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

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 e...

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Main Authors: O. M. Kozachkova, N. V. Tsaryk, V. V. Trachevskyi, A. B. Rozhenko, Yu. H. Shermolovich, O. I. Guzyr, N. I. Sharykina, V. F. Chekhun, V. I. Pekhnyo
Format: Article
Language:English
Published: National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 2017-02-01
Series:The Ukrainian Biochemical Journal
Online Access:http://ukrbiochemjournal.org/wp-content/uploads/2017/04/Kozachkova_2_17.pdf
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author O. M. Kozachkova
N. V. Tsaryk
V. V. Trachevskyi
A. B. Rozhenko
Yu. H. Shermolovich
O. I. Guzyr
N. I. Sharykina
V. F. Chekhun
V. I. Pekhnyo
author_facet O. M. Kozachkova
N. V. Tsaryk
V. V. Trachevskyi
A. B. Rozhenko
Yu. H. Shermolovich
O. I. Guzyr
N. I. Sharykina
V. F. Chekhun
V. I. Pekhnyo
author_sort O. M. Kozachkova
collection DOAJ
description 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.
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spelling doaj.art-40e60e25ee924aea84e07d25a11628792023-12-02T12:56:56ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032017-02-0189210611510.15407/ubj89.02.106Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activityO. M. Kozachkova0N. V. Tsaryk1V. V. Trachevskyi2A. B. Rozhenko3Yu. H. Shermolovich4O. I. Guzyr5N. I. Sharykina6V. F. Chekhun7V. I. Pekhnyo8Vernadsky Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, KyivVernadsky Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, KyivTechnical Centre of National Academy of Sciences of Ukraine, KyivInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, KyivInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, KyivInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, KyivSI “Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine”, KyivKavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, KyivVernadsky Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, KyivComplex 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.http://ukrbiochemjournal.org/wp-content/uploads/2017/04/Kozachkova_2_17.pdf
spellingShingle O. M. Kozachkova
N. V. Tsaryk
V. V. Trachevskyi
A. B. Rozhenko
Yu. H. Shermolovich
O. I. Guzyr
N. I. Sharykina
V. F. Chekhun
V. I. Pekhnyo
Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
The Ukrainian Biochemical Journal
title Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
title_full Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
title_fullStr Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
title_full_unstemmed Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
title_short Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
title_sort complexes of palladium ii with 1 phenyl 1 hydroxymethylene bisphosphoniс acid and their antitumor activity
url http://ukrbiochemjournal.org/wp-content/uploads/2017/04/Kozachkova_2_17.pdf
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