PCTH: A novel orally active chelator of the aroylhydrazone class that induces iron excretion from mice

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1739, Issue 1, 2004, Pages 70-80

  Wong, C S M ^b   Kwok, J C ^b   Richardson, D R ^a  

^a Iron Metab and Chelation Program   (Australia)

^b NONE

Author keywords

Iron; Iron chelator; Pyridoxal isonicotinoyl hydrazone

Indexed keywords

2 PYRIDYLCARBOXALDEHYDE 2 THIOPHENECARBOXYL HYDRAZONE; CHELATING AGENT; DEFERIPRONE; HYDRAZONE DERIVATIVE; PYRIDOXAL ISONICOTINOYL HYDRAZONE; UNCLASSIFIED DRUG;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BETA THALASSEMIA; BIOACCUMULATION; CELL CULTURE; CHELATION; CONTROLLED STUDY; EXCRETION; HEART MUSCLE CELL; IN VITRO STUDY; IN VIVO STUDY; IRON EXCRETION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; REDUCTION; TOXICITY; WEIGHT REDUCTION;

ADMINISTRATION, ORAL; ANIMALS; BLOOD CHEMICAL ANALYSIS; BODY WEIGHT; CELLS, CULTURED; EATING; FECES; IRON; IRON CHELATING AGENTS; LIVER; MALE; MICE; MICE, INBRED BALB C; MYOCYTES, CARDIAC; ORGAN SIZE; PYRIDONES; RATS; THIOPHENES; TRANSFERRIN;

EID: 10644295737     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2004.09.001     Document Type: Article

References (61)

1. C. Hershko Control of disease by selective iron depletion: a novel therapeutic strategy utilizing iron chelators, Bailliére's Clin. Haematol. 7 1994 965 1000
2. N.F. Olivieri, and G.M. Brittenham Iron chelation therapy and the treatment of thalassemia Blood 89 1997 739 761
3. C. Wong, and D.R. Richardson Beta-thalassaemia: emergence of new and improved iron chelators for treatment Int. J. Biochem. Cell Biol. 35 2003 1144 1149
4. D.R. Richardson The controversial role of deferiprone in the treatment of thalassemia J. Lab. Clin. Med. 137 2001 324 329
5. L.J. Anderson, B. Wonke, E. Prescott, S. Holden, J.M. Walker, and D.J. Pennell Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia Lancet 360 2002 516 520
6. A. Maggio, G. D'Amico, A. Morabito, M. Capra, C. Ciaccio, P. Cianciulli, F. Di Gregorio, G. Garozzo, R. Malizia, C. Magnano, A. Mangiagli, G. Quarta, M. Rizzo, D.G. D'Ascola, A. Rizzo, and A. Midiri Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial Blood Cells Mol. Diseases 28 2002 196 208
7. A.R. Cohen, R. Galanello, A. Piga, V. De Sanctis, and F. Tricta Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone Blood 102 2003 1583 1587
8. G.J. Kontoghiorghes, K. Neocleous, and A. Kolnagou Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine Drug Safety 26 2003 553 584
9. N.F. Olivieri, G.M. Brittenham, C.E. McLaren, D.M. Templeton, R.G. Cameron, R.A. McClelland, A.D. Burt, and K.A. Fleming Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major N. Engl. J. Med. 339 1998 417 423
10. A.V. Hoffbrand, F. Al-Refaie, B. Davis, N. Siritanakatkul, B.F. Jackson, J. Cochrane, E. Prescott, and B. Wonke Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients Blood 91 1998 295 300
11. C. Hershko, M.D. Cappellini, R. Galanello, A. Piga, G. Tognoni, and G. Masera Purging iron from the heart Br. J. Haematol. 125 2004 545 551
12. K.H. Wu, J.S. Chang, C.H. Tsai, and C.T. Peng Combined therapy with deferiprone and desferrioxamine successfully regresses severe heart failure in patients with beta-thalassemia major Ann. Hematol. 83 2004 471 473
13. S. Gomber, R. Saxena, and N. Madan Comparative efficacy of desferrioxamine, deferiprone and in combination on iron chelation in thalassemic children Indian Pediatr. 41 2004 21 27
14. P. Ponka, J. Borova, J. Neuwirt, and O. Fuchs Mobilization of iron from reticulocytes. Identification of pyridoxal isonicotinoyl hydrazone as a new iron chelating agent FEBS Lett. 97 1979 317 321
15. P. Ponka, J. Borova, J. Neuwirt, O. Fuchs, and E. Necas A study of intracellular iron metabolism using pyridoxal isonicotinoyl hydrazone and other synthetic chelating agents Biochim. Biophys. Acta 586 1979 278 297
16. T. Hoy, J. Humphreys, A. Jacobs, A. Williams, and P. Ponka Effective iron chelation following oral administration of an isoniazid pyridoxal hydrazone Br. J. Haematol. 43 1979 443 449
17. M. Cikrt, P. Ponka, E. Necas, and J. Neuwirt Biliary iron excretion in rats following pyridoxal isonicotinoyl hydrazone Br. J. Haematol. 45 1980 275 283
18. E. Baker, D. Richardson, S. Gross, and P. Ponka Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture Hepatology 15 1992 492 501
19. G.M. Brittenham Pyridoxal isonicotinoyl hydrazone: an effective chelator after oral administration Semin. Hematol. 27 1990 112 116
20. E. Becker, and D.R. Richardson Development of novel aroylhydrazone ligands for iron chelation therapy: 2-pyridylcarboxaldehyde isonicotinoyl hydrazone analogs J. Lab. Clin. Med. 134 1999 510 521
21. D.R. Richardson, C. Mouralian, P. Ponka, and E. Becker Development of potential iron chelators for the treatment of Friedreich's ataxia: ligands that mobilize mitochondrial iron Biochim. Biophys. Acta 1536 2001 133 140
22. D.R. Richardson, P.V. Bernhardt, E. Becker, Iron Chelators and Uses Thereof, International Patent Application No. PCT/AU00/01050. 2000 4th September, 2000.
23. T.B. Chaston, and D.R. Richardson Interactions of the pyridine-2-carboxaldehyde isonicotinoyl hydrazone class of chelators with iron and DNA: implications for toxicity in the treatment of iron overload disease J. Biol. Inorg. Chem. 8 2003 427 438
24. M.B. Delatyki, J. Camakaris, H. Brooks, T. Evans-Whipp, D.R. Thorburn, R. Williamson, and S.M. Forrest Direct evidence that mitochondrial iron accumulation occurs in Friedreich ataxia Ann. Neurol. 45 1999 673 675
25. H. Puccio, D. Simon, M. Cossee, P. Criqui-Filipe, F. Tiziano, J. Melki, C. Hindelang, R. Matyas, P. Rustin, and M. Koenig Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits Nat. Genet. 27 2001 181 186
26. E. Becker, and D.R. Richardson Frataxin: its role in iron metabolism and the pathogenesis of Friedreich's ataxia Int. J. Biochem. Cell Biol. 33 2001 1 10
27. M. Pandolfo Friedreich ataxia Semin. Pediatr. Neurol. 10 2003 163 172
28. E. Becker, J. Greer, P. Ponka, and D.R. Richardson Erythroid differentiation and protoporphyrin IX down-regulate frataxin expression in Friend cells: characterisation of frataxin expression compared to molecules involved in iron metabolism and hemoglobinisation Blood 99 2002 3813 3822
29. T. Yoon, and J.A. Cowan Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis J. Biol. Chem. 279 2004 25943 25946
30. G. Isaya, H.A. O'Neill, O. Gakh, S. Park, R. Mantcheva, and S.M. Mooney Functional studies of frataxin Acta Paediatr., Suppl. 93 2004 68 71
31. A. Wong, J. Yang, P. Cavadini, C. Gellera, B. Lonnerdal, F. Taroni, and G. Cortopassi The Friedreich's ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis Hum. Mol. Genet. 8 1999 425 430
32. J.L. Bradely, S. Homayoun, P.E. Hart, A.H. Shapira, and J.M. Cooper Role of oxidative damage in Friedreich's ataxia Neurochem. Res. 29 2004 561 567
33. P.V. Bernhardt, P. Chin, and D.R. Richardson Unprecedented oxidation of a biologically active aroylhydrazone chelator catalysed by iron(III): serendipitous identification of diacylhydrazone ligands with high iron chelation efficacy J. Biol. Inorg. Chem. 6 2001 801 809
34. C.M. Armstrong, P.V. Bernhardt, P. Chin, and D.R. Richardson Structural variations and formation constants of first row transition metal complexes of biologically active aroylhydrazones Eur. J. Inorg. Chem. 2003 1145 1156
35. G. Link, A. Pinson, and C. Hershko Heart cells in culture: a model of myocardial iron overload and chelation J. Lab. Clin. Med. 106 1985 147 153
36. C. Hershko, G. Link, M. Tzahor, J.P. Kaltwasser, P. Athias, A. Grynberg, and A. Pinson Anthracycline toxicity is potentiated by iron and inhibited by deferoxamine: studies in rat heart cells in culture J. Lab. Clin. Med. 122 1993 245 251
37. G. Link, R. Tirosh, A. Pinson, and C. Hershko Role of iron in the potentiation of anthracycline cardiotoxicity: identification of heart cell mitochondria as a major site of iron anthracycline interaction J. Lab. Clin. Med. 127 1996 272 278
38. A. Terman, and U.T. Brunk On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes Mech. Ageing Dev. 100 1998 145 156
39. E.J. Goncharova, Z. Kam, and B. Geiger The involvement of adherens juction components in myofibrillogenesis in cultured cardiac myocytes Development 114 1992 173 183
40. J.C. Kwok, and D.R. Richardson Anthracyclines induce accumulation of ferritin iron in normal and neoplastic cells: inhibition of the ferritin Fe mobilization pathway Mol. Pharmacol. 63 2003 849 861
41. D.R. Richardson, and E. Baker The uptake of iron and transferrin by the human malignant melanoma cell Biochim. Biophys. Acta 1053 1990 1 12
42. D.R. Richardson, and E. Baker Two mechanisms of iron uptake from transferrin by melanoma cells. The effect of desferrioxamine and ferric ammonium citrate J. Biol. Chem. 267 1992 13972 13979
43. D.R. Richardson, and K. Milnes The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents: II. The mechanism of action of ligands derived from salicylaldehyde benzoyl hydrazone and 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone Blood 89 1997 3025 3038
44. J.B. Porter, J. Morgan, K.P. Hoyes, L.C. Burke, E.R. Huehns, and R.C. Hider Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice Blood 76 1990 2389 2396
45. D.R. Richardson, P. Ponka, and D. Vyoral Distribution of iron in reticulocytes after inhibition of heme synthesis with succinylacetone: examination of the intermediates involved in iron metabolism Blood 87 1996 3477 3488
46. D.R. Richardson, E.H. Tran, and P. Ponka The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective anti-proliferative agents Blood 86 1995 4295 4306
47. G. Darnell, and D.R. Richardson The potential of analogues of the pyridoxal isonicotinoyl hydrazone class as effective anti-proliferative agents III: the effect of the ligands on molecular targets involved in proliferation Blood 94 1999 781 792
48. C.H. Campbell, D. Crocker, J.J. Cruntmeir, M. Head, T. Kelly, M.I. Langfur, and A.H. Leimer Purification of a novel glycosylated ferritin from horse heart J. Cell. Biochem. 53 1993 420 432
49. S.C. Andrews, A. Treffry, and P.M. Harrison A new form of ferritin heterogeneity explained. Isolation and identification of a nineteen-amino-acid- residue fragment from siderosomal ferritin of rat liver Biochem. J. 245 1987 447 453
50. C. Hershko, A.M. Konijn, H.P. Nick, W. Breuer, Z.I. Cabantchik, and G. Link ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture Blood 97 2001 1115 1122
51. R. Galanello, A. Piga, D. Alberti, M.C. Rouan, H. Bigler, and R. Sechaud Safety tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia J. Clin. Pharmacol. 43 2003 565 572
52. M. Ferrali, D. Donati, S. Bambagioni, M. Fontani, G. Giorgi, and A. Pietrangelo 3-Hydroxy (4H)-benzopyran-4-ones as potential iron chelating agents in vivo Bioorg. Med. Chem. 9 2001 3041 3047
53. R.A. Yokel, A.M. Fredenburg, P.W. Durbin, J. Xu, M.K. Rayens, and K.N. Raymond The hexadentate hydroxypyridinonate TREN-(Me-3,2-HOPO) is a more orally active iron chelator than its bidentate analogue J. Pharm. Sci. 89 2000 545 555
54. P. Ponka, D. Richardson, E. Baker, H.M. Schulman, and J.T. Edward Effect of pyridoxal isonicotinoyl hydrazone (PIH) and other hydrazones on iron release from macrophages, reticulocytes and hepatocytes Biochim. Biophys. Acta 967 1988 122 129
55. D.R. Richardson, and P. Ponka Pyridoxal isonicotinoyl hydrazone and its analogs: potential orally effective iron-chelating agents for the treatment of iron overload disease J. Lab. Clin. Med. 131 1998 306 315
56. K. Blaha, M. Cikrt, J. Nerudova, and P. Ponka Biliary iron excretion in rats following treatment with analogs of pyridoxal isonicotinoyl hydrazone Blood 91 1998 4368 4372
57. C. Hershko, S. Avramovici-Grisaru, G. Link, L. Gelfand, and S. Sarel Mechanism of in vivo iron chelation by pyridoxal isonicotinoyl hydrazone and other imino derivatives of pyridoxal J. Lab. Clin. Med. 98 1981 99 108
58. G. Link, P. Ponka, A.M. Konijn, W. Breuer, Z.I. Cabantchik, and C. Hershko Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells Blood 101 2003 4172 4179
59. D.R. Richardson, and P. Ponka The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells Biochim. Biophys. Acta 1331 1997 1 40
60. T.B. Chaston, and D.R. Richardson Iron chelators for the treatment of iron overload disease: the relationship between structure, redox activity and toxicity Am. J. Hematol. 73 2003 200 210
61. T.G. St. Pierre, D.R. Richardson, E. Baker, and J. Webb A low-spin iron complex in human melanoma and rat hepatoma cells and a high-spin iron(II) complex in rat hepatoma cells Biochim. Biophys. Acta 1135 1992 154 158