Iron Chelating Agents for Iron Overload Diseases

Abstract

Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical practice in the seventies of last century to defend thalassemic patients from the effects of iron overload and, in spite of all its limitations, it has dramatically changed both life expectancy and quality of life of patients. It has to be considered that the drugs in clinical use present some disadvantages too, this makes urgent new more suitable chelating agents. The requirements of an iron chelator have been better and better defined over the years and in this paper they will be discussed in detail. As a final point the most interesting ligands studied in the last years will be presented.

Klinik Olarak Faydalı Demir Bağlayıcı Ligandların Tasarım Özellikleri

“…Aksine, azalan redoks potansiyelleri ile nitelendirilen azot esaslı ligandlar kullanıldığında, koordine edilmiş demir daha fazla korunmaz ve enzimatik olarak indirgenebilir. Bu durumda demir yakalamak için kullanılan moleküller için istenmeyen bir özelliktir 8,12,10 .…”

“…Bu koşullara uymak için, demir şelatörlerin seçimi sınırlıdır ve çoğu hekzadentat ligandları, molekül ağırlığı 500 Da'dan fazla olduğu için bu durumdan hariç tutulur. Daha düşük molekül ağırlıkları nedeniyle iki dişli ve üç dişli ligandlar daha yüksek emilim için üstün adaylardır 8,10,17,18 .…”

Synthesis, characterization and electrochemistry studies of iron(III) complex with curcumin ligand

“…Iron chelation therapy involves the use of ligating drugs that avidly bind iron for the treatment of iron overload. These ligands promote the excretion and subsequent depletion of iron in biological systems . The goals of iron chelation therapy are to prevent iron concentration from reaching levels at which tissue damage occurs and to remove excess iron in the tissues, thereby reversing tissue/organ dysfunction .…”

“…DFP therapy may be associated with several adverse effects although the oral administration of DFP is associated with better patient compliance. Moreover, although DFP and DFX are highly useful in the treatment of iron overload, they present several disadvantages that implicate the urgent need of novel chelating agents …”

“…Experimentally screening large numbers of compounds to find promising candidates is a costly and time‐consuming process and is just the first step in bringing a new drug to market . The failure to find the ideal iron chelator can be ascribed to the inherent difficulties deriving from the biological and clinical restraints . Curcuminoids are natural compounds existing in turmeric, which is a popular spice.…”