Pyrazolone-Based Zn(II) Complexes Display Antitumor Effects in Mutant p53-Carrying Cancer Cells

The synthesis and characterization of nine Schiff bases
of pyrazolone
ligands HLn (n = 1–9) and the corresponding zinc(II) complexes 1–9 of composition [Zn(Ln)2] (n = 1–9) are reported.
The molecular structures of complexes 2, 3, 4, 8, and 9 were determined
by single-crystal X-ray diffraction analysis, highlighting in all
cases a distorted tetrahedral geometry around the Zn(II) ion. Density
functional theory studies are performed on both the HLn ligands and the derived
complexes. A mechanism of dissociation and hydrolyzation of the coordinated
Schiff base ligands is suggested, confirmed experimentally by powder
X-ray diffraction study and photophysical studies. Complexes 1–9 were investigated in vitro as anticancer agents,
along with mutant p53 (mutp53) protein levels in human cancer cell
lines carrying R175H and R273H mutp53 proteins. Only those complexes
with the highest Zn(II) ion release via dissociation have shown a
significant cytotoxic activity with reduction of mutp53 protein levels.