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Klinik Olarak Faydalı Demir Bağlayıcı Ligandların Tasarım Özellikleri

Year 2017, Volume: 26 Issue: 3, 320 - 329, 30.09.2017
https://doi.org/10.17827/aktd.303588

Abstract

İnsan vücudunda belirli fizyolojik koşullar altında üretilen fazla miktardaki serbest demirin ortadan kaldırılması, terapistler için daima büyük problem oluşturmuştur. Çünkü insan vücudu aşırı demir yükünü gidermek için fizyolojik bir mekanizmaya sahip değildir. Bu nedenle, demir molekülüne bağlanabilecek özgül ligandların sentezlenmesi ve derecelendirilmesi önem arz etmektedir. Günümüzde çok sayıda demir bağlayıcı ligand olmasına rağmen klinik kullanım için ideal ligandlar halen araştırılmaktadır. İdeal bir demir bağlayıcı ligand belirlemek için de dikkatli tasarım gerekmektedir. Terapötik açıdan yararlı oral olarak aktif demir bağlayıcı ligandların tasarımı için gerekli olan kritik özellikler, bu tür ligandların tasarımına yönelik göz önüne alınması gereken faktörler ile birlikte bu derlemede sunulmuştur.

References

  • 1. Gupta KC, Sutar A. Catalytic actiivities of Schiff Base transition metal complexes, Coordination Chemistry Reviews. Coordination Chemistry Reviews, 2008; 252, 1420–1450.
  • 2. Olivieri NF, Brittenham GM. Iron chelating therapy and the treatment of thalassemia. Blood, 1997;89:739-61.
  • 3. Hershko C, Link GM, Konijn AM, Cabantchik ZI. Iron chelation therapy. Curr Hematol Rep., 2005; 4:110-116.
  • 4. Hamilton JL. Kizhakkedathu JN. Polymeric nanocarriers for the treatment of systemic iron overload. Mol Cell Ther. 2015; 24(3):2-15.
  • 5. Franz KJ. Clawing Back: Broadening The Notion Of Metal Chelators In Medicine. Current Opinion In Chemical Biology. 2013; 17: 143–149.
  • 6. Gürtunca S. Metal Şelatları. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 1968; 15(2): 271-278
  • 7. Gabutti V, Piga A. Results of long-term iron chelation therapy. Acta Haematol., 1996, 95: 26-36.
  • 8. Liu ZD, Hider RC. Design of clinically usefull iron (III)-selective chelators. Med.Res Rev. 2002;22:26-64.
  • 9. Hider R. Recent developments centered on orally active iron chelators. Thalassemia Reports 2014; 2261(4): 19-27.
  • 10. Crisponi G, Nurchi1 VM, Zoroddu MA. Iron Chelating Agents for Iron Overload Diseases. Thalassemia reports, 2014;4:2.
  • 11. Nurchi VM, Lachowicz JI, Crisponi G, Murgia S. Arca M, Pintus A et al. Kojic acid derivatives as powerful chelators for iron(III) and aluminium(III). Dalton Trans., 2011; 14;40(22):5984-98.
  • 12. Zhou T, Ma Y. Kong, Hider RC. Design of iron chelators with therapeutic application. Dalton Trans.2012; 41(21): 6371-6389
  • 13. Hider RC, Kong X. Chemistry and biology of siderophores. Nat Prod Rep.,2010; 27: 637-657.
  • 14. Raymond KN, Carrano CJ. Coordination chemistry and microbial iron transport. Acc Chem Res.,1979;12:183-90.
  • 15. Moridani MY, Tilbrook GS, Khodr HH, Hider RC. Synthesis and physicochemical assessment of novel 2-substituted 3-hydroxypyridin- 4-ones, novel iron chelators. Pharm Pharmacol., 2002;54:349-64.
  • 16. Cappellini M, Cohen A, Piga A. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood, 2006; 107 (9): 3455-3462.
  • 17. Hider RC, Liu ZD. Emerging understanding of the advantage of small molecules such as hydroxypyridinones in the treatment of iron overload. Curr Med Chem., 2003;10:1051-64.
  • 18. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev., 1997; 23(1-3): 3-25.

Design Features of Clinically Useful Iron-Binding Ligands

Year 2017, Volume: 26 Issue: 3, 320 - 329, 30.09.2017
https://doi.org/10.17827/aktd.303588

Abstract

Removal of excess of free iron, produced under certain physiological conditions in human body, has always been of great problem for therapists. The human body does not have any a physiological mechanism to eliminate iron overload resulting from transfusion. Therefore it is important to synthesize and grade specific ligands that can be attached to the iron molecule. Although there are a large number of iron-binding ligands today, the ideal iron-binding ligands for clinical use are still being searched.  In order to identify an ideal iron-binding ligands for clinical use, careful design consideration is essential.  The critical features necessary for the design of therapeutically useful orally active iron-binding ligands are presented in this review, together with factors to consider for  design of such iron-binding ligands.

References

  • 1. Gupta KC, Sutar A. Catalytic actiivities of Schiff Base transition metal complexes, Coordination Chemistry Reviews. Coordination Chemistry Reviews, 2008; 252, 1420–1450.
  • 2. Olivieri NF, Brittenham GM. Iron chelating therapy and the treatment of thalassemia. Blood, 1997;89:739-61.
  • 3. Hershko C, Link GM, Konijn AM, Cabantchik ZI. Iron chelation therapy. Curr Hematol Rep., 2005; 4:110-116.
  • 4. Hamilton JL. Kizhakkedathu JN. Polymeric nanocarriers for the treatment of systemic iron overload. Mol Cell Ther. 2015; 24(3):2-15.
  • 5. Franz KJ. Clawing Back: Broadening The Notion Of Metal Chelators In Medicine. Current Opinion In Chemical Biology. 2013; 17: 143–149.
  • 6. Gürtunca S. Metal Şelatları. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 1968; 15(2): 271-278
  • 7. Gabutti V, Piga A. Results of long-term iron chelation therapy. Acta Haematol., 1996, 95: 26-36.
  • 8. Liu ZD, Hider RC. Design of clinically usefull iron (III)-selective chelators. Med.Res Rev. 2002;22:26-64.
  • 9. Hider R. Recent developments centered on orally active iron chelators. Thalassemia Reports 2014; 2261(4): 19-27.
  • 10. Crisponi G, Nurchi1 VM, Zoroddu MA. Iron Chelating Agents for Iron Overload Diseases. Thalassemia reports, 2014;4:2.
  • 11. Nurchi VM, Lachowicz JI, Crisponi G, Murgia S. Arca M, Pintus A et al. Kojic acid derivatives as powerful chelators for iron(III) and aluminium(III). Dalton Trans., 2011; 14;40(22):5984-98.
  • 12. Zhou T, Ma Y. Kong, Hider RC. Design of iron chelators with therapeutic application. Dalton Trans.2012; 41(21): 6371-6389
  • 13. Hider RC, Kong X. Chemistry and biology of siderophores. Nat Prod Rep.,2010; 27: 637-657.
  • 14. Raymond KN, Carrano CJ. Coordination chemistry and microbial iron transport. Acc Chem Res.,1979;12:183-90.
  • 15. Moridani MY, Tilbrook GS, Khodr HH, Hider RC. Synthesis and physicochemical assessment of novel 2-substituted 3-hydroxypyridin- 4-ones, novel iron chelators. Pharm Pharmacol., 2002;54:349-64.
  • 16. Cappellini M, Cohen A, Piga A. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood, 2006; 107 (9): 3455-3462.
  • 17. Hider RC, Liu ZD. Emerging understanding of the advantage of small molecules such as hydroxypyridinones in the treatment of iron overload. Curr Med Chem., 2003;10:1051-64.
  • 18. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev., 1997; 23(1-3): 3-25.
There are 18 citations in total.

Details

Subjects Health Care Administration
Journal Section Review
Authors

Guluzar Özbolat

Abdullah Tuli This is me

Publication Date September 30, 2017
Acceptance Date March 4, 2017
Published in Issue Year 2017 Volume: 26 Issue: 3

Cite

AMA Özbolat G, Tuli A. Klinik Olarak Faydalı Demir Bağlayıcı Ligandların Tasarım Özellikleri. aktd. September 2017;26(3):320-329. doi:10.17827/aktd.303588