New lanthanide complexes of 4-methyl-7-hydroxycoumarin and their pharmacological activity (original) (raw)
Related papers
New metal complexes of 4-methyl-7-hydroxycoumarin sodium salt and their pharmacological activity
Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL) 2 ·nH 2 O, where Met = Cu, Zn, Ni, Co; n= 2, 3 or 4 and Fe(HL) 3 ·5H 2 O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.
Stability of Neodymium(III) Complexes of 4-Hydroxycoumarins with Anticoagulant Activity
American Journal of Pharmacology and …, 2006
Complexes of neodymium(III) with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one, 4-hydroxy-3-[1-(4-chlorophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one and 4-hydroxy-3-[1-(4nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one were synthesized by mixing of water solutions of neodymium(III) nitrate and the respective ligands, in amounts equal to metal: ligand molar ratio of 1: 3. The complexes were characterized and identified by elemental analysis, conductivity, IR and 1 H NMR spectral data. DTA and TGA have been applied to confirm the compositions of the compounds. The formation of the complexes was studied by IR-and 1 H-NMR-spectroscopy. The complexation reactions were studied in detail by spectrophotometric method. The stepwise formation of the complexes has been established in the pH region studied. The equilibrium constants for the complexes have been determined. The complexes of neodymium(III) with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one, 4-hydroxy-3-[1-(4-chlorophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one and 4hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one were assayed for acute intraperitoneal and per oral toxicity and for influence on blood clotting time.
Cytotoxic activity of new lanthanum (III) complexes of bis-coumarins
European Journal of Medicinal Chemistry, 2005
Complexes of lanthanum (III) with bis-coumarins: bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-2-yl-methane; bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-3-yl-methane and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-4-yl-methane were synthesized by reaction of lanthanum (III) salt and the ligands, in amounts equal to metal/ligand molar ratio of 1:2. The complexes were prepared by adding an aqueous solution of lanthanum (III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to ca. 5.0 by adding dilute solution of sodium hydroxide. The lanthanum (III) complexes with bis-coumarins were characterized by different physicochemical methods-elemental analysis, IR-, 1 H-and 13 C-NMR spectroscopies and mass-spectral data. The spectral data of lanthanum (III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the La (III) complexes the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the m(C=O) red shift observed, participation of the carbonyl groups in the coordination to the metal ion was also suggested. Cytotoxic screening by MTT assay was carried out. In the present study, we performed comparative evaluation of the cytotoxic effects of the three newly synthesized lanthanum complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia (CML)-derived BV-173. In addition the cytotoxic effects of La (III) complex with bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-2-yl-methane were evaluated on the SKW-3 cells. In order to elucidate some of the mechanistic aspects of the observed cytotoxic effects we evaluated the ability of this complex to trigger programmed cell death (apoptosis by means of agarose gel electrophoretic analysis of DNA), isolated from the cytosolic fraction of treated SKW-3 cells. In addition, microscopic morphological evaluation of the treated cells was carried out in order to establish morphological features indicative for programmed cell death.
European Journal of Medicinal Chemistry, 1999
The complexes of the types Ln(HW) 3 •nH 2 O and Ln(HC) 3 •nH 2 O [where Ln = Ce, La, Nd; HW = Warfarin; HC = Coumachlor] have been synthesized by reaction of Warfarin Sodium, resp. Coumachlor Sodium and the appropriate lanthanide nitrates in various stoichiometric ratios. The formation of the complexes have been proved on the basis of elemental analysis, conductivities, IR spectroscopy and 1 H-NMR spectroscopy. It is concluded that the lacton-and the keto-carbonyl groups of the ligands are bonded to the metal ion as bidentate ligand. The conductivity measurements show non-electrolytic nature of the complexes. Cytotoxicity determination by MTT-assay shows that the inorganic salts and the complexes with Warfarin did not show any significant activity. The complexes with Coumachlor were found to be more cytotoxic. The most active compound was the complex of Cerium with Coumachlor. All tested complexes showed similar in vitro cytotoxic profiles. This fact is in agreement with the formation of the complexes. © Elsevier, Paris metal complexes of Warfarin / Coumachlor / lanthanides / cytotoxic screening
Applied Organometallic Chemistry, 2007
Complexes of cerium(III), lanthanum(III) and neodymium(III) with coumarin-3-carboxylic acid (HCCA) were synthesized by mixing of equimolar amounts of the respective metal nitrates and coumarin-3-carboxylic acid in ethanol. The complexes were characterized and identified by elemental analysis, IR and Raman spectroscopy. DTA and TGA were applied to study the compositions of the compounds. The vibrational study showed bidentate coordination of CCA− to Ln(III) ions through the carbonyl oxygen and the carboxylic oxygen atoms. The newly synthesized compounds were assayed for cytotoxicity against SKW-3, HL-60 and Reh cells. The complexes of cerium(III) and lanthanum(III) showed marginal cytotoxic activity against SKW-3 and Reh cells as compared with the inorganic salts at concentration 200 µM. The complex of neodymium(III) induced approximately 50% reduction of the survival HL-60 and SKW-3 cells at concentration 200 µM. Copyright © 2007 John Wiley & Sons, Ltd.
Acta pharmaceutica (Zagreb, Croatia), 2004
A complex of cerium(III) with 4-methyl-7-hydroxycoumarin was synthesized by mixing water solutions of cerium(III) nitrate and 4-methyl-7-hydroxycoumarin sodium salt in a metal-to-ligand molar ratio of 1:2. The complex was characterized and identified by elemental analysis, conductometry, IR, 1H and 13C NMR-spectroscopy, mass spectral data, DTA and TGA. Thermal analysis of the complex indicated the formation of a compound of the composition CeR2(OH).5H2O, R standing for the ligand. The reaction of cerium(III) with 4-methyl-7-hydroxycoumarin was studied in detail by the spectrophotometric method. The stepwise formation of two complexes, vis., CeR2+ and CeR2+, was established in the pH region studied. The equilibrium constants for 1:1 and 1:2 complexes were determined to be 10.72 and 9.22, respectively.
New cerium(III) complexes of coumarins – Synthesis, characterization and cytotoxicity evaluation
European Journal of Medicinal Chemistry, 2008
Complexes of cerium(III) with bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-2-yl-methane, bis(4-hydroxy-2-oxo-2H-chromen-3-yl)pyridin-3-yl-methane and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-4-yl-methane were synthesized by reaction of cerium(III) salt and the ligands, in amounts equal to metaleligand molar ratio of 1:2. The cerium(III) complexes with bis-coumarins were characterized by different physicochemical methods e elemental analysis, IR-, Raman-, 1 H NMR-and 13 C NMR-spectroscopy and mass-spectral data. The spectral data of cerium(III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the Ce(III) complexes the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the n(C]O) red shift observed, participation of the carbonyl groups in the coordination to the metal ion was also suggested. Cytotoxic screening by MTT assay was carried out. In the present study we performed comparative evaluation of the cytotoxic effects of the three newly synthesized cerium complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia (CML)-derived BV-173. In addition the cytotoxic effects of Ce(III) complex with bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-2-yl-methane were evaluated on the SKW-3 cells. In order to elucidate some of the mechanistic aspects of the observed cytotoxic effects we evaluated the ability of this complex to trigger programmed cell death (apoptosis by means of agarose gel electrophoretic analysis of DNA, isolated from the cytosolic fraction of treated SKW-3 cells). In addition, microscopic morphological evaluation of the treated cells was carried out in order to establish morphological features indicative of programmed cell death.
Acta pharmaceutica (Zagreb, Croatia), 2004
A complex of neodymium(III) with 4-hydroxy-3[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one (acenocoumarol) was synthesized by mixing water solutions of neodymium(III) nitrate and the ligand (metal to ligand molar ratio of 1:3). The complex was characterized and identified by elemental analysis, conductivity, IR, 1H NMR and mass spectral data. DTA and TGA were applied to study the composition of the compound. Elemental and mass spectral analysis of the complex indicated the formation of a compound of the composition NdR3 x 6H2O, where R = C19H14NO6-) The reaction of neodymium(III) with acenocoumarol was studied in detail by the spectrophotometric method. The stepwise formation of three complexes, vis., NdR2+, NdR2+ and NdR3 was established in the pH region studied (pH 3.0-7.5). The equilibrium constants for 1:1, 1:2 and 1:3 complexes were determined to be log K1 = 6.20 +/- 0.06; log K2 = 3.46 +/- 0.07 and log K2) = 2.58 +/- 0.05, respectively.
Cytotoxic activity of new neodymium (III) complexes of bis-coumarins
European Journal of Medicinal Chemistry, 2004
Complexes of neodymium (III) with bis-coumarins: 3,3′-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one); bis(4-hydroxy-2-oxo-2Hchromen-3-yl)-piridin-2-yl-methane; bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-4-yl-methane; bis(4-hydroxy-2-oxo-2H-chromen-3yl)-(1H-pyrazol-3-yl)-methane were synthesized by reaction of neodymium (III) salt and the ligands, in amounts equal to metal:ligand molar ratio of 1:2. The complexes were prepared by adding an aqueous solution of neodymium (III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to ca. 5.0 by adding dilute solution of sodium hydroxide. The neodymium (III) complexes with bis-coumarins were characterized by different physicochemical methods-elemental analysis, IR-, 1 H-and 13 C-NMR-spectroscopies and mass-spectral data. The spectral data of neodymium (III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the Nd (III) complexes the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the m(C=O) red shift observed, participation of the carbonyl groups in the coordination to the metal ion was also suggested. Cytotoxic screening by MTT assay was carried out. The complexes were tested on HL-60, HL-60/Dox and SKW-3 cell lines. The overall results from the preliminary screening program revealed that all of the new Nd (III) complexes reach 50% inhibition of the malignant cells proliferation and thus could be considered as biologically active. On the basis of the IC 50 values obtained compounds Nd(L 1 )(OH).H 2 O and Nd(L 3 )(OH).2H 2 O were found to exert superior activity in comparison to the remaining complexes.