N-丁基-9 H-嘧啶并[4,5-b]吲哚-2-甲酰胺通过NLRP3/Caspase-1抑制巨噬细胞泡沫化及焦亡作用

目的设计并合成了嘧啶并吲哚类衍生物N-丁基-9 H-嘧啶并[4,5-b]吲哚-2-甲酰胺(BFPI),探讨其是否通过NLRP3/Caspase-1通路抑制巨噬细胞焦亡和泡沫化作用。方法以2,4,6-三乙氧羰基-1,3,5-三嗪和2-氨基吲哚为起始原料合成BFPI,并通过1H NMR、13 C NMR、ESI-MS对其结构进行表征。将体外培养的小鼠单核巨噬细胞株RAW264.7分为空白组、模型组(PA)组和治疗组(BFPI)组,各组细胞用对应培养液处理24 h后,用MTT法检测其增殖活力,油红O染色检测细胞内脂滴形成情况,并用Western blot和RT-qPCR检测NLRP3、Caspase-1和MCP-1 mRNA和蛋白表达水平。结果与空白组比较,模型组细胞增殖活力明显下降,脂滴形成量明显增加,与模型组比较,治疗组细胞增殖活力明显增加,脂滴形成量明显降低,差异均有统计学意义(P<0.01);与空白组比较,模型组细胞NLRP3、Caspase-1和MCP-1的mRNA和蛋白表达水平均明显增加,与模型组比较,治疗组细胞上述指标表达水平均明显下降,差异有统计学意义(P<0.01)。结论BFPI可通过抑制巨噬细胞NLRP3、Caspase-1和MCP-1的表达进而促进其增殖并抑制脂质吞噬能力,有助于延缓动脉粥化时巨噬细胞来源的泡沫细胞形成。

基于1H-吡唑并[3,4-b]吡啶母核PI3Kδ抑制剂的设计合成

恶性肿瘤严重危害人类健康与生命,磷脂酰肌醇-3激酶家族(PI3Ks)在细胞增殖、分化过程中起着重要作用,该激酶及其相关通路的其他激酶可被药物干预,是抗癌药物的热门靶点。在以往的PI3K抑制剂中,均有1H-吡唑并[3,4-b]吡啶母核,通过虚拟筛选以及合成路线设计,合成了一系列1H-吡唑并[3,4-b]吡啶类化合物,该类化合物可能对PI3Kδ具有潜在抑制作用。

Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

基于二萘并[2,3-B∶2′,3′-D]呋喃基团的高效窄发射蓝光OLED器件

高效率窄光谱蓝色有机电致发光器件(OLED)是柔性显示领域的研究重点之一。本文以二萘并[2,3-B∶2′,3′-D]呋喃为弱电子受体、N-(4-联苯基)-1-萘胺作为电子给体设计合成了一种D-A-D型蓝光分子DPF-NA,其在正己烷溶液中的发射峰位于441 nm。理论计算与光物理测试结果显示DPF-NA具有杂化局域电荷转移激发态(HLCT)特性,兼具局域态(LE)高发光效率与电荷转移态(CT)高激子利用率特征,在二氯甲烷溶液中的光致发光量子效率(PLQY)为81.2%。基于质量分数3%DPF-NA掺杂浓度的OLED器件电致发光(EL)峰位于455 nm,半峰宽(FWHM)仅为26 nm,CIE(x,y)坐标为(0.14,0.08),最大外量子效率(EQEmax)为6.76%。

n(Bi_(2)O_(3))/n(SiO_(2))对Bi_(2)O_(3)-B2O_(3)-SiO_(2)系光伏玻璃背板油墨微观结构和反射率的影响

随着光伏发射极和背面钝化电池双面双玻组件产业的兴起,光伏玻璃背板用光伏油墨的需求量逐年递增。光伏油墨制备成涂层后,其致密程度将直接影响自身的反射率,进而对光伏电池的光电转化效率产生影响。本文通过改变n(Bi_(2)O_(3))/n(SiO_(2)),探究玻璃熔剂析晶和其对Bi_(2)O_(3)-B_(2)O_(3)-SiO_(2)系玻璃熔剂所制备光伏油墨的影响。采用DSC和Raman对玻璃熔剂的特征行为进行了表征,采用XRD、SEM、色度仪对不同光伏油墨涂层的微观结构和反射率进行了研究,并提出了光伏油墨涂层的光反射增强机制。研究表明,n(Bi_(2)O_(3))/n(SiO_(2))的升高会使[BiO_(3)]和[BiO_(6)]基团含量增多,破坏[SiO_(4)]玻璃网络的能力增强,玻璃熔剂的转变温度和析晶峰温度逐渐降低,玻璃熔剂的析晶能力逐渐增大。在短时间内烤制后的玻璃熔剂涂层中会逐渐析出大量的片状Bi_(2)SiO_(5)晶粒,将其制备成光伏油墨涂层后,涂层的反射率会随着n(Bi_(2)O_(3))/n(SiO_(2))的升高而逐渐升高。当n(Bi_(2)O_(3))/n(SiO_(2))为30∶60时,光伏油墨涂层的反射率在近红外波长范围内可提升到82.66%。这主要是因为油墨涂层中的孔隙和空洞作为异相界面,可促使Bi_(2)SiO_(5)晶粒析出并填充在光伏油墨涂层的孔隙和空洞中,使油墨涂层的致密度提高,从而增强光伏油墨涂层对光线的反射能力。

A novel synthesis of pyrazolo[3,4-b]pyridine derivatives through multi-component reaction in ionic liquid

An efficient and novel procedure for the preparation of pyrazolo[3,4-b]pyridine derivatives through multi-component reaction of aldehyde, 5-amino-3-methyl-1-phenylpyrazole and malononitrile or cyanoacetate in [bmim][BF4] is described in this paper. Advantages of the method presented here include mild conditions, high yields together with a green nature and ease of recovery and reuse of the reaction medium.

Synthesis, Crystal Structure and Property of a Series of Supramolecular Polymers Based on Novel 3,5-Dimethyl- 2,6-bis(3-(pyrid-2-yl)-1,2,4-triazolyl)pyridine Ligand

Solvothermal reactions of 3,5-dimethyl-2,6-bis（3-（pyrid-2-yl）-1,2,4-triazolyl） pyridine （L）, 1,4-benzendicarboxylic acid （H2bdc）, and transitional metal cations of M11 （M = Mn, Co, Cd） in the presence of oxalic acid （H2ox） afford three novel supramolecular polymers （CPs）, namely, {[M2（ox）（L）2][bdc][M2（Hox）2（OH）（H2O）4]·3H2O}n （M = Mn for 1, Co for 2, Cd for 3）. Single-crystal X-ray diffraction analysis reveals that complexes 1-3 are isostructural and the 3D supramolecular structure was connected through non-covalent interactions. With the help of H2ox, the L ligands cheated with center atoms forming a butterfly [M2（ox）（L）2]2＋ building block. The bdc2- ligand linked with the unprecedented [M2（Hox）2（OH）2（H2O）4] units through strong O-H...O hydrogen bonds forming a zigzag chain, which are further connected through π-π interactions between L and bdc2- ligands to form a 3D supramolecular structure. Moreover, elemental analyses, IR, thermogravimetric, PXRD and luminescence have been investigated.

Synthesis,Crystal Structure,and Magnetic Property of One 3D Nickel Coordination Polymer Based on 2-Hydroxy-5-(3',5'-terephthalic acid)Pyridine and 1,4-Bis(1-imdazoly)benzene

One novel nickel coordination polymer, {[Ni（OTP）（bib）1.5（H2O）]·2H2O}n（1, H2 OTP = 2-hydroxy-5-（3＇,5＇-terephthalic acid） pyridine, bib = 1,4-bis（1-imdazoly）benzene）, has been synthesized and characterized by elemental analysis（EA）, IR, powder X-ray diffraction（PXRD）, and thermogravimetric（TG） analyses. The crystal of 1 crystallizes in monoclinic, space group P21/n with a = 12.2860（5）, b = 13.8246（6）, c = 19.0140（8） A, β = 104.3870（1）°, V = 3128.2（2） A3, Z = 4, C32H28N7 Ni O8, Mr = 697.32, Dc = 1.481 g/cm^3, F（000） = 1444 and μ（Mo Kα） = 0.684 mm-1. The final R = 0.0704 and w R = 0.1764 for 5485 observed reflections with I 2σ（I） and R = 0.1087 and wR = 0.2010 for all data. Topology analysis reveals that complex 1 is a 3D 2-fold interpenetrated {4^4·6^6}-nov net based on the 1D [Ni（OTP）]n chain and the 2D [Ni2（bib）3]n sql sheet. And the variable-temperature magnetic susceptibility measurements exhibit weak antiferromagnetic coupling interaction.

New and Facile Synthesis of Substituted Pyrrole, Pyridine, Pyrazolo[4,3-b] Pyridine, Pyrano[3,2-c] Quinoline, Napthopyran, Naphthodipyran and Coumarin Derivatives

Several new pyrazolo[4,3-b] pyridines 7a, b were prepared by reacting arylidenemalononitriles 1a, c or 1i, j with 4-nitrosoantipyrine 4. Reacting 1a, b, d with 4-azidomethylcarbonylantipyrine 8 give 2-aminopyrrole 14. Pyrano[3,2-c] quinolines 20a, b and 23 were obtained by reacting 4-hydroxyquinoline 15 with 1g, h, 2b respectively. Reaction of 1 with naphthalenediols 24, 27 and 29 yield naphthodipyrans 26a, b, 28a, b and 30a。

Synthesis, Reactions and Characterization of 1,1’-(1,4-Phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(ethan-1-one)

Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). The reaction of 2 with hydrazine hydrate followed by diazotization reaction af-forded the 1,1’-(1,4-phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(e-than-1-one) (3) and 1,1’-(1,4-phenylenebis(3-(chlorodiazenyl)-6-methyl-1H-pyrazolo[3,4-b]-pyridine-4,5-diyl))bis(ethan-1-one) (4) respectively. On the other hand, reaction of 4 with malononitrile, 2-cyanoethanethioamide, ethyl acetoacetate, acetyl acetone, ethyl benzoylacetate, diethylmalonate, ethyl cyanoacetate and phenacylbromide aiming to build up pyrazolotriazine or pyrazole ring on the ring system of 4. Structures of all newly synthesized heterocyclic compounds in the present study were confirmed by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses.

Theoretical Study on the Reaction Mechanism of 2-Methoxybenzaldehyde,4-Bromo-indanone,Malononitrile and Ammonium Acetate One-pot to Form 6-(2-Methoxyphenyl)-2-amino-6-bromo-5H-indeno[1,2-b]pyridine-3-carbonitrile

The reaction mechanism of 2-methoxybenzaldehyde, 4-bromo-indanone, malononitrile and ammonium acetate one-pot to form 6-（2-methoxyphenyl）-2-amino-6-bromo-5 Hindeno[1,2-b]pyridine-3-carbonitrile was studied by density functional theory. The geometries of the reactants, transition states, intermediates and products were optimized at the PW91/DNP level. Vibration analysis was carried out to confirm the transition state structure. Reaction pathways were investigated in this study. The result indicates that the reaction Re→ TSB1→IMB1→ TSB2→ IMB2→TSB3→IMB3→TSB4→IMB4→TSB5→IMB5→TSB6→IMB6→TSB7→IMB7→ TSB8→IMB8→TSB9→IMB9→P2 is the main pathway, the activation energy of which is the lowest. The dominant product predicted theoretically is in agreement with the experiment results.

A New Diiminopyridyl Cobalt Complex [CoCl_2L](L=2,6-Bis(N,N'-bis(2,6-diisopropyl-4-(2,3-dimethyoxylbenzoylamide)phenylimino))pyridine)

The reaction of CoCl2·6H2O with 2,6-bis（N,N＇-bis（2,6-diisopropyl-4-（2,3-dimethy-oxyl-benzoylamide）phenylimino））pyridine（L） afforded the complex [CoCl2L],which was fully characterized by elemental analysis,UV-vis,IR spectroscopy,fluorescence,and X-ray diffraction analysis.The compound is of triclinic system,space group P1 with a = 13.058（3）,b = 13.798（3）,c = 16.695（3） ,α = 98.191（3）,β = 102.792（3）,γ = 101.820（3）°,V = 2815.0（9） 3,Z = 2,F（000） = 1122,μ = 0.45 mm-1,R = 0.061 and wR = 0.1349 for 9842 observed reflections（Ⅰ 〉 2σ（Ⅰ））.The Co（Ⅱ） center adopts a distorted square-pyramidal coordination geometry.The extended structure shows a one-dimensional zigzag double chain linked by hydrogen bonds and π-π stacking interactions.

3,4-二氢吡喃[3,2-b]-吲哚-2-酮的合成

目前合成3,4-二氢吡喃[3,2-b]-吲哚-2-酮的方法均以卡宾为催化剂。本文以碳酸铯为催化剂,乙腈为反应溶剂,吲哚-3-酮与α,β-不饱和N-酰基琥珀酰亚胺为原料,于25℃条件下发生迈克尔加成反应介导的环化反应,合成3,4-二氢吡喃[3,2-b]-吲哚-2-酮,收率74%~93%,所得化合物的结构经^(1)H NMR,^(13)C NMR和HR-MS表征。该合成方法具有较高的新颖性,对本类物质的合成具有重要的参考价值。

Heterosynthesis Using Nitriles: Novel Pyrrolo[2,3-<i>b</i>]pyridines

2-Amino-4-benzoyl-1-arylpyrrole-3-carbonitriles react with arylidene malonodinitriles, β-ketoesters and β- diketones to afford pyrrolo[2,3-b]pyridine derivatives.

芍药甘草汤对Oddi括约肌功能障碍豚鼠自噬相关蛋白Beclin1和LC3-B的影响

目的探讨芍药甘草汤对豚鼠Oddi括约肌功能障碍的治疗作用及其对自噬相关蛋白Beclin1和LC3-B表达的影响。方法30只豚鼠随机分为正常组、模型组和芍药甘草汤治疗组,每组10只。模型组和芍药甘草汤组按0.6 mg/kg体质量静脉注射吗啡注射液以诱导Oddi括约肌功能障碍模型,正常组豚鼠予等体积0.9%氯化钠溶液静脉注射,每周三次;从第一次造模起,芍药甘草汤组按12.5 g/kg灌胃治疗;正常组和模型组分别予等体积0.4%羧甲基纤维素钠(CMC-Na)灌胃,1次/d,共计4周。末次给药后禁食,收集血清和Oddi括约肌组织。全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平;H&E染色检测Oddi括约肌病理变化;qRT-PCR检测c-Kit、Beclin1、LC3-B mRNA表达;Western blot检测c-Kit、Beclin1、LC3-B蛋白表达。结果(1)与对照组相比,模型组豚鼠血清ALT、AST水平显著增高(P<0.01);与模型组相比,芍药甘草汤组豚鼠血清ALT、AST水平均明显下降(P<0.05)。(2)H&E染色显示,模型组豚鼠Oddi括约肌纤维排列不规则、部分紊乱,并可见炎性细胞浸润,黏膜下纤维组织增生明显、平滑肌层显著增厚;与模型组相比,芍药甘草汤组豚鼠Oddi括约肌组织中纤维排列紊乱、炎性细胞浸润及黏膜下纤维组织增生明显改善。(3)与正常组相比,模型组豚鼠Oddi括约肌中c-Kit的mRNA和蛋白表达显著降低(P<0.01,P<0.05),自噬相关Beclin1和LC3-B的mRNA和蛋白表达明显增加(P<0.01,P<0.05);与模型组相比,芍药甘草汤组c-Kit的mRNA和蛋白表达明显升高(P<0.01),Beclin1和LC3-B的mRNA和蛋白表达则显著减少(P<0.01)。结论芍药甘草汤可有效治疗吗啡诱导的豚鼠Oddi括约肌功能障碍,其作用机制可能是与减少细胞过度自噬、提升Cajal细胞活性有关。

Studies on the Synthesis of Pyridine Analogs of the Natural Product3,5,4'-Trimethoxystilbene

Five pyridine analogs of the natural product, 3, 5, 4'-trimethoxystilbene, were synthesized. The final compounds were characterized by 1H-NMR.

Synthesis of derivatives of imidazo[4,5-b]pyridine:Novel sulfur contained side chains for macrolide antibiotics

Two series of novel derivatives of imidazo[4,5-b]pyridine were synthesized. These compounds could be used as side chains of semisynthesised ketolide antibiotics. The side chains have free amine group which can attached to ketolide core. Macrolides with this kind of side chains will show obvious activities against erythromycin-resistant strains. The structure of the side chains was confirmed by ^1H, ^13C NMR, MS, HMBC spectra. 2007 Ping Sheng Lei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

A New Zn(Ⅱ) Coordination Polymer Constructed from 4-(1H-pyrazol-3-yl)pyridine as Fluorescent Sensor for Fe^(3+)

A new Zn(Ⅱ) coordination polymer, [Zn(4-PP)(1,4-BDC)?(H_2O)]_n(1, 4-PP = 4-(1 H-pyrazol-3-yl)pyridine, 1,4-H_2BDC = 1,4-benzenedicarboxylic acid), has been synthesized and structurally characterized by single-crystal X-ray diffraction as well as elemental analysis, IR spectra, XRPD and TG. Structural analysis reveals that Zn(Ⅱ) ions are bridged by COO-from 1,4-BDC^(2-)to form a binuclear structure as the second building units(SBUs). Zn_2 clusters can be clarified as 4-connected nodes, so the framework of 1 can be considered as a 2 D(44?62)-sql sheet. Fluorescence measurements show that 1 has highly selective and sensitive detection of Fe^(3+) in water medium.

Synthesis,Crystal Structure,DFT Studies and Biological Activity of a Novel Schiff Base Containing Triazolo[4,3-a]pyridine Moiety

The novel Schiff base（E）-8-chloro-NA-（4-（dimethylamino）benzylidene）-[1,2,4]triazolo[4,3-a]pyridine-3-carbohydrazide was synthesized and characterized by ^1H NMR,MS,elemental analysis and X-ray diffraction.The compound crystallizes in the monoclinic space group P2_1/c with a = 7.091（2）,b = 10.750（3）,c = 21.380（6） A,β = 96.299（6）°,V = 1619.7（8） A^3,Z = 4 and R = 0.0351.Theoretical calculation of the title compound was carried out with the B3LYP/6-31 G basis set.The frontier orbital energy and atomic net charges were discussed.It is found that the experimental data show good agreement with the calculated values.And the compound exhibits good antifungal activity against Stemphylium lycopersici（Enjoji） Yamamoto.

Preparation and Electrochemical Properties of 3-Pyridinyl-6-aryl-1,2,4-triazolo [3,4-b][1, 3,4]thiadiazoles

A series of 3-pyridinyl-6-aryl-l, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazoles(PATT) were prepared, the structures were confirmed by IR and H NMR spectra. The results of cyclic 1 voltammetry measurements imply that all these compounds have a higher electron affinity (EA) than 2-(4-biphenyl)-5-(4-tert-butyl phenyl)-1, 3, 4-oxadiazole (PBD) which implies that PATT could be acting as better electron acceptors than widely used electron transporting material PBD.