Anticancer and antimicrobial activity of new copper (II) complexes
Alina Climova, Ekaterina Pivovarova, Małgorzata Szczesio, Katarzyna Gobis, Dagmara Ziembicka, Agnieszka Korga-Plewko, Joanna Kubik, Magdalena Iwan, Małgorzata Antos-Bielska, Małgorzata Krzyżowska, Agnieszka Czylkowska
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.