Bifunctional 3-hydroxy-4-pyridinones as effective aluminium chelators: synthesis, solution equilibrium studies and in vivo evaluation.

Bifunctional 3-hydroxy-4-pyridinones as effective aluminium chelators: synthesis, solution equilibrium studies and in vivo evaluation.
J Inorg Biochem. 2018 May 30;186:116-129
Authors: Irto A, Cardiano P, Chand K, Cigala RM, Crea F, De Stefano C, Gano L, Sammartano S, Santos MA
Abstract
This paper reports the results on the study of a set of synthesized bifunctional 3-hydroxy-4-pyridinones chelators as potential aluminium sequestering agents. They were N-functionalized with alkyl-amino, -carboxylic and -(amino-carboxylic) groups, envisaging the improvement of the Al3+ sequestering capacity, in comparison with the marketed chelating drug deferiprone. The main focus of this work was given to the assessment of their binding ability towards Al3+, which was studied by potentiometric and UV-Vis spectrophotometric measurements carried out at T = 298.15 K. The speciation models were characterized by AlpLqHr(3p+r-qz) species with different stoichiometry. Depending on ligand side-chain structures and on their thermodynamic properties, different trends of stability was found. Furthermore, the sequestering ability of the ligands towards Al3+ was investigated by the calculation of pL0.5 values at different experimental conditions. These results clearly indicate that the presence of amino-carboxylic groups in the ligands increases the sequestering ability towards Al3+. The in silico evaluation of pharmacokinetic descriptors indicated no viol...

Source: Journal of Inorganic Biochemistry - May 30, 2018 Category: Biochemistry Authors: Irto A, Cardiano P, Chand K, Cigala RM, Crea F, De Stefano C, Gano L, Sammartano S, Santos MA Tags: J Inorg Biochem Source Type: research