Ukr.Biochem.J. 2017; Volume 89, Issue 2, Mar-Apr, pp. 106-115

doi: https://doi.org/10.15407/ubj89.02.106

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

24.04.2017   Uncategorized   No comments

O. M. Kozachkova1, N. V. Tsaryk1, V. V. Trachevskyi2,
A. B. Rozhenko3, Yu. H. Shermolovich3, O. I. Guzyr3,
N. I. Sharykina4, V. F. Chekhun5, V. I. Pekhnyo1

1Vernadsky Institute of General and Inorganic Chemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Technical Centre of National Academy of Sciences of Ukraine, Kyiv;
3Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
4SI “Institute of Pharmacology and Toxicology, National Academy
of Medical Sciences of Ukraine”, Kyiv;
5Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
e-mail: complex@ionc.kiev.ua

Complex formation of K2[PdCl4] with 1-phenyl-1-hydroxymethylene bisphosphonic acid (PhHMBP, H4L) has been studied by pH potentiometry, electron and NMR spectroscopy. It was found that in aqueous solution with physiological concentration of chlorine anions (0.15 mol/l KCl), anionic complexes of the equimolar compositions [PdHLCl2]3- (lgβ = 24.51 (0.3)) and [PdLCl2]4- (lgβ = 20.74 (0.02)) are formed. In the first coordination sphere palladium was surrounded by two oxygen atoms of two phosphonic groups of the bidentately coordinated ligand with closure of six-membered [O, O] ring, and two chlorine anions. The formation of palladium(II) equimolar complexes with PhHMBP and bidentate coordination of the ligand to the central metal cation was confirmed by 31P NMR spectroscopy. Cytotoxic activity (IC50 based on metal content) of the synthesized Pd(II) complexes with PhHMBP against human MG-63 osteosarcoma and MCF-7 mammary tumor cells was compared with cisplatin on in vitro models. It was established that cytotoxic activity of the Pd complexes was lower than that of cisplatin. The acute toxicity (LD50 based on metal content) of solutions of Pd(II) complexes with PhHMBP was found to be lower compared to cisplatin. It was shown that the use of solutions of palladium(II) complexes with PhHMBP inhibited tumor growth in mice with sarcoma 180.

Keywords: , , ,

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