4-Hydroxy-3,5-pyridinedicarboxylic Acids

Synthesis, Complexation Properties Towards Fe(III), Al(III), Cu(II), Zn(II), Human Serum Albumin, and Cellular Toxicity

Annalisa Dean, Maria Grazia Ferlin, Davide Carta, T. Jakusch, Tamas Kiss, Fernanda Fabiola Faccioli, Sofia Parrasia, Daniele Marton, Alfonso Venzo, Valerio B. Di Marco

Research output: Contribution to journalArticle

Abstract

4-hydroxy-3,5-pyridinedicarboxylic acid (DQ58) and 4-hydroxy-1-methyl-3,5-pyridinedicarboxylic acid (DQ71508) have been synthesized, and their Fe(III), Al(III), Cu(II), and Zn(II) coordination properties have been studied by potentiometry, UV–Vis spectroscopy (in the case of Fe(III), Al(III), Cu(II)), 1H-NMR (for Al(III)) and EPR (for Cu(II)). The thermodynamic results were used to model the extent of the toxic metal ions decorporation (Fe(III) or Al(III)) in the presence of the essential metal ions (Cu(II) or Zn(II)). DQ58 and DQ71508 were demonstrated to interact with human serum albumin (HSA), which is assumed to be the main serum transporter of the chelators, and binding constants have been obtained by ultrafiltration. IC50 values of 5.185 × 10−3 and 1.033 × 10−3 mol·L−1 were collected after 24 and 48 h of treatment with DQ71508 towards human embryonic kidney HEK-293 cells, demonstrating the relatively low cytotoxicity of this compound. According to these results, both DQ58 and DQ71508 seem to be potential candidates for Fe chelation therapy, and DQ58 is a better Fe(III) chelator than DQ71508.

Original languageEnglish
Pages (from-to)92-106
Number of pages15
JournalJournal of Solution Chemistry
Volume47
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Chelating Agents
Complexation
albumins
Serum Albumin
toxicity
serums
Metal ions
Toxicity
metal ions
Metals
Potentiometry
Ions
Chelation Therapy
potentiometric analysis
transporter
acids
chelation
HEK293 Cells
Poisons
Ultrafiltration

Keywords

  • Aluminium
  • Chelation therapy
  • Cytotoxicity
  • Hydroxypyridinedicarboxylic acids
  • Iron
  • Potentiometry

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Physical and Theoretical Chemistry

Cite this

4-Hydroxy-3,5-pyridinedicarboxylic Acids : Synthesis, Complexation Properties Towards Fe(III), Al(III), Cu(II), Zn(II), Human Serum Albumin, and Cellular Toxicity. / Dean, Annalisa; Ferlin, Maria Grazia; Carta, Davide; Jakusch, T.; Kiss, Tamas; Faccioli, Fernanda Fabiola; Parrasia, Sofia; Marton, Daniele; Venzo, Alfonso; Di Marco, Valerio B.

In: Journal of Solution Chemistry, Vol. 47, No. 1, 01.01.2018, p. 92-106.

Research output: Contribution to journalArticle

Dean, Annalisa ; Ferlin, Maria Grazia ; Carta, Davide ; Jakusch, T. ; Kiss, Tamas ; Faccioli, Fernanda Fabiola ; Parrasia, Sofia ; Marton, Daniele ; Venzo, Alfonso ; Di Marco, Valerio B. / 4-Hydroxy-3,5-pyridinedicarboxylic Acids : Synthesis, Complexation Properties Towards Fe(III), Al(III), Cu(II), Zn(II), Human Serum Albumin, and Cellular Toxicity. In: Journal of Solution Chemistry. 2018 ; Vol. 47, No. 1. pp. 92-106.
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AU - Carta, Davide

AU - Jakusch, T.

AU - Kiss, Tamas

AU - Faccioli, Fernanda Fabiola

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AU - Marton, Daniele

AU - Venzo, Alfonso

AU - Di Marco, Valerio B.

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AB - 4-hydroxy-3,5-pyridinedicarboxylic acid (DQ58) and 4-hydroxy-1-methyl-3,5-pyridinedicarboxylic acid (DQ71508) have been synthesized, and their Fe(III), Al(III), Cu(II), and Zn(II) coordination properties have been studied by potentiometry, UV–Vis spectroscopy (in the case of Fe(III), Al(III), Cu(II)), 1H-NMR (for Al(III)) and EPR (for Cu(II)). The thermodynamic results were used to model the extent of the toxic metal ions decorporation (Fe(III) or Al(III)) in the presence of the essential metal ions (Cu(II) or Zn(II)). DQ58 and DQ71508 were demonstrated to interact with human serum albumin (HSA), which is assumed to be the main serum transporter of the chelators, and binding constants have been obtained by ultrafiltration. IC50 values of 5.185 × 10−3 and 1.033 × 10−3 mol·L−1 were collected after 24 and 48 h of treatment with DQ71508 towards human embryonic kidney HEK-293 cells, demonstrating the relatively low cytotoxicity of this compound. According to these results, both DQ58 and DQ71508 seem to be potential candidates for Fe chelation therapy, and DQ58 is a better Fe(III) chelator than DQ71508.

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