Design, synthesis, and physicochemical and biological characterization of a new iron chelator of the family of hydroxychromenes.
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.
Ferrali
Marco
M
Department of Physiopathology and Experimental Medicine, University of Siena, via Aldo Moro, I-53100 Siena, Italy. ferrali@unisi.it
Bambagioni
Sabrina
S
Ceccanti
Antonio
A
Donati
Donato
D
Giorgi
Gianluca
G
Fontani
Marco
M
Laschi
Franco
F
Zanello
Piero
P
Casolaro
Mario
M
Pietrangelo
Antonello
A
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
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