984 resultados para II inhibitor
Resumo:
New complexes, [Ni(HL)(PPh3)]Cl (1), [Pd(L)(PPh3)](2), and [Pd(L)(AsPh3)](3), were synthesized from the reactions of 4-chloro-5-methyl-salicylaldehyde thiosemicarbazone [H2L] with [NiCl2(PPh3)(2)], [PdCl2(PPh3)(2)] and [PdCl2(AsPh3)(2)]. They were characterized by IR, electronic, H-1-NMR spectral data. Further, the structures of the complexes have been determined by single crystal X-ray diffraction. While the thiosemicarbazone coordinated as binegative tridentate (ONS) in complexes 2 and 3, it is coordinated as mono negative tridentate (ONS) in 1. The interactions of the new complexes with calf thymus DNA was examined by absorption and emission spectra, and viscosity measurements. Moreover, the antioxidant properties of the new complexes have also been tested against DPPH radical in which complex 1 exhibited better activity than that of the other two complexes 2 and 3. The in vitro cytotoxicity of complexes 1-3 against A549 and HepG2 cell lines was assayed, and the new complexes exhibited higher cytotoxic activity with lower IC50 values indicating their efficiency in killing the cancer cells even at very low concentrations.
Resumo:
The mononuclear Cu(II) complex [Cu(phen)(H2O)(NO3)(2)] (1), obtained by the reaction of 1,10-phenanthroline with Cu(NO3)(2)center dot 3H(2)O in methanol solution, reacts with anionic ligands SCN-, AcO-, N-3(-) and PhCO2- in MeOH solution to form the stable binuclear complexes [Cu-2(H2O)(2)(phen)(2)(mu-X)(2)](2) (NO3)(2), where X = SCN- (2), AcO- (3), N-3(-) (4) or PhCO2- (5). The molecular structure of complex 3 was determined by single-crystal X-ray diffraction studies. These complexes were characterized by electronic, IR, ESR, magnetic moments and conductivity measurements. The electrochemical behaviour of the complexes was investigated by cyclic voltammetry. The interactions of these complexes with calf thymus DNA have been investigated using absorption spectrophotometry. Their DNA cleavage activity was studied on double-stranded pBR322 plasmid DNA using gel electrophoresis experiments in the absence and presence of H2O2 as oxidant.
Resumo:
The mononuclear Cu(II) complex [Cu(phen)(H2O)(NO3)(2)] (1), obtained by the reaction of 1,10-phenanthroline with Cu(NO3)(2)center dot 3H(2)O in methanol solution, reacts with anionic ligands SCN-, AcO-, N-3(-) and PhCO2- in MeOH solution to form the stable binuclear complexes [Cu-2(H2O)(2)(phen)(2)(mu-X)(2)](2) (NO3)(2), where X = SCN- (2), AcO- (3), N-3(-) (4) or PhCO2- (5). The molecular structure of complex 3 was determined by single-crystal X-ray diffraction studies. These complexes were characterized by electronic, IR, ESR, magnetic moments and conductivity measurements. The electrochemical behaviour of the complexes was investigated by cyclic voltammetry. The interactions of these complexes with calf thymus DNA have been investigated using absorption spectrophotometry. Their DNA cleavage activity was studied on double-stranded pBR322 plasmid DNA using gel electrophoresis experiments in the absence and presence of H2O2 as oxidant.
Resumo:
Histone deacetylase inhibitors (HDIs) have attracted considerable attention as potential drug molecules in tumour biology. In order to optimise chemotherapy, it is important to understand the mechanisms of regulation of histone deacetylase (HDAC) enzymes and modifications brought by various HDIs. In the present study, we have employed Fourier transform infrared microspectroscopy (FT-IRMS) to evaluate modifications in cellular macromolecules subsequent to treatment with various HDIs. In addition to CH3 (methyl) stretching bands at 2872 and 2960 cm1, which arises due to acetylation, we also found major changes in bands at 2851 and 2922 cm1, which originates from stretching vibrations of CH2 (methylene) groups, in valproic acid treated cells. We further demonstrate that the changes in CH2 stretching are concentration-dependent and also induced by several other HDIs. Recently, HDIs have been shown to induce propionylation besides acetylation [1]. Since propionylation involves CH2 groups, we hypothesized that CH2 vibrational frequency changes seen in HDI treated cells could arise due to propionylation. As verification, pre-treatment of cells with propionyl CoA synthetase inhibitor resulted in loss of CH2 vibrational changes in histones, purified from valproic acid treated cells. This was further proved by western blot using propionyl-lysine specific antibody. Thus we demonstrate for the first time that propionylation could be monitored by studying CH2 stretching using IR spectroscopy and further provide a platform for monitoring HDI induced multiple changes in cells. (C) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Resumo:
Coordination-driven self-assembly of binuclear half-sandwich p-cymene ruthenium(II) complexes [Ru-2(mu-eta(4)-C2O4)(MeOH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (1a) or [Ru-2(mu-eta(4)-N,N'-diphenyloxamidato)(MeOH)(2)(eta(6)-p-cymene)(2)]( O3SCF3)(2) (1b) separately with an imidazole-based tetratopic donor L in methanol affords two tetranuclear metallamacrocycles 2a and 2b, respectively. Conversely, the similar combination of L with 2,5-dihydroxy-1,4-benzoquinonato (dhbq) bridged binuclear complex [Ru-2(mu-eta(C6H2O4)-C-4)(MeOH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (1c) in 1:2 molar ratio resulted in an octanuclear macrocyclic cage 2c. All the self-assembled macrocycles 2a-2c were isolated as their triflate salts in high yields and were characterized fully by multinuclear (H-1, C-13 and F-19) NMR, infrared (IR) and electrospray ionization mass spectrometry (ESIMS). In addition, the molecular structure of macrocycle 2a was established unequivocally by single-crystal X-ray diffraction analysis and adopts a tetranuclear rectangular geometry with the dimensions of 5.53 angstrom x 12.39 angstrom. Furthermore, the photo-and electrochemical properties of these newly synthesized assemblies have been studied by using UV-vis absorption and cyclic voltammetry analysis.
Resumo:
The single-crystal X-ray structure of a cation-templated manganese-oxalate coordination polymer [NH(C2H5)(3)][Mn-2(ox)(3)]center dot(5H(2)O)] (1) is reported. In 1, triethylammonium cation is entrapped between the cavities of 2-D honeycomb layers constructed by oxalate and water. The acyclic tetrameric water clusters and discrete water assemble the parallel 2-D honeycomb oxalate layers via an intricate array of hydrogen bonds into an overall 3-D network. The magnetic susceptibility, with and without the water cluster, are reported with infrared and EPR studies.
Resumo:
The GasBench II peripheral along with MAT 253 combination provides a more sensitive platform for the determination of water isotope ratios. Here, we examined the role of adsorbed moisture within the gas chromatography (GC) column of the GasBench II on measurement uncertainties. The uncertainty in O-18/O-16 ratio measurements is determined by several factors, including the presence of water in the GC. The contamination of GC with water originating from samples as water vapour over a longer timeframe is a critical factor in determining the reproducibility of O-18/O-16 ratios in water samples. The shift in isotope ratios observed in the experiment under dry and wet conditions correlates strongly with the retention time of analyte CO2, indicating the effect of accumulated moisture. Two possible methods to circumvent or minimise the effect of adsorbed water on isotope ratios are presented here. The proposed methodology includes either the regular baking of the GC column at a higher temperature (120 degrees C) after analysis of a batch of 32 sample entries or conducting the experiment at a low GC column temperature (22.5 degrees C). The effects of water contamination on long-term reproducibility of reference water, with and without baking protocol, have been described.
Resumo:
Ferrocene-conjugated reduced Schiff base (Fc-metH) copper(II) complexes of L-methionine and phenanthroline bases, namely, Cu(Fc-met)(B)](NO3), where B is 1,10-phenanthroline (phen in 1), dipyrido3,2-d:2',3'-f]quinoxaline (dpq in 2), dipyrido3,2-a:2',3'-c]phenazine (dppz in 3), and 2-(naphthalen-1-yl)-1H-imidazo4,5-f]1,10]phenanthroline (nip in 4), were prepared and characterized and their photocytotoxicity studied (Fc = ferrocenyl moiety). Complexes Cu(Ph-met)(B)](NO3) of the reduced Schiff base from benzaldehyde and L-methionine (Ph-metH) and B (phen in 5, dppz in 6) were prepared and used as control species. Complexes 1 and 5 were structurally characterized by X-ray crystallography. Complex 1 as a discrete monomer has a CuN3OS core with the thiomethyl group as the axial ligand. Complex 5 has a polymeric structure with a CuN3O2 core in the solid state. Complexes 5 and 6 are formulated as Cu(Ph-met)(B)(H2O)] (NO3) in an aqueous phase based on the mass spectral data. Complexes 1-4 showed the Cu(II)-Cu(I) and Fc(+)-Fc redox couples at similar to 0.0 and similar to 0.5 V vs SCE, respectively, in DMF-0.1 M (Bu4N)-N-n](ClO4). A Cu(II)-based weak d-d band near 600 nm and a relatively strong ferrocenyl band at similar to 450 nm were observed in DMF-Tris-HCl buffer (1:4 v/v). The complexes bind to calf thymus DNA, exhibit moderate chemical nuclease activity forming (OH)-O-center dot radical species, and are efficient photocleavers of pUC19 DNA in visible light of 454, 568, and 647 rim, forming (OH)-O-center dot radical as the reactive oxygen species. They are cytotoxic in HeLa (human cervical cancer) and MCF-7 (human breast cancer) cells, showing an enhancement of cytotoxicity upon visible light irradiation. Significant change in the nuclear morphology of the HeLa cells was observed with 3 in visible light compared to the nonirradiated sample. Confocal imaging using 4 showed its nuclear localization within the HeLa cells.
Resumo:
Divalent metal complexes of general formula M(2-nb)(2)(mc)(2)].2(2-nbH), where M = Co(II), Ni(II), Cu(II) or Zn(II), 2-nbH = 2-nitrobenzoic acid and mc = methyl carbazate (NH2NHCOOCH3), have been prepared and characterized by physicochemical and spectroscopic methods. Single-crystal X-ray study of the Cu(II) complex revealed that the molecule is centrosymmetric, with two N,O-chelating mc ligands in equatorial positions and a pair of monodentate 2-nb anions in the axial positions. The lattice 2-nbH molecules help to establish the packing of monomers through hydrogen-bonding interactions. Thermal stability and reactivity of the complexes were studied by TG-DTA. Emission studies show that these complexes are fluorescent.
Resumo:
The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.
Resumo:
Two new one-dimensional heterometallic complexes, Mn3Na(L)(4)(CH3CO2)(MeOH)(2)]-(ClO4)(2)center dot 3H(2)O (1), Mn3Na(L)(4)(CH3CH2CO2)-(MeOH)(2)](ClO4)(2)center dot 2MeOH center dot H2O (2) LH2 = 2-methyl-2-(2-pyridyl)propane-1,3-diol], have been synthesized and characterized by X-ray crystallography. Both complexes feature Mn-II and Na-I ions in trigonal-prismatic geometries that are linked to octahedral Mn-IV ions by alkoxy bridges. Variable-temperature direct- and alternating-current magnetic susceptibility data indicated a spin ground state of S = 11/2 for both complexes. Density functional theory calculations performed on 1 supported this conclusion.
Resumo:
A new class of macrobicyclic dinickel(II) complexes Ni2L1,2 B](ClO4)(4) (1-6), where L-1,L-2 are polyaza macrobicyclic binucleating ligands, and B is a N,N-donor heterocyclic base (viz. 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)) are synthesized and characterized. The redox, catalytic, DNA binding and DNA cleavage properties were studied. They exhibit two irreversible waves in the cathodic region around E-pc = -0.95 V and E-pa = -0.85 V vs. Ag/Ag+ in CH3CN-0.1 M TBAP, respectively. The first order rate constants for the hydrolysis of 4-nitrophenylphosphate to 4-nitrophenolate by the dinickel(II) complexes 1-6 are in the range from 3.36 x 10(-5) to 10.83 x 10(-5) Ms-1. The complexes 3 and 6 show good binding propensity to calf thymus DNA giving binding constant values (K-b) in the range from 3.08 x 10(5) to 5.37 x 10(5) M-1. The binding site sizes and viscosity data suggest the DNA intercalative and/or groove binding nature of the complexes. The complexes display significant hydrolytic cleavage of supercoiled pBR322DNA at pH 7.2 and 37 degrees C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo Michaelis-Menten kinetic parameters k(cat) = 5.44 x 10(-2) h(-1) and K-M = 6.23 x 10(-3) M for complex 3 were obtained. Complex 3 also shows an enormous enhancement of the cleavage rate, of 1.5 x 10(6), in comparison to the uncatalysed hydrolysis rate (k = 3.6 x 10(-8) h(-1)) of ds-DNA.