4-Hydroxy-3,5-pyridinedicarboxylic Acids: Synthesis, Complexation Properties Towards Fe(III), Al(III), Cu(II), Zn(II), Human Serum Albumin, and Cellular Toxicity

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 9 10-3 and 1.033 9 10-3 molL-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.