Anticancer and antimicrobial activity of new copper (II) complexes

Abstract

In this study, three new organic ligands N'-(benzylidene)-6-chloropyrazine-2-carbohydrazonamide (L₁), 6-chloro-N'-(4-nitrobenzylidene)picolinohydrazonamide(L₂), and N'-(benzylidene)-4-chloropicolinohydrazonamide (L₃) and three copper coordination compounds (Cu(L₁)Cl₂, Cu(L₂)Cl₂ and Cu(L₃)Cl₂) based on them were synthesized. All obtained compounds were characterized using appropriate analytical techniques: elemental analysis (EA), thermogravimetric analysis (TG-DTG), Fourier transform infrared spectroscopy (FTIR) and flame-atomic absorption spectrometry (F-AAS). These methods of physicochemical analyses helped to assume that the complexation in three cases proceeds in a bidentate manner. The X-ray investigation confirmed the synthesis pathway and molecular structures for L₁ and L₃ ligands. The antimicrobial activity of the obtained compounds was then comprehensively investigated, where Cu(L₃)Cl₂ showed the strongest antibacterial properties against all tested bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli). LN229 human glioma cells and BJ human normal fibroblasts cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The effect of complexing on antitumor activity has been investigated. The ligand L₁ and its complex showed similar activity against normal cells while complexation increases toxicity against cancer cells in concentrations of 50 and 100 μM. For the one pair of ligand/complex compounds the apoptosis detection, cell cycle analysis and gene expression analysis (qRT-PCR) were performed. Cu(L₁)Cl₂ showed the stronger toxic effect in comparison with L₁ due to the population of early apoptotic cells which revealed metabolic activity in MTT assay.