PROTECTION OF ELECTROACUPUNCTURE ON HIPPOCAMPAL INJURY INDUCED BY QUINOLINIC ACID IN RATS

Objective To probe into the protective mechanism of electro-acupuncture （EA） on anti-oxygen stress in dementia-model rats. Methods A total of 30 male SD rats of cleaning grade were randomized into three groups, named sham-operation （n = 10）, model （n = 10）, model＋ EA （n = 10）. The dementia-model rat was made with hippocampal GA1 lesions by quinolinic acid （QA）. On the second day of modeling, in model＋ EA group, EA （3 Hz, 2-4 mA, continuous waves） was applied to ＂Dàzhuī＂ （大椎 GV 14） and ＂Shènshū＂ （肾俞 BL 23） for 10 min. The capability of learning and memory was evaluated by step-down test to observe the changes of nitric oxide （NO）, nitric oxide synthase （NOS） activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） of the hippocampal tissues in rats separately by biochemical methods. Results EA improved learning and memory of dementia rats with hippocampal CA1 lesions induced by QA at different degrees. It significantly increased SOD activity, reduced MDA content and improved NO level and NOS activity. Conclusion EA improves significantly the learning and memory of the dementia rats due to hippocampal CA1 lesions induced by QA, which is probably relevant with the anti-oxygen stress of EA.

Neurotoxicity of Quinolinic Acid to Spiral Ganglion Cells in Rats

Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs,and analyzed the role of QA in otitis media with effusion(OME)-induced sensorineural hearing loss(SNHL).After culture in vitro for 72 h,SGCs were exposed to different media and divided into 4 groups:the blank control group,the QA injury group,the MK-801 treatment group,and the MgCl2 protection group.The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later.SGCs were cultured in vitro for 72 h and divided into four groups:the low concentration QA group,the high concentration QA group,the MK-801 group,the MgCl2 group.The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy.Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group(both P0.05).In high concentration QA group,there was an obvious increase of the intracellular calcium concentration in SGCs,which didn’t present in low concentration QA group.In MgCl2 group,the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened,but the intracellular calcium concentration in SGCs had no significant change in MK-801 group.It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane,which might be the mechanism by which OME induced SNHL,while Mg2+ could protect the SCGs from the neurotoxicity of QA.

Research progress of quinolinic acid in neuropsychiatric diseases

Quinolinic acid is a neurotoxic substance produced by tryptophan through the kynurenine metabolism pathway.Quinolinic acid is involved in the pathological processes of Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,encephalitis,depression,and schizophrenia.The above process is realized through pathophysiological processes such as excitatory neurotoxicity,metabolic damage,free radical generation and oxidative stress,participation in inflammatory response,induction of neuron and astrocytic apoptosis.This article will explain the metabolic regulation,biological characteristics,and neurotoxicity of quinolinic acid.The research progress of quinolinic acid in Alzheimer's disease,Parkinson's disease,Huntington's disease,depression and subacute sclerosing panencephalitis is also described.

Facile and efficient synthesis of quinoline-4-carboxylic acids under microwave irradiation

A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.

Highly Efficient Synthesis of Novel Fluorine Bearing Quinoline-4-carboxylic Acid and the Related Compounds as Amylolytic Agents

Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilides 2 in boiling DMF, to give the target 3. Decarboxylation of 3 produced 6-fluoro-2-phenyl-3-(substituted amino)-keto-quinolines 4, while that reaction underwent refluxing, afforded 7-fluoro-1-(aryl)-3-phenyl-pyrrolo[3,4-c] quinoline-2,9-diones 5. Structure of the products has been established from their elemental and spectral analysis. All targets exhibited a high to moderate activity against some Aspergillus fungi as amylolytic agents.

Visible-light-induced deoxygenative C2-sulfonylation of quinoline N-oxides with sulfinic acids for the synthesis of 2-sulfonylquinoline via radical reactions

A simple and efficient method for the synthesis of 2-sulfonylquinoline from deoxygenative C2-sulfonylation of quinoline N-oxides with sulfinic acid induced by visible light is presented.This protocol shows a broad substrate scope,and desired products with various substituents can be formed in moderate to high yields at room temperature.

Two Novel Mercury(Ⅱ) and Copper(Ⅱ) Complexes Based on(5-Chloro-quinolin-8-yloxy)acetic Acid

Two novel mononuclear complexes with 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L）, namely, HgLBr2 1 and CuL2Cl2 2, have been prepared by solvothermal reaction of（5-chloro-quinolin-8-yloxy）acetic acid with HgBr2 and CuCl2, respectively. Their structures were characterized by IR, elemental analysis, UV-Vis-NIR spectra, TG and single-crystal X-ray diffraction analysis. Interestingly,（5-chloro-quinolin-8-yloxy）acetic acid is changed as 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L） in complexes 1 and 2. Crystal data for 1： C12H10Br2 Cl Hg NO3, Mr = 612.07, triclinic, space group P1 with a = 8.5983（7）, b = 9.7726（6）, c = 10.1549（6） A, α = 66.355（6）, β = 77.067（8）, γ = 78.803（8）°, V = 756.6（9）A^3, Z = 2, Dc = 2.687 g/cm^3, F（000） = 560, μ = 15.633 mm^-1, R = 0.0351 and w R = 0.0504. Crystal data for 2： C24H20Cl4 Cu N2O6, Mr = 637.76, triclinic, space group P1 with a = 10.5324（9）, b = 11.2377（16）, c = 12.0143（12） ？, α = 83.413（11）, β = 64.475（9）, γ = 83.144（11）°, V = 1270.9（2） ？3, Z = 2, Dc = 1.667 g/cm3, F（000） = 646, μ = 1.324 mm-1, R = 0.0408 and wR = 0.0922. In 1, the HgII centre is a distorted trigonal planar geometry comprised of two Br atoms and one quinoline N atom of L. Intermolecular π-π, C–H…π stacking interactions and intermolecular C–H…Br hydrogen bonds are observed in the molecular packing of 1. In complex 2, each CuII center has a distorted octahedral geometry comprised of two chloride ions, two quinoline N atoms and two O atoms of two L ligands. Intermolecular C–H…Cl hydrogen bonds exist in the molecular packing of 2. The fluorescence emission peak of complexes 1 and 2 appears near 406 and 410 nm, respectively. Optical diffuse-reflection spectral results suggest complex 1 has the property of semiconductor.

草酸离子液体脱除模拟油中的碱性氮化物

以草酸为原料,采用一步法合成了N-甲基吡咯烷酮草酸盐离子液体催化剂,将其应用于模拟油脱除碱性氮工艺。考察了离子液体催化剂反应时间、温度、剂油比、H_(2)O_(2)用量对喹啉脱除率的影响。实验结果表明:在反应温度为45℃,反应时间为40 min、剂油比为1∶10、无氧化剂条件下,喹啉脱除率可达98.59%,让离子液体重复使用4次后喹啉脱除率可达85.49%。

柠檬酸离子液体脱除汽油中的碱性氮化物

合成了N-甲基吡咯烷酮柠檬酸盐离子液体,通过表征表明,反应产物结构与设想合成产物结构一致。使用合成的离子液体催化剂对喹啉模拟汽油进行碱性氮脱除反应,考察不同反应条件下对碱性氮脱除率的影响,确定碱性氮脱除反应最佳工艺条件。实验结果表明,工艺条件条件为60℃、40min、剂油比1∶10时碱性氮脱除效果最佳,可达96.94%。在重复回收使用4次后碱性氮脱除率仍可达71.85%,碱性氮脱除效果较好。

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

Mn(acac)_(3)诱导1-异腈基-2-[1-(三氟甲基)乙烯基]苯自由基环化合成4-三氟甲基喹啉衍生物

开发了一种新的由锰[Mn(Ⅲ)/Mn(Ⅱ)]催化1-异腈基-2-[1-(三氟甲基)乙烯基]苯与芳基硼酸的自由基6-endo-trig环化反应.该反应条件温和,可在没有任何外部氧化剂、配体或添加剂的情况下,得到各种高区域选择性和化学选择性的4-三氟甲基-2-芳基喹啉衍生物.

淫羊藿苷对小鼠慢性低氧诱导学习记忆功能降低的防护作用及机制

目的探究淫羊藿苷(ICA)对小鼠慢性低氧环境暴露诱导记忆障碍的主要保护作用机制。方法选择8周龄雄性C57BL/6小鼠40只,建立模拟海拔6000 m低氧环境暴露动物模型。40只小鼠随机分至常氧组、常氧+ICA组、低氧组、低氧+ICA组(每组10只)。暴露28 d后进行Y迷宫、新物体识别实验评测小鼠空间记忆功能。利用免疫荧光染色观察小鼠海马组织小胶质细胞活化程度和神经元损伤情况,利用qRT-PCR方法检测海马组织iNOS、IL-1β、TNF-α、Cxcl-1、IL-4等炎性分子表达。使用喹啉酸试剂盒检测海马组织色氨酸犬尿氨酸途径代谢产物喹啉酸含量,使用qRT-PCR方法检测色氨酸犬尿氨酸代谢途径Ido1、Kmo、Haao、Kynu、Kyat3相关分子mRNA表达情况。结果与常氧组相比,Y迷宫及新物体识别实验结果显示低氧组小鼠出现明显空间记忆障碍(P<0.01);免疫荧光染色组织切片可见低氧组较常氧组海马小胶质细胞活化及神经元损伤明显(P<0.01);低氧组海马组织喹啉酸含量较常氧组升高(P<0.01);qRT-PCR检测发现低氧组海马组织炎症相关分子表达较常氧组显著升高(P<0.01),色氨酸犬尿氨酸代谢相关分子Ido1(P<0.01)、Kmo(P<0.01)、Haao(P<0.01)表达较常氧组明显升高,Kynu(P<0.01)、Kyat3(P<0.01)较常氧组表达降低。低氧+ICA组与低氧组小鼠相比,空间记忆能力有所改善(P<0.05),海马区小胶质细胞活化及神经元损伤相对减弱(P<0.05),炎症相关分子(P<0.01)及色氨酸犬尿氨酸代谢相关分子(P<0.01)表达均有相应回调。结论ICA可通过调控小胶质细胞色氨酸犬尿氨酸代谢,抑制小胶质细胞炎性活化和喹啉酸生成,缓解慢性低氧诱导小鼠海马神经元损伤,改善记忆功能减退。

第四代喹诺酮类抗菌药盐酸莫西沙星合成工艺进展与优化

盐酸莫西沙星是第四代氟喹诺酮类药物,临床应用领域广、效果良好,市场需求巨大,因此,研究盐酸莫西沙星合成工艺实现降本增产,对于制药行业和患者双方都有着很强的现实意义。通过对近年来盐酸莫西沙星合成工艺的进展与优化情况进行综述,探讨几种主要方法的优劣,并尝试汇总出一条较为可行、具有探索实验意义的工艺路线。

Corrosion behavior of aluminum alloy 2024-T3 by 8-hydroxy-quinoline and its derivative in 3.5% chloride solution

The corrosion behavior of aluminum alloy 2024-T3 was studied in 3.5% NaCl solution with two fluorescence quinoline compounds named 8-hydroxy-quinoline(8HQ) and 8-hydroxy-quinoline-5-sulfonic acid(HQS). The open circuit potential(OCP) test result indicates that both compounds change the alloy corrosion potential by adsorbing on the electrode surface. Polarization measurements show that 8HQ is a mixed type inhibitor by blocking the active sites of the metal surface, while HQS is a corrosion accelerator by activating the cathodic reaction. Changes of the impedance parameters in the electrochemical impedance spectroscopy(EIS) are related to the adsorption of 8HQ on the metal surface, which leads to the formation of a protective layer. The impedance diagram in the solution with HQS is similar to the one without additional organic compounds. The morphology and composition of the protective layer were studied by using SEM/EDS. The result confirms the function of the additions that the effect of 8HQ is due to the insoluble aluminum chelate, Al(HQ)3, to prevent adsorption of chloride ion, while the effect of HQS is to break down the oxide film.

A Novel Two-dimensional Lead(Ⅱ) Coordination Polymer Based on Dinuclear Lead(Ⅱ) Unit Containing(5-Chloro-quinolin-8-yloxy) Acetate

A novel two-dimensional lead（II） coordination polymer 1, [C11H7Cl2NO3Pb]n, has been prepared by solvothermal reaction of new bridging ligand（5-chloro-quinolin-8-yloxy）acetic acid（HL） with PbCl2, and its structure was characterized by IR, elemental analysis, TG-DTA and single-crystal X-ray diffraction analysis. The crystal is of monoclinic system, space group P21/c with a = 16.7603（7）, b = 8.6907（4）, c = 8.4745（3）A, β = 101.1110（11）°, C11H7Cl2NO3 Pb, Mr = 479.27, V = 1211.25（9）A3, Z = 4, Dc = 2.628 g/cm^3, F（000） = 880, μ = 14.367 mm^-1, R = 0.0173 and wR = 0.0508. The asymmetric unit contains one lead（II） cation, one（5-chloro-quinolin-8-yloxy）acetate（L） ligand and a chloride ion. The PbII center is hepta-coordinated in a distorted pentagonal bipyramidal geometry. The coordination sphere of the Pb atom is completed by two oxygen atoms and one nitrogen atom of the same L ligand, two bridging chloride ions and two bridging oxygen atoms of two adjacent L ligands. Two PbII centers are linked by the two L ligands to form a C2-symmetric dimer unit with a planar [Pb2O2] ring. Each dimer unit acts as a secondary building unit（SBU） and links adjacent four dimer units by the chloride atoms and oxygen atoms of carboxylate groups of L, forming a two-dimensional array. Such two-dimensional layers are packed through intermolecular C–H…Cl hydrogen bonds into a three-dimensional supramolecular structure. When the dimer unit is viewed as a 4-connected node, 1 is simplified as a 4-nodal 2-D network with square lattices of the diagonal lengths to be 6.079（1）A. The fluorescence emission peak of complex 1 appears near 407 nm.

Syntheses of Benzoxepinoquinolinone and Benzothiepinoquinolinone

l-Benzoxepino(3, 4-b)quinolin-l3(6H)-one and its halogen,alkyl, alkoxy derivatives Va'-d' and 1-benzothiepino(3,4-b}-quinolin- 13 ( 6H)-one Vf, and its alkyl derivatives Vg, weresynthesized through cyclization of 2-(substituted phenoxymethyl)-3-quinolinecarboxylic acids Va-d and 2-[ (un)substituted phen-ylthiomethyll-3-quinolinecarboxylic acids IVf-g in the presence ofpolyphosphoric acid.The acids IV were obtained from the corresponding ethyl-esters @ whcih were prepared through refluxing ethyl 2-bromo-methyl-3-quinolinecarboxylate(1) with substituted phenol or (un)substituted thiophenol in the presence of NaOEt.The compound Vg, was allowed to react with NBS, KaBH4, NH2OH-HCl to give compounds VII , VIII, and IX, respectively.The structures of 24 new compounds have been confirmed by elemental analysis, IR and 1H NMR.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

Synthesis, Structural Study and Spectroscopic Characterization of a Quinolin-8-Yloxy Derivative with Potential Biological Properties

We have prepared the (5-chloro-quinolin-8-yloxy) acetic acid and characterized it by using infrared, Raman and multi-dimensional nuclear magnetic resonance spectroscopies. The density functional theory (DFT) together with the 6-31G* and 6-311++G** basis sets were used to study its structure and vibrational properties. Three stable conformations of the compound were theoretically determined in gas phase and probably these conformations are present in the solid phase. The harmonic vibrational wavenumbers for the optimized geometries were calculated at the same theory levels. For a complete assignment of the observed bands in the vibrational spectra, the DFT calculations were combined with Pulay’s scaled quantum mechanical force field (SQMFF) methodology in order to fit the theoretical wavenumber values to the experimental ones. Besides, the force constants of the three conformers of (5-chloro-quinolin-8-yloxy) acetic acid were calculated and compared with those obtained by us for the 2-(quinolin-8-yloxy) acetic acid. In addition, the characteristics of the electronic delocalization of those structures were performed by using natural bond orbital (NBO), while the corresponding topological properties of electronic charge density are analysed by employing Bader’s atoms in molecules theory (AIM).

犬尿氨酸途径:帕金森病运动防治的一种可能新机制

帕金森病(Parkinson’s disease,PD)是一种与年龄相关的神经退行性疾病。犬尿氨酸途径(Kynurenine pathway,KP)是PD发生发展相关因素(中枢神经炎症、谷氨酸兴奋性毒作用和多巴胺耗竭等)的共同作用通路。KP主要酶系的调节剂(如抑制剂或激动剂)及其主要神经保护性代谢产物对缓解PD进展有益。运动可显著改善PD相关行为功能障碍,也可以影响KP代谢动力学。促进KP产生神经保护性活性代谢产物可能是运动改善PD相关行为功能障碍的中枢机制之一。本文从KP入手,对其在PD神经退行性病变及PD运动防治中的可能作用进行综述。

线粒体靶向的次氯酸荧光探针的构建及其生物成像研究

次氯酸(HClO)是生物体中重要的活性氧(ROS)物种之一,它在免疫系统中起着重要的杀菌作用,然而HClO浓度偏高与许多疾病的发生有关,如心血管疾病、关节炎、甚至癌症。本文将10-羟基苯并喹啉通过共轭双键与半花菁单元相连,构建了探针QUIN,该探针具有大的斯托克斯位移(151 nm),能以较高的灵敏度(LOD为0.13μmol·L^(-1))实现HClO的比率检测,而且探针QUIN成功检测了HeLa细胞中靶向线粒体的HClO水平,并实现了小鼠HClO水平的可视化。