2-乙酰噻吩吖嗪及其过渡金属配合物的合成与活性

目的 研究2-乙酰噻吩吖嗪及其过渡金属Cu^2 ，Fe^3 配合物的合成与生物活性。方法 从2-乙酰噻吩和水合肼出发合成2-乙酰噻吩吖嗪，进而合成了其过渡金属Cu^2 ，Fe^3 的配合物。用MS，^1H—NMR对配体进行了确认。通过元素分析、摩尔电导率、红外光谱、紫外光谱等手段对配合物进行了表征。用NBT法研究了配合物对超氧阴离子自由基的抑制作用；并利用MTT法和SRB法对其进行了抗肿瘤活性体外筛选实验。结果 发现配体和配合物都具有一定的生物活性，且Cu配合物活性较好。结论 配合物的生物活性可能与中心离子的最外层d轨道的电子结构有关。     

新型Cu(Ⅱ)配合物的合成与生物活性比较

<正> Schiff碱衍生物与许多金属配合物合成、应用的 研究近年来是人们研究的热点之一。研究表明,某 些Schiff碱衍生物具有抗癌、抗病毒、抑制细菌生长 等生物活性,配合物的生物活性常随配体组成的微 小变化而有明显的差异。因此,我们首先合成了以 水杨醛亚胺Schiff碱为配体的Cu(Ⅱ)配合物,为了 寻找活性最高,抗菌谱更广的抗癌抑菌药物,我们对 配体进行了结构修饰,合成了理化性及抑菌活性均 优于前者的4种Cu(Ⅱ)配合物。配体A(B)分别是 3——硝基(5—硝基)—N(2—羟基乙基)水杨醛亚胺 Schiff碱。     

葡萄糖胺和麦芽糖胺-过渡金属配合物的合成和结构表征Δ

摘要：目的研究葡萄糖胺和麦芽糖胺-过渡金属配合物的结构,为其应用奠定基础,合成及表征了4个葡萄糖胺和麦芽糖胺-过渡金属配合物。方法以葡萄糖和麦芽糖为原料,将合成的双葡萄糖丙二胺配体及双麦芽糖丙二胺配体分别与过渡金属Cu(II)、Ni(II)形成配合物。结果以33.9 %~73.8 % 的产率制备了4个葡萄糖胺和麦芽糖胺-过渡金属配合物,并通过紫外、红外、元素分析、摩尔电导等数据推测出了配合物的结构式。结论过渡离子与配体的摩尔比为1 : 2,Cu(II)配合物含有两种配位构型分别为不规则四边形和三角双锥,而Ni(II)配合物的构型为2分子水参与的八面体构型。     

硝基糠醛缩氨基硫脲及其Cu(Ⅱ)配合物的合成与生物活性

缩氨基硫脲及其过渡金属配合物具有广泛的生物活性。为了寻找理想的杀菌抑霉药物,设计合成了5-硝基糠醛缩氨基硫脲和它的7种N~4-取代衍生物;8个糠醛缩氨基硫     

3,5-二硝基水杨醛缩甘氨酸铜(Ⅱ)配合物的合成、表征及其抗O-.2活性

在水杨醛苯环上引入吸电子基并与甘氨酸缩合,设计合成了3,5-二硝基水杨醛缩甘氨酸席夫碱及其铜(Ⅱ)配合物,对配合物进行了元素分析、摩尔电导、红外光谱、紫外光谱等系列表征,讨论了配合物中金属配体键合作用以及配合物的结构,并用黄嘌呤-黄嘌呤氧化酶-鲁米诺化学发光法测定了其歧化超氧阴离子的活性,与超氧化物歧化酶(SOD)作了对照,发现该配合物有较强的清除O-.2作用,显示较强的SOD样活性,在一定程度上具有模拟SOD酶的作用.     

新型Ni~(2+)配合物的合成及活性测试

<正> 过渡金属配合物的生物活性是人们所共知的。本文合成了两种过渡金属Ni~(2+)的配合物,并对它们进行了红外光谱、元素分析及抑菌活性实验,结果表明:两种配合物对几种受试细菌敏感。实验与结果1,配体的合成 取N~4—苯基—取代氨基硫脲0.1mol溶于95％乙醇,加入糠醛1ml,搅拌回流,收集沉淀,无水乙醇     

金属微量元素的配合物在中药中的应用

目的:对金属微量元素的生理作用,以及金属微量元素与各类中药化学成分形成的配合物在中药中的应用进行探讨.方法:整理总结一些重要金属微量元素生理作用,以研究实例对比金属配合物与原配体生物活性强弱.结果:金属配合物的多方面生理活性均强于配体.结论:金属配合物开发潜力大,应用前景广阔.     

双取代乙二胺金属配合物的合成及抗菌活性

目的 设计合成一系列双取代乙二胺过渡金属配合物并寻找抗菌活性药物。方法以N，N’-双取代乙二胺为配体合成过渡金属配合物，并进行体外抑菌活性筛选。结果合成了6个(Ⅲ1-6)新配合物，其结构经红外光谱、元素分析确证。结论初步抑菌实验表明，合成的配合物对多种菌株有明显的抑制活性，有进一步研究的价值。     

木犀草素缩苯胺席夫碱配合物的合成及抑菌活性

目的：基于木犀草素的生物活性和席夫碱的特有性质基础上，设计与金属形成一系列新型席夫碱金属配合物。方法：利用缩合反应，在无水乙醇中合成未见报道的黄酮类席夫碱过渡金属配合物。并通过元素分析、紫外光谱、红外光谱、摩尔电导等手段对其进行了结构表征和抗菌活性实验。结果：通过分析，初步确定了其分子式、结构和其．生物活性。结论：结构式为：配合物MLx．nC2H5OH。形成配合物后抑菌活性大大增强。     

糖类缩氨基硫脲衍生物及其过渡金属配合物的合成和生物活性的研究

缩氨基硫脲衍生物及其金属配合物具有抗肿瘤、抗病毒、抗真菌及抗细菌活性。但这类化合物却很少应用于临床,原因之一是其水溶性很小。因此,我们设计在这类化合物中引入了一个或多个亲水性基团。本研究合成了9种糖类缩氨基硫脲衍生物及它们的5种过渡金属配合物。其中,1种糖衍生物及其     

Protein binding of xanthine derivatives to guinea pig serum albumin.

Binding of the bronchodilators N3-alkylxanthine and N3-alkyl-N1-methylxanthine derivatives to guinea pig serum albumin was investigated in vitro using the ultrafiltration method. A marked difference in the binding parameters of xanthine derivatives was observed, and binding was shown to be concentration dependent. Significant relations were observed among their binding parameter, dissociation constant (Kd), and hydrophobicity (log PC). The extent of binding of xanthine derivatives was increased both when a N3-methyl group was replaced by a longer alkyl chain and when a N3-alkylxanthine molecule was additionally replaced by a methyl group. Reversed-phase HPLC retention, as an index of hydrophobicity of xanthine derivatives, was also determined. Significant relationships were found between the adjusted retention time data for each xanthine derivative and their hydrophobicity or biological activities, such as their abilities to cause muscle relaxation and cyclic AMP phosphodiesterase (PDE) inhibition. These findings indicate that the difference in the extent of binding among xanthine derivatives is related to hydrophobicity, which is an important determinant of their biological activities.     

DNA-Binding Interaction Studies of Microwave Assisted Synthesized Sulfonamide Substituted 8-Hydroxyquinoline Derivatives

Sulfonamide substituted 8-hydroxyquinoline derivatives were prepared using a microwave synthesizer. The interaction of sulfonamide substituted 8-hydroxyquinoline derivatives and their transition metal complexes with Plasmid (pUC 19) DNA and Calf Thymus DNA were investigated by UV spectroscopic studies and gel electrophoresis measurements. The interaction between ligand/metal complexes and DNA was carried out by increasing the concentration of DNA from 0 to 12 μl in UV spectroscopic study, while the concentration of DNA in gel electrophoresis remained constant at 10 μl. These studies supported the fact that, the complex binds to DNA by intercalation via ligand into the base pairs of DNA. The relative binding efficacy of the complexes to DNA was much higher than the binding efficacy of ligands, especially the complex of Cu-AHQMBSH had the highest binding ability to DNA. The mobility of the bands decreased as the concentration of the complex was increased, indicating that there was increase in the interaction between the metal ion and DNA. Complexes of AHQMBSH were excellent for DNA binding as compared to HQMABS.     

肿瘤的化学治疗——ⅩⅩⅥ.胺羧类金属络合物抗癌作用的研究

化合物Ⅰ及Ⅱ为氨三乙酸(NTA)的类似物,其中一或三个羧甲基分别换以β-巯基乙基,与若干过渡元素及锑或砷所形成的金属衍生物,其比例为1:1.相当于集二分子EDTA于一体的Ⅲ,不与亚锑酸作用,与若干过渡元素所形成的比例为一分子络合剂与二原子金属.上述金属衍生物供动物肿瘤试验,初步报告,Ⅱ-As、Ⅲ-Cu及Ⅲ-Co对肉瘤180稍有抑制作用。     

Di- and triorganotin(IV) esters of 3,4-methylenedioxyphenylpropenoic acid: synthesis, spectroscopic characterization and biological screening for antimicrobial, cytotoxic and antitumor activities

Nine biologically significant organotin(IV) esters of 3,4-Methylenedioxyphenylpropenoic acid (L) were synthesized with the general formulae [R2SnL2], where R includes Me(1), Et(3), But(4), Oct(5), Ph(8), and [R3SnL], in which R is Me(2), Cy(6), Ph(7), and But(9). The acid and its compounds were characterized by basic analytical techniques comprising elemental analysis, FTIR and mass spectrometry in solid state and by Multinuclear (1H, 13C and 119Sn) NMR in solution form, which provides some important information about the different coordination behaviors of metal in both solid and solution. Methylenedioxy moiety in these compounds enhances the biological activity of these compounds. These compounds were screened for a range of biological activities. Antibacterial activities were determined against six pathogenic bacterial strains, three gram-positive and three gram-negative, the activities were measured in terms of inhibition zones (mm). Results demonstrate that diorganotin derivatives are more active than triorganotin derivatives and ligand acid. Antifungal activity was determined against six pathogenic fungal strains, cytotoxicity by the brine shrimp lethality assay, and antitumor activity by crown gall tumor inhibition (potato disc) assay. Results for antifungal activity, cytotoxicity, and antitumor activity of these compounds demonstrate that triorganotin derivatives are more active than diorganotin derivatives and ligand. Finally, the results were compared with similar reports in the literature.     

Metal chelates of a bispyridyl-tetrahydrothiazine dioxide

Metal Chelates of a Bispyridyl-tetrahydrothiazine dioxide A tetrahydrothiazine dioxide which has pyridyl-(2)-substituents at C-3 and C-5 forms metal chelates with salts of bivalent transition metals. In the IR-spectra of the chelates, some of the ligand bands are shifted in a characteristics manner, especially ν_8a - und ν_16b of the pyridine rings. Very probably the tetrahydrothiazine dioxide reacts as a tridentate ligand with the metal ion.     

Multifunctional ligands in medicinal inorganic chemistry--current trends and future directions

This review will highlight recent advances in ligand design for innovative applications in medicinal inorganic chemistry. Ligands that effectively bind metal ions and also include specific features to enhance targeting, reporting, and overall efficacy are driving innovation in areas of disease diagnosis and therapy. Increasing the potency of therapeutic compounds, while limiting side-effects, is a common goal in medicinal chemistry. In an effort to achieve this goal, compounds are being developed that either target a disease site, or are activated by a disease specific biological process. Metal complexes containing targeting functions and/or bioactive ligands, as well as agents that are activated by specific enzymes, or changes in pH and pO2, provide new avenues for drug development. Radiodiagnostic compounds, magnetic resonance imaging agents, and optical probes containing transition metals offer versatility unavailable to organic imaging agents. In certain cases, dual modality agents have been developed, and will be highlighted. Finally, we will discuss targeted metal binding compounds for treatment of metal overload disorders, and the recent application to neurodegenerative disease.     

Characterization and activity of cephalosporin metal complexes

Semi-synthetic cephalosporin antibiotics have structures similar to that of penicillins, and both groups of compounds are characterized by similar properties and determined by the same methods. Most antibiotics, including cephalosporins and their decomposition products, contain electron donor groups that can bind naturally occurring metal ions in vivo. Cephalosporin antibiotics exhibit a change in their toxicological properties and biological performance when they were tested as metal complexes. The proposed reason for such a behavior is the capability of chelate binding of the cephalosporins to the metals. In an attempt to understand the coordination mode of metals with cephalosporins, different spectroscopic techniques such as IR, UV-visible, NMR spectroscopy and voltammetric measurements were carried out to elucidate the structure of the metal-cephalosporin complexes. Synthesis, characterization and biological screening of the cephalosporins and of the cephalosporin-metal complexes are discussed in this review. However, little information is available on the influence of the metal ions on the pharmacokinetics of the cephalosporin derivatives.     

Using multiple metal-gill binding models and the toxic unit concept to help reconcile multiple-metal toxicity results

Metal-gill binding models and biotic ligand models (BLMs) in general are designed to predict metal toxicity to aquatic organisms. These models calculate the amount of a metal-binding to a sensitive biological membrane, such as a fish gill, which equates with metal toxicity. Cation competition at the metal-binding site and anionic complexation in the water decrease metal-binding to the membrane, decreasing metal toxicity. These models have, to date, been developed for individual metals. To assess how these models handle multiple-metal interactions, metal-gill binding models for two to six metals were created and their behavior tested against the toxic unit (TU) concept assuming strict additivity. The multiple-metal models yield greater than strict additivity at low aqueous metal concentrations (Sigma < 1 TU), strict additivity at intermediate metal concentrations (Sigma = 1 TU), and less than strict additivity at high metal concentrations (Sigma > 1 TU), independent of the combination of metals. Deviations from strict additivity are due to the non-linear nature of the models, where greater than linear filling of binding sites occurs at low metal concentrations, and where strong competition for binding sites occurs at high metal concentrations, with a point of strict additivity between, where the metals sum to one toxic unit. Simulations with natural organic matter (NOM) show similar trends but are complex. Mathematical modeling of multiple-metal interactions may help in the interpretation of toxicity results from mixed-metal exposures to aquatic organisms.     

Effects of phthalate ester derivatives including oxidized metabolites on coactivator recruiting by PPARalpha and PPARgamma

Phthalate esters (PEs), a group of environmental chemicals, affect biological systems via endocrine and lipid metabolism modulations. These effects are believed to be mediated in part by peroxisome proliferator-activated receptors (PPARs). Evaluations of PE activities as ligands toward PPARs have been investigated in many studies on their primary metabolites, monoesters. However, the activities of various other metabolites, including oxidized derivatives, remain to be determined. Here, we have evaluated the PPAR ligand activities of these PE derivatives by in vitro coactivator recruiting assay. Mono(2-ethyl-5-hydroxyhexyl)phthalate, the most abundant metabolite of di-(2-ethylhexyl)phthalate (DEHP), was less active than mono(2-ethylhexyl)phthalate (MEHP) as a PPAR ligand. Other derivatives oxidized at the alkyl group and benzene ring of DEHP, MEHP, dibutyl phthalate and its monoester were also investigated and some affected PPAR activities. Unexpectedly, MEHP as well as its further oxidized metabolite did not show clear activity for PPARalpha, although MEHP is believed to interact with PPARalpha. This might imply indirect PPAR-mediated mechanisms that lead to observed biological effects such as peroxisome proliferation.     

Synthesis,characterization and DNA photocleavage study of a novel dehydroacetic acid based hydrazone Schiff’s base and its metal complexes

A series of some novel colored complexes of Co(II), Ni(II), Cu(II), Mn(II) and Zn(II) with a novel dehydroacetic acid based hydrazone Schiff’s base has been synthesized and evaluated for their DNA photocleavage potential. The ligand utilized in the present investigation was synthesized via a condensation reaction between cyanoacetic acid hydrazide and dehydroacetic acid. Further, the ligand was treated with different metal acetates of first transition series in 1:1 and 1:2 (metal to ligand) ratios, respectively, to obtain metal complexes with different ligand to metal stoichiometry. Ligand as well as all the synthesized metal complexes were characterized on the basis of data obtained from the techniques like ¹H and ¹³C NMR, IR spectroscopy, mass spectrometry, UV visible spectroscopy, elemental analysis and molar conductance. ¹H NMR spectrum of Zn(II) complexes showed the coordination of enolic oxygen atom without deprotonation, but in case of DLCu, the deprotonation of enolic proton was occurred prior to coordination. IR data revealed the participation of a carbonyl oxygen atom of ligand in coordination with metal ions. UV visible data confirmed the square-planar and octahedral geometry of the complexes. Mass spectrum showed the formation of both 1:1 and 1:2 metals to ligand stoichiometry. Most of metal complexes exhibited very good DNA photocleavage activities.