Synthesis, characterization and cytotoxicity of Mn(II) and Cu(II) complexes with N-substituted glycine hydrazone

The ligand HLCl, (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride, was synthesized by the reaction of Girard’s reagent T and 2-acetylthiazole in water.

Reaction of the ligand HLCl with Cu(BF₄)₂·6H₂O and NaN₃ in molar ratio 1 : 1 : 4 in methanol resulted in formation of the mononuclear azido Cu(II) complex with composition [CuL(N₃)(MeOH)]BF₄. The complex has distorted square-pyramidal geometry according to the X-ray. The tridentate hydrazone ligand is coordinated in deprotonated form to the Cu(II) with a NNO set of donor atoms, while the other two coordination sites are occupied by azido ligand and one molecule of solvent.

Reaction of ligand HLCl with MnCl₂·4H₂O and NaN₃ in molar ratio 1 : 1 : 4 in methanol resulted in formation of the binuclear azido bridged Mn(II) complex with composition [Mn₂L₂(_µ-1,1-N₃)₂(N₃)₂]MeOH. The ligands are coordinated in deprotonated form to Mn(II) ions with a NNO set of donor atoms, while three remaining coordination sites are occupied with two azido bridged ligands, and one terminal azido ligand.

The cytotoxic effects of the complexes and its precursor ligand were examined against five human malignant cell lines: cervical adenocarcinoma HeLa, melanoma A375, breast adenocarcinoma MCF7, prostate adenocarcinoma PC-3, and lung carcinoma A549, as well as against normal human keratinocyte cell line HaCaT. Mn(II) and Cu(II) complexes exerted strong to moderate cytotoxic activities against tested malignant cell lines. Cu(II) complex showed higher cytotoxic effects on malignant cells when compared to Mn(II) complex, except against MCF7 cells.

Both complexes exhibited higher cytotoxicity in comparison with its ligand HLCl.