Recent insights on the medicinal chemistry of sickle cell disease

Current Medicinal Chemistry

Volumn 18, Issue 15, 2011, Pages 2339-2358

  Dos Santos, J L ^a   Chin, C M ^a  

^a SÃO PAULO STATE UNIVERSITY UNESP   (Brazil)

Author keywords

Chelating agents; Drug discovery; Erythrocyte dehydratation; Fetal hemoglobin; Gardos channel; Hemoglobin inducers; Hemoglobin modifiers; Hydroxyurea; Nitric oxide; Phytomedicines; Sickle cell disease; Sickle cell treatment; Vasodilatation; Vasodilation

Indexed keywords

1 ALLYL 2 METHYL 3 HYDROXYPYRID 4 ONE; 4 PHENYLBUTYRIC ACID; 5 AZA 2' DEOXYCYTIDINE; ALPHA KETOHYDROXYPYRIDINE; AN 10; ANTHRAQUINONE; AZACITIDINE; BUTYRIC ACID DERIVATIVE; CHELATING AGENT; CYTARABINE; CYTOTOXIC AGENT; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; ERYTHROPOIETIN; GLUTAMIC ACID; HEMOGLOBIN BETA CHAIN; HEMOGLOBIN F; HISTONE DEACETYLASE INHIBITOR; HYDRAZONE DERIVATIVE; HYDROXYUREA; LENALIDOMIDE; NALIDIXIC ACID; PIVALOYLOXYMETHYL BUTYRATE; POMALIDOMIDE; RECOMBINANT ERYTHROPOIETIN; THALIDOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALINE; VALPROIC ACID;

AGRANULOCYTOSIS; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLERGIC REACTION; ARTHRALGIA; ARTHRITIS; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOIMMUNE DISEASE; BONE MARROW SUPPRESSION; CARCINOGENICITY; CELL SHAPE; CREATINE KINASE BLOOD LEVEL; CYTOSKELETON; DEOXYGENATION; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG ERUPTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; DRUG WITHDRAWAL; ERYTHROCYTE; EYE TOXICITY; GASTROINTESTINAL TOXICITY; GROWTH RETARDATION; HEARING IMPAIRMENT; HEART DISEASE; HEMATOLOGIC DISEASE; HUMAN; HYPERPIGMENTATION; INFLAMMATION; IRON OVERLOAD; LEUKOPENIA; LOW DRUG DOSE; MULTIPLE MYELOMA; NEUROTOXICITY; NEUTROPENIA; NONHUMAN; PATHOPHYSIOLOGY; POINT MUTATION; POLYMERIZATION; SICKLE CELL ANEMIA; SIDE EFFECT; SKIN INFECTION; SKIN MANIFESTATION; TERATOGENICITY; THROMBOCYTOPENIA; ULCER; VASODILATATION;

EID: 79957939291     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986711795656117     Document Type: Article

References (199)

1. Ingram, V.M. Abnormal human haemoglobins. III. The chemical difference between normal and sickle cell haemoglobins. Biochim. Biophys. Acta., 1959, 36, 402-411.
2. Pauling, L.; Itano, H.A.; Singer, S.J.; Wells, I.C. Sickle cell anemia: a molecular disease. Science, 1949, 110, 543-548.
3. Perutz, M.F.; Rossmann, M.G.; Cullis, A.F. Structure of haemoglobin: a three-dimensional Fourrier synthesis at 5-5A resolution obtained by X-ray analysis. Nature, 1960, 185, 416-422.
4. Weatherall, D. Red blood cell genes and malaria. Genetic Susc. Infec.Diseases., 2008, 107-119.
5. Piel, F.B.; Patil, A.P.; Howes, R.E.; Nyangiri, O.A.; Gething, P.W.; Williams, T.N.; Weatherall, D.J.; Hay, S.I. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat. Commun., 2010, 1(8), 104.
6. Nsiah, K.; Dzogbefia, V.P.; Ansong, D.; Boateng, H.; Ocloo, D.; Osei- Frempong, E.; KenaFrempong, N.; Osei Akoto A. The incidence of malaria and the comparasion of the hematological and biochemical indices of Plasmaodium falciparum-parasitemic and aparasitemic sickle cell disease (SCD). Int. J. Lab. Hematol., 2010, 32(6), 197-207.
7. Derebail, V.K.; Nachman, P.H.; Key, N.S.; Ansede, H.; Falk, R.J.; Kshirsagar, A.V. High Prevalence of Sickle Cell Trait in African Americans with ESRD. J. Am. Soc. Nephrol., 2010, 21, 413-417.
8. Ware, R.E. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood, 2010, 115(26), 5300-5311.
9. Adachi, K.; Kim, J.; Ballas, S.; Surrey, S.; Asakura, T. Facilitation of Hb S polymerization by the substitution of Glu for Gln at α121. J. Biol. Chem., 1988, 263(12), 5607-5610.
10. Safo, M.K.; Abdulmalik, O.; Danso-Danquat, R.; Burnett, J.C.; Nokuri, S.; Joshi, G.S.;Musayev, F.N.; Asakura, T.; Abraham, D.J. Structural basis for the potent antisickiling effects of a novel class of five membered heterocyclic aldehydic compounds. J. Med. Chem., 2004, 47, 4665-4676. (Pubitemid 39195557)
11. Shilpa, J.; Gladwin, M.T. Arginine metabolism and nitric oxide bioavaiability in sickle cell disease. J. Pedriat. Hematol. Oncol., 2010, 32(7), 247-248.
12. Fathallah, H.; Atweh, G.F. Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology, 2006, 2006(1), 58-62.
13. Matsui, N.M.; Borsig, L.; Rosen, S.D.; Yaghmai, M.; Varki, A.; Embury, S.H. P-selectin mediates the adhesion of sickle erythrocyte to the endothelium. Blood, 2001, 98, 1955-1962.
14. Platt, O.S.; Brambilla, D.J.; Rosse, W.F.; Milner, P.F.; Castro, O.; Steinberg, M.H.; Klugg, P.P. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N. Engl. J. Med., 1994, 330(23), 1639-1644.
15. Okpala, I. Leukocyte adhesion and the pathophysiology of sickle cell disease. Curr. Opin. Hematol., 2006, 13(1), 40-44.
16. Browne, P.V.; Mosher, D.F.; Steinberg, M.H.; Hebbel, R.P. Disturbance of plasma and platelet thrombospondin levels in sickle cell disease. Am. J. Hematol., 1996, 51, 296-301. (Pubitemid 26116369)
17. Perrine, R.P.; Pembrey, M.E.; John, P.; Perrine, S.; Shoup, F. Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects. Ann. Intern. Med., 1978, 88, 1-6. (Pubitemid 8265449)
18. Watson, J.; Stahman, A. W.; Billelo, F.P. The significance of the paucity of sickle cells in neighborn negro infants. Am. J. Med. Scie., 1948, 215, 419-423.
19. Dos Santos, J.L.; Lanaro, C.; Chin, C.M. Advances in Sickle Cell Disease Treatment: from Drug Discovery until the Patient Monitoring. Cardiovasc. Hematol. Agents Med. Chem., 2011, [Epub ahead of print]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21401492 . Acessed March 14, 2011.
20. Powars, D.R.; Weiss, J.N.; Chan, L.S.; Schroeder, W.A. Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood, 1984, 63, 921-926. (Pubitemid 14141316)
21. Saunthararajah, Y.; Lavelle, D.; DeSimone, J. DNA hypo-methylating agents and sickle cell disease. Br. J. Haematol., 2004, 126(5), 629-636. (Pubitemid 39221297)
22. DeSimone, J.; Heller, P.; Hall, L.; Zwiers, D. 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons. Proc. Natl. Acad. Sci. USA, 1982, 79, 4428-4431. (Pubitemid 12045807)
23. Dover, G.J.; Charache, S.H.; Boyer, S.H.; Talbot, C.C. Jr.; Smith, K.D. 5- Azacytidine increases fetal hemoglobin production in a patient with sickle cell disease. Prog. Clin. Biol. Res., 1983, 134, 475-488.
24. Ley, T.J.; DeSimone, J.; Noguchi, C.T.; Turner, P.H.; Schechter, A.N.; Heller, P.; Nienhuis, A.W. 5-Azacytidine increases gammaglobin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia. Blood, 1983, 62, 370-380. (Pubitemid 13036087)
25. Mabaera, R.; Greene, M.R.; Richardson, C.A.; Conine, S.J.; Kozul, C.D.; Lowrey, C.H. Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin. Blood, 2008, 111(1), 411-420.
26. Humphries, R. K.; Dover, G.; Young, N.S.; Moore, J.G.; Charache, S.; Ley, T.; Nienhuis, A.W. 5 - Azacytidine acts directly on both erythroid precursors and progenitors to increase production of fetal hemoglobin. J.Clin. Invest., 1985, 75(2), 547-557. (Pubitemid 15143495)
27. Carr, B.I.; Rahbar, S.; Asmeron, Y.; Riggs, A.; Winberg, C.D. Carcinogenicity and haemoglobin synthesis induction by cytidine analogues. Brit. J. Cancer, 1988, 57, 395-402.
28. DeSimone, J.; Heller, P.; Molokie, R.; Hall, L.; Zwiers, D. Tetrahydrouridine, cytidine analogues, and hemoglobin F. Am. J. Hematol., 1985, 9, 217-226.
29. DeSimone, J.; Koshy, M.; Dorn, L.; Lavelle, D.; Bressler, L.; Molokie, R.; Talischy, N. Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia. Blood, 2002, 99(11), 3905-3908. (Pubitemid 35332025)
30. Saunthararajah, Y.; Hillery, C.A.; Lavelle, D.; Molokie, R.; Dorn, L.; Bressler, L.; Gavazova, S.; Chen, Y.H.; Hoffman, R.; DeSimone, J. Effects of 5-aza-2-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood, 2003, 102, 3865-3870. (Pubitemid 37486964)
31. Laird, P.W.; Jackson-Grusby, L.; Fazeli, A.; Dickinson, S.L.; Jung, W.E.; Li, E.; Weinberg, R.A.; Jaenisch, R. Suppression of intestinal neoplasia by DNA hypomethylation. Cell, 1995, 81, 197-205.
32. Lantry, L.E.; Zhang, Z.; Crist, K.A.; Wang, Y.; Kelloff, G.J.; Lubet, R.A.; You, M. 5-Aza-2¢-deoxycytidine is chemopreventive in a 4-(methylnitrosamino)- 1- (3-pyridyl)-1-butanone-induced primary mouse lung tumor model. Carcinogenesis, 1999, 20, 343-346. (Pubitemid 29057571)
33. Collins, A.F.; Pearson, H.A.; Giardina, P.; McDonagh, K.T.; Brusilow, S.W.; Dover, G.J. Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. Blood, 1995, 85, 43-49.
34. Hines, P.; Dover, G.J.; Resar, L.M. Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia. Pediat. Blood Canc., 2008, 50, 357-359.
35. Resar, L.M.; Segal, J.B.; Fitzpatric, L.K.; Friedmann, A.; Brusilow, S.W.; Dover, G.J. Induction of fetal hemoglobin synthesis in children with sickle cell anemia on low-dose oral sodium phenylbutyrate therapy. J. Pediat. Hematol. Oncol., 2002, 24, 737-741. (Pubitemid 35448739)
36. Chung, M.C.; Ferreira, E.I.; Santos, J.L.; Giarolla, J.; Rando, D.G.; Almeida, A.E.; Bosquesi, P.L.; Menegon, R.F.; Blau, L. Prodrugs for the treatment of neglected diseases. Molecules, 2008, 13(3), 616-677.
37. Nudelman, A.; Gnizi, E.; Katz, Y.; Azulai, R.; Cohen-Ohana, M.; Zhuk, R.; Sampson, S.R.; Langzam, L.; Fibach, E.; Prus, E.; Pugach, V.; Rephaeli, A. Prodrugs of butyric acid. Novel derivatives possessing increased aqueous solubility and potential for treating cancer and blood diseases. Eur. J. Med. Chem. 2001, 36, 63-74. (Pubitemid 32174854)
38. Nudelman A.; Shaklai M.; Aviram A.; Rabizadeh E.; Zimra, Y.; Ruse M.; Rephaeli, A.J. Novel anticancer prodrug of butyric acid.2. J. Med. Chem., 1992, 35, 687-694.
39. Dover, G.J.; Brusilow, S.; Charache, S. Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate. Blood, 1994, 84, 339-343. (Pubitemid 24193840)
40. Kieslich, M.; Schwabe, D.; Cinatl, J. Jr.; Driever, P.H. Increase of fetal hemoglobin synthesis indicating differentiation induction in children receiving valproic acid. Pediatr. Hematol. Oncol., 2003, 20(1), 15-22. (Pubitemid 36033620)
41. Rönndahl, G.; Mönkemeyer, S.; Schulze, S.; Pekrun, A.; Eikel, D.; Nau, H.; Witt, O. Novel valproic acid derivatives with hemoglobin F inducing activity. Am. J. Hematol., 2006, 81(5), 374-6.
42. Trompeter, S.; Roberts, I. Haemoglobin H modulation in childhood sickle cell disease. Br. J. Haematol., 2008, 114, 308-316.
43. Al-Khatti, A.; Veith, R.W.; Papayannopoulou, T.; Fritsch, E.F.; Goldwasser, E.; Stamatoyannopoulos, G. Stimulation of fetal hemoglobin synthesis by erythropoietin in baboos. N. Engl. J. Med., 1987, 317, 415-420. (Pubitemid 17131178)
44. Little, J.A.; McGowan, V.R.; Kato, G.J.; Partovi, K.S.; Feld, J.J.; Maric, I., Martyr, S.; Taylor, J.G.; Machado, R.F.; Heller, T.; Castro, O.; Gladwin, M.T. Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience from the National Institute of Health and a literature review. Haematologica, 2006, 91, 1076-1083. (Pubitemid 44204773)
45. McBride, W. Thalidomide and congenital abnormalities. Lancet, 1961, 2, 368.
46. Eriksson, T.; Bjorkman, S.; Hoglund, P. Clinical pharmacology of thalidomide. Eur. J. Clin. Pharmacol., 2001, 57, 365-376. (Pubitemid 33787187)
47. Raza, A.; Meyer, P.; Dutt, D.; Zorat, F.; Lisak, L.; Nascimben, F.; du Randt, M.; Kaspar, C.; Goldberg, C.; Lowel, J.; Dar, S.; Gezer, S.; Venugopal, P.; Zeldis, J. Thalidomide produces transfusions independence in long-standing refractory anemias of patients with myelodysplastic syndrome. Blood, 2001, 98, 958-965.
48. Aerbajinai, W.; Zhu, J.; Gao, Z.; Chin, K.; Rodgers, G.P. Thalidomide induces gamma-globin gene expression through increased reactive oxygen species-mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis. Blood, 2007, 110(8), 2864-2871. (Pubitemid 350006939)
49. Hsiao, C.H.; Li, W.; Lou, T.F.; Baliga, B.S.; Pace, B.S. Fetal hemoglobin induction by histone deacetylase inhibitors involves generation of reactive oxygen species. Exp. Hematol., 2006, 34, 264-273.
50. Muller, G.W.; Chen, R.; Huang, S.Y.; Corral, L.G.; Wong, L.M.; Patterson, R.T.; Chen, Y.; Kaplan, G.; Stirling, D.I. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg. Med. Chem. Lett., 1999, 9, 1635-1630.
51. Moutouh-de-Parseval, L.A.; Verhelle, D.; Glezer, E.; Jensen-Pergakes, K.; Ferguson, G.D.; Corral, L.G.; Morris, C.L.; Muller, G.; Brady, H.; Chan, K. Pomalidomide and lenalidomide regulate erythopoiesis and fetal hemoglobin production in human CD34+ cells. J. Clin. Invest., 2008, 118(1), 248-258.
52. Meiler, S.E.; Wade, M.; Chen, Z.; Ramalingam, P.; Moutouhde Parseval, L.A.; Corral, L.G.; Kutlar, F.; Kutlar, A. Pomalidomide augments erythropoiesis and fetal hemoglobin production in a humanized mouse model of sickle cell disease. Blood (ASH Annual Meeting Abstracts), 2008, 112, 536.
53. Letvin, N.L.; Linch, D.C.; Beardsley, G.P.; McIntyre, K.W.; Nathan, D.G. Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. N. Engl. J. Med., 1984, 310, 869-873. (Pubitemid 14173178)
54. Charache, S.; Terrin, M.L.; Moore, R.D.; Dover, G.J.; Barton, F.B.; Eckert, S.V.; Macmahon, R.P.; Bonds, D.R. The investigators of the multicenter study of hydroxyurea in sickle cell anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N. Engl. J. Med., 1995, 332, 1313-1322.
55. Steinberg, M.H.; Barton, F.; Castro, O.; Pegelow, C.H.; Ballas, S.K.; Kutlar, A. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia. Risk and benefits up to 9 years of treatment. JAMA, 2003, 289, 1645-1651. (Pubitemid 37430269)
56. Steinberg, M.H.; Lu, Z.H.; Barton, F.B.; Terrin, M.L.; Charache, S.; Dover, G.J. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter study of hydroxyurea. Blood, 1997, 89, 1078-1088. (Pubitemid 27121303)
57. Stamatoyannopoulos, G. Control of globin gene expression during the development and erythroid differentiation. Exp. Hematol., 2005, 33, 259-271. (Pubitemid 40261307)
58. Cokic, V.P.; Smith, R.D.; Beleslin-Cokic, B.B.; Njoroge, J.M.; Miller, J.L.; Gladwin, M.T.; Schecheter, A.N. Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase. J. Clin. Invest., 2003, 111, 231-239. (Pubitemid 36105922)
59. Hillery, C.A.; Du, M.C.; Wang, W.C.; Scott, J.P. Hydroxyurea therapy decreases the in vivo adhesion of sickle erythrocytes to thrombospondin and laminin. Br. J. Haematol., 2000, 109, 322-327. (Pubitemid 30350711)
60. Lou, T.F.; Singh, M.; Mackie, A.; Li, W.; Pace, B.S. Hydroxyurea generates nitric oxide in human erythroid cells: mechanisms for gamma-globin gene activation. Exp. Biol. Med., 2009, 234(11), 1374-1382.
61. Conran, N.; Oresco-santos, C.; Acosta, H.C.; Fattori, A.; Saad, S.T.; Costa, F.F. Increased soluble guanylate cyclase activity in the red blood cells of sickle cell patients. Br. J. Haematol., 2004, 124, 547-554. (Pubitemid 38230601)
62. Huang, J.; Zou, Z.; Kim-Shapiro, D.B.; Ballas, S.K.; King, B. Hydroxyurea analogs as kinetic and mechanistic probes of nitric oxide producing reactions of hydroxyurea and oxyhemoglobin. J. Med. Chem., 2003, 46, 3748-3753. (Pubitemid 36988660)
63. Huang, J.; Kim-Shapiro, D.B.; King, S.B. Catalase-mediated nitric oxide formation from hydroxyurea. J. Med. Chem., 2004, 47, 3495-3501. (Pubitemid 38822011)
64. Nahavandi, M.; Perlin, E.; Kassim, O.O.; Wyche, M.O.; Castro, O.; Tavakkoli, F. Upregulation of TNF-α by hydroxyurea in patients with sickle cell anemia. Blood, 2000, 96(11), 14.
65. Fruchtman, S.M.; Mack, K.; Kaplan, M.E.; Peterson, P.; Berk, P.D.; Wasserman, L.R. From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in patients with polycythemia vera. Semin. Hematol., 1997, 34, 17-23. (Pubitemid 27063138)
66. Ferm, V.H. Severe development malformations: malformations induced by urethane and hydroxyurea in the hamster. Arch. Pathol., 1966, 81, 174-177.
67. DePass, L.R.; Weaver, E.V. Comparison of teratogenic effects of aspirin and hydroxyurea in the Fischer 344 and Wistar strains. J. Toxicol. Environ. Health., 1982, 10(2), 297-305.
68. Santos, J.L.; Varanda, E.A.; Lima, L.M.; Chung, M.C. Mutagenicity of new lead compounds to treat sickle cell disease symptoms in Salmonella/microsome assay. Int. J. Mol. Sci., 2010, 11, 779-788.
69. Aliyu Z.Y.; Tumblin, A.R.; Kato G.J. Current therapy of sickle cell disease. Haematologica, 2005, 90, 7-12.
70. Inati, A.; Khoriaty, E.; Musallam, K.M.; Taher, A.T. Iron chelation therapy for patients with sickle cell disease and iron overload. Am. J. Hematol., 2010, 85, 782-786.
71. Wanko, S.O.; Telen, M.J. Transfusion management in sickle cell disease. Hematol. Oncol. Clin. N. Am., 2005, 19, 803-826. (Pubitemid 41427111)
72. Navaid, M.; Melvin, T. A palliative care approach in treating patients with sickle cell disease using exchange transfusion. Am. J. Hosp. Palliat. Care, 2010, 27(3), 215-218.
73. Alhashimi, D.; Fedorowicz, Z.; Alhashimi, F.; Dastgiri, S. Blood.. transfusions for treating acute chest syndrome in people with sickle cell disease. Cochrane Database Syst. Rev., 2010, 20(1), CD007843.
74. Riddington, C.; Wang, W. Blood transfusion for preventing stroke in people with sickle cell disease. Cochrane Database Syst. Rev. 2002, 1, CD003146.
75. Telen, M.J. Principles and problems of transfusion in sickle cell disease. Sem. Hematol., 2001, 38(4), 315-323. (Pubitemid 32995600)
76. Adams, R.J.; McKie, V.C.; Hsu, L.; Files, B.; Vichinsky, E.; Pegelow, C.; Abboud, M.; Gallagher, D.; Kutlar, A.; Nichols, F.T.; Bonds, D.R.; Brambilla, D. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N. Engl. J. Med., 1998, 339, 5-11. (Pubitemid 28304491)
77. Koshy, M.; Burd, L.; Wallace, D.; Moawad, A.; Baron, J. Prophylactic redcell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study. N. Engl. J. Med., 1988, 319(22), 1447-1452.
78. Raghupathy, R.; Manwani, D.; Little, J.A. Iron overload in sickle cell disease. Adv. Hematol. 2010, 2010, 1-9.
79. Cappellini, M.D.; Piga, A. Current status in iron chelation in hemoglobinopathies. Curr. Mol. Med., 2008, 8(7), 663-674.
80. Maggio, A. Light and shadows in the iron chelation treatment of haematological diseases. Br. J. Haematol., 2007, 138(4), 407-421. (Pubitemid 47063024)
81. Dhungana, S.; White, P. S.; Crumbliss, A. L. Crystal Structure of Ferrioxamine B: A Comparative Analysis and Implications for Molecular Recognition. J. Biol. Inorg. Chem. 2001, 6, 810-818. (Pubitemid 33078035)
82. Codd, R. Traversing the Coordination Chemistry and Chemical Biology of Hydroxamic Acids. Coord. Chem. Rev. 2008, 252, 1387-1408
83. Liu, J.; Obando, D.; Schipanski, L.G.; Groebler, L.K.; Witting, P.K.; Kalinowski, D.S.; Richardson, D.R.; Codd, R. Conjugates of desferrioxamine B (DFOB) with derivatives of adamantine or with orally available chelators as potential agents for treating iron overload. J. Med. Chem., 2010, 53(3), 1370-1382.
84. Brittenham, G.M.; Griffith, P.M.; Nienhuis, A.W.; McLaren, C.E.; Young, N.S.; Tucker, E.E.; Allen, C.J.; Farrell, D.E.; Harris, J.W. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N. Engl. J. Med., 1994, 331, 567-573. (Pubitemid 24265698)
85. Ihnat, P.M.; Vennerstrom J.L.; Robinson, D.H. Synthesis and solution properties of deferoxamine amides. J. Pharm. Sci., 2000, 89(12), 1525-1536.
86. Rodgers, S.J.; Raymond, K.N. Ferric ion sequestering agents. 11. Synthesis and kinetics of iron removal from transferring of catechoyl derivative of desferrioxamine B. J. Med. Chem., 1983, 26(3), 439-442. (Pubitemid 13143324)
87. Ghosh, M.; Lambert, L.J.; Huber, P.W.; Miller, M.J. Synthesis, bioactivity, and DNA-cleaving ability of desferrioxamine B-nalidixic acid and anthraquinone carboxylic acid conjugates. Bioorg. Med. Chem. Lett., 1995, 5(20), 2337-2340.
88. Diarra, M.S.; Lavoie, M.C.; Jacques, M.; Darwish, I.; Dolence, E.K.; Dolence, J.A.; Ghosh, A.; Ghosh, M.; Miller, M.J.; Malouin, F. Species selectivity of new sidephore-drug conjugates that use specific iron uptake for entry into bacteria. Antimicrob. Agents Chemother., 1996, 40(11), 2610-2617. (Pubitemid 26367653)
89. Kontoghiorghes, G.J.; Evans, R.W. Site specificity of iron removal from transferring by alpha-ketohydroxypyridine chelators. FEBS Lett., Sep 9, 1985, 189(1), 141-4. (Pubitemid 15227722)
90. Olivieri, N.F.; Koren, G.; St Louis, P.; Freedman, M.H.; McClelland, R.A,; Templeton, D.M. Studies of the oral chelator 1,2-dimethyl-3-hydroxypyrid- 4-one in thalassemia patients. Semin. Hematol., 1990, 27(2), 101-104. (Pubitemid 20141854)
91. Shalev, O.; Repka, T.; Goldfarb, A.; Grinberg, L.; Abrahamov, A.; Olivieri, N.F.; Rachmilewitz, E.A.; Hebbel, R.P. Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red Blood.. cells both in vitro and in vivo. Blood, 1995, 86(5), 2008-2013.
92. Voskaridou, E.; Douskou, M.; Terpos, E.; Stamoulakatou, A.; Meletis, J.; Ourailidis, A.; Papassotiriou, I.; Loukopoulos, D. Deferiprone as na oral iron chelator in sickle cell disease. Ann. Hematol., 2005, 84(7), 434-440. (Pubitemid 40867919)
93. Cappellini, M. D.; Pattoneri, P. Oral Iron Chelators. Annu. Rev. Med. 2009, 60, 25-38.
94. Kontoghiorghes, G.J.; Goddard, J.G.; Bartlett, A.N.; Sheppard, L. Pharmacokinetic studies in humans with the oral iron chelator 1,2-dimethyl- 3-hydroxypyrid-4-one. Clin. Pharmacol. Ther., 1990, 48(3), 255-261. (Pubitemid 20323651)
95. Limenta, L.M.; Jirasomprasert, T.; Jittangprasert, P.; Wilairat, P.; Yamanont, P.; Chantharaksri, U.; Fucharoen, S.; Morales, NP. Pharmacokinetics of Deferiprone in Patients with α-Thalassaemia: Impact of Splenectomy and Iron Status. Clin. Pharmacokinet., 2011, 50(1), 41-50.
96. Hershko, C.; Konijn, A.M.; Link, G. Iron chelators for thalassaemia. Br. J. Haematol., 1998, 101(3), 399-406. (Pubitemid 28266928)
97. Kontoghioghes, G.J.; Eracleous, E.; Economides, C.; Kolnagou, A. Advances in iron overload therapies. prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and their combinations. Curr. Med. Chem., 2005, 12(23), 2663-2681. (Pubitemid 41601566)
98. Kontoghioghes, G.J.; Pattichis, K.; Neocleous, K.; Kolnagou, A. The design and development of deferiprone (L1) and other iron chelators for clinical use: targeting methods and application prospects. Curr. Med. Chem., 2004, 11(16), 2161-2183. (Pubitemid 38967737)
99. Kontoghiorghes, G. J.; Barr, J.; Nortey, P.; Sheppard, L. Selection of a new generation of orally active alpha-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload. Am. J. Hematol., 1993, 42(4), 340-9. (Pubitemid 23104804)
100. Kontoghiorghes, G.J.; Aldouri, M.A.; Sheppard, L.; Hoffbrand, A.V. 1,2- Dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet, 1987, 1(8545), 1294-1295. (Pubitemid 17072195)
101. Porter, JB. Deferasirox - current knowledge and future challenges. Ann N.Y. Acad. Sci., 2010, 1202, 87-93
102. Barton, J.C. Deferasirox Novartis. Curr. Opin. Investig. Drugs, 2005, 6(3), 327-335. (Pubitemid 40424742)
103. Nisbet-Brown, E.; Olivieri, N.F.; Giardina, P.J.; Grady, R.W.; Neufeld, E.J.; Séchaud, R.; Krebs-Brown, A.J.; Anderson, J.R.; Alberti, D.; Sizer, K.C.; Nathan, D.G. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, doseescalation trial. Lancet, 2003, 361(9369), 1597-1602. (Pubitemid 36578996)
104. Séchaud, R.; Dutreix, C.; Balez, S.; Pommier, F.; Dumortier, T.; Morisson, S.; Brun, E. Relative bioavailability of deferasirox tablets administered without dispersion and dispersed in various drinks. Int. J. Clin. Pharmacol. Ther., 2008, 46(2), 102-108. (Pubitemid 351233796)
105. Séchaud, R.; Robeva, A.; Belleli, R.; Balez, S. Absolute oral bioavaiability and disposition of deferasirox in healthy human subjects. J. Clin. Pharmacol., 2008, 48(8), 919-925. (Pubitemid 352009486)
106. Waldmeier, F.; Bruin, G.J.; Glaenzel, U.; Hazell, K.; Sechaud, R.; Warrington, S.; Porter, J.B. Pharmacokinetics, metabolism, and disposition of deferasirox in beta thalassemic patients with transfusion-dependent iron overload who are at pharmacokinetic steady state. Drug Metab. Dispos., 2010, 38(5), 808-816.
107. Liu, Z.D.; Hider, R.C. Design of clinically useful iron(III)-selective chelators. Med. Res. Rev., 2002, 22, 26-64. (Pubitemid 34023572)
108. Hider, R.C.; Zhou, T. The design of orally active iron chelators. Ann. N. Y. Acad. Sci., 2005, 1054, 141-154. (Pubitemid 43031019)
109. Nick, H.; Acklin, P.; Lattmann, R.; Buehlmayer, P.; Hauffe, S.; Schupp, J.; Alberti, D. Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr. Med. Chem., 2003, 10(12), 1065-1076. (Pubitemid 36582249)
110. Kalinowski, D. S.; Sharpe, P. C.; Bernhardt, P. V.; Richardson, D. R. Structure-Activity Relationships of Novel Iron Chelators for the Treatment of Iron Overload Disease: The Methyl Pyrazinylketone IsonicotinoylHydrazone Series. J. Med. Chem., 2008, 51, 331-344.
111. Richardson, D. R.; Kalinowski, D. S.; Richardson, V.; Sharpe, P. C.; Lovejoy,D. B.; Islam,M.; Bernhardt, P. V. 2-Acetylpyridine Thiosemicarbazones are Potent Iron Chelators and Antiproliferatuve Agents: Redox Activity, Iron Complexation and Characterization of their Antitumor Activity. J. Med. Chem. 2009, 52, 1459-1470.
112. Turcot, I.; Stintzi,A.; Xu, J.;Raymond, K.N. Fast Biological Iron Chelators: Kinetics of Iron Removal from Human Diferric Transferrin by Multidentate Hydroxypyridonate. J. Biol. Inorg. Chem., 2000, 5, 634-641.
113. Durpès, M.C.; Nebor, D.; DuMesnil, P.C.; Mougenel, D.; Decastel, M.; Elion, J.; Hardy-Dessources, M.D. Effect of interleukin-8 and RANTES on the Gardos channel activity in sickle human red blood cells: role of the Duffy antigen receptor for chemokines. Blood. Cells Mol. Dis., 2010, 44(4), 219-223.
114. Flatman, P.W. Regulation of Na-K-2Cl cotransport in red cells. Adv. Exp. Med. Biol. 2004, 559, 77-88.
115. De Franceschi, L.; Bachir, D.; Galacteros, F.; Tchernia, G.; Cynober, T.; Neuberg, D.; Beuzard, Y.; Brugnara, C. Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease. Br. J. Haematol., 2000, 108(2), 284-289. (Pubitemid 30143642)
116. Steinberg, M.H. Pathophysiologically based drug treatment of sickle cell disease. Trends Pharmacol. Sci., 2006, 4, 204-210.
117. Hankins, J.S.; Wynn, L.W.; Brugnara, C.; Hillery, C.A.; Li, C.S.; Wang, W.C. Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia. Br. J. Haematol., 2008, 140(1), 80-85. (Pubitemid 350233253)
118. Gardos, G. The function of calcium in the potassium permeability of human erythrocytes. Biochim. Biophys. Acta, 1958, 30, 653-654.
119. Cao, Y.J.; Houamed, K.M. Activation of recombinant human SK4 channels by metal cations. FEBS Lett., 1999, 446, 137-141. (Pubitemid 29127265)
120. Maher, A.D.; Kuchel, P.W. The Gardós channel: a review of the Ca+2 - activated K+ channel in human erythrocytes. Int. J. Biochem. Cell Biol. 2003, 35, 1182-1197. (Pubitemid 36577309)
121. Rivera, A.; Jarolim, P.; Brugnara, C. Modulation of Gardos channel activity by cytokines in sickle erythrocytes. Blood, 2002, 99(1), 357-603.
122. Benjamin, L.J.; Kokkini, G.; Peterson, C.M. Cetiedil: its potential usefulness in sickle cell disease. Blood, 1980, 55(2), 265-70. (Pubitemid 10161201)
123. Asakura, T.; Ohnishi, S.T.; Adachi, K.; Ozguc, M.; Hashimoto, K.; Singer, M.; Russell, M.O.; Schwartz, E. Effect of cetiedil on erythrocyte sickling: new type of antisickling agent that may affect erythrocyte membranes. Proc. Natl. Acad. Sci., 1980, 77(5), 2955-2959. (Pubitemid 10049856)
124. Berkowitz, L.R.; Orringer, E.P. Effect of cetiedil, an in vitro antisickling agent, on erythrocyte membrane cation permeability. J. Clin. Invest., 1981, 68(5), 1215-1220. (Pubitemid 12235022)
125. Abu-Salah K. M.; Gambo A. H. An analysis of the mechanism by which cetiedil inhibits sickling. Life Sci., 2002, 70(9), 1003-1011. (Pubitemid 34085092)
126. Benjamin, L.J.; Berkowitz, L.R.; Orringer, E.P.; Mankad, V.N.; Prasad, A.S.; Lewkow, L.M.; Chillar, R.K. and Peterson, C.M. A collaborative, doubleblind randomized study of cetiedil citrate in sickle cell crises. Blood, 1986, 67, 1442-1447. (Pubitemid 16080617)
127. Lewis, G.P.; Cho, Y.W. Tolerance of healthy adult males in intravenous infusion of cetiedil, a vasoerythroactive drug. J. Clin. Pharmacol., 1982, 22(5-6), 243-249. (Pubitemid 12081302)
128. Roxburgh, C.J.; Ganellin, C.R.; Athmani, S.; Bisi, A.; Quaglia, W.; Benton, D.C.; Shiner, M.A.; Malik-Hall, M.; Haylett, D.G.; Jenkinson, D.H. Synthesis and structure-activity relationships of cetiedil analogues as blockers of the Ca(2+)-activated K+ permeability of erythrocytes. J. Med. Chem., 2001, 44(20), 3244-3253. (Pubitemid 32917104)
129. Ellory, J.C.; Nash, G.B.; Stone, P.C.; Culliford, S.J.; Horwitz, E.; Stuart, J. Mode of action and comparative efficacy of pharmacological agents that inhibit calcium-dependent dehydration of sickle cells. Br. J. Pharmacol., 1992, 106(4), 972-977.
130. Koçak, R.; Balamili, F.; Güvenç, B.; Tamer, L.; Aikimbaev, K.S.; Isbir, T. Bencyclane as an anti-sickling agent. Br. J. Haematol., 1996, 92(2), 329-331. (Pubitemid 26042928)
131. Reilly, M.P.; Asakura, T. Antisickling effect of bepridil. Lancet, 1986, 1(8485), 848. (Pubitemid 16128960)
132. Johnston, M.N.; Ellory, J.C.; Stuart, J. Bepridil protects sickle cells against the adverse rheological effects of cyclical deoxygenation. Br. J. Haematol., 1989, 73(4), 522-526. (Pubitemid 20014894)
133. Brugnara, C.; De Franceschi, L. and Alper, S.L. C21-activated K1 transport of human and rabbit erythrocytes: comparison of binding and transport inhibition by scorpion toxins. J. Biol. Chem, 1993, 268, 8760-8768. (Pubitemid 23118664)
134. Brugnara, C.; De Franceschi, L.; Alper, S.L. Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. J. Clin. Invest., 1993, 92(1), 520-526. (Pubitemid 23209038)
135. De Franceschi, L.; Rouyer-Fessard, P.; Alper, S.L.; Jouault, H.; Brugnara, C.; Beuzard, Y. Combination therapy of erythropoietin, hydroxyurea, and clotrimazole in a beta thalassemic mouse: a model for human therapy. Blood, 1996, 87(3), 1188-1195. (Pubitemid 26043548)
136. De Franceschi, L.; Sadane, N.; Trudel, M.; Alper, S.L.; Brugnara, C.; Beuzard, Y. Treatment with oral clotrimazole blocks Ca(2+)-activated K+ transport and reverses erythrocyte dehydration in transgenic SAD mice. A model for therapy of sickle cell disease. J. Clin. Invest. 1994, 93(4), 1670-1676.
137. Brugnara, C.; Armsby, C.C.; Sakamoto, M.; Rifai, N.; Alper, S.L.; Platt, O. Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity. J. Pharmacol. Exp. Ther., 1995, 273(1), 266-272.
138. Stocker, J. W.; De Franceschi, L.; McNaughton-Smith, G.A.; Corrocher, R.; Beuzard, Y.; Brugnara, C. ICA - 17043 , a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood, 2003, 101(6), 2412-2418. (Pubitemid 36302090)
139. Ataga, K.I.; Orringer, E.P.; Styles, L.; Vichinsky , E. P.; Swerdlow, P.; Davis, G.A.; Desimone, P.A.; Stocker, J.W. Dose-escalation study of ICA- 17043 in patients with sickle cell disease. Pharmacotherapy, 2006, 26(11), 1557-64. (Pubitemid 44704467)
140. Ataga, K.I.; Smith, W.R.; De Castro, L.M.; Swerdlow, P.; Saunthararajah, Y.; Castro, O.; Vichinsky, E.; Kutlar, A.; Orringer, E.P.; Rigdon, G.C.; Stocker, J.W.; ICA-17043-05 Investigators. Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood, 2008, 111(8), 3991-3997.
141. Ataga, K.I.; Stocker, J. Senicapoc (ICA-17043): a potential therapy for the prevention and treatment of hemolysis-associated complications in sickle cell anemia. Expert Opin. Investig. Drugs, 2009, 18(2), 231-239.
142. Ataga, K.I. Novel therapies in sickle cell disease. Hematology Am. Soc. Hematol. Educ. Program, 2009, 54-61.
143. McNaughton-Smith G.A.; Burns, J.F.; Stocker, J.W.; Rigdon, G.C.; Creech, C.; Arrington, S.; Shelton. T.; De Franceschi, L. Novel inhibitors of the Gardos channel for the treatment of sickle cell disease. J. Med. Chem., 2008, 51(4), 976-982. (Pubitemid 351304705)
144. Etzion, Z.; Tiffert, T.; Bookchin, R.M. and Lew, V.L. Effects of deoxygenation on active and passive Ca2 transport and on the cytoplasmic Ca2 levels of sickle cell anemia red cells. J. Clin. Invest., 1993, 92, 2489-2498. (Pubitemid 23333559)
145. Tiffert, T., Spivak, J.L.; Lew, V.L. Magnitude of calcium influx required to induce dehydration of normal human red cells. Biochim. Biophys. Acta., 1988, 943, 157-165.
146. Niehaus, W. G.; Wold, F. Crosslinking of erythrocyte membranes with dimethyl adipimidate. Biochim. Biophys. Acta., 1970, 196, 170-175.
147. Lubin, B.H.; Pena, V.; Mentzer, W.C.; Bymun, E.; Bradley, T.B.; Packer, L. Dimethyl Adipimidate: A New Antisickling Agent. Proc. Nat. Acad. Sci., 1975, 72(1), 43-46.
148. Gibson, J.S.; Stewart, G.W.; Ellory, J.C. Effect of dimethyl adipimidate on K+ transport and shape change in red Blood cells from sickle cell patients. FEBS Lett., 2000, 480, 179-183.
149. Bennekou, P.; Pedersen, O.; Moller, A.; Christophersen, P. Volume control in sickle cells is facilitated by the novel anion conductance inhibitor NS1652. Blood, 2000, 95(5), 1842-1848. (Pubitemid 30120851)
150. Bennekou, P.; De Franceschi, L.; Pedersen, O.; Lian, L.; Asakura, T.; Evans, G.; Brugnara, C.; Christophersen, P. Treatment with NS3623, a novel Clconductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease. Blood, 2001, 97(5), 1451-1457. (Pubitemid 32183772)
151. Joiner, C.H.; Jiang, M.; Claussen, W.J.; Roszell, N.J.; Yasin, Z.;
152. Harrington, D.J.; Adachi, K.; Royer, W.E.J. The high-resolution crystal structure of deoxyhemoglobin S. J. Mol. Biol., 1997, 272, 398-407.
153. Benjamin, L.J. Membrane modifiers in sickle cell disease. Ann. N. Y. Acad. Sci., 1989, 565, 247-261. (Pubitemid 19227155)
154. Waterman, M.R.; Yamaoka, K.; Dahm, L.; Taylor, J.; Cottam, G.L. Noncovalent modification of deoxyhemoglobin S solubility and erythrocyte sickling. Proc. Natl. Acad. Sci., 1974, 71(6), 2222-2225.
155. Chang, H.; Ewert, S.M.; Bookchin, R.M.; Nagel, R.L. Comparative evaluation of fifteen anti-sickling agents. Blood, 1983, 61, 693-704. (Pubitemid 13115369)
156. Ueno, H.; Bai, Y.; Manning, J.M. Covalent chemical modifiers of sickle cell hemoglobin. Ann. N. Y. Acad. Sci., 1989, 565, 239-246. (Pubitemid 19227154)
157. Mehanna, A.S.; Abraham, D.J. Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers. Biochemistry, 1990, 29(16), 3944-3952. (Pubitemid 20151309)
158. Randad, R.S.; Mahran, M.A.; Mehanna, A.S.; Abraham DJ. Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing and strucutureallosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents., J. Med. Chem., 1991, 34(2), 752-757.
159. Wireko, F.C.; Kellogg, G.E.; Abraham, D.J. Allosteric modifiers of hemoglobin. 2. Crystallographically determined binding sites and hydrophobic binding/interaction analysis of novel hemoglobin oxygen effectors. J. Med. Chem., 1991, 34(2), 758-767.
160. Abraham, D. J.; Joshi, G. S.; Randad, R. S.; Panikker, J. Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored Blood.. U.S. Patent 5,731,454, Mar 24, 1990.
161. Abraham, D. J.; Mehanna, A. S.; Mahran, M. A.; Randad, R. S. Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored Blood.. U.S. Patent 5,094,695, Feb 12, 1990.
162. Phelps Grella, M.; Danso-Danquah, R.; Safo, M.K.; Joshi, G.S.; Kister, J.; Marden, M.; Hoffman, S.J.; Abraham, D.J. Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin. J. Med. Chem., 2000, 43(25), 4726-4737. (Pubitemid 32002684)
163. Youssef, A.M.; Safo, M.K.; Danso-Danquah, R.; Joshi, G.S.; Kister, J.; Marden, M.C.; Abraham, D.J. Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin. J. Med. Chem., 2002, 45(6), 1184-1195. (Pubitemid 34263555)
164. Park, S.; Hayes, B.L.; Marankan, F.; Mulhearn, D.C.; Wanna, L.; Mesecar, A.D.; Santarsiero, B.D.; Johnson, M.E.; Venton, D.L. Regioselective covalent modification of hemoglobin in search of antisickling agents. J. Med. Chem., 2003, 46(6), 936-953. (Pubitemid 36423141)
165. Zaugg, R.H.; Walder, J.A.; Klotz, I.M. Schiff base adducts of hemoglobin. Modifications that inhibit erythrocyte sickling. J. Biol. Chem., 1977, 252, 8542-8548. (Pubitemid 8243734)
166. Beddell, C.R.; Goodford, P.J.; Kneen, G.; White, R.D.; Wilkinson, S.; Wootton, R. Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes. Brit. J. Pharmacol., 1984, 82, 397-407. (Pubitemid 14117019)
167. Keidan, A.J.; Franklin, I.M.; White, R.D.; Joy, M.; Huehns, E.R.; Stuart, J. Effect of BW12C on oxygen affinity of haemoglobin in sickle-cell disease. Lancet, 1986, 1, 831-834.
168. Abraham, D.J.; Mehanna, A.S.; Wireko, F.C.; Whitney, J.; Thomas, R.P.; Orringer, E.P. Vanillin, a potential agent for the treatment of sickle cell anemia. Blood, 1991, 77, 1334-1341.
169. Zhang, C.; Li, X.; Lian, L.; Chen, Q.; Abdulmalik, O.; Vassilev, V.; Lai, C.S.; Asakura, T.; Antisickling effect of MX-1520, a prodrug of vanillin: an in vivo study using rodents. Br. J. Haematol. 2004, 125, 788-795. (Pubitemid 38813606)
170. Nnamani, I.N.; Joshi, G.S.; Danso-Danquah, R.; Abdulmalik, O.; Asakura, T.; Abraham, D.J.; Safo, M.K. Pyridyl derivatives of benzaldehyde as potential antisickling agents. Chem. Biod., 2008, 5(2008), 1762-1769.
171. Reiter, C.D.; Wang, X.; Tanus-Santos, J.E.; Hogg, N.; Cannon III, R.O.; Schwchter, A.N.; Gladwin, M.T. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat. Med., 2002, 8, 1383-1389. (Pubitemid 36019423)
172. Canalli, A.A.; Franco-Penteado, C.F.; Saad, S.T.; Conran, N.; Costa, F.F. Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation. Haematologica, 2008, 93, 605-609. (Pubitemid 351536391)
173. Mack, A.K.; Kato, G.J. Sickle cell disease and nitric oxide: a paradigm shift? Int. J. Biochem. Cell Biol., 2006, 38, 1237-1243.
174. Atz, A.M.; Wessel, D.L. Inhaled nitric oxide in sickle cell disease with acute chest syndrome. Anesthesiology, 1997, 87, 988-990. (Pubitemid 27456256)
175. Morris, C.R. Hemolysis-associated pulmonary hypertension in sickle cell disease: global disruption of the arginine-nitric oxide pathway. Curr. Hypert. Rev., 2007, 3, 223-230. (Pubitemid 47244072)
176. Hunter, C.J.; Dejam, A.; Blood, A.B.; Shields, H.; Kim-Shapiro, D.B; Machado, R.F. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat. Med., 2004, 10(10), 1122-1127. (Pubitemid 39424875)
177. Santos, J.L.; Chung, M.C.; Lima, L.M.; Costa, F.F.; Lanaro, C. Use of phthalimide and/or sulphonamide derivatives in the treatment of diseases which require reducing the TNF-alpha levels and an exogenous source of nitric oxide, phthalimide derivatives, sulphonamide derivatives, ans a method for obtaining a sulphonamide derivative. WO/2009/073940, Jun 18, 2009.
178. Santos, J.L. Design, synthesis and pharmacological evaluation of hybrid compounds that are potentially active in the treatment of sickle cell disease. Rev. Bras. Hematol. Hemoter., 2010, 32(4), 341-342.
179. Santos, J.L. Synthesis and pharmacological evaluation of drug candidates to treat sickle cell disease symptoms. PhD Thesis, School of Pharmaceutical Science - Sate University of São Paulo (UNESP): Araraquara, February, 2009.
180. Scatena, R.; Bottoni, P.; Pontoglio, A.; Giardina, B. Phamracological modulation of nitric oxide release: new pharmacological perspectives, potential benefits and risks. Curr. Med. Chem., 2010, 17, 61-73.
181. Morris, C.R.; Kuypers, F.A.; Larkin, S.; Vichinsky, E.P.; Styles, F.A. Patterns of arginine and nitric oxide in patients with sickle cell disease with vasoocclusive crisis and acute chest syndrome. .J Pediatr. Hematol. Oncol., 2000, 22, 515-520.
182. Morris, C.R.; Kuypers, F.A.; Larkin, S.; Sweeters, N.; Simnon, J.; Vichinsky, E.P.; Styles, L.A. Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease. Br. J. Haematol., 2000, 111, 498-500.
183. Romero, J.R.; Suzuka, S.M.; Nagel, R.L.; Fabry, M.E. Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood, 2002, 99, 1103-1108. (Pubitemid 34547059)
184. Dasgupta, T.; Hebbel, R.P.; Kaul, D.K. Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic. Biol. Med., 2006, 41, 1771-1780. (Pubitemid 44839141)
185. Styles, L.; Kuypers, F.A.; Kesler, K.; Reiss, U.; Lebeau, P.; Nagel, R.L.; Fabry, M.E. Arginine therapy does not benefit children with sickle cell anemia - results of the CSCC clinical trial consortium multi-institutional study. Blood (ASH Annual Meeting Abstracts), 2007, 110, Abstract 2252.
186. Villagra, J.; Shiva, S.; Hunter, L.A.; Machado, R.F.; Gladwin, M.T.; Kato, G.J. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension and nitric oxide scavenging by cell-gree hemoglobin. Blood, 2007, 110, 2166-2172. (Pubitemid 47443936)
187. Machado, R.F.; Martyr, S.; Kato, G.J.; Barst, R.J.; Anthi, A.; Robinson, M.R.; Hunter, L.; Coles, W.; Nichols, J.; Hunter, C.; Sachdev, V.; Castro, O.; Gladwin, M.T. Sildenafil therapy in patients with sickle cell disease and pulmonary hipertension. Br. J. Haematol., 2005, 130(3), 445-453. (Pubitemid 43899595)
188. Rosch, J.W.; Boyd, A.R.; Hinojosa, E.; Pestina, T.; Hu, Y.; Persons, D.A.; Orihuela, C.J.; Tuomanen, E.I. Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease. J. Clin. Invest., 2010, 120(2), 627-635.
189. Solovey, A.; Kollander, R.; Shet, A.; Milbauer, L.C.; Choong, S.; Panoskaltsis-Mortari, A.; Blazar, B.R.; Kelm Jr, R.J.; Hebbel, R.P. Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin. Blood, 2004, 104, 840-846. (Pubitemid 38970583)
190. Ekeke, G.I.; Shode, F.O. The reversion of sickle cells by Cajanus cajan. Planta Med., 1985, 51(6), 504-507. (Pubitemid 16176648)
191. Akojie, F.O.; Fung, L.W. Antisickling activity of hydroxybenzoic acid in Cajanus cajan. Planta Med., 1992, 58(4), 317-320.
192. Akinsulie, A.O.; Temiye, E.O.; Akanmu, A.S.; Lesi, F.E.; Whyte, C.O. Clinical evaluation of extract of Cajanus cajan (Ciklavit) in sickle cell anaemia. J. Trop. Pediatr., 2005, 51(4), 200-205. (Pubitemid 41444436)
193. Wambebe, C.; Khamofu, H.; Momoh, J.A.; Ekpeyong, M.; Audu, B.S.; Njoku, O.S.; Bamgboye, E.A.; Nasipuri, R.N.; Kunle, O.O.; Okogun, J.I.; Enwerem, M.N.; Audam, J.G.; Gamaniel, K.S.; Obodozie, O.O.; Samuel, B.; Fojule, G.; Ogunyale, O. Double-blind, placebo-controlled, randomised cross-over clinical trial of niprisan in patients with sickle cell disorder. Phytomedicine, 2001, 8(4), 252-261. (Pubitemid 32758340)
194. Iyamu, E.W.; Turner, E.A.; Asakura, T. Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. Br. J. Haematol., 2003, 122(6), 1001-1008. (Pubitemid 37174622)
195. Oniyangi, O.; Cohal, D.H. Phytomedicines (medicines derived from plants) for sickle cell disease. Cochrane Database Syst. Rev., 2010, 10, CD004448.
196. Adams-Graves, P.; Kedar A.; Koshy M.; Steinberg M.; Veith, R.; Ward, D.; Crawford, R.; Edwards, S.; Bustrack, J.; Emanuele, M. RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study. Blood, 1997, 90(5), 2041-2046. (Pubitemid 27377318)
197. Orringer, E.P.; Casella, J,F.; Ataga, K.I.; Koshy, M.; Adams-Graves, P.; Luchtman-Jones, L.; Wun, T.; Watanabe, M.; Shafer, F.; Kutlar, A.; Abboud, M.; Steinberg, M.; Adler, B.; Swerdlow, P.; Terregino, C.; Saccente, S.; Files, B.; Ballas, S.; Brown, R.; Wojtowicz-Praga, S.; Grindel, J.M. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial. JAMA. 2001, 286(17), 2099-2106. (Pubitemid 34041594)
198. Ballas, S.K.; Files, B.; Luchtman-Jones, L.; Benjamin, L.; Swerdlow, P.; Hilliard, L.; Coates, T.; Abboud, M.; Wojtowicz-Praga, S.; Grindel, J.M. Safety of purified poloxamer 188 in sickle cell disease: phase I study of a non-ionic surfactant in the management of acute chest syndrome. Hemoglobin, 2004, 28(2), 85-102. (Pubitemid 38669607)
199. Cheung, A.T.; Chan, M.S.; Ramanujam, S.; Rangaswami, A.; Curl, K.; Franklin, P.; Wun, T. Effects of poloxamer 188 treatment on sickle cell vasoocclusive crisis: computer-assisted intravital microscopy study. J. Investig. Med., 2004, 52(6), 402-406. (Pubitemid 39552610)