Design,Synthesis,and Biological Evaluation of 5H-Thiazolo[3,2-a]pyrimidine-6-carboxylic Acid Ethyl Ester Derivatives as a Novel Series of Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.

Antibacterial Activity of 9-Octadecanoic Acid-Hexadecanoic Acid-Tetrahydrofuran-3,4-Diyl Ester from Neem Oil

The 9-octadecanoic acid-hexadecanoic acid-tetrahydrofuran-3,4-diyl ester from neem oil was investigated for antibacterial activity against three bacterial strains viz., Staphylococcus aureus ATCC No. 25923, Escherichia coli ATCC No. 44102 and Salmonella sp. ATCC No. 50 041 in vitro. The minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） values of the 9-octadecanoic acid-hexadecanoic acid-tetrahydrofuran-3,4-diyl ester were determined by using the broth microdilution dilution （BMD） method at different concentrations ranging from 20 to 0.625 mg mL-1. Its time-inhibition curve against E. coli was also tested and showed that the MIC values for the bacterial strains S. aureus, E. coli and Salmonella sp. were 20, 5 and 10 mg mL-1, respectively. Its MBC values were 20, 20 and 10 mg mL-1, respectively. The antibacterial activity of 9-octadecanoic acid-hexadecanoic acid-tetrahydrofuran-3,4-diyl ester against three strain tested showed the relationship with time and concentration.

Synthesis and Crystal Structure of 4-(4,6-Dimethoxylpyrimidin-2-yl)-3-thiourea Carboxylic Acid Ethyl Ester

4-（4,6-Dimethoxyl-pyrimidin-2-yl）-3-thiourea carboxylic acid ethyl ester was synthesized by the reaction of 2-amino-4,6-dimethoxyl pyrimidine, potassium thiocyanate and methyl chloroformate in ethyl acetate. Single crystals suitable for X-ray measurement were obtained by recrystallization with the solvent of dimethyl formamide at room temperature. The crystal structure was determined by X-ray diffraction analysis. Crystallographic data： C10H14N4O4S, M, = 286.31, monoclinic, space group C2/c with a = 2.5309（3）, b = 0.67682（6）, c = 1.74237（19） nm, β = 114.744（3）°, V= 2.7106（5） nm3, Dc = 1.403 g/cm3, p = 0.225 mm-1, F（000） = 1200, Z= 8, R= 0.0514 and wR= 0.1529.

Supercritical Synthesis of Ethyl Esters via Transesterification from Waste Cooking Oil Using a Co-Solvent

Biofuels became more promising alternative to the fossil fuels because of the depletion of fossil resources, renewability, environmental benefits, and energy security. Ethanolysis of waste cooking oil with hexane as co-solvent was carried out for the production of fatty acid ethyl ester (FAEE). This process reduced the severity of process parameters with high purity biodiesel yield. Process variables such as co-solvent ratio, ethanol to oil molar ratio, reaction temperature and reaction time were optimized. The maximum biodiesel yield of 88% was obtained at ethanol/oil molar ratio of 40:1, co-solvent (hexane) to oil ratio of 0.2% (v/v), reaction temperature of 300°C in 20 min of reaction time. Fatty acid ethyl ester (biodiesel) samples produced from this process were measured and evaluated using GC-MS analytical instrument. Thermo gravimetric analysis (TGA) was also performed to examine the thermal stability of waste cooking oil, ethyl esters and fuel blends. Fuel properties of ethyl esters were determined and compared with the ASTM standards for biodiesel, regular diesel and ethyl esters from different feedstock.

Sensitized photooxygenation^+——VI. Kinetic studies on the singlet oxygenation of 6-ethyl-3,4-dihydro-2H-pyran-5-carboxylic acid ethyl ester and 6-isopropyl-3,4-dihydro-2H-pyran-5-carboxylic acid ethyl ester

Kinetic studies of the singlet oxygenation of the title compounds were performed accord- ing to Monroe's method. The reaction rate increases with temperature decreasing, leading to a ne- gative activation enthalpy and a large negative activation entropy. These data are interpreted as the evidence for the intermediacy of an exciplex. The solvent effect on the reaction rate suggests that the “dioxetane” path involves a transition state or an intermediate with significant zwitterionic character. The electronic effect of the substituent is obvious, with electron-withdrawing substituent retarding the reaction and electron-donating substituent increasing the reaction rate. However, steric bulkiness at the 6-position does not play an important role in the reaction rate.

Azacarbazole n-3 and n-6 polyunsaturated fatty acids ethyl esters nanoemulsion with enhanced efficacy against Plasmodium falciparum

Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance.However,many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems,which seriously limits their activity.To address this problem,we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10(chloroquine-sensitive)and W2(chloroquine-resistant)strains of P.falciparum.The most active compound,9H-3-azacarbazole(3),was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase,Smix(Tween 80 and Transcutol HP)and water.This formulation was further analyzed using transmission electron microscopy,dynamic light scattering and in vitro and in vivo studies.It was shown that droplets of the 3-loaded nanosystem were spherical,with satisfactory stability,without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for P.falciparum.Moreover,the nanoemulsion with this type of oil phase was internalized by Caco-2 cells.Additionally,pharmacokinetics demonstrated rapid absorption of compound 3(tmax=5.0 min)after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice,with penetration of compound 3 to deep compartments.The 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite,respectively,compared to non-encapsulated 3.Our findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs.

Extraction Separation of Scandium，Iron and Lutetium with Isopropyl Phosphonic Acid Mono（1－hexyl－4－ethyl）OctylEster

The extraction and stripping of scandium from its sulfate solutions by isopropyl phosphonic acid mono (1-hexyl-4-ethyl) octyl ester (PT-2, HL) diluted with n-hexane are reported. A high efficiency of separation between scandium, iron and lutetium can be achieved by controlling aqueous acidity. Different mechanisms of Sc3+ with PT-2 in various acid range have been proposed.At lower aqueous acidity, it is a cation exchange reaction, while at higher acidity. a solvation reaction was ascertained. Its IR and NMR spectra have been discussed. The effect of temperature on extraction of Sc3+ was observed and thermodynamic functions were calculated.

Utilizing zebrafish and okadaic acid to study Alzheimer's disease

Despite the many years of extensive research using rodent models to study Alzheimer＇s disease （AD）, no cure or disease halting drug exists. An increasing number of people are suffering from the disease and a therapeutic intervention is needed. Therefore, it is necessary to have complementary models to aid in the drug discovery. The zebrafish animal model is emerging as a valuable model for the investigation of AD and neurodegenerative drug discovery. The main genes involved in human AD have homologous counter- parts in zebrafish and have conserved function. The basic brain structure of the zebrafish is also conserved when compared to the mammalian brain. Recently an AD model was established by administering okadaic acid to zebrafish. It was used to test the efficacy of a novel drug, lanthionine ketimine-5-ethyl ester, and to elucidate its mechanism of action. This demonstrated the ability of the okadaic acid-induced AD zebrafish model to be implemented in the drug discovery process for therapeutics against AD.

Chemical profiling of bioactive compounds in the methanolic extract of wild leaf and callus of Vitex negundo using gas chromatographymass spectrometry

BACKGROUND The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques for drug therapy.Vitex negundo(V.negundo),a perennial herb belonging to the Varbanaceae family,is extensively used in conventional medication.AIM To determine the existence of therapeutic components in leaf and callus extracts from wild V.negundo plants using gas chromatography-mass spectrometry(GCMS).METHODS In this study,we conducted GC-MS on wild plant leaf extracts and correlated the presence of constituents with those in callus extracts.Various growth regulators such as 6-benzylaminopurine(BAP),2,4-dichlorophenoxyacetic acid(2,4-D),α-naphthylacetic acid(NAA),and di-phenylurea(DPU)were added to plant leaves and in-vitro callus and grown on MS medium.RESULTS The results clearly indicated that the addition of BAP(2.0 mg/L),2,4-D(0.2 mg/mL),DPU(2.0 mg/L)and 2,4-D(0.2 mg/mL)in MS medium resulted in rapid callus development.The plant profile of Vitex extracts by GC-MS analysis showed that 24,10,and 14 bioactive constituents were detected in the methanolic extract of leaf,green callus and the methanolic extract of white loose callus,respectively.CONCLUSION Octadecadienoic acid,hexadecanoic acid and methyl ester were the major constituents in the leaf and callus methanolic extract.Octadecadienoic acid was the most common constituent in all samples.The maximum concentration of octadecadienoic acid in leaves,green callus and white loose callus was 21.93%,47.79%and 40.38%,respectively.These findings demonstrate that the concentration of octadecadienoic acid doubles in-vitro compared to in-vivo.In addition to octadecadienoic acid;butyric acid,benzene,1-methoxy-4-(1-propenyl),dospan,tridecanedialdehyde,methylcyclohexenylbutanol,chlorpyrifos,n-secondary terpene diester,anflunine and other important active compounds were also detected.All these components were only available in callus formed in-vitro.This study showed that the callus contained additional botanical characteristics compared with wild plants.Due to the presence of numerous bioactive compounds,the medical use of Vitex for various diseases has been accepted and the plant is considered an important source of therapeutics for research and development.

Synthesis, Spectroscopic and Crystal Structure Studies on Ethyl 5,7-Dimethyl Coumarin-4-Acetate

Ethyl ester of 5,7-dimethyl coumarin-4-acetic acid has been synthesized from 3,5-Xylenol in a two step sequence of reaction involving Pechmann cyclisation and acid catalyzed esterification. The title compound 2 crystallizes in Monoclinic form, space group P 1 21/c 1, with a = 8.6248(4) ?, b = 18.9103(8) , c = 8.4204(4)?, β = 101.241(2)?, V = 1347.00(11) ?, D cal = 1.283 Mg/cm3, Z = 4. The molecule is stabilized by intermolecular C-H … O bonds.

磁性固相萃取-气质联用-同位素内标法精准检测白酒中8种高级脂肪酸乙酯

高级脂肪酸乙酯是引起酒体浑浊的关键因素之一。为系统分析白酒中的高级脂肪酸乙酯以改善白酒生产过程中的浑浊问题,建立了一种基于氨基化四氧化三铁(Fe_(3)O_(4)-NH_(2))磁性固相萃取结合气质联用技术的方法,用以同时测定白酒中8种高级脂肪酸乙酯。通过考察酒样的pH值、离子强度、吸附剂用量、吸附时间、解吸溶剂种类、解吸溶剂酸碱度、解吸时间等因素,确定了较佳的萃取条件。结果表明:这8种高级脂肪酸乙酯在各自的质量浓度范围内线性关系良好,相关系数R 2均大于0.99;方法检出限和定量限分别为9.1~42.9μg/L和5.2~200.0μg/L;回收率为79.6%~99.3%,相对标准偏差(n=3)为8.0%~10.7%。应用此方法,并结合同位素内标法对24种不同香型和品牌的白酒样品中8种高级脂肪酸乙酯进行精准定量,发现它们的种类和质量浓度存在显著差异。其中,在酱香型白酒中,高级脂肪酸乙酯的检出率最高,达到100%。该方法简便快捷,样品萃取只需10 min,具有高灵敏度和准确性,能够有效避免传统液-液萃取技术的背景干扰问题,可为实现白酒中高级脂肪酸乙酯的精准检测提供一种新的方法。

多元化学计量学结合分子感官组学探究长链脂肪酸乙酯对不同白酒馏段品质的影响

该研究运用分子感官组学与多元化学计量学手段,对馏酒工艺过程的5种代表性长链脂肪酸乙酯(LCFAEEs)分布特性进行解析,从视觉、嗅觉、味觉和饮后评价四个维度对样品组进行感官品评实验,明确LCFAEEs与不同白酒馏段品质的对应关系。结果表明,不同馏段白酒中LCFAEEs的含量分布存在显著差异(P<0.05),LCFAEEs含量随着馏酒过程进行呈下降趋势。馏酒前段样品中的LCFAEEs总含量最高,平均值为5.77 mg/L,其中棕榈酸乙酯(EP)的含量最高,平均值为1.77 mg/L。馏酒后段样品中的LCFAEEs总含量最低,平均值为0.75 mg/L。结合酒体感知分析可以发现,LCFAEEs总含量对白酒品质具有极显著影响(P<0.01),尤其是对酒体的果香、花香、柔顺度、酒体风格具有极显著正相关作用(P<0.01,R>0.8)、对酒体的酸味、醇味、异杂味具有极显著负相关作用(P<0.01,R<-0.8)。十六酸乙酯(EP)的添加为白酒带来了更为浓郁的果香和花香,同时提升了甜香和口感的柔顺度。该研究为白酒关键品质因子的挖掘,以及工艺的优化提供了数据支撑。

叉枝蒿对粘虫杀虫活性成分及作用机制研究

【目的】探究叉枝蒿对粘虫的杀虫活性及杀虫机制,为粘虫的高效绿色防控提供理论依据。【方法】采用浸虫浸叶法测定10种蒿属植物提取物及叉枝蒿不同极性4部分萃取物对粘虫3龄幼虫的杀虫活性;分别采用小叶碟添加法、浸叶法和浸虫法确定叉枝蒿石油醚萃取物对粘虫的主要杀虫方式;通过浸虫法测定叉枝蒿石油醚萃取物、馏分及主要成分对粘虫3龄幼虫的触杀活性。叉枝蒿石油醚萃取物经柱层析分离及气相色谱—质谱分析,确定其活性成分,并测定活性成分对粘虫体内4种酶活力的影响。【结果】叉枝蒿石油醚萃取物对粘虫3龄幼虫的触杀活性最好,处理第7 d时对粘虫的致死中浓度(LC_(50))为6.85 mg/mL。经硅胶柱色谱分离,从叉枝蒿石油醚萃取物中得到21个馏分,其中馏分8表现出最好的触杀活性;气相色谱—质谱分析结果显示,馏分8的主要化合物为棕榈酸乙酯(49.57%)、十三烷(14.55%)、硬脂酸乙酯(4.86%)和壬烷(4.74%),4种化合物中以棕榈酸乙酯的触杀活性最好,处理后第7 d时对粘虫的LC_(50)为1.82 mg/mL。棕榈酸乙酯LC_(50)处理粘虫第7 d时扫描电镜显示,粘虫表皮蜡质层颗粒排列疏松,间隙增大。棕榈酸乙酯LC_(50)处理粘虫1、3、5和7 d时,粘虫体内乙酰胆碱酯酶(AChE)和Na^(+)-K^(+)-ATP酶随时间的推移表现出抑制作用,羧酸酯酶(CarE)表现出先激活后抑制作用,过氧化氢酶(CAT)表现出先抑制后激活作用。【结论】叉枝蒿对粘虫具有良好的杀虫活性。叉枝蒿石油醚萃取物中的棕榈酸乙酯对粘虫的触杀活性最好,可作为粘虫生物防治的潜力化合物进行开发利用。

血浆脂肪酸乙酯与酒精性急性胰腺炎炎症和疾病严重程度的相关性研究

目的分析血浆脂肪酸乙酯(FAEE)与酒精性急性胰腺炎(AAP)炎症和疾病严重程度的相关性。方法回顾性分析2017年1月至2022年1月该院收治的227例AAP患者及213例非酒精性急性胰腺炎(AP)组患者数据。根据Bathazar计算机断层扫描严重指数将AAP患者的疾病严重程度分为轻度、中度、重度。通过气相色谱分析患者血浆FAEE和游离脂肪酸(NEFA)水平。结果AAP组患者血浆FAEE(P<0.001)和NEFA(P=0.019)水平相较于非酒精性AP组更高。然而,经受试者工作特征(ROC)曲线分析,血浆FAEE对鉴别诊断AAP与非酒精性AP有良好效能,曲线下面积(AUC)为0.926(95%CI:0.901~0.951)。中度[158.77(127.01~230.55)nmol/L]和重度[274.49(208.32~309.31)nmol/L]AAP患者血浆FAEE水平高于轻度患者[126.15(84.37~166.52)nmol/L],而且重度患者较中度患者更高(H=64.069,P<0.001)。血浆FAEE水平>146.61 nmol/L为重度AAP发生的危险因素(P<0.05),且其对重度AAP有较好的预测价值,AUC为0.786(95%CI:0.705~0.867)。Spearman秩相关分析结果显示,AAP患者血浆FAEE水平与白细胞介素(IL)-1β、IL-6及NEFA水平呈正相关(rS=0.298、0.475、0.302,均P<0.001)。结论血浆FAEE有可能成为AAP鉴别诊断和预测疾病严重程度的潜在生物标志物。

黄花蒿对粘虫杀虫活性成分及机制研究

为研究黄花蒿石油醚萃取物对粘虫3龄幼虫杀虫活性成分及初步作用机制,采用硅胶柱色谱进行分离,气相-质谱法分析化学成分,浸虫法测定不同馏分及主要成分的触杀活性,并进一步对活性成分进行粘虫幼虫体内靶标酶和代谢酶活性测定。结果表明,黄花蒿石油醚萃取物经硅胶柱色谱分离,共得到27个馏分,其中馏分8表现出较好的触杀活性。经气相色谱-质谱法检测,十三烷、4-喹啉甲醛、石竹烯氧化物、亚油酸乙酯和亚麻酸乙酯为主要化合物,含量分别为7.9%、72.8%、3.6%、2.4%、3.1%。这5种化合物处理粘虫7 d的半数致死浓度(LC50)分别为7.9、2.5、3.6、5.4和1.5 mg·mL^(-1),即亚麻酸乙酯对粘虫的触杀活性最好。扫描电镜结果显示,1.5 mg·mL^(-1)亚麻酸乙酯处理粘虫7 d,粘虫表皮蜡质层结构排列疏松,蜡质层颗粒明显消失,蜡花间隙增大;在处理过程中,粘虫的乙酰胆碱酯酶和羧酸酯酶表现出先激活后抑制作用;Na^(+)-K^(+)-ATPase表现出持续抑制作用;过氧化氢酶表现出先抑制后激活作用。综上,亚麻酸乙酯为黄花蒿对粘虫杀虫活性的主要化合物,研究结果为黄花蒿资源的开发利用以及将亚麻酸乙酯作为生物防治粘虫的潜力化合物提供参考。

白酒中高级脂肪酸乙酯去除技术研究进展

高级脂肪酸乙酯引起的白酒浑浊沉淀现象一直是行业普遍存在的难题,尽管各企业采取了相应措施进行处理,但仍会面临能耗高、酒损大及环保压力等问题,并没有从根本上解决问题。基于此,本文从高级脂肪酸乙酯造成白酒浑浊原理、高级脂肪酸乙酯如何进入白酒中、如何进行控制以及未来该从哪些方面着手解决等进行了全面总结分析,旨在为正在面临该难题的企业提供理论依据及操作经验,也为深入研究和彻底解决该难题提供了思路和方向,以期共同推动白酒行业的高质量发展。

浓香型白酒超声波陈化方法条件优化

陈化对白酒的风味有重要影响。本研究以酸酯总量为指标研究超声陈化温度、超声陈化功率、超声陈化时间对浓香型白酒中酸酯总量的影响,以乙酸乙酯为指标通过正交实验优化超声陈化条件。研究表明,超声温度为65℃,超声功率为350 W,超声时间为40 min时,能够达到较好的陈化效果。

气相色谱—串联质谱法测定阿哌沙班中2-氯乙酰乙酸乙酯的残留量

目的:建立一种气相色谱—串联质谱(GC-MS/MS)方法,用于测定阿哌沙班中潜在基因毒性杂质2-氯乙酰乙酸乙酯的残留量。方法:用聚乙二醇[VF-WAXms(30 mm×0.25 mm×0.25μm)]为固定液的毛细管色谱柱;进样口温度为230℃;流速1.0 mL/min;载气:氦气;不分流进样。采用电子轰击离子源(EI),选择离子监测模式(SIM)。结果:2-氯乙酰乙酸乙酯在0.05~1.02μg/mL质量浓度范围内呈现良好的线性关系(r=0.9985);定量限浓度是0.02μg/mL;检出限是0.01μg/mL;三份不同浓度水平的平均回收率为97.9%(RSD=4.2%)。结论:所建立的GC-MS/MS测定方法灵敏度高、专属性强和准确度好,可用于阿哌沙班中2-氯乙酰乙酸乙酯的测定。

2-乙酰己酸乙酯的质谱分析

2-Acetyl-hexanoic acid ethyl ester is one of important derivatives.It has been used widely useful materials as anesthetics,spice,medicine and so on.The reaction liquid of acetyl-acetic acid ethyl ester with n-butane bromide was analyzed by gas chromatograph-mass spectrometry.The results show that there are four kinds of compounds in the reaction liquid.The main yield is 2-acetyl-hexanoic acid ethyl ester,while by-products are 2-acetyl-2-butyl-hexanoic acid ethyl ester and 3-butoxy-2-butenoic acid ethyl ester.

黄连中1个新型生物碱的研究

目的 研究黄连Coptis chinensis Franch中1个新型生物碱。方法 黄连75%乙醇提取物采用硅胶、ODS、semi-pre HPLC进行分离纯化,根据理化性质及波谱数据对鉴定所得化合物的结构。结果 从中分离得到3个化合物,分别鉴定为6-([1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxybenzoic acid ethyl ester(1)、oxohydrastinine(2)、pinoresinol(3)。结论 化合物1为新型苄基异喹啉生物碱。