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Combined chelation of bi-functional bis-hydroxypiridinone and mono-hydroxypiridinone: synthesis, solution and in vivo evaluation
- Source :
- Journal of inorganic biochemistry. 103(2)
- Publication Year :
- 2008
-
Abstract
- 3-Hydroxy-4-pyridinones (3,4-HP) are well known iron-chelators with applications in medicinal chemistry, mainly associated with their high affinity towards trivalent hard metal ions (e.g. M(3+), M=Fe, Al, Ga) and use as decorporating agents in situations of metal accumulation. The polydenticity and the extra-functionality of 3,4-HP derivatives have been explored, aimed at improving the chelating efficacy and the selectivity of the interaction with specific biological receptors. However, the ideal conjugation of both features in one molecular unity usually leads to high molecular weight compounds which can have crossing-membrane limitations. Herein, a different approach is used combining a arylpiperazine-containing bis-hydroxypyridone (H(2)L(1)) with a biomimetic mono-hydroxypyridinone, ornithine-derivative (HL(2)), to assess the potential coadjuvating effect that could result from the administration of both compounds for the decorporation of hard metal ions. This work reports the results of solution and in vivo studies on their chelating efficacy either as a simple binary or a ternary system (H(2)L(1):HL(2):M(3+)), using potentiometric and spectrophotometric methods. The solution complexation studies with Fe(III) indicate that the solubility of the complexes is considerably increased in the ternary system, an important feature for the metal complex excretion, upon the metal sequestration. The results of the in vivo studies with (67)Ga-injected mice show differences on the biodistribution profiles of the radiotracer, upon the administration of each chelating agent, that are mainly ascribed to the differences of their extra-functional groups and lipo/hydrophilic character. However, administration of both chelating agents leads to a more steady metal mobilization, which may be attributed to an improved access to different cellular compartments.
- Subjects :
- Biodistribution
Pyridones
Iron
Inorganic chemistry
Potentiometric titration
Glycine
Iron Chelating Agents
Ligands
Biochemistry
Inorganic Chemistry
Metal
Galium
Mice
Természettudományok
Animals
Chelation
Tissue Distribution
Solubility
Kémiai tudományok
Ternary complex
Ternary numeral system
Hard metal
Chemistry
Combinatorial chemistry
visual_art
visual_art.visual_art_medium
Female
Aluminum
Subjects
Details
- ISSN :
- 18733344
- Volume :
- 103
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of inorganic biochemistry
- Accession number :
- edsair.doi.dedup.....cac6550629a7b2bebcf9f9e4382ac197