不同降解方法制备褐藻胶甘露糖醛酸寡糖的结构特点

综述了以不同降解方法制备的甘露糖醛酸寡糖的结构特点,及其甘露糖醛酸寡糖在质谱、核磁共振氢谱及碳谱等谱图上的特征。     

咖啡酸苯乙酯及其苯甲酰基衍生物:合成和单晶X衍射分析(英文)

在Na2CO3的催化下,咖啡酸和β溴乙基苯在非质子性混合溶剂HMPACH3CN中高收率地合成天然蜂胶中主要的生物活性成分咖啡酸苯乙酯(CAPE)。为了更好地探究CAPE的构效关系和活性机理,我们首次成功地合成了单、双苯甲酰基取代的咖啡酸苯乙酯产物,同时单苯甲酰基取代产物结构通过单晶X衍射被确定。     

Physico-chemical and structural characterization of diacerhein

The physico-chemical and structural characterization of diacerhein, an anthraquinone with antiinflammatory activity, employed in the symptomatic treatment of inflammatory osteoarthritis, is reported. The combined use of FT-IR, DSC, X-ray powder and single-crystal diffraction has provided a valuable tool to fully characterize the title compound. The X-ray diffraction study has revealed the existence of hydrogen-bond assisted tight packing of the quasi-planar molecules in the solid. The collected results are intended to implement the information required for the compilation of drug master files.     

Infectious mononucleosis: etiology, immunological variants, methods of correction

Clinical options of infectious mononucleosis course depending on infecting agent etiology are presented for Epstein-Barr virus (EBV), cytomegalovirus (CMV), mono and mixed forms of the disease. Examined cytokine profiles demonstrate analogous changes of serum cytokines in the acute stage of the disease irrespective of etiological factors. Data show that it is important and useful clinically and immunologically to include immunomodulators--in particular, cycloferon--info a complex therapy of different types of mononucleosis.     

Oromucosal film preparations: classification and characterization methods

Introduction: Recently, the regulatory authorities have enlarged the variety of ‘oromucosal preparations' by buccal films and orodispersible films. Various film preparations have entered the market and pharmacopoeias. Due to the novelty of the official monographs, no standardized characterization methods and quality specifications are included.

Areas covered: This review reports the methods of choice to characterize oromucosal film preparations with respect to biorelevant characterization and quality control. Commonly used dissolution tests for other dosage forms are not transferable for films in all cases. Alternatives and guidance on decision, which methods are favorable for film preparations are discussed. Furthermore, issues about requirements for film dosage forms are reflected.

Expert opinion: Oromucosal film preparations offer a wide spectrum of opportunities. There are a lot of suggestions in the literature on how to control the quality of these innovative products, but no standardized tests are available. Regulatory authorities need to define the standards and quality requirements more precisely.     

Isolation and structural characterization by spectroscopic methods of two glucuronide metabolites of mexiletine after N-oxidation and deamination.

Urine samples from control and mexiletine-treated human subjects or rabbits (test group) were collected and passed through an ion exchange resin to isolate polar compounds. Methanolic eluates from control and test urines were analyzed by TLC. Exposure to p-dimethylaminocinnamaldehyde gave an additional intense pink band at Rt 0.40-0.45 in TLC analysis of test urine eluate when compared to control urine eluate. Non-exposed silica at this Rt was scraped and metabolites were extracted with methanol. Hydrolysis of this methanolic extract at 100 degrees C with hydrochloric acid released mexiletine. GC/MS and fast atom bombardment mass spectrometry analyses of nonhydrolyzed methanolic extracts evidenced the presence of two conjugated metabolites of mexiletine, namely, N-hydroxymexiletine glucuronide and mexiletine alcohol glucuronide. Synthetic compounds corresponding to these metabolites were obtained and spectra compared with those of isolated metabolites from urine. Definite structure assignment of N-hydroxymexiletine glucuronide was obtained from NMR spectrometry which confirmed the structure to be a hydoxylamine glucuronide (N-O-C link) and showed that the glycoside moiety was in the beta configuration. Thus, it is proposed that N-hydroxymexiletine glucuronide corresponds to mexiletine acid-labile conjugate and represents a major metabolic pathway in the disposition of mexiletine.     

Analysis of structural relationship between drug consumption and its influencing factors using multivariate statistical methods

Based upon various multivariate statistical methods consumption data of antihypertensive drugs and their causal or functional relationship with different influencing factors were investigated, exploratively and exemplarily. Several analytical examinations (principal components analysis, factor analysis, cluster analysis) were performed aiming at the reflection of these factors in a classified and quantified form.     

Phenothiazines: potential management of Creutzfeldt-Jacob disease and its variants.

Creutzfeldt-Jakob disease acquired from bovines (nvCJD) has been responsible for nearly 100 deaths in the UK and thousands more may die in the years to come. New variant CJD (nvCJD) is incurable and although clinical diagnosis is becoming more precise, the diagnosis is only certain at autopsy. Phenothiazine derivatives inhibit production of prions, the disease causing agent, in cultured neuroblastoma cells, and an advanced case of nvCJD was recently brought to remission by the use of these agents in combination with an antimalarial. In this review we present direct and circumstantial evidence in support of a model describing the manner by which the intracellular antimicrobial activity of phenothiazines might cause the destruction of intracellular prions.     

Stability studies and structural characterization of pramipexole

Stability studies of pramipexole dihydrochloride performed under following conditions of temperature and relative humidity (RH): 25 °C 60% RH and 40 °C 75% RH revealed its tendency to the water sorption and the monohydrate formation. The structural changes occurring during storage were studied by infrared spectroscopy and X-ray powder diffraction methods. The thermogravimetry technique was used to control the water sorption by the substance. Pramipexole dihydrochloride monohydrate was characterized by nuclear magnetic resonance and X-ray single crystal diffraction methods. The monohydrate crystallizes in the orthorhombic crystal system in the space group P212121.     

Isolation and structural characterization of acrylamide-pyridoxamine adducts

Pyridoxamine (PM) is an effective inhibitor of the formation of the carcinogen acrylamide (AA) from its precursors in low-moisture model systems. Although AA is widely assumed to act by scavenging carbonyl compounds, no alternative pathways have to date been explored. In this work, we found AA to directly react with PM in a low-moisture acrylamide-pyridoxamine model system heated at 140 °C for up to 40 min. The reaction products gave four major chromatographic peaks that were assigned to acrylamide-pyridoxamine adducts. Two of the adducts (AA-PM-1 and AA-PM-3) were selected for isolation and structural characterization with various spectroscopic (UV, fluorescence, IR, and NMR) and mass spectrometric techniques (MS, MS/MS). As shown by the proposed reaction scheme, PM can directly react with AA via Michael addition. The reaction involves a nucleophilic attack of the PM amine group on AA (an α,β-unsaturated carbonyl compound) to give adduct AA-PM-3, which was identified as 3-(((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)amino)propanamide. However, AA-PM-3 further reacts with any additional AA present in the medium to give adduct AA-PM-1 identified as 3,3'-(((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)azanediyl)dipropanamide. The time courses of these adduct formation reactions were studied in cookies supplemented with PM, where AA-PM-3 was found to be the predominant structure.     

Incorporation of hydrophobic porphyrins into liposomes: characterization and structural requirements

The ability of photosensitisers to give reactive oxygenated products is considered decisive for photodynamic applications, but the hydrophobic nature of many porphyrins makes necessary to obtain suitable pharmaceutical formulations. This paper reports the structural photosensitiser features that allow the preparation of stable liposomal formulations. Metallated and non-metallated TPPs and TPyPs and different lipid/porphyrin ratios were considered in order to procure liposomal preparations containing porphyrin concentrations adequate to necessary doses. The results show that the incorporation of porphyrins into liposomes can be related with their ability to form aggregates in a watery media. Thus, ZnTPP, which structural properties avoid the formation of aggregates, was efficiently incorporated into stable liposomes. Moreover, the efficient generation of singlet oxygen by ZnTPP liposomal suspensions has been shown. Because of this, the synthesis of hydrophobic porphyrin derived structures or other sensitisers, which do not aggregate in a watery media and with Q-bands shifted to higher lambda values than ZnTPP, will be efficiently incorporated into liposomes and useful for clinical applications.     

Isolation and structural characterization of colistin components

Preparative-scale separation of colistin sulphate bulk sample was carried out on a preparative poly(styrene-divinylbenzene) stationary phase. Isocratic elution with acetonitrile-sodium sulphate solution (0.7% m/v; pH adjusted to 2.5 with TFA) - water (16:50:34, % v/v/v) was carried out at a flow rate of 4.0 ml min(-1). Six colistin components were isolated and characterized using 1H and 13C NMR. The molecular weights were confirmed by mass spectrometry. The structures of 2 components were determined for the first time. Polymyxin E7 was identified as having the same composition as polymyxin E1, except that the fatty acid moiety was 7-methyloctanoic acid. Isoleucine polymyxin E8 was characterized as having the same composition as isoleucine polymyxin E1 with 7-methylnonanoic acid as the fatty acid moiety.     

Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes

Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three beta-cyclodextrins, namely, unsubstituted beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) on the chemical stability and water solubility of quercetin, and to elucidate the complexation mechanisms of these beta-CDs with quercetin. Quercetin-beta-CD complexes in solution were characterized by stability assessment, phase solubility measurements, and 1H-nuclear magnetic resonance (NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of the beta-CDs with quercetin. Solubility enhancements of quercetin obtained with the three beta-CDs followed the rank order: SBE-beta-CD > HP-beta-CD > beta-CD. The stability of quercetin at alkaline pHs also showed substantial improvement. NMR spectroscopic analysis suggested that the B-ring, C-ring, and part of the A-ring of quercetin display favorable interaction with the hydrophobic cavity of the beta-CDs, which was confirmed by molecular dynamics (MD) simulations using a solvated model of the quercetin-beta-CD complex. An inclusion complex model has been established for explaining the observed augmentation of solubility and stability of quercetin in water by beta-CDs.     

新型含硫酰基吡唑啉酮席夫碱稀土配合物的合成与结构表征

目的 :含硫席夫碱配合物的研究。方法 :在无水溶剂中 ,通过溶解、回流合成了未见报道的吡唑啉酮席夫碱两种稀土金属配合物。对所合成的配体和配合物进行了元素分析、电子光谱、红外光谱、差热—热重 ,并辅电导测定 ,从而初步确定了它们的分子结构式。结果 :通过分析可以基本得到稀土配合物的分子式和结构 :ML3(NO- 3) 3.3H2 O。结论 :得到所合成配合物。     

Plasticity of CYP2B enzymes: structural and solution biophysical methods

In the past three years, major advances in understanding cytochrome P450 2B (CYP2B) structure-function relationships have been made through determination of multiple ligand-bound and one ligand-free X-ray crystal structure of CYP2B4 and one ligand-bound X-ray crystal structure of CYP2B6. These structures have provided insight into the features that provide the high degree of plasticity of the enzymes. A combination of a phenylalanine cluster that allows for concerted movement of helices F through G and a conserved set of electrostatic interactions involving Arg(262) facilitates movement of this region to accommodate binding of ligands of various sizes without perturbing most of the P450 fold. Integrating solution based techniques such as NMR or deuterium exchange mass spectrometry (DXMS) with computational methods including molecular docking has provided further insight into enzyme behavior upon ligand binding. In addition, extended molecular dynamics simulations have provided a link between an open and a closed conformation of ligand-free CYP2B4 found in crystal structures. Other studies revealed the utility of rational engineering in improving stability of P450s to facilitate structural studies. The solution and computational results combined with the X-ray crystal structures yield a comprehensive picture of how these enzymes adopt different conformations to bind various ligands.     

Functional characterization of human xanthine oxidase allelic variants

OBJECTIVE: Xanthine oxidase (XO) catalyzes the oxidation of endogenous and exogenous purines and pyrimidines. In this study, we speculated that individual variations in XO activity are caused by genetic variations in the XO gene. METHODS: To investigate the genetic variations in XO in 96 Japanese participants, denaturing high-performance liquid chromatography was used. To assess the effects of these variations on enzymatic activity, wild-type XO and 21 types of variant XO--including those in the database and those just discovered--were transiently expressed in COS-7 cells. RESULTS: Three nonsynonymous single nucleotide polymorphisms, including 514G>A (Gly172Arg), 3326A>C (Asp1109Thr), and 3662A>G (His1221Arg) were identified in Japanese participants. Functional characterization of 21 XO variants showed a deficiency in enzyme activity in two variants (Arg149Cys and Thr910Lys); low activity (intrinsic clearance, CLint: 22-69% compared with the wild-type) in six variants (Pro555Ser, Arg607Gln, Thr623Ile, Asn909Lys, Pro1150Arg, and Cys1318Tyr); and high activity (CLint: approximately two-fold higher than that in the wild-type) in two variants (Ile703Val and His1221Arg). CONCLUSION: These results suggest that several single nucleotide polymorphisms in the XO gene are involved in individual variations in XO activity. In addition, such findings will be useful to identify xanthinuria patients.