Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology

Abstract

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτó)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

“…1b) that is derived from the plants Mimosa and Leucaena genara endowed with a range of bioactivities including anti-cancer, anti-inflammatory, anti-viral, anti-fibrotic, etc. [26,27]. Previously, L-mimosine was shown to i) inhibit tyrosinase and thyroxine decarboxylases, ii) induce cell death and cell cycle growth arrest, iii) suppress elongation of DNA replication, iv) disrupt deoxyribonucleotide metabolism and v) inhibit the transcription of serine hydroxymethyltransferase [28][29][30][31][32][33][34][35][36][37][38][39].…”

Advances on Chelation and Chelator Metal Complexes in Medicine

“…Metal ions such as iron, copper and zinc are essential for life. Chelators (Chele, greek χειλή-claw of a crab) are organic molecules possessing specific ligands which have high affinity and can bind/carry metal ions and play very important roles in living systems e.g., haemoglobin, transferrin, phytochelators and microbial siderophores [1].…”

“…Similarly, many hundreds of thousands of patients are affected by iron overload due to regular red blood cell transfusions. Among the principal categories of patients with negative consequences from transfusional iron overload are chronic haematological and malignant diseases including thalassaemia, haematopoietic stem cell transplantation, sickle cell anaemia, aplastic anaemia and cancer [1]. There are also many cases of iron and copper overload as a result of increased gastrointestinal absorption, such as iron overload in idiopathic haemochromatosis or copper overload in Wilson's disease.…”

“…In general, the accumulation of excess metal ions including iron, copper, zinc and aluminium in any organ, as well as in cellular and sub-cellular compartments is a negative prognostic factor for many diseases [1].…”

Improving Decorporation Efficacy of DTPA and HOPO Using Chitosan/TPP Nanoparticles: Preparation, Characterization and Release Testing

“…The stability constants of metal-DTPA interaction are in the following order Fe > Cu >Al >Zn [85] . The stability constants are 28.6 and 21.5, respectively Fe(Ⅲ)-DTPA and Cu(Ⅱ)-DTPA.…”