硼氢阴离子交换树脂还原醛糖

制备了聚合物硼氢阴离子交换树脂（ＢＥＲ）,用ＢＥＲ－ＣｕＣｌ作还原剂,对醛糖进行催化氢化还原。实验结果表明：用ＢＥＲ作还原剂,反应条件温和,产品单一无副反应,产品产率高,产物易于分离。操作简便,ＢＥＲ价廉易制,还原容量高,树脂可再生反复使用     

还原糖测定方法的研究

介绍了4种还原糖的测定方法原理及各种方法的适用范围及特点.     

HMG-CoA还原酶抑制剂-瑞舒伐他汀的合成研究

以4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰基氨基)嘧啶-5-甲醇为起始原料,经缩合、水解去保护、酯化、水解、成钙盐等反应,重新设计并优化了缩合工艺和纯化工艺,制得降血脂药瑞舒伐他汀钙,合成的目标化合物,总收率为34.3%,纯度达到99.5%以上.并通过质谱、核磁共振氢谱和碳谱对目标产物进行了结构表征....     

合成对苯二甲醛新方法研究

报道了一种合成对七二甲醛的新方法,对硝基甲苯经氧化还原反应合成对氨基苯甲醛,再重氮化与甲醛肟反应生成对苯二甲醛,探索了影响对苯二甲醛产率的各种因素。     

烟草中水溶性总糖与还原糖的分析研究进展

烟草中的水溶性总糖和还原糖对烟气的香吃味都有良好的作用,并能减少烟气的刺激性,对烟叶品质影响巨大,是决定烟叶品质的重要化学成分,是烟草化学常规分析中的重要项目.就烟草中水溶性总糖与还原糖的几种分析方法,如铜还原-滴定法、比色法、近红外光谱法、连续流动法等进行了综述,铜还原-滴定法是经典的方法,DNS定糖法建立了批量连续测定烟草样品中还原糖、水溶性总糖的方法,该方法具有快速省时、操作简便、试剂消耗少等优点,近红外光谱法是一种方便、高效、无污染、非破坏性、低成本的绿色分析技术,准确度高、操作方便,最新的烟草行业标准采用连续流动仪测定水溶性糖.以期对烟草中水溶性总糖与还原糖的研究具有一定的指导作用.     

硫代硫酸钠滴定法测定还原糖含量的探讨

本文叙述了硫代硫酸钠滴定法测定还原糖含量的方法，并对其操作条件进行试验和探讨。     

醛／酮与胺还原烷基化反应的研究进展

介绍了实现醛／酮与胺的还原烷基化是制备高级胺反应的2种重要方法：催化加氢和硼氢化物化学还原,叙述了这2种反应体系的主要研究进展。介绍了催化加氢中常用的催化剂,指出对金属催化剂进行硫化处理是提高选择性的有效方法：介绍了硼氢化物化学还原法中常用的催化体系,讨论了醛／酮与胺还原烷基化反应中的影响因素,特别是原料的空间住阻、脱水剂、原料配比和溶剂等因素的影响,指出可以通过改变原料配比和溶剂等条件提高目标产物的选择性。     

纤维素酶水解纤维素还原糖的测定

对不同类菌种在不同培养基中的酶活性进行比较,测定了其底物得糖率,最高达８．５９％,可对纤维素酶的进一步研究提供实验参照。     

Structure‐Based Optimization of Aldose Reductase Inhibitors Originating from Virtual Screening

Virtual screening discovered two prospective hits as potential leads for aldose reductase inhibition. Based on their crystal structures with the enzyme, a systematic optimization has been performed to reveal a first structure–activity relationship. A central thiophen moiety and a terminal nitro group exhibit the best binding properties.

     

The Role of Aldose Reductase in Beta-Amyloid-Induced Microglia Activation

The occurrence of Alzheimer’s disease has been associated with the accumulation of beta-amyloid (β-amyloid) plaques. These plaques activate microglia to secrete inflammatory molecules, which damage neurons in the brain. Thus, understanding the underlying mechanism of microglia activation can provide a therapeutic strategy for alleviating microglia-induced neuroinflammation. The aldose reductase (AR) enzyme catalyzes the reduction of glucose to sorbitol in the polyol pathway. In addition to mediating diabetic complications in hyperglycemic environments, AR also helps regulate inflammation in microglia. However, little is known about the role of AR in β-amyloid-induced inflammation in microglia and subsequent neuronal death. In this study, we confirmed that AR inhibition attenuates increased β-amyloid-induced reactive oxygen species and tumor necrosis factor α secretion by suppressing ERK signaling in BV₂ cells. In addition, we are the first to report that AR inhibition reduced the phagocytotic capability and cell migration of BV₂ cells in response to β-amyloid. To further investigate the protective role of the AR inhibitor sorbinil in neurons, we co-cultured β-amyloid-induced microglia with stem cell-induced neurons. sorbinil ameliorated neuronal damage in both cells in the co-culture system. In summary, our findings reveal AR regulation of microglia activation as a novel therapeutic target for Alzheimer’s disease.     

Rational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors

A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesised based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a methyl group to bring the molecular weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesised compounds in addition to the previously identified hits were subjected to molecular docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimised to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimised ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesised compounds indicate that these compounds possess good pharmacokinetic properties.     

Improved Tricyclic Inhibitors of Trypanothione Reductase by Screening and Chemical Synthesis

Trypanothione reductase (TryR) is a key validated enzyme in the trypanothione‐based redox metabolism of pathogenic trypanosomes and leishmania parasites. This system is absent in humans, being replaced with glutathione and glutathione reductase, and as such offers a target for selective inhibition. As part of a program to discover antiparasitic drugs, the LOPAC1280 library of 1266 compounds was screened against TryR and the top hits evaluated against glutathione reductase and T. brucei parasites. The top hits included a number of known tricyclic neuroleptic drugs along with other new scaffolds for TryR. Three novel druglike hits were identified and SAR studies on one of these using information from the tricyclic neuroleptic agents led to the discovery of a competitive inhibitor (K_i=330 nM ) with an improved potency against T. brucei (EC₅₀=775 nM ).     

Binding to Large Enzyme Pockets: Small‐Molecule Inhibitors of Trypanothione Reductase

The causative agents of the parasitic disease human African trypanosomiasis belong to the family of trypanosomatids. These parasitic protozoa exhibit a unique thiol redox metabolism that is based on the flavoenzyme trypanothione reductase (TR). TR was identified as a potential drug target and features a large active site that allows a multitude of possible ligand orientations, which renders rational structure‐based inhibitor design highly challenging. Herein we describe the synthesis, binding properties, and kinetic analysis of a new series of small‐molecule inhibitors of TR. The conjunction of biological activities, mutation studies, and virtual ligand docking simulations led to the prediction of a binding mode that was confirmed by crystal structure analysis. The crystal structures revealed that the ligands bind to the hydrophobic wall of the so‐called “mepacrine binding site”. The binding conformation and potency of the inhibitors varied for TR from Trypanosoma brucei and T. cruzi.     

Pharmacophore and Molecular Docking Guided 3D-QSAR Study of Bacterial Enoyl-ACP Reductase (FabI) Inhibitors

Enoyl acyl carrier protein (ACP) reductase (FabI) is a potential target for the development of antibacterial agents. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for substituted formamides series of FabI inhibitors were investigated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Pharmacophore and molecular docking methods were used for construction of the molecular alignments. A training set of 36 compounds was performed to create the 3D-QSAR models and their external predictivity was proven using a test set of 11 compounds. Graphical interpretation of the results revealed important structural features of the formamides related to the active site of FabI. The results may be exploited for further optimization of the design of new potent FabI inhibitors.