Romanian Society of Pharmaceutical Sciences

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SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION OF Ni(II), Cu(II) AND Zn(II) COMPLEXES WITH DEOXYCHOLATE LIGAND

DANIELA C. CULITA 1#*, LORA DYAKOVA 2#, GABRIELA MARINESCU 1, TANYA ZHIVKOVA 3,
MILENA GEORGIEVA 4, BELA VASILEVA 4, ROSSEN SPASOV 5, GEORGE MILOSHEV 4,
RENI KALFIN 2, MELITA VIDAKOVIC 6, OVIDIU OPREA 7, RADOSTINA ALEXANDROVA 3

1“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, Bucharest, Romania
2Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
3Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
4“Acad. Roumen Tsanev” Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria
5Faculty of Medicine, “St. Kliment Ohridski” Sofia University, Sofia, Bulgaria
6Institute for Biological Research, Belgrade, Serbia
7Politehnica University of Bucharest, Faculty of Applied Chemistry and Materials Science, Bucharest, Romania

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Three new complexes of Ni(II), Cu(II) and Zn(II) with deoxycholate anion, of the type M(DCA)2 · nH2O (M = Cu(II) n = 4, M = Ni(II) n = 3 and M = Zn(II) n = 2) have been synthesized and characterized on the basis of elemental analysis, FTIR and UV-Vis spectroscopy, thermal analysis, molar conductivity and magnetic measurements. The cytotoxicity of the synthesized complexes was tested against HT29 human colorectal cancer cells. Applied at a concentration range of 10 - 200 µg/mL, sodium deoxycholate and its metal complexes have been found to decrease viability and growth of cultured HT29 cells in a time- and concentration-dependent manner in short-term and long-term experiments. The ability of the complexes to induce pathological changes, genotoxicity and apoptosis in the treated cells has also been proved. In addition, the complexes demonstrated a cytotoxic effect in HT29-OxPt (resistant to oxaliplatin) cells, allowing to conclude that they are more pronounced cytotoxic agents as compared to the sodium deoxycholate alone.