DIBI, a 3-hydroxypyridin-4-one chelator iron-binding polymer with enhanced antimicrobial activity

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Protoporphyria induced by the orally active iron chelator 1,2-diethyl-3-hydroxypyridin-4-one in C57BL/10ScSn mice.

Administration in the drinking water of the orally-active iron chelator 1,2-diethyl-3-hydroxypyridin-4-one (CP94) to C57BL/10ScSn mice caused the development of hepatic protoporphyria. This was detected after 1 week and continued as long as the chelator was given (15 weeks). The more hydrophilic 1,2-dimethyl- and 1-hydroxyethyl,2-ethyl-analogues (CP20 and CP102) were also tested, but they were ...

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Evaluation of Liver Toxicity of 2-Methyl-3-Hydroxypyridin-4-one in Iron Overloaded Rats

      Hydroxypyridinone iron chelators are currently the main candidates for development of orally active iron chelating alternatives to desferrioxamine (DFO). In the present study, the relative efficacy and liver toxicity of a bidentate chelator, 2-methyl-3-hydroxypyridin-4-one (MHPO), was studied in iron overloaded rats and compared with those of DFO. For iron overloading, rats received i.p. ...

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Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice

Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising effective iron chelators for the treatment of iron overload in -thalassemia patients; nonetheless, their side effects have also been reported. 3-Hydroxypyridinone derivatives are being developed as a safer new chelator and in combined chelation therapy. We evaluated the iron-chelating activity of 1-(N-acetyl-6-aminohe...

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Amido-3-hydroxypyridin-4-ones as iron(III) ligands.

The synthesis and physicochemical properties of a range of 2- and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pK(a) values than 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pK(a) values of the 3-hydroxy group in 1-nonsubstituted pyridinones are dramatica...

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Synthesis of polymers containing 3-hydroxypyridin-4-one bidentate ligands for treatment of iron overload

Iron overload is a clinical problem which can be prevented by using iron chelating agents. An alternative method of relieving iron overload is to reduce iron absorption from the intestine by administering specific iron chelating agents, which can bind iron to form nonabsorbable complexes. Based on this strategy, a series of polymeric ligands containing the chelating moiety 3-hydroxypyridin-4-on...

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ژورنال

عنوان ژورنال: MedChemComm

سال: 2018

ISSN: 2040-2503,2040-2511

DOI: 10.1039/c8md00192h