Repozytorium

Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one.

Streszczenie

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the
evaluation of its coordination ability towards Fe3+, studied by a combination of chemical, computational,
and animal approaches. The use of complementary analytical techniques has allowed us to give evidence
of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating
ability of P1 towards Fe3+. The pFe3+ value 22.0 of P1-iron complexes is noticeably higher than that of
deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases.
This is due on one side to the tautomeric change to the catechol form, and on the other to the lower
protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the
efficacy of P1. Furthermore the coordinating ability toward Al3+, Cu2+ and Zn2+ has been studied to evaluate
the possible use of P1 against a second toxic metal ion (Al3+), and to envisage its potential influence
on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not
higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron
chelator.

Licencja otwartego dostępu

CC-BY-NC

Licencja ta pozwala na kopiowanie, zmienianie, remiksowanie, rozprowadzanie, przedstawienie i wykonywanie utworu jedynie w celach niekomercyjnych. Warunek ten nie obejmuje jednak utworów zależnych (mogą zostać objęte inną licencją).

Pełny tekst licencji: https://creativecommons.org/licenses/by-nc/4.0/legalcode

Adres publiczny

http://dx.doi.org/10.1039/c6dt00129g

Strona internetowa wydawcy

https://www.rsc.org/

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