Iron chelators as anti-neoplastic agents: current developments and promise of the PIH class of chelators.

  title={Iron chelators as anti-neoplastic agents: current developments and promise of the PIH class of chelators.},
  author={David B. Lovejoy and Des R. Richardson},
  journal={Current medicinal chemistry},
  volume={10 12},
The chelator currently used to treat iron (Fe) overload disease, desferrioxamine (DFO), has shown anti-proliferative activity against leukemia and neuroblastoma cells in vitro, in vivo and in clinical trials. Collectively, these studies suggest that Fe-deprivation may be a useful anti-cancer strategy. However, the efficacy of DFO is severely limited due to its poor ability to permeate cell membranes and bind intracellular Fe pools. These limitations have encouraged the development of other Fe… 

Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment.

Dp44mT is a novel, highly effective antitumor agent in vitro and in vivo that induces apoptosis and was the greatest yet observed for an Fe chelator.

Potent Antitumor Activity of Novel Iron Chelators Derived from Di-2-Pyridylketone Isonicotinoyl Hydrazone Involves Fenton-Derived Free Radical Generation

The results suggest that the antiproliferative effects of these chelators relates to intracellular iron chelation, followed by the stimulation of iron-mediated free radical generation via the so-formed iron complex.

The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer

This review focuses on the evolution of iron chelators from initial lead compounds through to the development of novel chelating agents, many of which show great potential to be clinically applied in the treatment of iron overload disease and cancer.

Competing pathways of iron chelation: Angiogenesis or anti‐tumor activity: Targeting different molecules to induce specific effects

It is suggested that CPX may not be suited toward the treatment of cancer in vivo but could possibly be used to increase angiogenesis for wound healing and several laboratories have developed novel Fe chelators that have high membrane permeability and marked anti-proliferative activity compared to DFO.

Anticancer activity of the antibiotic clioquinol.

Results show that clioquinol has anticancer effects both in vitro and in vivo, and indicates that Transition metal ionophores may be a subclass of metal chelators with anticancer activity deserving of further development.

Metal ionophores – An emerging class of anticancer drugs

A biologically based classification of metal‐binding compounds is provided that allows an experimental distinction between chelators and ionophores that can be readily used by biologists, which may lead to further study and classification ofMetal‐binding drugs.

Exploiting Cancer Metal Metabolism using Anti-Cancer Metal- Binding Agents.

The role and changes in homeostasis of metals in cancer is highlighted and the pre-clinical development and clinical assessment of metal ion-binding agents, namely, thiosemicarbazones, as antitumor agents are emphasized.

Tuning the antiproliferative activity of biologically active iron chelators: characterization of the coordination chemistry and biological efficacy of 2-acetylpyridine and 2-benzoylpyridine hydrazone ligands

Novel structure–activity relationships of aroylhydrazone chelators are described that will be useful in designing new ligands or fine-tuning the activity of others, including toxic Fenton-derived free radicals.

Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation.

Increased Ndrg1 expression following Fe chelation was related to the permeability and antiproliferative activity of chelators and could be reversed by Fe repletion, suggesting NDrg1 is a novel link between Fe metabolism and the control of proliferation.