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91.
Matthias Tacke Lorcan T. Allen William M. Gallagher Oscar Mendoza Franz-Josef K. Rehmann 《Journal of organometallic chemistry》2004,689(13):2242-2249
Starting from 6-(p−N,N-dimethylanilinyl)fulvene (1a) or 6-(pentamethylphenyl)fulvene (1b) [1,2-di(cyclopentadienyl)-1,2-di(p−N,N-dimethylaminophenyl)ethanediyl] titanium dichloride (2a) and [1,2-di(cyclopentadienyl)-1,2-bis(pentamethylphenyl)ethanediyl] titanium dichloride (2b) and their corresponding dithiocyanato complexes (3a, 3b) were synthesized. Titanocene 2b did not show a cytotoxic effect, but when 2a was tested against pig kidney carcinoma cells (LLC-PK) or human ovarian carcinoma cells (A2780/cp70) inhibitory concentrations (IC50) of 2.7 × 10−4 and 1.9 × 10−4 M, respectively, were observed. 相似文献
92.
Krauth-Siegel RL Bauer H Schirmer RH 《Angewandte Chemie (International ed. in English)》2005,44(5):690-715
Parasitic diseases such as sleeping sickness, Chagas' heart disease, and malaria are major health problems in poverty-stricken areas. Antiparasitic drugs that are not only active but also affordable and readily available are urgently required. One approach to finding new drugs and rediscovering old ones is based on enzyme inhibitors that paralyze antioxidant systems in the pathogens. These antioxidant ensembles are essential to the parasites as they are attacked in the human host by strong oxidants such as peroxynitrite, hypochlorite, and H2O2. The pathogen-protecting system consists of some 20 thiol and dithiol proteins, which buffer the intraparasitic redox milieu at a potential of -250 mV. In trypanosomes and leishmania the network is centered around the unique dithiol trypanothione (N1,N8-bis(glutathionyl)spermidine). In contrast, malaria parasites have a more conservative dual antioxidative system based on glutathione and thioredoxin. Inhibitors of antioxidant enzymes such as trypanothione reductase are, indeed, parasiticidal but they can also delay or prevent resistance against a number of other antiparasitic drugs. 相似文献
93.
Peptides represent an extensive class of biologically active molecules. They may be used as leads in the development of novel therapeutic agents provided the pharmacophoric information present within them can be translated into non-peptide analogs that lack the peptide backbone and are stable to proteolysis. This is the rationale for peptidomimetic drug design. Frequently, the -turn has been implicated as a conformation important for biological recognition of peptides. Empirical evidence from known peptidomimetics, coupled with a theoretical model of peptide binding and the observation that glycine and proline residues are common within the -turn, has suggested the design of molecules to mimic placement of between two and four of the side-chains. The moderate number of different -turn conformations, combined with the combinatoric nature of side-chain selection complicates the procedure. In this paper, cluster analysis has been used to classify the arrangement of C_ atoms about the various fragments of the -turn. Recombination of the observed patterns provides a general model for the -turn which may be used as an effective screen for potential peptidomimetic scaffolds in chemical databases. 相似文献
94.
Factor Xa is a serine protease which activates thrombin and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is at the crossroads of the extrinsic and intrinsic pathways of coagulation and, hence, has become an important target for the design of anti-thrombotics (inhibitors). It is not known to be involved in other processes than hemostasis and its binding site is different to that of other serine proteases, thus facilitating selective inhibition. The design of high-affinity selective inhibitors of factor Xa requires knowledge of the structural and dynamical characteristics of its active site. The three-dimensional structure of factor Xa was resolved by X-ray crystallography and refined at 2.2 Å resolution by Padmanabhan and collaborators. In this article we present results from molecular dynamics simulations of the catalytic domain of factor Xa in aqueous solution. The simulations were performed to characterise the mobility and flexibility of the residues delimiting the unoccupied binding site of the enzyme, and to determine hydrogen bonding propensities (with protein and with solvent atoms) of those residues in the active site that could interact with a substrate or a potential inhibitor. The simulation data is aimed at facilitating the design of high-affinity selective inhibitors of factor Xa. 相似文献
95.
Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability. 相似文献
96.
建立了分散固相萃取净化-超高效液相色谱-串联质谱法快速测定鱼和虾中3类(磺胺类、喹诺酮类、氯霉素类)18种抗生素及2种三苯甲烷类(孔雀石绿、隐色孔雀石绿)兽药残留。样品经磷酸氢二钾溶液水解分散,乙腈提取,提取液经氯化钠脱水、盐析后取乙腈层,经旋转蒸发仪浓缩至近干,残留物用甲醇定容至1.0 mL,C18和PSA(N-丙基乙二胺)填料分散固相萃取净化,过滤膜后经ZORBAX C18色谱柱(50 mm×2.1 mm,1.8 μm)分离,正、负离子多反应监测模式采集数据,同位素内标法定量。实验结果表明,20种兽药在0.2~300 μg/L范围内具有良好的线性关系,检出限为0.1~0.6 μg/kg,定量限为0.3~1.8 μg/kg,相关系数均大于0.99。在1、5和20倍定量限加标浓度水平下,平均回收率为72.5%~118%,相对标准偏差(RSD)为1.9%~9.8%。该方法具有前处理简单、检测效率高、成本低等优点,适用于鱼和虾中多类兽药残留的同时测定。 相似文献
97.
Study on surfactant coating of polymeric nanoparticles for controlled delivery of anticancer drug 总被引:1,自引:0,他引:1
Li?MuEmail author Pei-Hsing?Seow Sheu-Ngo?Ang Si-Shen?Feng 《Colloid and polymer science》2004,283(1):58-65
Biodegradable nanoparticles loaded with anticancer drug paclitaxel and appropriately coated with polyvinyl alcohol (PVA), polyethylene glycol (PEG) as well as d--tocopheryl polyethylene glycol 1000 succinate (TPGS) were produced and characterised by various analysis techniques such as laser light scattering (LLS) for particle size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for particle morphology, X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared-Photoacoustic Spectroscopy (FTIR-PAS) for surface chemistry, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency (EE) and in vitro release kinetics. The emphasis was given to the possible effects of surface coating on the physicochemical and pharmaceutical properties of paclitaxel loaded nanoparticles. It was found that the type and amount of the surfactant could significantly affect the drug EE in the nanoparticles, the particles characteristics and their in vitro release behaviour. The surfactants dominated on the nanoparticles surface and the coated nanoparticles displayed in spherical shape with relative smooth surface within the resolution scope of the equipment. The particle size and size distribution showed close relation to the surface coating, which may also be responsible for the drug encapsulation efficiency and the in vitro release kinetics. A favourable formulation of drug loaded nanoparticles of desired properties could be obtained by optimising the fabrication parameters. 相似文献
98.
We report the design and validation of a fast empirical function for scoring RNA-ligand interactions, and describe its implementation within RiboDock, a virtual screening system for automated flexible docking. Building on well-known protein-ligand scoring function foundations, features were added to describe the interactions of common RNA-binding functional groups that were not handled adequately by conventional terms, to disfavour non-complementary polar contacts, and to control non-specific charged interactions. The results of validation experiments against known structures of RNA-ligand complexes compare favourably with previously reported methods. Binding modes were well predicted in most cases and good discrimination was achieved between native and non-native ligands for each binding site, and between native and non-native binding sites for each ligand. Further evidence of the ability of the method to identify true RNA binders is provided by compound selection ('enrichment factor') experiments based around a series of HIV-1 TAR RNA-binding ligands. Significant enrichment in true binders was achieved amongst high scoring docking hits, even when selection was from a library of structurally related, positively charged molecules. Coupled with a semi-automated cavity detection algorithm for identification of putative ligand binding sites, also described here, the method is suitable for the screening of very large databases of molecules against RNA and RNA-protein interfaces, such as those presented by the bacterial ribosome. 相似文献
99.
Yousry M. Issa Hosny Ibrahim Adel F. Shoukry Sabry K. Mohamed 《Mikrochimica acta》1995,118(3-4):257-263
Ion-association complexes of antazoline HCl [I], hydralazine HCl [II], amiloride HCl [III] and quinine sulphate [IV] with [Co(SCN)4]2– and [Co(NO2)6]3– were precipitated and the excess unreacted cobalt complex was determined. A new method using atomic emission and atomic absorption spectrometry for the determination of the above drugs in pure solutions and pharmaceutical preparations is given. The drugs can be determined in the ranges 0.3–3.0, 0.19–1.96, 0.3–3.0, and 0.78–7.82 mg/25 ml solutions of I, II, III, and IV, respectively, with mean relative standard deviations of 0.65–2.03 % and recovery values of 95.76–101.2% indicating high precision and accuracy. 相似文献
100.
Pilar Campíns-Falcó Adela Sevillano-Cabeza Luisa Gallo-Martínez Francisco Bosch-Reig Isidro Monzó-Mansanet 《Mikrochimica acta》1997,126(3-4):207-215
This paper discusses the spectrophotometric determination of cephalexin as the intact cephalexin or as its acid-induced degradation product. Cephalexin can be determined in the range 1 × 10–5–18 × 10–5
M with relative standard deviations of 5-1%. The limits of quantitation and detection were 10–5 and 0.3 × 10–5
M, respectively. These procedures were compared with reversed-phase HPLC determination. No interference was observed in the presence of common pharmaceutical adjuvants. The H-point standard additions method was applied in order to correct for the possible presence of the cephalexin precursor, 7-aminocephalosporanic acid; this improves the selectivity of the UV-vis spectrophotometric method. 相似文献