Copper(II) complexes with pyridoxal dithiocarbazate and thiosemicarbazone ligands: crystal structure, spectroscopic analysis and cytotoxic activity

The present study reports the synthesis and crystal structures of Cu(II) complexes with pyridoxal S -allyldithiocarbazate (H 2 L 1 ) and pyridoxal thiosemicarbazones (H 2 L 2 = pyridoxal- N 4 -phenyl-3-thiosemicarbazone and H 2 L 3 = pyridoxal- N 4 -semicarbazone). The single-crystal X-ray study reveals that in all cases, the Schiff base coordinated tridentately through the ONS -donor atoms, resulting in distorted square planar coordination geometries with the copper atoms. The Cu(II) complexes with pyridoxal dithiocarbazate, [Cu(HL 1 )Cl]·H 2 O and [Cu(HL 1 )Br]·H 2 O, as well as three complexes with pyridoxal thiosemicarbazone, [Cu(HL 2 )Cl]·dmf, [Cu(HL 2 )Br]·H 2 O·dmf and [Cu(H 2 L 3 )Br]Br·H 2 O, were also characterized by spectroscopic and physical–chemical analyses. The cytotoxicity of the complexes toward two kinds of cancerous cells (Ehrlich and S-180 cells) was evaluated by an MTT assay. The complex [Cu(H 2 L 3 )Br]Br·H 2 O was selected to study both the cellular and molecular mechanisms underlying its promising cytotoxicity. The Hoechst 33342/PI dual-staining assay showed the typical apoptotic morphology of cancer cells, and the RT-qPCR analysis revealed that the expressions of Bax , Casp3 , Casp8 , Casp9 and TP53 were markedly increased in both the Ehrlich and S-180 cells exposed to 10 μM for 3 h. According to our results, this complex induces cell death through apoptosis, showing potential as a future drug against cancer. Graphical abstract Five stable copper(II) complexes with pyridoxal have been synthesized and their crystal structure has been studied. Spectroscopy experiments and cytotoxic assays against S-180 and Ehrlich cancer cell lines were performed and showed promising results as novel antitumor drugs.