Iron binding dendrimers: a novel approach for the treatment of haemochromatosis.
A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.
Zhou
Tao
T
Department of Pharmacy and Drug Control Centre, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Neubert
Hendrik
H
Liu
Ding Yong
DY
Liu
Zu Dong
ZD
Ma
Yong Min
YM
Kong
Xiao Le
XL
Luo
Wei
W
Mark
Sykes
S
Hider
Robert C
RC
D000818:Animals; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006432:Hemochromatosis / Q000188:drug therapy*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D050091:Dendrimers; D007502:Iron Chelating Agents; D011728:Pyridones; D007501:Iron