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Synthesis 2010(21): 3631-3636  
DOI: 10.1055/s-0030-1258245
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Design, Synthesis, and Testing of Polyamine Vectored Iron Chelators

Raymond J. Bergeron*, Shailendra Singh, Neelam Bharti, Yi Jiang
Department of Medicinal Chemistry, University of Florida, Box 100485 JHMHC, Gainesville, FL, 32610-0485, USA
Fax: +1(352)3928406; e-Mail: rayb@ufl.edu;
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Publication History

Received 7 May 2010
Publication Date:
03 September 2010 (online)

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Abstract

Iron chelators have been shown to control the growth of cancer cells in culture by sequestering exogenous iron in the media. Thus, the ligands prevent cellular access to the metal. However, because transferrin provides iron to tumor cells in animals, chelators have not been effective antitumor agents. Polyamine chelator conjugates in which the polyamine vectored ligands into cells were far more active than the free chelators themselves. However, the free ligands were not released from the vector once in the cell. The current study focuses on the synthesis and preliminary evaluation of a polyamine chelator conjugate capable of releasing the free ligand intracellularly via a nonspecific esterase.

Key words

iron - chelator - conjugate - polyamine vector - intracellular esterase

    References

  • 1a Bergeron RJ. Trends Biochem. Sci.  1986,  11:  133 
    Google Scholar
  • 1b Bergeron RJ. Braylan R. Goldey S. Ingeno MJ. Biochem. Biophys. Res. Commun.  1986,  136:  273 
    Google Scholar
  • 1c Hershko C. Bailliere’s Clin. Haematol.  1994,  7:  965 
    Google Scholar
  • 1d Chenoufi N. Drenou B. Loreal O. Pigeon C. Brissot P. Lescoat G. Biochem. Pharmacol.  1998,  56:  431 
    Google Scholar
  • 2a Bergeron RJ. Ingeno MJ. Cancer Res.  1987,  47:  6010 
    Google Scholar
  • 2b Taetle R. Honeysett JM. Bergeron RJ. J. Natl. Cancer Inst.  1989,  81:  1229 
    Google Scholar
  • 2c Nyholm S. Mann GJ. Johannson AG. Bergeron RJ. Graslund A. Thelander L. J. Biol. Chem.  1993,  268:  26200 
    Google Scholar
  • 3 Porter JB. Gyparaki M. Burke LC. Huehns ER. Sarpong P. Saez V. Hider RC. Blood  1988,  72:  1497 
    Google Scholar
  • 4 Selig RA. White L. Gramacho C. Sterling-Levis K. Fraser IW. Naidoo D. Cancer Res.  1998,  58:  473 
    Google Scholar
  • 5a Marton LJ. Pegg AE. Annu. Rev. Pharm. Toxicol.  1995,  35:  55 
    Google Scholar
  • 5b Thomas T. Balabhadrapathruni S. Gallo MA. Thomas TJ. Oncol. Res.  2002,  13:  123 
    Google Scholar
  • 5c Wallace HM. Fraser AV. Biochem. Soc. Trans.  2003,  31:  393 
    Google Scholar
  • 6a Porter CW. McManis J. Casero RA. Bergeron RJ. Cancer Res.  1987,  47:  2821 
    Google Scholar
  • 6b Bergeron RJ. Neims AH. McManis JS. Hawthorne TR. Vinson JRT. Bortell R. Ingeno MJ. J. Med. Chem.  1988,  31:  1183 
    Google Scholar
  • 6c Pegg AE. Madhubala R. Kameji T. Bergeron RJ. J. Biol. Chem.  1988,  263:  11008 
    Google Scholar
  • 6d Porter CW. Bergeron RJ. Adv. Enzyme Regul.  1988,  27:  57 
    Google Scholar
  • 6e Bergeron RJ. Hawthorne TR. Vinson JRT. Beck DE. Ingeno MJ. Cancer Res.  1989,  49:  2959 
    Google Scholar
  • 7a Libby PR. Bergeron RJ. Porter CW. Biochem. Pharmacol.  1989,  38:  1435 
    Google Scholar
  • 7b Porter CW. Pegg AE. Ganis B. Madhabala R. Bergeron RJ. Biochem. J.  1990,  268:  207 
    Google Scholar
  • 7c Bernacki RJ. Bergeron RJ. Porter CW. Cancer Res.  1992,  52:  2424 
    Google Scholar
  • 7d Bergeron RJ. McManis JS. Liu CZ. Feng Y. Weimar WR. Luchetta GR. Wu Q. Ortiz-Ocasio J. Vinson JRT. Kramer D. Porter C. J. Med. Chem.  1994,  37:  3464 
    Google Scholar
  • 7e Bergeron RJ. McManis JS. Weimar WR. Schreier KM. Gao F. Wu Q. Ortiz-Ocasio J. Luchetta GR. Porter C. Vinson JRT. J. Med. Chem.  1995,  38:  2278 
    Google Scholar
  • 7f Bergeron RJ. Feng Y. Weimar WR. McManis JS. Dimova H. Porter C. Raisler B. Phanstiel O. J. Med. Chem.  1997,  40:  1475 
    Google Scholar
  • 7g Bergeron RJ. Müller R. Bussenius J. McManis JS. Merriman RL. Smith RE. Yao H. Weimar WR. J. Med. Chem.  2000,  43:  224 
    Google Scholar
  • 7h Bergeron RJ. Müller R. Huang G. McManis JS. Algee SE. Yao H. Weimar WR. Wiegand J. J. Med. Chem.  2001,  44:  2451 
    Google Scholar
  • 8 Delcros J.-G. Tomasi S. Carrington S. Martin B. Renault J. Blagbrough IS. Uriac P. J. Med. Chem.  2002,  45:  5098 
    CrossrefGoogle Scholar
  • 9 Bergeron RJ. Bharti N. Wiegand J. McManis JS. Yao H. Prokai L. J. Med. Chem.  2005,  48:  4120 
    CrossrefGoogle Scholar
  • 10 Bergeron RJ. McManis JS. Franklin AM. Yao H. Weimar WR. J. Med. Chem.  2003,  46:  5478 
    CrossrefGoogle Scholar
  • 11 Krapcho AP. Kuell CS. Synth. Commun.  1990,  20:  2559 
    CrossrefGoogle Scholar
  • 12a Bordwell FG. Acc. Chem. Res.  1988,  21:  456 
    Google Scholar
  • 12b Nyasse B. Grehn L. Ragnarsson U. Maia HLS. Monteiro LS. Leito I. Koppel I. Koppel J. J. Chem. Soc., Perkin Trans. 1  1995,  2025 
    Google Scholar
  • 13 Liu W.-Q. Vidal M. Gresh N. Roques BP. Garbay C. J. Med. Chem.  1999,  42:  3737 
    CrossrefGoogle Scholar
  • 14a Bergeron RJ. Wiegand J. McManis JS. Bussenius J. Smith RE. Weimar WR. J. Med. Chem.  2003,  46:  1470 
    Google Scholar
  • 14b Bergeron RJ. Wiegand J. McManis JS. Vinson JRT. Yao H. Bharti N. Rocca JR. J. Med.Chem.  2006,  49:  2772 
    Google Scholar
  • 14c Bergeron RJ. Bharti N. Wiegand J. McManis JS. Singh S. Abboud KA. J. Med. Chem.  2010,  53:  2843 
    Google Scholar