共查询到20条相似文献,搜索用时 46 毫秒
1.
Chen GJ Qiao X Qiao PQ Xu GJ Xu JY Tian JL Gu W Liu X Yan SP 《Journal of inorganic biochemistry》2011,105(2):119-126
Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] () and [Cu(acac)(dppz)Cl] () (acac = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2-a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes show good binding propensity to calf thymus DNA in the order: 2(dppz) > 1(dpq). Furthermore, two complexes exhibit efficient DNA cleavage activity on natural light or UV-A (365 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The photo-induced DNA cleavage activity of the dppz complex 2 is found to be more efficient than its dpq analogue. In vitro study of the photocytotoxicity of two complexes on HeLa cells indicate that both of them have the potential to act as effective anticancer drugs, with IC50 values of 5.25 ± 0.83 μM (1) and 4.40 ± 0.52 μM (2) in the natural light, and 2.57 ± 0.92 μM (1) and 2.18 ± 0.52 μM (2) in UV-A light. In addition, to detect an apoptotic HeLa body, cells were stained with Hoechst 33342 dye. 相似文献
2.
Venugopal Rajendiran Vaiyapuri Subbarayan Periasamy 《Journal of inorganic biochemistry》2010,104(2):217-364
The ‘molecular light switch’ complexes [Ru(bpy)2(dppz)]2+ (1) and [Ru(phen)2(dppz)]2+ (2), where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and dppz = dipyrido[3,2-a:2′,3′-c]phenazine, have been explored as probes for diagnosing and staining nuclear components. The phen complex acts as a better staining agent for nonviable cells than for viable cells and exhibits a staining efficiency in tail region of comet more specific and stronger than the already known dye Hoechst 33258. 相似文献
3.
Two new ruthenium complexes [Ru(bpy)2(mitatp)](ClO4)21 and [Ru(bpy)2(nitatp)](ClO4)22 (bpy = 2,2′-bipyridine, mitatp = 5-methoxy-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene, nitatp = 5-nitro-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) have been synthesized and characterized by elemental analysis, 1H NMR, mass spectrometry and cyclic voltammetry. Spectroscopic and viscosity measurements proved that the two Ru(II) complexes intercalate DNA with larger binding constants than that of [Ru(bpy)2(dppz)]2+ (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) and possess the excited lifetime of microsecond scale upon binding to DNA. Both complexes can efficiently photocleave pBR322 DNA in vitro under irradiation. Singlet oxygen (1O2) was proved to contribute to the DNA photocleavage process, the 1O2 quantum yields was determined to be 0.43 and 0.36 for 1 and 2, respectively. Moreover, a photoinduced electron transfer mechanism was also found to be involved in the DNA cleavage process. 相似文献
4.
Yi Sun Qian-Xiong Zhou Yuan-Jun Hou Xue-Song Wang Bao-Wen Zhang 《Journal of inorganic biochemistry》2009,103(12):1658-1665
Four cobalt(III) polypyridyl complexes, [Co(phen)3−n(dpq)n]3+ (phen = 1,10-phenanthroline, dpq = dipyrido[3,2-f:2′,3′-h]-quinoxaline) (n = 0, 1, 2, and 3) were synthesized and the influences of the dpq ligand on the photophysical properties, electrochemical properties, DNA binding affinities, as well as photonuclease activities of the complexes, were examined in detail. The presence of dpq ligand increases the DNA binding affinities of the corresponding complexes remarkably with respect to [Co(phen)3]3+. With the sequential substitution of phen ligand by dpq ligand, the 1O2 quantum yields of the corresponding complexes are enhanced greatly. As a result, the photonuclease activities follow the order of [Co(dpq)3]3+ > [Co(phen)(dpq)2]3+ > [Co(phen)2(dpq)]3+ ? [Co(phen)3]3+. It was found all the examined complexes can generate OH upon UV irradiation, and OH is also involved in DNA photocleavage as reactive oxygen species. 相似文献
5.
The Rh(III) polypyridyl complexes of the type [RhCl(pp)([9]aneS3)]2+ [(pp) = 2,2′-bipyridine (bpy), 2,2′-bipyrimidine (bpm),1,10-phenanthroline (phen), pyrazino[2,3-f]quinoxaline (tap), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[2,3-a:2′,3′-c]phenazine (dppz)] 2-7 have been prepared in a stepwise manner by treatment of RhCl3 · 3H2O with the appropriate polypyridyl ligand (pp) followed by 1,4,7-trithiacyclononane. Interactions of the polypyridyl complexes with DNA were investigated by CD and UV/visible spectroscopy and by gel electrophoresis. The dpq complex 6 cleaves DNA exiguously in the dark, but UV irradiation is required to induce nuclease activity for the bpy complex 2. Whereas 2 [IC50 values: 12.8 (±0.2) and 4.4 (±0.1) μM] exhibits significantly higher cytotoxicities towards MCF-7 and HT-29 cells than 4 [IC50 values: 36.3 (±6.0) and 72.2 (±8.0)], the activity of complexes in the series 4/6/7 correlates directly with the size of the polypyridyl ligand, as documented by their respective IC50 values of 72.2 (±8.0), 20.9 (±2.8) and 7.4 (±2.2) towards HT-29 cells. Complexes of the nitrogen-rich ligands bpm (3) [IC50 values: 1.7 (±0.5) and 1.9 (±0.1) μM] and tap (5) [IC50 values: 11.5 (±0.6) and 7.6 (±4.8) μM] are considerably more potent than their bpy and phen counterparts 2 and 4. Measurement of the lactate dehydrogenase release for lymphoma (BJAB) cells after 1 h incubation demonstrates that unspecific necrosis is negligible for the most active compounds 3 and 7. Specific cell death apoptosis via DNA fragmentation was detected for BJAB cells after 72 h incubation and significant loss of the mitochondrial membrane potential in lymphoma cells indicates that the intrinsic pathway is involved. 相似文献
6.
Ioannis Bratsos Stephanie Jedner Alberta Bergamo Gianni Sava Teresa Gianferrara Ennio Zangrando Enzo Alessio 《Journal of inorganic biochemistry》2008,102(5-6):1120
The preparation, structural characterization, and chemical behavior in aqueous solution of a series of new Ru[9]aneS3 half-sandwich complexes of the type [Ru([9]aneS3)Cl(NN)][CF3SO3] and [Ru([9]aneS3)(dmso-S)(NN)][CF3SO3]2 (5–15, NN = substituted bpy or 2 × 1-methylimidazole) are described. The X-ray structures of [Ru([9]aneS3)Cl(3,3′-H2dcbpy)][CF3SO3] (9) (3,3′-H2dcbpy = 3,3′-dicarboxy-2,2′-bipyridine), [Ru([9]aneS3)Cl(4,4′-dmobpy)][CF3SO3] (13) (4,4′-dmobpy = 4,4′-dimethoxy-2,2′-bipyridine), and [Ru([9]aneS3)Cl(1-MeIm)2][CF3SO3] (15) (1-MeIm = 1-methylimidazole) were also determined. The new compounds are structurally similar to anticancer-active organometallic half-sandwich complexes of formula [Ru(η6-arene)Cl(NN)][PF6]. Three chloro compounds (5, 9, 15) were tested in vitro for cytotoxic activity against two human cancer cell lines in comparison with the previously described [Ru([9]aneS3)Cl(en)][CF3SO3] (1, en = ethylenediamine), [Ru([9]aneS3)Cl(bpy)][CF3SO3] (2), and with their common dmso precursor [Ru([9]aneS3)Cl(dmso-S)2][CF3SO3] (3). Only the ethylenediamine complex 1 showed some antiproliferative activity, ca. one order of magnitude lower than the reference organometallic half-sandwich compound RM175 that contains biphenyl instead of [9]aneS3. This compound was further tested against a panel of human cancer cell lines (including one resistant to cisplatin). 相似文献
7.
Ruthenium complexes with one dipyrido[3,2-a:2′-3′-c]phenazine (dppz) ligand, e.g. [Ru(phen)2(dppz)]2+ (phen = phenanthroline), shows strong binding to double helical DNA and are well-known DNA “light-switch” molecules. We have here investigated four new [Ru(phen)2(dppz)]2+ derivatives with different bulky quaternary ammonium substituents on the dppz ligand to find relationships between molecular structure and intercalation kinetics, which is considered to be of importance for antitumor applicability. Linear dichroism spectroscopy shows that the enantiomers of the new complexes exhibit very similar binding geometries (intercalation of dppz moiety between adjacent DNA base pairs) as the enantiomers of the parent [Ru(phen)2(dppz)]2+ complex. Absorption spectra and luminescence properties provide further evidence for a final intercalative binding mode which has to be reached by threading of a bulky moiety between the strands of the DNA. Δ-enantiomers of all the new complexes show much slower association and dissociation kinetics than that of a reference complex without a cationic substituent. Kinetics were not very different whether the bulky quaternary group was derived from hexamethylene tetramine or 1,4-diazabicyclo-(2,2,2)octane (DABCO) or whether it had one or two positive charges. However, a complex in which the hexamethylene tetramine substituent is attached via a phenyl group showed a lowered association rate, in addition to an improved quantum yield of luminescence. A second positive charge on the DABCO substituent resulted in a much slower dissociation rate, suggesting that the distance from the Ru-centre and the amount of charge are both important for threading intercalation kinetics. 相似文献
8.
The DNA binding and in vitro cytotoxicity of the dinuclear Ir(III) polypyridyl complexes [{(η5-C5Me5)Ir(dppz)}2(μ-pyz)](CF3SO3)41 and [{(η5-C5Me5)Ir(pp)}2(μ-4,4′-bpy)](CF3SO3)42-4 (pp = dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[2,3-a:2′,3′-c]phenazine (dppz), benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn)) with the rigid bridging ligands pyrazine (pyz) or 4,4′-bipyridine (4,4′-bpy) have been studied. Stable intercalative binding into CT DNA (calf thymus DNA) is indicated for the dppz complexes 1 and 3 by induced negative CD bands at about 300 nm and large viscosity increases, with the individual measurements being in accordance with intrastrand bis-intercalation for 3 and mono-intercalation for 1. The observed interruption of specific interresidue NOE cross peaks from the relevant nucleobase H6/H8 protons to the sugar H2′/H2″ protons of the preceding nucleotide is in accordance with bis-intercalation of complex 3 between the C3G18 and G4C17 base pairs and the T5A16 and A6T15 base pairs of the decanucleotide d(5′-CGCGTAGGCC-3′). Complexes 1 and 3 exhibit a greatly improved uptake by HT-29 (colon carcinoma) cells and significantly improved in vitro IC50 values of 1.8 ± 0.1 and 3.8 ± 0.1 μM towards this cell line in comparison to the mononuclear complex [(η5-C5Me5)IrCl(dppz)](CF3SO3) (IC50 = 7.4 ± 0.9 μM). 相似文献
9.
To investigate the structure-activity relationship of vanadium complexes in inhibiting protein tyrosine phosphatase1B (PTP1B), eight mixed-ligand oxovanadium(IV) complexes, [VIVO(SalAla)(NN)] (H2SalAla for salicylidene alanine, NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4)), [VIVO(SalLys)(dpq)] (5), [VIVO(SalLys)(dppz)] (6), [VIVO(SalAsp)(dppz)], (7) and [VIVO(SalTrp)(dppz)] (8)), of which 3-8 are new, have been prepared and characterized by elemental analysis, infrared, UV-visible, electrospray ionization mass spectrometry and conductivity. The molar conductance data confirmed the non-electrolytic nature of the complexes in DMSO solution. The coordination in [VIVO (SalAla)(phen)] (2) was confirmed by X-ray crystal structure analysis. The oxidation state of V(IV) with d1 configuration in 2 was confirmed by EPR. The speciation of VO-SalAla-phen in aqueous solution was investigated by potentiometric pH titrations. The results indicate that the main species are two ternary complexes at the pH range 7.0-7.4. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of PTP1B with IC50 values in the range of 62-597 nM, approximately 3-10 fold weaker in potency than those of similar mixed-ligand oxovanadium(IV) complexes of salicylidene anthranilic acid (SAA) derivative with polypyridyl ligands, except complex 8, which exhibits comparable or better inhibition activity than those of the mixed-ligand oxovanadium(IV) complexes of SAA derivative with polypyridyl ligands. The results demonstrate that the structures of vanadium complexes influence the PTP1B inhibition activity. Kinetics assays reveal that complex 2 inhibits PTP1B in a competitive manner. 相似文献
10.
Anitha M. Thomas 《Inorganica chimica acta》2004,357(8):2315-2323
New ternary copper(II) complexes of formulations [Cu(Ph-tsc)B] (B=1,10-phenanthroline, phen (1); dipyridoquinoxaline, dpq (2); dipyridophenazine, dppz (3); Ph-H2tsc, salicylaldehyde-N(4)-phenylthiosemicarbazone) and [Cu(Me-tsc)(phen)] (4, Me-H2tsc, salicylaldehyde-N(4)-methylthiosemicarbazone) are prepared, and their DNA binding and cleavage properties studied. Complex 1 has been characterized by single crystal X-ray crystallography. The molecular structure shows a distorted square pyramidal (4 + 1) geometry of the complex with the dianionic NSO-donor N(4)-phenyl-substituted thiosemicarbazone binding at the basal plane and the NN-donor planar heterocyclic base (phen) displaying axial-equatorial coordination. The one-electron paramagnetic complexes exhibit axial EPR spectra and show a d-d band near 580 nm for the phen and near 720 nm for the dpq, dppz complexes in their electronic spectra in DMF. The complexes show quasireversible cyclic voltammetric response near 0.08 V vs. SCE in DMF-0.1 M TBAP assignable to the Cu(II)/Cu(I) couple. The Ph-tsc complexes display good binding propensity to calf thymus (CT) DNA. They also show oxidative cleavage of supercoiled (SC) pUC19 DNA in dark under aerobic condition in the presence of mercaptopropionic acid. The complexes exhibit light-induced DNA cleavage activity at 312 and 532 nm. Mechanistic investigations reveal DNA minor groove binding for the phen and dpq complexes, and major groove binding for the dppz species. The complexes are cleavage inactive under argon atmosphere. In the ternary structure, the thiosemicarbazones, dpq and dppz act as photosensitizers, while the planar heterocyclic bases are binder to DNA. The mechanistic pathways involved and the role of metal in the DNA cleavage reactions are discussed. 相似文献
11.
Oxovanadium(IV) complexes [VO(L)(B)] (1-3), where H2L is a Schiff base ligand 2-(2-hydroxybenzylideneamino)phenol and B is 1,10-phenanthroline (phen for 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq for 2) or dipyrido[3,2-a:2′,3′-c]phenazine (dppz for 3), have been prepared, characterized and their DNA binding property and photo-induced DNA cleavage activity studied. Complex 3 which is structurally characterized by X-ray crystallography shows the presence of an oxovanadium(IV) moiety in a six coordinate VO3N3 coordination geometry. The complexes show a d-d band within 800-850 nm in DMF. The complexes display an oxidative response near 0.7 V versus SCE for V(V)-V(IV) and a reductive response within −1.1 to −1.3 V due to V(IV)-V(III) couple in DMF-0.1 M TBAP. The complexes are avid binders to calf thymus DNA giving binding constant values of 4.2 × 104 to 1.2 × 105 M−1. The complexes do not show any “chemical nuclease” activity in dark. The dpq and dppz complexes are photocleavers of plasmid DNA in UV-A light of 365 nm via 1O2 pathway and in near-IR light (752.5 to 799.3 nm IR optics) by HO• pathway. Complex 3 exhibits significant photocytotoxicity in visible light in HeLa cells giving IC50 value of 13 μM, while it is less toxic in dark (IC50 = 97 μM). 相似文献
12.
Ternary oxovanadium(IV) complexes [VO(salmdtc)(B)] (1-3), where salmdtc is dianionic N-salicylidene-S-methyldithiocarbazate and B is N,N-donor phenanthroline bases like 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 3), are prepared, characterized and their DNA binding and DNA cleavage activity studied. Complex 3 is structurally characterized by single-crystal X-ray crystallography. The molecular structure shows the presence of a vanadyl group in six-coordinate VN3O2S coordination geometry. The S-methyldithiocarbazate Schiff base acts as a tridentate NSO-donor ligand in a meridional binding mode. The N,N-donor heterocyclic base displays a chelating mode of binding with an N-donor site trans to the vanadyl oxo-group. The complexes show a d-d band in the range of 675-707 nm in DMF. They exhibit an irreversible oxidative cyclic voltammetric response near 0.9 V due to the V(V)/V(IV) couple and a quasi-reversible reductive V(IV)/V(III) redox couple near −1.0 V vs. SCE in DMF-0.1 M TBAP. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range of 7.4 × 104-2.3 × 105 M−1. The thermal denaturation and viscosity binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor chemical nuclease activity in dark in the presence of 3-mercaptopropionic acid (MPA) or hydrogen peroxide. The dpq and dppz complexes show efficient DNA cleavage activity in UV-A light of 365 nm via a type-II mechanistic pathway involving formation of singlet oxygen (1O2) as the reactive species. 相似文献
13.
Caixia Yuan Yanbo Wu Maolin Guo Shu Xing Miaoli Zhu 《Journal of inorganic biochemistry》2010,104(9):978-12934
Seven new mixed-ligand vanadyl complexes, [VIVO(5-Br-SAA)(NN)] and [VIVO(2-OH-NAA)(NN)] (1-7) (5-Br-SAA for 5-bromosalicylidene anthranilic acid, 2-OH-NAA for 2-hydroxy-1-naphthaldehyde anthranilic acid and NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1 and 5), 1,10-phenanthroline (phen, 2 and 6), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3 and 7), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4)), were synthesized and characterized. X-ray crystal structure of [VIVO(5-Br-SAA)(phen)] revealed a distorted octahedral geometry with the Schiff base ligand coordinated in a tridentate ONO-fashion and the phenanthroline ligand in a bidentate fashion. Density-functional theory (DFT) calculations suggest a similar structure and the same coordination mode for all the other oxovanadium complexes synthesized. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of protein tyrosine phosphatase 1B (PTP1B), with IC50 values approximately 41-75 nM. Kinetics assays suggest that the complexes inhibit PTP1B in a competitive manner. Notably, they had moderate selectivity of PTP1B over T-cell protein tyrosine phosphatase (TCPTP) (about 2-fold) and good selectivity over Src homology phosphatase 1 (SHP-1) (about 4∼7-fold). Thus, these mixed-ligand complexes represent a promising class of PTP1B inhibitors for future development as anti-diabetic agents. 相似文献
14.
The reaction of the monofunctional [Pt(Gly-Gly-N,N′,O)I]− complex, in which Gly-Gly is the dipeptide glycyl-glycine coordinated through two nitrogen and oxygen atoms, with the N-acetylated dipeptide l-methionyl-l-histidine (MeCOMet-His) studied by 1H NMR spectroscopy. All reactions were carried out in 50 mM phosphate buffer at pD 7.4 and at 25 °C. In the initial stage of the reaction, the platinum(II) complex forms the kinetically favored [Pt(Gly-Gly-N,N′,O)(MeCOMet-His-S)]− complex, with unidentate coordination of the MeCOMet-His dipeptide through the sulfur atom of the methionine residue. In the second stage of the reaction, complete intramolecular migration of the [Pt(Gly-Gly-N,N′,O)] unit from the sulfur to the N3 nitrogen atom of imidazole was observed and a new platinum(II)-peptide complex, [Pt(Gly-Gly-N,N′,O)(MeCOMet-His-N3)]− was formed. In comparison with previous results obtained for the reaction of [Pt(dien)Cl]+ with different methionine- and histidine-containing peptides, this migration reaction was sufficiently fast and strongly selective to the N3 atom of the imidazole ring of the histidine side chain. This study is an important step in the development of new platinum(II) complexes for selective covalent modification of peptides and proteins. 相似文献
15.
Shveta Chaudhary J. David Van Horn 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2006,610(1-2):56
Kinetics for the breakdown of the trinuclear chromium acetate cluster with a series of monoprotic and diprotic amino acid ligands and with glutathione in aqueous media have been investigated spectrophotometrically at pH 3.5–5.5 and in a temperature range of 45–60 °C. Under pseudo-first-order conditions, reactions with these ligands exhibited biphasic kinetic behavior that can be accounted for by a consecutive two-step reaction, A → B → C, where A is assumed to be a forced ion pair, B an intermediate and C is the product; experimental data fit to a biexponential equation for the transformation. Rates for kshort, klong, and kobs were determined by manual extrapolation of absorbance data or curve-fitting routines; associated activation parameters for each step of the reaction were calculated using the Eyring equation. Rates for the first and second steps of the reaction are on the order of 10−4 and 10−5 s−1, respectively. The large negative values of ΔS‡ and smaller ΔH‡ in the first step indicate an associative step, while high positive values of ΔS‡ in the second step indicate dissociation. To account for the results mechanistically, the results are interpreted to be a first step of ligand exchange with a pseudo-axial aqua ligand, followed by a dissociative step involving acetate or oxo ligand displacement. The dissociative step is the rate determining step, with kobs ≈ klong.The results demonstrate reaction pathways that are available to the Cr(III) metal centers that may be physiologically relevant in the ligand-rich environment of biological systems. Under general conditions Cr(III) clusters may be expected to be broken down, unless some unique biological environment stabilizes the cluster. The present study has application to the processes related to Cr(III) transport and excretion, to potential mechanisms of Cr(III) action in a biological setting, and to the pharmacokinetics of Cr(III) supplements for animal and human consumption. 相似文献
16.
Four structurally diverse complexes, [Cd(dppz)(bdoa)]n (1), [Zn(dppz)(bdoa)(H2O)]n (2), [Fe(dppz)2(bdoa)]n·2nH2O (3), and [Co2(dppz)2(bdoa)2(H2O)]n·3nH2O (4), where H2bdoa = benzene-1,4-dioxyacetic acid and dppz = dipyrido[3,2-a:2′,3′-c]phenazine, have been hydrothermally synthesized. Compounds 1-4 feature chain structures. There exist π-π interactions in the structures of 1, 2 and 4. Two neighboring chains of 1 are linked through the π-π interactions into a double chain supramolecular structure. The chains of 2 and 4 are further extended by the π-π interactions to form 3D and 2D supramolecular structures, respectively. The structural differences among such complexes show that the transition metals have important influences on their structures. The photoluminescent property of complex 2 and the magnetic property of complex 4 have also been investigated. 相似文献
17.
β-Amyloid peptide (Aβ) 1–42, involved in the pathogenesis of Alzheimer’s disease, binds copper ions to form Aβ · Cun complexes that are able to generate H2O2 in the presence of a reductant and O2. The production of H2O2 can be stopped with chelators. More reactive than H2O2 itself, hydroxyl radicals HO (generated when a reduced redox active metal complex interacts with H2O2) are also probably involved in the oxidative stress that creates brain damage during the disease. We report in the present work a method to monitor the effect of chelating agents on the production of hydrogen peroxide by metallo-amyloid peptides. The addition of H2O2 associated to a pre-incubation step between ascorbate and Aβ · Cun allows to study the formation of H2O2 but also, at the same time, its transformation by the copper complexes. Aβ · Cun peptides produce but do not efficiently degrade H2O2. The reported analytic method, associated to precipitation experiments of copper-containing amyloid peptides, allows to study the inhibition of H2O2 production by chelators. The action of a ligand such as EDTA is probably due to the removal of the copper ions from Aβ · Cun, whereas bidentate ligands such as 8-hydroxyquinolines probably act via the formation of ternary complexes with Aβ · Cun. The redox activity of these bidentate ligands can be modulated by the incorporation or the modification of substituents on the quinoline heterocycle. 相似文献
18.
Caixia Yuan Liping Lu Xiaoli Gao Yanbo Wu Maolin Guo Ying Li Xueqi Fu Miaoli Zhu 《Journal of biological inorganic chemistry》2009,14(6):841-851
Abstract A series of oxovanadium complexes with mixed ligands, a tridentate ONO-donor Schiff base ligand [viz., salicylidene anthranilic
acid (SAA)], and a bidentate NN ligand [viz., 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[3,2-a:2′,3′-c]phenazine (dppz), or 7-methyldipyrido[3,2-a:2′,3′-c]phenazine (dppm)], have been synthesized and characterized by elemental analysis, electrospray ionization mass spectrometry,
UV–vis spectroscopy, Fourier transform IR spectroscopy, EPR spectroscopy, and X-ray crystallography. Crystal structures of
both complexes, [VIVO(SAA)(bpy)]·0.25bpy and [VIVO(SAA)(phen)]·0.33H2O, reveal that oxovanadium(IV) is coordinated with one nitrogen and two oxygen atoms from the Schiff base and two nitrogen
atoms from the bidentate planar ligands, in a distorted octahedral geometry (VO3N3). The oxidation state of V(IV) with d
1 configuration was confirmed by EPR spectroscopy. The speciation of VO–SAA–bpy in aqueous solution was investigated by potentiomtreic
pH titrations, and the results revealed that the main species are two ternary complexes at a pH range of 7.0–7.4, and one
is the isolated crystalline complex. The complexes have been found to be potent inhibitors against human protein tyrosine
phosphatase 1B (PTP1B) (IC50 approximately 30–61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly,
the [VIVO(SAA)(bpy)] complex selectively inhibits PTP1B over the other two phosphatases (approximate ninefold selectivity against
SHP-1 and about twofold selectivity against TCPTP). Kinetics assays suggest that the complexes inhibit PTP1B in a competitive
and reversible manner. These suggest that the complexes may be promising candidates as novel antidiabetic agents.
Graphical Abstract
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
19.
The reaction of the bisguanidine copper(I) compounds [Cu(btmgp)I] and [Cu2(btmgp)2][PF6]2 with molecular oxygen afforded at low temperatures complexes containing the bis-μ-oxo dicopper(III) core, which is capable to hydroxylate one of the N-CH3-groups of the {bis(tetramethyl)guanidino}propane ligands. The formation of the novel ligand {bis(trimethylmethoxy)guanidino}propane (btmmO) is reported as it represents the first hydroxylation of a N-methyl group. The products of this reaction are novel alkoxo-bridged binuclear copper complexes, namely [Cu2(btmmO)2I]+ containing an iodide ion in a novel bridging situation, as well as [Cu2(btmmO)2]2+ which have been identified in their complex salts and [Cu2(btmmO)2][PF6]2 · 2MeCN, respectively. Concomitantly, the hydroxo-bridged binuclear copper compounds [Cu2(btmgp)2(μ-OH)2]I2 and [Cu2(btmgp)2(μ-OH)2][PF6]2 are formed as couple products. The formation of the bis-μ-oxodicopper(III) complexes was monitored by UV/Vis-spectroscopy, and the reaction products were characterised by X-ray diffraction, vibrational spectroscopy and elemental analysis. 相似文献
20.
Franck Talmont Laura Piedra Garcia Honor Mazarguil Jean-Marie Zajac Catherine Mollereau 《Neurochemistry international》2009,55(8):815-819
The binding characteristics of [3H]-NPVF and [3H]-EYF, the two first tritiated probes for the respective labelling of NPFF1 and NPFF2 receptors, are presented. In membranes from CHO cells transfected with the human NPFF1 receptor, [3H]-NPVF labelled one class of binding sites with a high affinity (Bmax = 4 pmol/mg protein, Kd = 2.65 nM). In membranes from CHO cells transfected with the human NPFF2 receptor, [3H]-EYF labelled one class of binding sites with a high affinity (Bmax = 16 pmol/mg protein, Kd = 0.54 nM). Both radioligands exhibited time-dependent binding, low (10–20%) non-specific binding and poor cross-reactivity towards the related receptor subtype. The potency of different NPFF ligands to displace [3H]-NPVF and [3H]-EYF binding profiles was in good agreement with the profile previously measured by using 125I-probes (NPFF1 receptor: NPVF ≥ 1DMe = SPA-NPFF > NPFF = SQA-NPFF = QFW-NPSF > NPSF > RF9; NPFF2 receptor: SPA-NPFF > > SQA-NPFF = QFW-NPSF = 1DMe = NPFF NPSF = NPVF > RF9). Therefore, [3H]-NPVF and [3H]-EYF are new valuable tools for performing binding on NPFF receptors. 相似文献