Green and Efficient Synthesis of 3-Pyrazolyl Indoles in Water

A green and efficient synthesis of 3-pyrazolyl indoles was developed by the eye 1 ocondensation reactionof β-ethylthio-β-indolyl-α,β-unsaturated ketones with semi carbazide hydrochloride as hydrazine equivalent in thepresence of 3 equiv. of PEG400(la/PEG mole ratio of 1:3) in reflux water. This procedure did not require toxichydrazine and product purification, eliminating the use of toxic liquid chemicals.

吲哚-3-丙酸通过调节脂肪组织代谢改善高脂饮食诱导代谢相关脂肪性肝病的作用及机制研究

目的 探索吲哚-3-丙酸(indole-3-propionic acid, IPA)在高脂饮食诱导代谢相关脂肪性肝病(metabolic associated fatty liver disease, MAFLD)发生发展中的作用,揭示脂肪组织代谢在其中的作用及相关机制。方法 建立高脂饮食(high-fat diet, HFD)喂养诱导的MAFLD动物模型,6~7周龄的雄性C57BL/6J小鼠按随机数字表法分为3组,即对照组(CON)、高脂饮食组(HFD)、高脂+IPA干预组(HFD+IPA)。CON组以对照饲料喂养,HFD组和HFD+IPA组均以60%高脂饲料喂养,实验周期为12周,第7周开始HFD+IPA组以20 mg/(kg·d)IPA灌胃6周。每周监测各组小鼠体质量与摄食量。干预结束后使用动物体成分分析仪检测小鼠体成分。小鼠处死后,HE染色观察肝脏和脂肪组织形态学和结构变化,全自动血生化仪和生化试剂盒检测血清及肝脏和脂肪组织中脂代谢相关指标,qRT-PCR检测脂代谢和炎性相关基因mRNA的表达。结果 与CON组相比,HFD组小鼠体质量和体脂肪比例显著增加,肝脏出现明显的脂质沉积,血清丙氨酸氨基转移酶、天冬氨酸氨基转氨酶以及肝脏甘油三酯和总胆固醇水平显著升高(P<0.05),肝组织脂肪酸转运分子CD36的mRNA水平明显升高(P<0.05),IPA干预显著逆转了上述变化(P<0.05)。IPA干预能够显著抑制高脂饮食诱导的内脏和棕色脂肪细胞增大,降低内脏脂肪组织(visceral adipose tissue, VAT)和血清中游离脂肪酸含量(P<0.05),增加VAT脂解基因(HSL、CGI58)和棕色化(Cidea、ND5、UCP1、Prdm16)以及棕色脂肪组织(brown adipose tissue, BAT)脂肪酸β氧化(Cpt1a、PPARα)相关基因的mRNA表达水平(P<0.05),同时降低VAT炎性因子TNF-α以及BAT中TNF-α、IL-1β、CXCL1、CCL2的mRNA表达水平(P<0.05)。结论 IPA可以改善高脂饮食诱导的MAFLD的发生,其机制可能与调节白色和棕色脂肪组织结构、代谢功能及炎性相关基因的表达有关。

新型醛糖还原酶抑制1-乙酰基-1H-吲哚-3-乙酸酯的合成及其抑制活性

醛糖还原酶抑制剂(ARIs)抑制多元醇途径的醛糖还原酶是治疗糖尿病并发症的重要策略。以2-氯苯甲酸为起始原料,在碱性条件下经铜催化,与甘氨酸反应生成氯代邻羧基苯基甘氨酸,再与乙酸酐反应,生成N-乙酰基邻羧基苯甲酸。然后在吡啶催化下合环,生成1-乙酰基-^(1)H-吲哚-3-乙酸酯(AIA),总收率为79.0%,纯度为99.0%。通过^(1)H NMR、^(13)C NMR和MS(ESI)对其结构进行表征,并对该化合物的的醛糖还原酶抑制活性进行测定,IC 50=9.4×10^(-2)μM。

活体检测吲哚-3-乙酸的电化学传感器研究

吲哚-3-乙酸(IAA)作为一种重要的植物激素,在植物生长发育的整个过程中起着至关重要的作用。本文根据植物活体检测的实际需要,发展了适合植物茎秆活体检测的四阵列电极及用于植物果实活体检测的六阵列电极,通过一步法在铂(Pt)丝工作电极上沉积铂纳米颗粒(PtNPs)和还原氧化石墨烯(rGO)纳米复合膜,从而增强催化效果,提高生物传感器的灵敏度。实验结果表明,所研制的传感器在IAA浓度0.1~200μmol/L范围内,具有良好的线性关系,相关系数为R~2=0.986,检测限为0.01μmol/L(S/N=3)。进一步利用所制备的传感器活体检测了黄瓜茎秆和黄瓜果实(CF)内的IAA含量,表明该传感器在植物生理状态的活体检测中具有重要应用前景。

3′-吲哚-3-氧化吲哚与苯基溴化物的多样性转化及其产物对肿瘤细胞A549和HepG2的抑制作用

3′-吲哚-3-氧化吲哚作为一类重要的合成子,实现其C3-位和吲哚C2-位选择性转化具有一定的挑战性。本文以3′-吲哚-3-氧化吲哚与不同的苯基溴化物为起始原料,在金属钯和无机碱等条件的参与作用下,分别合成得到了3-(2-溴苄基)-3-(3′-吲哚基)氧化吲哚(3a~3d,收率75%~90%)、螺[5,6-二氢苯并咔唑-11,3′-氧化吲哚](4a~4d,收率45%~60%)、螺[5H-茚并吲哚-10,3′-氧化吲哚](6a~6c,收率42%~48%)、(2-苯基-1H-吲哚-3-基)氧化吲哚(8a、 8b,收率51%和69%),产物结构由^(1)H NMR、^(13)C NMR、高分辨质谱和单晶X-射线衍射分析表征。对合成得到的部分化合物考察了其对肿瘤细胞的抑制活性,发现部分化合物对肿瘤细胞A549(3a, IC_(50)=25.285μmol/L)和HepG2(3a, IC_(50)=21.806μmol/L;3d, IC_(50)=32.732μmol/L;4d, IC_(50)=26.923μmol/L)具有一定的抑制作用。

TsOH·H₂O-Catalyzed Friedel-Crafts of Indoles of 3-Hydroxyisobenzofuran-1(3<i>H</i>)-One with Indoles: Highly Synthesis of 3-Indolyl-Substituted Phthalides

An efficient and facile method for the synthesis of 3-indolyl-substituted phthalides by Friedel-Crafts alkylation of indoles with 3-hydroxyisobenzofuran-1(3H)-one has been developed. Using only 2 mol-% TsOH·H2O as the catalyst, various substituted indoles can react smoothly at room temperature to give the corresponding phthalides products in good to excellent yields (up to 96%).

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。

Effect of Indole 3-Butyric Acid and Media Type on Adventitious Root Formation in Sheanut Tree (<i>Vitellaria paradoxa</i>C. F. Gaertn.) Stem Cuttings

Shea nuts play an important role in food security for rural folks within sub-Sahara Africa, serving as the main source of income for many people living in Northern Ghana. Unfortunately, the full economic potential of the Sheanut tree has not been fully realized due to the difficulty involved in its domestication. This difficulty in vegetatively propagating sheanut trees has greatly hindered its cultivation and the realization of its true economic potential. Two experiments were conducted to investigate the effects of rooting media and varying indole 3-butyric acid (IBA) concentrations on adventitious root formation in cuttings taken from coppiced sheanut trees. Results indicated that 3000 ppm produced significantly (p 0.05) better rooting (57.5%) than 5000 ppm (30%), 7000 ppm (45.0%) and the control (7.5%). Although the levels of soluble sugars (SS) and total free phenols (TFP) in the cutting were significantly (p 0.05) higher at the end of the experiment (after IBA treatment) compared to the start (prior to IBA treatment), the SS and TFP trends observed did not clearly explain the rooting differences found between the IBA levels investigated. Callus formation was significantly (p 0.05) higher (35.0%) in the control (no IBA). Generally, callus formation decreased with increasing IBA concentration. In the rooting media experiment, rooting was significantly (p 0.05) higher in the rice husk medium (35.0%) compared to that in the palm fiber (18.3%), saw dust (14.1%) and top soil (16.7%) media.

An efficient synthesis of 2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-one catalyzed by recyclable solid superacid SO_4^(2-)/TiO_2 under grinding condition

An efficient synthesis of symmetrical 2,2-bis（1H-indol-3-yl）-2H-acenaphthen-1-one is achieved via a reaction of acenaphthe-nequinone and indoles catalyzed by solid superacid SO4^2-/TiO2 under solvent-free conditions at room temperature by grinding, which provides an efficient route to the synthesis of symmetrical 2,2-bis（1H-indol-3-yl）-2H-acenaphthen-1-one.This procedure offers several advantages including solvent-free conditions,excellent yields of products,simple work-up as well as reuse of catalysts which makes it a useful and attractive protocol for the synthesis of these compounds.

Apoptosis of pancreatic cancer BXPC-3 cells induced by indole-3-acetic acid in combination with horseradish peroxidase

AIM: To explore the mechanisms underlying the apoptosis of human pancreatic cancer BXPC-3 cells induced by indole-3-acetic acid (TAA) in combination with horseradish peroxidase (HRP).METHODS: BXPC-3 cells derived from human pancreatic cancer were exposed to 40 or 80 μmol/L IAA and 1.2 μg/mL HRP at different times. Then, MTT assay was used to detect the cell proliferation. Flow cytometry was performed to analyze cell cycle. Terminal deoxynucleotidyl transferasemediated dUTP nick end labeling assay was used to detect apoptosis. 2,7-Dichlorofluorescin diacetate uptake was measured by confocal microscopy to determine free radicals. Level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were measured by biochemical methods.RESULTS: IAA/HRP initiated growth inhibition of BXPC-3 cells in a dose- and time-dependent manner. Flow cytometry revealed that the cells treated for 48 h were arrested at G1/G0. After exposure to 80 μmol/L IAA plus 1.2 μg/mL HRP for 72 h, the apoptosis rate increased to 72.5‰,which was nine times that of control. Content of MDA and activity of SOD increased respectively after treatment compared to control. Meanwhile, IAA/HRP stimulated the formation of free radicals.CONCLUSION: The combination of IAA and HRP can inhibit the growth of human pancreatic cancer BXPC-3 cells in vitro by inducing apoptosis.

Synthesis and in vitro-Anti-hepatitis B Virus Activities of Several Ethyl 5-Hydroxy-1H-indole-3-carboxylates

A series of ethyl 5-hydroxyindole-3-earboxylates 6a-10r was designed and synthesized. The structures of all the compounds were confirmed by IR, ^1H NMR, and MS and their anti-hepatitis B virus （HBV） activities were evaluated in 2.2.15 cells. Among them, compound 7g { ethyl 5-hydroxy-2- [ （ 3-methoxyphenylsulfinyl ） methyl ] -1-methyl-4- [ （4-methylpiperazin-1-yl） methyl ]-1H-indole-3-carboxylate} displays a significant anti-HBV activity, which is more potent than the positive control lamivudine.

SbCl_3 Catalyzed Solventless Synthesis of Bis(indolyl)alkanes under Grinding

A clean and efficient method for the synthesis of bis（indolyl）alkanes with antimony trichloride（SbCl3） as the catalyst under solvent-free grinding conditions is described. This method provides several advantages, such as simple work-up procedure, neutral conditions and high yields.

Theoretical Studies on the Aminolysis of Ester: Effects of the Catalysis and Substituent to the Reaction of Methyl Indole-3-acetate with Ammonia

A comprehensive exploration of the aminolysis mechanism for methyl indole-3-acetate with ammonia is carried out by employing the B3 LYP/6-311++G(d,p), M06-2 X/6-311++G(d,p) and MP2/6-311++G(d,p)//M06-2 X/6-311++G(d,p) levels. Two alterative reaction channels of the concerted and addition/elimination stepwise processes including the uncatalyzed, base-catalyzed reactions are taken into consideration. Subsequently, the substituent effects and solvent effects in methanol are also evaluated at the M06-2 X/6-311++G(d,p) level. The calculated results indicate that the calculated values of M06-2 X level are quite close to those of MP2, the stepwise pathway has more advantages to the concerted one for all of the reaction processes and the catalyst facilitates the proton migration and decreases the energy barriers as well. It is shown that the most preferred mechanism is the based-catalyzed stepwise process, the substituent of NH2 group slightly accelerates all the aminolysis reaction processes, and the solvent effect does not remarkably change the mechanism of the reaction.

Effect of newly synthesized 1,2,4-triazino[5,6-b]indole-3-thione derivatives on olfactory bulbectomy induced depression in rats

Objective:To study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized(OBX)rats.Out of various derivatives tested for acute tail suspension test,the two derivatives showiug prominent action were.selected for bilateral olfactory bulbeetomy rsodel of ehronic depression in rats.Methods:The sub aeute effects of 14-day oral pretreatment of two derivatives labeled as 3a(70 mg/kg)and 3r(70 mg/kg),imipramine(20 mg/kg),fluoxetiue(30 mg/kg)and moclobemide(15 mg/kg)were evaluated on bilateral bulbectomy induced rise in body weight,hyperphagia,hyperactivity,and on sexual dysfunction.The serum sodium concentration,body temperature,and heart rate were also recorded.Results:The derivatives3a and 3r showed reversal of drop in body weight,reversed OBX indueed hyperactivity,normalized body temperature,heart rate,and serum sodium concentration.In elevated maze test,moclobemide,3a,3r treatment significantly redueed time spent in open arm as compared to OBX rats.3a and 3r also irsproved sexual behavior parameters.Conclusions:The present study shows promising antidepressant action and provides a proof of concept for the chronic treatrsent of 3a,3r to treat depression.

Endogenous nitric oxide and hydrogen peroxide detection in indole-3-butyric acid-induced adventitious root formation in Camellia sinensis

Nitric oxide（NO）and hydrogen peroxide（H2O2）are essential signaling molecules with key roles in auxin induced adventitious root formation in many plants.However,whether they are the sole determinants for adventitious root formation is worth further study.In this study,endogenous NO and H2O2 were monitored in tea cutting with or without indole-3-butyric acid（IBA）treatment by using the fluorescent probes diaminofluorescein diacetate（DAF-2DA）and 2＇,7＇-dichlorodihydrofluorescein diacetate（DCF-DA）,respectively.The overproduction of NO and H2O2 was detected in the rooting parts of tea cuttings treated with or without IBA.But little NO and H2O2 was detected before the initiation phase of tea cuttings even with IBA treatment indicating that they might be not directly induced by IBA.Further carbon and nitrogen analysis found that the overproduction of NO and H2O2 were coincident with the consumption of soluble sugars and the assimilation of nitrogen.These results suggest that rooting phases should be taken into consideration with the hypothesis that auxin induces adventitious root formation via NO-and H2O2-dependent pathways and sink establishment might be a prerequisite for NO and H2O2 mediated adventitious root formation.

Effect of Different Indole-3-Buteric Acid(IBA)Concentrations and Cutting Types on Plane Trees(Platanus orientalis L.)

Effects of different Indole-3-Buteric Acid （IBA） concentrations （0, 1 000, 1 500 and 2 500 ppm） and curing types （soft wood, semi hard and hard wood） of plane tree were investigated with Randomized Complete Block Design （RCBD） at the Agricultural research station, Charsadda. The maximum survival percentage, plant height （cm）, root length （era）, numbers of roots and root weight per cutting were significantly higher in hard wood cuttings. IBA concentration had no speculative effect on plane tree cuttings. Thus, hard wood cutting was the best choice for plan tree propagation.

Rooting of Stem Cuttings with Different Indole 3 Butyric Acid (IBA) Treatments and Development of Micropropagation Protocol for <i>Piper betle</i>L. Node Culture

The present study, conducted during 2016 and 2017 seasons, aimed to investigate the effect of IBA on rooting of Piper betle L. stem cuttings (softwood and semi-hardwood). The experiment was undertaken in misting house field 2 UPM using the sand media to determine the adventitious roots initiation and development using the histological method. The cuttings were treated with different IBA concentrations (0, 500, 1000, 1500 and 2000 mg/L). The nodes explants were used in the development of a protocol for in vitro propagation of P. betle L., with different concentrations of Clorox with different times of immersion (20% Clorox 10 minutes, 30% Clorox 10 minutes, 20% Clorox 20 minutes, and 30% 20 minutes). In multiplication of the plantlets, Murashige and Skoog (MS) medium with different concentrations of BAP (0, 0.5, 1.0, 2.0 mg/L) were used to investigate the rooting of the explants. The results indicated that the types of the cuttings were different in the rooting capacity and the length of the roots. Moreover, it was found that in comparison with the control treatment, by a rise in the concentrations of the IBA, there was a significant upsurge in the rooting percentage, the root diameter, and the number of the roots. The results indicated that the types of cutting with 1000, 1500 and 2000 mg/L IBA perform better in the root percentage (100%) in the semi hardwood cuttings. The best results, however, were 2000 mg/L IBA in the semi hardwood cuttings, with the number of the roots to be 35.05, and the fresh weight of the roots to be 3.94 g, the dry weight of the roots to be 0.33 g, the length of the roots to be 391.88 cm, the roots diameter to be 1.21 mm, the surface area of the roots to be 121.83 cm2, and the root volume to be 2.99 cm3. Nonetheless, the optimal concentration of Clorox with the time immersion was 20% with the 20-minute immersion time, which produced a shoot induction percentage of 30% dead explants and a mean number of 70.00 shoots per explant and the optimal concentration of benzylaminopurine (BAP) at 1.0 mg/L. It is of note that a shoot induction percentage of 22.29% and a mean number of 4.1% number of auxiliary bud per treatment. P. betle shoots in MS medium without PGR MS (0.0) yielded a good rooting.

Synthesis, Crystal Structure and Antitumor Activities of N-(2-(1H-indol-3-yl)ethyl)-2-nitroaniline

The title compound, N-(2-(1H-indol-3-yl)ethyl)-2-nitroaniline(C16H15N3O2, Mr = 281.31), has been synthesized by the multicomponent reaction of milder Ullmann, and its structure was characterized by 1H NMR, 13 C NMR, IR, H RMS(ESI) and single-crystal X-ray diffraction. It crystallizes in monoclinic, space group I2/c with a = 15.0212(10), b = 9.4911(6), c = 20.3075(13) A, β = 100.776(7)o, V = 2844.1(3)A3, Z = 8, Dc = 1.314 g/cm3, F(000) = 1184.0, μ = 0.089 mm-1, the final R = 0.0574 and w R = 0.1688 for 1701 observed reflections(I 】 2σ(I)). X-ray analysis indicates three major N(2)–H(2)···O(2), C(13)–H(13)···O(2), N(2)–H(2)···N(3) hydrogen bonds and π-π stacking interactions in the crystal structure. The preliminary biological test shows that the title compound has a good antitumor activity against A549 in vitro with the IC50 value of 35 μmol/L.

Synthesis and Crystal Structure of 3-(1-Ethyl-1H-indole-3-carbonyl)aminopropionic Acid

3-（1-Ethyl-1H-indole-3-carbonyl）aminopropionic acid has been synthesized by alkylation of 3-（1H-indole-3-carbonyl）aminopropionic acid methyl ester with bromoethane,follo-wed by saponifying and acidating,in 89.0% yield.Its crystal structure was gotten and determined by X-ray diffraction method.The crystal is of orthorhombic,space group P212121 with a = 8.9490（12）,b = 11.1010（15）,c = 13.0475（18） ,V = 1296.2（3） 3,Z = 4,Dc = 1.334 g/cm3,λ = 0.71073 ,μ（MoKα） = 0.095 mm-1,Mr = 260.29 and F（000） = 552.The structure was refined to R = 0.0306 and wR = 0.1445 for 2612 observed reflections with I 2σ（I）.In the crystal structure,molecules are linked to each other through hydrogen bonds of N（2）-H（2）···O（1） and O（3）-H（3）···O（1）,generating a three-dimensional network.

Synthesis and Crystal Structure of Methyl 3-(5-Bromo-1-ethyl-1H-indole-3-carbonyl)aminopropionate

Methyl 3-（5-bromo-l-ethyl-lH-indole-3-carbonyl）aminopropionate has been synthesized by the acylation of 5-bromo-3-trichloroacetylindole with β-alanine methyl ester, followed by alkylation with ethyl iodide, in 82.6% yield. Its crystal structure was gotten and determined by X-ray diffraction method. The crystal is of monoclinic, space group P2/c with a = 11.7927（8）, b = 14.9342（8）, c = 9.0060（5） A, β = 101.558（6）°, V = 1553.93（16） A3, Z = 4, Dc= 1.510 g/cm3, 2 = 0.71073 A,μ（MoKa） = 2.656 mm-1, Mr = 353.22 and F（000） = 720. The structure was refined to R = 0.0401 and wR = 0.0825 for 1704 observed reflections with I 〉 2σ（I）. In the crystal structure, intermolecular N（2）-H（2）...O（1） hydrogen bond and weak intermolecular bonds （C（1）-H（1）...O（1） and C（10）-H（10B）-O（2）） are formed, and π-π stacking also exists.