Ligands of the aroylhydrazone class have shown much promise as potential chelators for treatment of iron overload disease and perhaps cancer (Johnson et al., 1982; Baker et al., 1992; Richardson et al., 1995; Richardson & Milnes, 1997). Our previous investigations have demonstrated that 2-hydroxy-1naphthaldehyde isonicotinoyl hydrazone, (II), and several other aroylhydrazone chelators possess a...

Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and est...

Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities...

Inside the human body, reactive derivatives of oxygen, known as reactive oxygen species (ROS) such as the superoxide radical (O2•), hydroxyl radical (•OH) and hydrogen peroxide (H2O2), are constantly generated. The ROS easily cause oxidative damage to various biomolecules such as proteins, lipids and DNA leading to various disease conditions. Iron chelators function as antioxidants by scavengin...

Iron chelators of the hydroxamate class arrest in vitro proliferation of malaria parasites end of mammalian cells. The factors determining the biological activity of the chelators have classically been attributed to the chelators' capacity for binding iron and to their ability to traverse membranes as free chelators and as chelator-iron complexes. We show in this work that the nature of the che...

Chelating drugs and chelator metal complexes are used for the prevention, diagnosis and treatment of cancer. Cancer cells and normal cells require essential metal ions such as iron, copper and zinc for growth and proliferation. Chelators can target the metabolic pathways of cancer cells through the control of proteins involved in the regulation of these metals and also of other molecules involv...

Cancer is one of the leading causes of death worldwide and there is an increasing need for novel anti-tumor therapeutics with greater selectivity and potency. A new strategy in the treatment of cancer has focused on targeting an essential cell metabolite, iron (Fe). Iron is vital for cell growth and metabolism, forming a crucial component of the active site of ribonucleotide reductase (RR), the...

Red blood cells (RBCs) from patients with sickle cell anemia and thalassemia carry abnormal accumulations of molecular Fe(III) at the cytosol/membrane interface. The avidity of the red cell membrane for this iron has not been defined. Using open ghost membranes prepared from sickle RBC, we examined the ability of membrane-associated Fe(III) to resist removal by 15 chelators representing a 40-lo...

Labile iron in hemosiderotic plasma and tissue are sources of iron toxicity. We compared the iron chelators deferoxamine, deferiprone and deferasirox as scavengers of labile iron in plasma and cardiomyocytes at therapeutic concentrations. This comprised: chelation of labile plasma iron (LPI) in samples from thalassemia patients; extraction of total cellular iron; accessing labile iron accumulat...