Syntheses and Biological Studies of Cu(II) Complexes Bearing Bis(pyrazol-1-yl)- and Bis(triazol-1-yl)-acetato Heteroscorpionate Ligands.

Copper(II) complexes of bis(pyrazol-1-yl)- and bis(triazol-1-yl)-acetate heteroscorpionate ligands have been synthesized. The copper(II) complexes [HC(COOH)(pz^Me2)₂]Cu[HC(COO)(pz^Me2)₂]·ClO₄, [HC(COOH)(pz)₂]₂Cu(ClO₄)₂ (pz^Me2 = 3,5-dimethylpyrazole; pz = pyrazole) were prepared by the reaction of Cu(ClO₄)₂·6H₂O with bis(3,5-dimethylpyrazol-1-yl)acetic acid (HC(COOH)(pz^Me2)₂) and bis(pyrazol-1-yl)acetic acid (HC(COOH)(pz)₂) ligands in ethanol solution. The copper(II) complex [HC(COOH)(tz)₂]₂Cu(ClO₄)₂·CH₃OH (tz = 1,2,4-triazole) was prepared by the reaction of Cu(ClO₄)₂·6H₂O with bis(1,2,4-triazol-1-yl)acetic acid (HC(COOH)(tz)₂) ligand in methanol solution. The synthesized Cu(II) complexes, as well as the corresponding uncoordinated ligands, were evaluated for their cytotoxic activity in monolayer and 3D spheroid cancer cell cultures with different Pt(II)-sensitivity. The results showed that [HC(COOH)(pz^Me2)₂]Cu[HC(COO)(pz^Me2)₂]·ClO₄ was active against cancer cell lines derived from solid tumors at low IC₅₀ and this effect was retained in the spheroid model. Structure and ultra-structure changes of treated cancer cells analyzed by Transmission Electron Microscopy (TEM) highlighted the induction of a cytoplasmic vacuolization, thus suggesting paraptotic-like cancer cell death triggering. [ABSTRACT FROM AUTHOR]