Pyrazolone-Based\nZn(II) Complexes Display Antitumor\nEffects in Mutant p53-Carrying Cancer Cells

The synthesis and characterization of nine Schiff bases\nof pyrazolone\nligands <b>HL</b><sup><b><i>n</i></b></sup> (<i>n</i> = 1–9) and the corresponding zinc(II) complexes <b>1</b>–<b>9</b> of composition [Zn(L<sup><i>n</i></sup>)<sub>2</sub>] (<i>n</i> = 1–9) are reported.\nThe molecular structures of complexes <b>2</b>, <b>3</b>, <b>4</b>, <b>8</b>, and <b>9</b> were determined\nby single-crystal X-ray diffraction analysis, highlighting in all\ncases a distorted tetrahedral geometry around the Zn(II) ion. Density\nfunctional theory studies are performed on both the <b>HL</b><sup><b><i>n</i></b></sup> ligands and the derived\ncomplexes. A mechanism of dissociation and hydrolyzation of the coordinated\nSchiff base ligands is suggested, confirmed experimentally by powder\nX-ray diffraction study and photophysical studies. Complexes <b>1–9</b> were investigated in vitro as anticancer agents,\nalong with mutant p53 (mutp53) protein levels in human cancer cell\nlines carrying R175H and R273H mutp53 proteins. Only those complexes\nwith the highest Zn(II) ion release via dissociation have shown a\nsignificant cytotoxic activity with reduction of mutp53 protein levels.