title: Design, synthesis, and physicochemical and biological characterization of a new iron chelator of the family of hydroxychromenes.
abstract: Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalized from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, postischaemic reperfusion, xenobiotic intoxications, etc.). In the present work, we appropriately modified an iron chelator of the hydroxychromene family in order to obtain a tridentate chelator that would inactivate the iron redox cycle after its complexation, with a view to using this molecule in human therapy and/or in disease prevention. We synthesized such a chelator for the first time and show, by different physicochemical analysis, its tridentate nature and, importantly, its capacity to chelate iron with enough strength to inhibit both iron-dependent H(2)O(2) generation and lipid peroxidation in in vitro biological systems.
authors.affiliation: Department of Physiopathology and Experimental Medicine, University of Siena, via Aldo Moro, I-53100 Siena, Italy. ferrali@unisi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrali
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bambagioni
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceccanti
authors.forename: Donato
authors.initials: D
authors.lastname: Donati
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giorgi
authors.forename: Marco
authors.initials: M
authors.lastname: Fontani
authors.forename: Franco
authors.initials: F
authors.lastname: Laschi
authors.forename: Piero
authors.initials: P
authors.lastname: Zanello
authors.forename: Mario
authors.initials: M
authors.lastname: Casolaro
authors.forename: Antonello
authors.initials: A
authors.lastname: Pietrangelo
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism; D011199:Potentiometry; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C470209:3-hydroxy-2-(5-hydroxypentyl)chromen-4-one; D001578:Benzopyrans; D002867:Chromones; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D017392:Thiobarbituric Acid Reactive Substances; D006861:Hydrogen Peroxide