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DOI: 10.1055/s-0030-1258245
Design, Synthesis, and Testing of Polyamine Vectored Iron Chelators
Publikationsverlauf
Publikationsdatum:
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
-
1a
Bergeron RJ. Trends Biochem. Sci. 1986, 11: 133 -
1b
Bergeron RJ.Braylan R.Goldey S.Ingeno MJ. Biochem. Biophys. Res. Commun. 1986, 136: 273 -
1c
Hershko C. Bailliere’s Clin. Haematol. 1994, 7: 965 -
1d
Chenoufi N.Drenou B.Loreal O.Pigeon C.Brissot P.Lescoat G. Biochem. Pharmacol. 1998, 56: 431 -
2a
Bergeron RJ.Ingeno MJ. Cancer Res. 1987, 47: 6010 -
2b
Taetle R.Honeysett JM.Bergeron RJ. J. Natl. Cancer Inst. 1989, 81: 1229 -
2c
Nyholm S.Mann GJ.Johannson AG.Bergeron RJ.Graslund A.Thelander L. J. Biol. Chem. 1993, 268: 26200 - 3
Porter JB.Gyparaki M.Burke LC.Huehns ER.Sarpong P.Saez V.Hider RC. Blood 1988, 72: 1497 - 4
Selig RA.White L.Gramacho C.Sterling-Levis K.Fraser IW.Naidoo D. Cancer Res. 1998, 58: 473 -
5a
Marton LJ.Pegg AE. Annu. Rev. Pharm. Toxicol. 1995, 35: 55 -
5b
Thomas T.Balabhadrapathruni S.Gallo MA.Thomas TJ. Oncol. Res. 2002, 13: 123 -
5c
Wallace HM.Fraser AV. Biochem. Soc. Trans. 2003, 31: 393 -
6a
Porter CW.McManis J.Casero RA.Bergeron RJ. Cancer Res. 1987, 47: 2821 -
6b
Bergeron RJ.Neims AH.McManis JS.Hawthorne TR.Vinson JRT.Bortell R.Ingeno MJ. J. Med. Chem. 1988, 31: 1183 -
6c
Pegg AE.Madhubala R.Kameji T.Bergeron RJ. J. Biol. Chem. 1988, 263: 11008 -
6d
Porter CW.Bergeron RJ. Adv. Enzyme Regul. 1988, 27: 57 -
6e
Bergeron RJ.Hawthorne TR.Vinson JRT.Beck DE.Ingeno MJ. Cancer Res. 1989, 49: 2959 -
7a
Libby PR.Bergeron RJ.Porter CW. Biochem. Pharmacol. 1989, 38: 1435 -
7b
Porter CW.Pegg AE.Ganis B.Madhabala R.Bergeron RJ. Biochem. J. 1990, 268: 207 -
7c
Bernacki RJ.Bergeron RJ.Porter CW. Cancer Res. 1992, 52: 2424 -
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 -
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 -
7f
Bergeron RJ.Feng Y.Weimar WR.McManis JS.Dimova H.Porter C.Raisler B.Phanstiel O. J. Med. Chem. 1997, 40: 1475 -
7g
Bergeron RJ.Müller R.Bussenius J.McManis JS.Merriman RL.Smith RE.Yao H.Weimar WR. J. Med. Chem. 2000, 43: 224 -
7h
Bergeron RJ.Müller R.Huang G.McManis JS.Algee SE.Yao H.Weimar WR.Wiegand J. J. Med. Chem. 2001, 44: 2451 - 8
Delcros J.-G.Tomasi S.Carrington S.Martin B.Renault J.Blagbrough IS.Uriac P. J. Med. Chem. 2002, 45: 5098 - 9
Bergeron RJ.Bharti N.Wiegand J.McManis JS.Yao H.Prokai L. J. Med. Chem. 2005, 48: 4120 - 10
Bergeron RJ.McManis JS.Franklin AM.Yao H.Weimar WR. J. Med. Chem. 2003, 46: 5478 - 11
Krapcho AP.Kuell CS. Synth. Commun. 1990, 20: 2559 -
12a
Bordwell FG. Acc. Chem. Res. 1988, 21: 456 -
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 - 13
Liu W.-Q.Vidal M.Gresh N.Roques BP.Garbay C. J. Med. Chem. 1999, 42: 3737 -
14a
Bergeron RJ.Wiegand J.McManis JS.Bussenius J.Smith RE.Weimar WR. J. Med. Chem. 2003, 46: 1470 -
14b
Bergeron RJ.Wiegand J.McManis JS.Vinson JRT.Yao H.Bharti N.Rocca JR. J. Med.Chem. 2006, 49: 2772 -
14c
Bergeron RJ.Bharti N.Wiegand J.McManis JS.Singh S.Abboud KA. J. Med. Chem. 2010, 53: 2843