title: Iron chelators in medicinal applications - chemical equilibrium considerations in pharmaceutical activity.
abstract: 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(2+,3+)-Hb] --> [Fe(2+,3+)-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 pH's. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca(2+), Zn(2+) or K(+). A number of siderophores and natural products that have the ability to bind Fe(3+)/Fe(2+) 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.
authors: Department of Chemistry, Valdosta State University, Valdosta, GA 31698, USA. tmanning@valdosta.edu
authors: Thomas
authors: T
authors: Manning
authors: Greg
authors: G
authors: Kean
authors: Jessica
authors: J
authors: Thomas
authors: Khaleh
authors: K
authors: Thomas
authors: Michael
authors: M
authors: Corbitt
authors: Donna
authors: D
authors: Gosnell
authors: Ronald
authors: R
authors: Ware
authors: Sonya
authors: S
authors: Fulp
authors: Joey
authors: J
authors: Jarrard
authors: Dennis
authors: D
authors: Phillips
mesh_terms: D000136:Acid-Base Equilibrium; D002412:Cations / Q000737:chemistry; D043844:Crown Ethers / Q000737:chemistry / Q000494:pharmacology; D003676:Deferoxamine / Q000737:chemistry / Q000494:pharmacology; D004492:Edetic Acid / Q000737:chemistry / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D004369:Pentetic Acid / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D017262:Siderophores / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002412:Cations; D043844:Crown Ethers; D007502:Iron Chelating Agents; D010455:Peptides; D017262:Siderophores; D004369:Pentetic Acid; D004492:Edetic Acid; D003676:Deferoxamine