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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Iron Chelators in Medicinal Applications - Chemical Equilibrium Considerations in Pharmaceutical Activity

Author(s): Thomas Manning, Greg Kean, Jessica Thomas, Khaleh Thomas, Michael Corbitt, Donna Gosnell, Ronald Ware, Sonya Fulp, Joey Jarrard and Dennis Phillips

Volume 16 , Issue 19 , 2009

Page: [2416 - 2429] Pages: 14

DOI: 10.2174/092986709788682128

Price: $65


Iron chelators are being examined as a potential class of pharmaceutical agents to battle different types of cancer as well as iron overload diseases. In recent studies, iron binding species such as desferrioxamine, triapine, tachpyridine, Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using published chemical equilibrium values (stability constants, equilibrium constants), it is argued that an iron chelator cannot competitively remove iron from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a cancerous cell to die. This type of reaction (DFO(aq) + [Fe , -Hb] → [Fe , -DFO] + Hb) has been proposed in a number of published studies using circumstantial evidence. It is argued that iron chelators can potentially interact with iron from ferritin or iron that has precipitated or flocculated as oxyhydroxide under physiological pHs. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca2+, Zn2+ or K+. A number of siderophores and natural products that have the ability to bind Fe /Fe as well as other cations are discussed in terms of their potential pharmaceutical activity as chelators. Chemical equilibria between cations and pharmaceutical agents, which are rarely quantitated in explaining medicinal mechanisms, are used to show that chelators can bind and remove iron and other cations from physiologically important systems required for cell survival and propagation.

Keywords: Chelator, iron, calcium, EDTA, mechanism, DFO, triapine, tachpyridine, PIH, cancer

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