Lippincott, Williams and Wilkins: Philadelphia, PA, 2001.
2. Gewirtz, D. A. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. 1999, 57, 727-741.
3. Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004, 56, 185-229.
4. Thigpen, J. T. Innovations in anthracycline therapy: overview. Community Oncol. 2005, 2 (S1), 3-7.
5. Arcamone, F. Doxorubicin Anticancer Antibiotics; Academic Press: New York, 1981; pp 246-254.
6. Chaires, J. B.; Satyanarayana, S.; Suh, D.; Fokt, I.; Przewloka, T.; et al. Parsing the free energy of anthracycline antibiotic binding to DNA. Biochemistry 1996, 35, 2047-2053.
7. Cullinane, C.; van Rosmalen, A.; Phillips, D. R. Does adriamycin induce interstrand cross-links in DNA? Biochemistry 1994, 33, 4632-4638.
8. Cullinane, C.; Cutts, S. M.; van Rosmalen, A.; Phillips, D. R. Formation of adriamycin-DNA adducts in vitro. Nucleic Acids Res. 1994, 22, 2296-2303.
9. Skladanowski, A.; Konopa, J. Interstrand DNA crosslinking induced by anthracyclines in tumour cells. Biochem. Pharmacol. 1994, 47, 2269-2278.
10. Wang, A. H. J.; Gao, Y. G.; Liaw, Y. C.; Li, Y. K. Formaldehyde cross-links daunorubicin and DNA efficiently: HPLC and X-ray diffraction studies. Biochemistry 1991, 30, 3812-3815.
11. Leng, F.; Savkur, R.; Fokt, I.; Przewloka, T.; Priebe, W.; et al. Base specific and regiospecific chemical cross-linking of daunorubicin to DNA. J. Am. Chem. Soc. 1996, 118, 4731-4738.
12. Taatjes, D. J.; Gaudiano, G.; Resing, K.; Koch, T. H. A redox pathway leading to the alkylation of DNA by the anthracycline, anti-tumor drugs, adriamycin and daunomycin. J. Med. Chem. 1997, 40, 1276-1286.
13. Zeman, S. M.; Phillips, D. R.; Crothers, D. M. Characterization of covalent adriamycin-DNA adducts. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 11561-11565.
14. Podell, E. R.; Harrington, D. J.; Taatjes, D. J.; Koch, T. H. Crystal structure of epidoxorubicin-formaldehyde virtual crosslink of DNA and evidence for its formation in human breast-cancer cells. Acta Crystallogr. 1999, D55, 1516-1523.
15. Taatjes, D. J.; Gaudiano, G.; Koch, T. H. Production of formaldehyde and DNA-adriamycin or -daunomycin adducts, initiated through redox chemistry of DTT/iron, xanthine oxidase/NADH/iron, or glutathione/iron. Chem. Res. Toxicol. 1997, 10, 953-961.
16. Kato, S.; Burke, P. J.; Fenick, D. J.; Taatjes, D. J.; Bierbaum, V. M.; et al. Mass spectrometric measurement of formaldehyde generated in breast cancer cells upon treatment with anthracycline antitumor drugs. Chem. Res. Toxicol. 2000, 13, 509-516.
17. Fenick, D. J.; Taatjes, D. J.; Koch, T. H. Doxoform and daunoform: Anthracycline-formaldehyde conjugates toxic to resistant tumor cells. J. Med. Chem. 1997, 40, 2452-2461.
18. Cogan, P. S.; Fowler, C. R.; Post, G. C.; Koch, T. H. Doxsaliform: A novel N-Mannich base prodrug of a doxorubicin formaldehyde conjugate. Lett. Drug Des. Dis. 2004, 1, 247-255.
19. Swift, L. P. C., S. M.; Rephaeli, A.; Nudelman, A.; Phillips, D. R. Activation of adriamycin by the pH-dependent formaldehyde-releasing prodrug hexamethylenetetramine. Mol. Cancer Ther. 2003, 2, 189-198.
20. Nudelman, A.; Levovich, I.; Cutts, S. M.; Phillips, D. R. The role of intracellularly released formaldehyde and butyric acid in the anticancer activity of acyloxyalkyl esters. J. Med. Chem. 2005, 48, 1042-1054.
21. Cutts, S. M.; Nudelman, A.; Rephaeli, A.; Phillips, D. R. The power and potential of doxorubicin-DNA adducts. IUBMB Life 2005, 5, 73-81.
22. Loudon, G. M.; Almond, M. R.; Jacob, J. N. Mechanism of hydrolysis ofJV-(1-aminoalkyl) amides. J. Am. Chem. Soc. 1981, 103, 4508-4515.
23. Wani, M. C.; Taylor, D. J.; Wall, M. E.; McPhail, A. T.; Onan, K. D. Antitumor agents. XIII. Isolation and absolute configuration of Carminomycin I from Streptosporangium sp. J. Am. Chem. Soc. 1975, 97, 5955-5957.
24. Pettit, G. R.; Einck, J. J.; Herald, C. L.; Ode, R. H.; Von Dreele, R. B.; et al. The structure of carminomycin I. J. Am. Chem. Soc. 1975, 97, 7387-7389.
25. Mimnaugh, E. G.; Fairchild, C. R.; Fruehauf, J. P.; Sinha, B. K. Biochemical and pharmacological characterization of MCF-7 drug-sensitive and Adr multidrug-resistant human breast tumor xenografts in athymic mice. Biochem. Pharmacol. 1991, 42, 391-402.
26. Lampidis, T. J.; Kolonias, D.; Podona, T.; Isreal, M.; Safa, A. R.; et al. Circumvention of P-GP MDR as a function of anthracycline lipophilicity and charge. Biochemistry 1997, 36, 2679-2685.
27. Crooke, S. T.; DuVernay, V. H. Fluorescence Quenching of Anthracyclines by Subcellular Fractions. Anthracyclines Current Status and New Developments; Academic Press: New York, 1980; pp 151-155.
28. Taatjes, D. J.; Fenick, D. J.; Koch, T. H. Epidoxoform: a hydrolytically more stable anthracycline-formaldehyde conjugate, cytotoxic to resistant tumor cells. J. Med. Chem. 1998, 41, 1306-1314.
29. Taatjes, D. J.; Koch, T. H. Growth inhibition, nuclear uptake, and retention of anthracycline-formaldehyde conjugates in prostate cancer cells relative to clinical anthracyclines. Anticancer Res. 1999, 19, 1201-1208.
30. Taylor, R.; Kennard, O. The molecular structures of nucleosides and nucleotides. 1. The influence of protonation on the geometries of nucleic constituents. J. Mol. Struct. 1982, 78, 1-28.
31. Rajski, S. R.; Williams, R. M. DNA interstrand cross-linking agents as antitumor drugs. Chem. Rev. 1998, 98, 2723-2796.
32. Norman, D.; Live, D.; Sastry, M.; Lipman, R.; Hingerty, B. E.; et al. NMR and computational characterization of mitomycin cross-linked to adjacent deoxyguanosines in the minor groove of the d(TACGTA)-d(TACGTA) duplex. Biochemistry 1990, 29, 2861-2875.
33. Taatjes, D. J.; Fenick, D. J.; Koch, T. H. Nuclear targeting and nuclear retention of anthracycline-formaldehyde conjugates implicates DNA covalent binding in the cytotoxic mechanism of anthracyclines. Chem. Res. Toxicol. 1999, 12, 588-596.
34. Cogan, P. S.; Koch, T. H. Rational design and synthesis of androgen receptor targeted non-steroidal anti-androgen ligands for the tumor specific delivery of a doxorubicin-formaldehyde conjugate. J. Med. Chem. 2003, 46, 5258-5270.
35. Cogan, P. S.; Koch, T. H. Studies of targeting and intracellular trafficking of an anti-androgen-doxorubicin-formaldehyde conjugate in PC-3 prostate cancer cells bearing androgen receptor-GFP chimera. J. Med. Chem., submitted.
36. Burke, P. J.; Koch, T. H. Design, synthesis, and biological evaluation of doxorubicin-formaldehyde conjugates targeted to breast cancer cells. J. Med. Chem. 2004, 47, 1193-1206.
37. Burke, P. J.; Kalet, B. T.; Koch, T. H. Antiestrogen binding site (AEBS) and estrogen receptor (ER) mediate uptake and distribution of 4-hydroxytamoxifen-targeted doxorubicin-formaldehyde conjugate in breast cancer cells. J. Med. Chem., submitted.
38. Burkhart, D. J.; Kalet, B. T.; Koch, T. H. Doxorubicin-formaldehyde conjugates targeting alpha-v beta-3 integrin. Mol. Cancer Ther. 2004, 3, 1593-1604.
39. Cutts, S. M.; Rephaeli, A; Nudelman, A.; Hmelnitsky, I.; Phillips, D. R. Molecular basis for the synergistic interaction of adriamycin with the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate (AN-9). Cancer Res. 2001, 61, 8194-8202.
40. Dernell, W. S.; Powers, B. E.; Taatjes, D. J.; Cogan, P.; Gaudiano, G.; et al. Evaluation of the epidoxorubicin-formaldehyde conjugate, epidoxoform, in a mouse mammary carcinoma model. Cancer Invest. 2002, 20, 712-723.