共查询到20条相似文献,搜索用时 15 毫秒
1.
Alessandra de Santana Braga Barbosa Ribeiro Cláudio Carlos da Silva Flávia de Castro Pereira Aliny Pereira de Lima Cesar Augusto Sam Tiago Vilanova-Costa Simone Santos Aguiar Luiz Alfredo Pavanin Aparecido Divino da Cruz Elisângela de Paula Silveira-Lacerda 《Biological trace element research》2009,130(3):249-261
Chemotherapeutic agents play an important role in cancer treatment mostly due their systemic action on human organism allowing
access to liquid tumors and even metastases. Among these drugs, ruthenium compounds have been showing promising results to
treat tumors and represent an important development of new antitumor therapy. This study presents the evaluation of cis-(dichloro)tetraammineruthenium(III) chloride, cis-[RuCl2(NH3)4]Cl, genotoxic effects using human peripheral blood lymphocytes cultured in vitro. Mitotic index (MI), chromosome aberrations
(CA), and DNA damage using the comet assay were analyzed. MI in human peripheral blood lymphocyte cultures treated with 1,
10, 100, and 1,000 μg mL−1
cis-[RuCl2(NH3)4]Cl were 5.9%, 4.6%, 3.9%, and 0%, respectively. Doxorubicin chloridate was used as the positive control. CA derived from
1, 10, and 100 μg mL−1 concentrations were defined as spontaneous when compared with the negative control, and at the concentration of 1,000 μg
mL−1, the cell cycle was inhibited (IM = 0%). Results obtained for the comet assay using cis-[RuCl2(NH3)4]Cl suggest that this compound has no genotoxic activity against cultured human peripheral blood lymphocytes. 相似文献
2.
Elisângela de Paula Silveira-Lacerda Cesar Augusto Sam Tiago Vilanova-Costa Amélia Hamaguchi Luiz Alfredo Pavanin Luiz Ricardo Goulart Maria Inês Homsi-Brandenburgo Wagner Batista dos Santos Andreimar Martins Soares Auro Nomizo 《Biological trace element research》2010,135(1-3):98-111
The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl2(NH3)4]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL?1) of cis-[RuCl2(NH3)4]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency. 相似文献
3.
Flávia de Castro Pereira Cesar Augusto Sam Tiago Vilanova-Costa Aliny Pereira de Lima Alessandra de Santana Braga Barbosa Ribeiro Hugo Delleon da Silva Luiz Alfredo Pavanin Elisângela de Paula Silveira-Lacerda 《Biological trace element research》2009,128(3):258-268
Ruthenium complexes have attracted much attention as possible building blocks for new transition-metal-based antitumor agents.
The present study examines the mitotoxic and clastogenic effects induced in the root tips of Allium cepa by cis-tetraammine(oxalato)ruthenium(III) dithionate {cis-[Ru(C2O2)(NH3)4]2(S2O6)} at different exposure durations and concentrations. Correlation tests were performed to determine the effects of the time
of exposure and concentration of ruthenium complex on mitotic index (MI) and mitotic aberration index. A comparison of MI
results of cis-[Ru(C2O2)(NH3)4]2(S2O6) to those of lead nitrate reveals that the ruthenium complex demonstrates an average mitotic inhibition eightfold higher
than lead, with the frequency of cellular abnormalities almost fourfold lower and mitotic aberration threefold lower. A. cepa root cells exposed to a range of ruthenium complex concentrations did not display significant clastogenic effects. Cis-tetraammine(oxalato)ruthenium(III) dithionate therefore exhibits a remarkable capacity to inhibit mitosis, perhaps by inhibiting
DNA synthesis or blocking the cell cycle in the G2 phase. Further investigation of the mechanisms of action of this ruthenium
complex will be important to define its clinical potential and to contribute to a novel and rational approach to developing
a new metal-based drug with antitumor properties complementary to those exhibited by the drugs already in clinical use. 相似文献
4.
Attempted syntheses of ruthenium(II) monosubstituted squarate complexes in acetonitrile using cis-[RuCl2(dmso)4] and anisole-, methoxy-, methyl- and diphenylamino-squarate ligands, respectively, resulted in the formation in each case of the monomer cis, fac-Ru(CH3CN)Cl2(dmso)3 (1) with the ruthenium atom in a distorted octahedral environment. A second crop of crystals harvested from the reaction with the methoxysquarate ligand was identified as the oxalato-bridged dimer [{cis-(CH3CN)(Cl)(dmso)2Ru}2(μ-C2O4)] (2). When cis-[RuCl2(dmso)4] and methylsquarate were reacted in aqueous solution instead of acetonitrile, the dimer [{fac-(Cl)(dmso)3Ru}2(μ-C2O4)] (3) was produced. The dimers 2 and 3 are formed from oxidation/ring opening of the methoxy- and methyl-squarate ligands, respectively. Use of the salts of these ligands instead of their non-ionised forms under different reaction conditions, afforded [Na] fac-[RuCl3(dmso)3] (4) and [(C4H9)4N]2[(C4O4)(C4H2O4)2] (7), respectively, which were shown to be products of competing reactions. The information acquired from these failed attempts has provided the basis for the development of a strategy to overcome these problems and lead to a successful synthetic route to ruthenium(II) monosubstituted squarates. 相似文献
5.
《Inorganica chimica acta》1987,135(1):33-35
Reactions of cis-[Ru(en)2(OH2)2]2+ (or cis-[Ru (NH3)4(OH2)2]2+) with Pseudomonas aeruginosa azurin (Az), horse heart myoglobin (Mbh), and horse heart cytochrome c (cyt c) give Ru-labelled proteins. The ruthenium binding sites in the singly modified derivatives are His-83 (Az), His-81 (Mbh), and His-33 (cyt c). Spectroscopic and electrochemical measurements indicate that the structures of the proteins are not perturbed by the surface-bound ruthenium complexes. The E°f values of the Ru(III)/(II) couple in these Ru-modified proteins fall between −0.07 and −0.13 V vs. NHE. 相似文献
6.
cis-Dichlorodiammineplatinum(II) [cis-PtCl2(NH3)2] and dichlorotetrakis (dimethylsulfoxide) ruthenium(II) [RuCl2(DMSO)4] have been tested as mutagens for strains of Salmonella typhimurium carrying the hisG46 missense mutation. Their activity, which has been compared with the activity of mitomycin C, depends on the presence in the test bacteria of the pKM101 plasmid and is affected in various ways by the function of the excision repair system. More precisely, mitomycin C is mutagenic only for strains with an intact uvr system. cisPtCl2(NH3)2 and RuCl2(DMSO)4 are mutagens both for uvrB and uvr+ strains, but cis-PtCl2(NH3)2 is more active on the latter, while the converse is true for RuCl2(DMSO)4. It seems, therefore, that each drug interacts with DNA by a different mechanism. 相似文献
7.
The multinuclear (1H, 15N, 31P and 195Pt) NMR spectroscopies, ES-MS and HPLC have been employed to investigate the structure-activity relationship for the reactions between guanosine 5′-monophosphate (5′-GMP) and the platinum(II)-triamine complexes of the general formulation cis-[Pt(NH3)2(Am)Cl]NO3 (where Am represents a substituted pyridine). The order of reaction rate of the reactions was found to be: 3-phpy > 4-phpy > py > 4-mepy > 3-mepy > 2-mepy. The two basic factors, steric and electronic, were attributed to the order of the binding rate constants. A possible mechanism of the reaction of cis-[Pt(NH3)2(Am)Cl]+ with 5′-GMP suggested that the reactions proceed via direct nucleophilic attack and no loss of ammonia. cis-[Pt(NH3)2(Am)Cl]+ binds to the N7 nitrogen of the guanine residue of 5′-GMP to form a coordinate bond with the Pt metal centre. This mechanism is apparently different from that of cisplatin. The pKa value of cis-[Pt(NH3)2(4-mepy)(H2O)](NO3)2 (5.63) has been determined at 298 K by the use of distortionless enhancement by polarization transfer (DEPT) 15N NMR spectroscopy and compared to the pKa value of cis-[PtCl(H2O)(NH3)2]+. 相似文献
8.
This study contributes to the investigation related to guest–host interactions between the chemotherapeutic agent cisplatin and a functionalised silica matrix in order to improve and find new materials such as drug carriers. The adsorption of cisplatin and its complexes, cis-[PtCl(NH3)2]+ and cis-[Pt(NH3)2]2+, on a SH-functionalised SiO2(111) surface has been studied by the atom superposition and electron delocalisation method. The adiabatic energy curves for the adsorption of the drug and its products on the delivery system were considered. The electronic structure and bonding analysis were also performed. The molecule and their complex are adsorbed on the functionalised surface resulting in a major absorption of the cis-[Pt(NH3)2]2+ complex. The molecule–surface interactions are formed via –SH group. The molecule/complexes SH electron-donating effect plays an important role in the catalytic reaction. The more important drug–carrier interactions occur through the Cl–H bond for the adsorption of cis-[PtCl2(NH3)2] and cis-[PtCl(NH3)2]+, and through the Pt–S and Pt–H interactions for cis-[Pt(NH3)2]2+ adsorption. When the new interactions are formed, the functionalised carrier maintains their matrix properties while the molecule is the most affected after adsorption. The Pt atomic orbitals present the most important changes during adsorption. 相似文献
9.
Cesar Augusto Sam Tiago Vilanova-Costa Hellen Karine Paes Porto Flávia de Castro Pereira Aliny Pereira de Lima Wagner Batista dos Santos Elisângela de Paula Silveira-Lacerda 《Biometals》2014,27(3):459-469
Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma accounts for approximately 75–85 % of all lung cancers. In the present work, we studied the antitumor activity of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl2(NH3)4]Cl} against human lung carcinoma tumor cell line A549. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human lung carcinoma cell lines A549 treated with cisCarboPt, cisCRu(III) and cisDRu(III). The ruthenium-based coordinated complexes presented low cytotoxic and antiproliferative activities, with high IC50 values, 196 (±15.49), 472 (±20.29) and 175 (±1.41) for cisCarboPt, cisCRu(III) and cisDRu(III), respectively. The tested compounds induced apoptosis in A549 tumor cells as evidenced by caspase 3 activation, but only at high concentrations. Results also revealed that the amplification of P-gp gene is greater in A549 cells exposed to cisCarboPt and cisCRu(III) than cisDRu(III). Taken together all these results strongly demonstrate that MDR-1 over-expression in A549 cells could be associated to a MDR phenotype of these cells and moreover, it is also contributing to the platinum, and structurally-related compound, resistance in these cells. The identification and characterization of novel mechanisms of drug resistance will enable the development of a new generation of anti-cancer drugs that increase cancer sensitivity and/or represent more effective chemotherapeutic agents. 相似文献
10.
Treatment of ‘RuCl3 · 3H2O’ with Ph2AsCH2AsPh2 (dpam) in hot EtOH gives either trans-[RuCl2(dpam-As,As′)(dpam-As)2] (1), or cis-[RuCl2(dpam-As,As′)2] (2), depending on the mole ratio. On exposure to light, solutions of 2 isomerise to trans-[RuCl2(dpam-As,As′)2] (3). Treatment of [RuCl2(PPh3)3] with two equivalents of dpam in CH2Cl2 gave a mixture of two products, from which trans-[RuCl2(PPh3) (dpam-As,As′)(dpam-As)] (4) was isolated by recrystallisation. The crystal structures of 1-4 are reported. Complexes 1-3 in CH2Cl2 undergo electrochemical oxidation to Ru(III), and the Ru(III) form of 2 undergoes isomerisation on the voltammetric timescale to the Ru(III) form of 3. 相似文献
11.
《Inorganica chimica acta》1986,111(1):73-76
The reaction of the ruthenium complexes RuCl2(PPh3)3, RuCl2(PPh3)4, RuCl2(PMe3)4, RuCl2(Me2SO)4, or RuBr2(PPh3)3 with the tripod tetrakis(tertiary) phosphine P(CH2CH2CH2PMe2)3 gave the compounds cis-RuCl2 [P(CH2CH2CH2PMe2)3] (1) and cis-RuBr2[P(CH2CH2CH2PMe2)3] (2). The coordination geometry of 1 and 2 was derived from the ABX2 type 31P NMR patterns of the complexes, as well as from an X-ray structure determination for the chloride 1. Crystals of 1 were found to be monoclinic, space group P21/n (Z = 4), with a = 942.0(3), b = 1446.2(4), c = 1680(1) pm, and β = 104.99(4)°. Anisotropic refinement of the structure converged at R = 0.040 and Rw = 0.034 (3318 data). Selected bond lengths are (in pm): RuP(CH2−)Me2 (trans-atom P), 235.8(1) and 239.3(1); RuP(CH2−)Me2 (trans-atom Cl), 227.9(1); RuP(CH2−)3, 225.3(1); RuCl (trans-group P(CH2−)3), 252.1(1); and RuCl (trans-group P(CH2)Me2), 250.5(1). Reaction of 1 with LiAlH4 yielded the hydro derivatives cis-Ru(H)Cl[P(CH2CH2CH2PMe2)3] (3) and cis-RuH2[P(CH2CH2CH2PMe2)3] (4), which were characterized by IR and 1H and 31p NMR spectroscopy. 相似文献
12.
Maxim N. Sokolov Natalia E. Fedorova Eugenia V. Peresypkina Richard Pätow Dieter Fenske 《Inorganica chimica acta》2005,358(13):3914-3918
Two new Re(III) and Re(IV) complexes with 2(2′-pyridyl)benzimidazole (pbimz) were prepared and their crystal and molecular structures established by single-crystal X-ray diffraction. Reaction of [ReOCl2(OEt)(PPh3)2] with the ligand gave red cis(Cl),trans(P)-[ReCl2(PPh3)2(pbimz)]Cl (1), while red [ReCl4(pbimz)] · OPPh3 (2) was obtained from [ReCl3(PhC(O)C(O)Ph)(PPh3)] and pbimz in the presence of perchlorate. The compounds were characterized by elemental analysis, FAB-MS, UV-Vis, IR, NMR spectroscopy and magnetic susceptibility measurements. 相似文献
13.
Hexammine ruthenium(III) chloride, (Ru[NH3]6)Cl3, a potent novel compound, eliminated 100% of pBR322 and pBR329 plasmids fromEscherichia coli, rendering the bacteria vulnerable to the antibiotic-resistance markers carried on these plasmids. However, the curing activity of hexammine ruthenium(III) chloride was pH dependent. 相似文献
14.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,759(1):81-89
Ruthenium(III) complexes of the general formula HL[RuCl4L2], with two trans-standing heterocyclic ligands L bound to ruthenium via nitrogen, show remarkable activity in different tumor models. To obtain a deeper insight into the mode of action of this class of anticancer compounds, we investigated the interaction of HIm trans-[RuCl4(im)2] (im, imidazole) and HInd trans-[RuCl4(ind)2] (ind, indazole) with all four nucleoside monophosphates in buffered solution by means of capillary electrophoresis. A preference for GMP- and AMP-coordination was found. A decrease of the pH resulted in a significantly increased amount of bound nucleotide. This feature seems to be interesting with regard to the lower pH values in solid tumors. 相似文献
15.
《Inorganica chimica acta》1988,148(1):97-100
Six photoproducts were observed in the photolysis of [Ru(bpy)3]2+ in N,N-dimethylformamide (DMF) in the presence of chloride ions. The primary products were cis-[Ru(bpy)2Cl2] and cis-[Ru(bpy)2-(DMF)Cl]+. The remaining ruthenium products, which were thermally unstable to varying degrees, were cis-[Ru(bpy)2Cl2]+, [Ru(bpy)3]+, and a binuclear species we have tentatively identified as [Ru(bpy)2Cl]2n+ (n = 3 or 4). 相似文献
16.
The template alkylation of Li2[Ru(CO)2(S2C6H4)2] (S2C6H42− = 1,2-benzenedithiolate(−2)) by S(C2H4Br)2 yields [Ru(CO)2(dpttd)] (dpttd2− = 3,11,12-dibenzo-1,4,7,10,13-pentathiatridecane(−2)) which is thermally converted into the monocarbonyl complex [Ru(CO)(dpttd)]. The reactions of dpttd-H2 or dpttd2− with [RuCl2(PPh3)3], [RuCl2(DMSO)4], [RuCl3(PhSCH3)3] and RuCl3(NO)·xH2O lead to [Ru(L)(dpttd)] and [Ru(L)(dpttd)]Cl (L = PPh3, DMSO, PhSCH3, NO), respectively, which are practically insoluble in all common solvents. Better soluble complexes are obtained with the new sterically demanding ligand tbu4-dpttd2− = 14,16,18,20-tetra(t-butyl)-2,3,11,12-dibenzo-1,4,7, 10,13-pentathiatridecane(−2); it is obtained in isomerically pure form by the reaction of tetrabuthylammonium-3,5-di (t-butyl)-1,2-benzenethiolthiolate, NBu4[tbu2-C6H2S(SH), with S(C2H4Br)2 and yields on reaction with [RuCl2(PPh3)3] the very soluble [Ru(PPh3)2(tbu4-dpttd)] as well as [Ru(PPh3(tbu4-dpttd)]. The 1H NMR and 31P NMR spectra indicate that in solution [Ru(PPh3)2(tbu4-dpttd)] exists as a mixture of diastereomers, whereas [Ru(PPh3)(tbu4-dpttd)] forms one pair of enantiomers only. This was confirmed by an X-ray structure determination of a single crystal. [Ru(PPh3)(tbu4-dpttd)] crystallizes in space group P21/n with a = 10.496(4), b = 14.888(6), c = 32.382(12) Å, β = 98.04(3)°, Z = 4 and Dcalc. = 1.27 g/cm3, R = 4.84; RW = 5.06%; the ruthenium center is coordinated pseudooctahedrally by one phosphorus, two thiolate and three thiother S atoms. 相似文献
17.
Reaction of platinum(II) salts with 5-ferrocenylpyrimidine (FcPM) afforded cis-[Pt(NH3)2(FcPM)2](PF6)2 (1), trans-[Pt(NH3)2(FcPM)2](PF6)2 (2), cis-[PtCl2(FcPM)2] (3), and cis-[PtCl2(DMSO)(FcPM)] (4): their spectroscopic and electrochemical properties were investigated. Complexes 1 and 2 were structurally characterized by X-ray crystallography. 相似文献
18.
K.K. Sarker S. Saha Halder T.K. Mondal P.K. Nanda C. Sinha 《Inorganica chimica acta》2010,363(12):2955-623
Reaction of Cu(ClO4)2·6H2O, SRaaiNR′ (1-alkyl-2-[(o-thioalkyl)phenylazo]imidazole) and NH4SCN (1:1:2 mol ratio) affords distorted square pyramidal, [CuII(SRaaiNR′)(SCN)2] (3) compound while identical reaction with [Cu(MeCN)4](ClO4) yields -SCN- bridged coordination polymer, [CuI(SRaaiNR′)(SCN)]n (4). These two redox states [CuII and CuI] are interconvertible; reduction of [CuII(SRaaiNR′)(SCN)2] by ascorbic acid yields [CuI(SRaaiNR′)(SCN)]n while the oxidation of [CuI(SRaaiNR′)(SCN)]n by H2O2 in presence of excess NH4SCN affords [CuII(SRaaiNR′)(SCN)2]. They are structurally confirmed by single crystal X-ray diffraction study. Cyclic voltammogram of the complexes show Cu(II)/Cu(I) redox couple at ∼0.4 V and azo reductions at negative to SCE. UV light irradiation in MeCN solution of [CuI(SRaaiNR′)(SCN)]n (4) show trans-to-cis isomerisation of coordinated azoimidazole. The reverse transformation, cis-to-trans, is very slow with visible light irradiation while the process is thermally accessible. Quantum yields (?t→c) of trans-to-cis isomerisation are calculated and free ligands show higher ? than their Cu(I) complexes. The activation energy (Ea) of cis-to-trans isomerisation is calculated by controlled temperature experiment. Copper(II) complexes, 3, do not show photochromism. DFT and TDDFT calculation of representative complexes have been used to determine the composition and energy of molecular levels and results have been used to explain the solution spectra, photochromism and redox properties of the complexes. 相似文献
19.
The structure of the cis-[Pt(NH3)2(3′-CMP)2]2? ion, isolated in a partially protonated form as its cesium salt, has been analyzed by single-crystal x-ray diffraction methods. The 3′-CMP ligands bind in a monodentate fashion through their N(3) atoms: in contrast to the structure of [Pt(en)(5′-CMP)]2, no covalent platinum-phosphate bonding is found. This compound represents the first example of a 1:2 cis-metal/cytosine complex structurally characterized. 相似文献
20.
《Inorganica chimica acta》1988,142(2):219-221
The compounds [MI2(CO)3(NCMe)2] (M = Mo or W) react with one equivalent of SC(NH2)Me in CH2Cl2 at room temperature to initially give the acetonitrile substituted products [MI2(CO)3(NCMe)- {SC(NH2)Me}] which was isolated for M = W. However, the molybdenum complex rapidly dimerizes with loss of acetonitrile to give the iodide-bridged compound [Mo(σ-I)I(CO)3 {SC(NH2)Me}]2. The tungsten complex does not appear to dimerize, even after stirring at room temperature for 72 h in CH2Cl2. Two equivalents of thioacetamide react with [MI2- (CO)3(NCMe)2] in CH2Cl2 at room temperature to give the new bisthioacetamide compounds [MI2- (CO)3{SC(NH2)Me}2] via displacement of the labile acetonitrile ligands. The low temperature (−70 °C) 13C NMR spectrum of [WI2(CO)3{SC(NH2)Me}2] indicates that the geometry of the complex is capped octahedral with a carbonyl ligand in the unique capping position. 相似文献