Stilbene

Stilbene
  • 文章类型: Journal Article
    白藜芦醇被肠道微生物群转化为各种代谢物。人和大鼠肝脏11β-羟基类固醇脱氢酶1(11β-HSD1)是糖皮质激素激活的关键,而肾脏中的11β-HSD2则有相反的反应。白藜芦醇及其类似物是否选择性抑制11β-HSD1仍不确定。在这项研究中,抑制强度,行动模式,构效关系(SAR),白藜芦醇类似物对人体的对接分析,rat,进行小鼠11β-HSD1和11β-HSD2。这些化学物质对人11β-HSD1的抑制强度为二氢松香素(6.91μM)>lunularin(45.44μM)>松二苯乙烯(46.82μM)>白藜芦醇(171.1μM)>松香素(193.8μM)>其他。抑制大鼠11β-HSD1的抑制强度为pinostilbene(9.67μM)>lunularin(17.39μM)>二氢pinosylvin(19.83μM)>二氢白藜芦醇(23.07μM)>其他,二氢二苯乙烯(27.84μM)和二氢二羟基二苯乙烯(85.09μM)抑制小鼠11μSDM。所有化学物质都没有抑制人类,rat,和小鼠11β-HSD2。发现双氢吡诺西尔文,lunularin,和pinostilbene是人11β-HSD1的竞争性抑制剂,lunularin,双氢匹诺西尔文,二氢松香素和二羟基二苯乙烯是大鼠11β-HSD1的混合抑制剂。对接分析表明,它们与人和大鼠11β-HSD1的类固醇结合位点结合。总之,白藜芦醇及其类似物可以选择性抑制人和大鼠11β-HSD1,而小鼠11β-HSD1对白藜芦醇类似物的抑制作用不敏感。
    Resveratrol is converted to various metabolites by gut microbiota. Human and rat liver 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) are critical for glucocorticoid activation, while 11β-HSD2 in the kidney does the opposite reaction. It is still uncertain whether resveratrol and its analogues selectively inhibit 11β-HSD1. In this study, the inhibitory strength, mode of action, structure-activity relationship (SAR), and docking analysis of resveratrol analogues on human, rat, and mouse 11β-HSD1 and 11β-HSD2 were performed. The inhibitory strength of these chemicals on human 11β-HSD1 was dihydropinosylvin (6.91 μM) > lunularin (45.44 μM) > pinostilbene (46.82 μM) > resveratrol (171.1 μM) > pinosylvin (193.8 μM) > others. The inhibitory strength of inhibiting rat 11β-HSD1 was pinostilbene (9.67 μM) > lunularin (17.39 μM) > dihydropinosylvin (19.83 μM) > dihydroresveratrol (23.07 μM) > dihydroxystilbene (27.84 μM) > others and dihydropinosylvin (85.09 μM) and pinostilbene (>100 μM) inhibited mouse 11β-HSD1. All chemicals did not inhibit human, rat, and mouse 11β-HSD2. It was found that dihydropinosylvin, lunularin, and pinostilbene were competitive inhibitors of human 11β-HSD1 and that pinostilbene, lunularin, dihydropinosylvin, dihydropinosylvin and dihydroxystilbene were mixed inhibitors of rat 11β-HSD1. Docking analysis showed that they bind to the steroid-binding site of human and rat 11β-HSD1. In conclusion, resveratrol and its analogues can selectively inhibit human and rat 11β-HSD1, and mouse 11β-HSD1 is insensitive to the inhibition of resveratrol analogues.
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  • 文章类型: Journal Article
    一系列的二苯乙烯类似物,其中一个苯环被吖嗪-3(2H)-一核取代,被设计和合成作为血小板聚集抑制剂进行探索。从简单的起始材料和Wittig's反应成功地获得了提出的二苯乙烯-吖嗪酮杂化物。与标准药物相比,大多数目标化合物显示出改善的体外活性,白藜芦醇,突出显示10d和10e类似物是最有效的,100µM时的抑制百分比为94.15%,50µM时的抑制百分比为100%,分别。还使用SwissADME和ProTox-II网络服务器估算了新型杂种的药代动力学和毒性(ADME/T)特性。
    A series of stilbene analogues, in which a phenyl ring was replaced by the pyridazin-3(2H)-one nucleus, was designed and synthesized to be explored as platelet aggregation inhibitors. The proposed stilbene-pyridazinone hybrids were successfully obtained from simple starting materials and by Wittig\'s reaction. Most of the target compounds displayed improved in vitro activity in comparison with the standard drug, resveratrol, highlighting as the most potent the analogues 10d and 10e, with inhibition percentages of 94.15 % at 100 µM and 100 % at 50 µM, respectively. The pharmacokinetic and toxicity (ADME/T) properties of the novel hybrids were also estimated with the SwissADME and ProTox-II web servers.
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  • 文章类型: Journal Article
    认知障碍,从轻度到重度,对日常功能产生不利影响,生活质量,和工作能力。尽管在过去十年中做出了巨大的努力,200多种有希望的候选药物在临床试验中失败。由于其悠久的历史和安全性,草药作为痴呆症的潜在治疗方法正在引起人们的兴趣,使它们对药物开发有价值。本文旨在探讨何首乌对认知功能影响的机制。
    这项研究主要关注何首乌及其化学成分对认知行为结果的影响,包括莫里斯水迷宫,被动回避测试,还有Y迷宫,以及认知障碍和阿尔茨海默病(AD)的致病目标,如淀粉样蛋白沉积,淀粉样前体蛋白,tau过度磷酸化,和认知能力下降。此外,对何首乌影响认知功能的机制进行了全面评估。我们回顾了在实验模型上进行的临床前研究的最新数据,特别是观察何首乌对认知衰退和AD的影响。
    根据最近的研究,何首乌及其生物活性成分,二苯乙烯,还有大黄素,影响认知行为结果,调节认知功能障碍和AD的病理目标。它们的作用机制包括减少氧化和线粒体损伤,调节神经炎症,停止凋亡,促进神经发生和突触发生。
    这篇综述是关于AD和其他与何首乌治疗效果相关的认知障碍模型的当前实验的综合汇编。我们相信这些发现可以作为未来临床试验的基础,并在人类神经系统疾病的治疗中具有潜在的应用。
    UNASSIGNED: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function.
    UNASSIGNED: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer\'s disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum\'s impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum\'s effects on cognitive decline and AD.
    UNASSIGNED: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis.
    UNASSIGNED: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.
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  • 文章类型: Journal Article
    苯氧基自由基偶联反应在自然界中广泛用于合成复杂分子如木质素。它们在实验室中的使用对于从多酚家族生产高价值化合物具有巨大的潜力。虽然负责产生自由基的酶是众所周知的,后者的行为仍然是神秘的,难以在反应烧瓶中控制。在我们的实验室中使用含有漆酶的B.cinerea酶促分泌组的先前工作表明,二苯乙烯的孵育会导致二聚体,而苯基丙烷类的孵育会导致二聚体以及更大的偶联产物。在这些先前研究的基础上,本文研究了不同结构特征在苯氧基自由基偶联中的作用。我们首先证明了环外共轭双键的存在在产生有效反应中起作用。此外,我们表明,苯丙素类三聚体和四聚体的形成可以通过脱羧反应再生该反应性部分进行。最后,这项研究调查了其他酚类化合物的反应性:二苯乙烯二聚体,一种二氢二苯乙烯,一种4-O-甲基-二苯乙烯和一种具有灰霉病菌酶促分泌组的简单酚。观察到的有效二聚反应始终与共轭到环外双键的对酚的存在相关。缺乏这种结构特征会导致不同的结果,一些化合物显示低转化率或根本没有反应。这项研究允许开发一种可控的方法来合成苯丙素衍生物和新型二苯乙烯衍生物的特定二聚体和四聚体,以及对可以促进有效自由基偶联反应的特征的理解。
    Phenoxy radical coupling reactions are widely used in nature for the synthesis of complex molecules such as lignin. Their use in the laboratory has great potential for the production of high value compounds from the polyphenol family. While the enzymes responsible for the generation of the radicals are well known, the behavior of the latter is still enigmatic and difficult to control in a reaction flask. Previous work in our laboratory using the enzymatic secretome of B. cinerea containing laccases has shown that incubation of stilbenes leads to dimers, while incubation of phenylpropanoids leads to dimers as well as larger coupling products. Building on these previous studies, this paper investigates the role of different structural features in phenoxy radical couplings. We first demonstrate that the presence of an exocyclic conjugated double bond plays a role in the generation of efficient reactions. In addition, we show that the formation of phenylpropanoid trimers and tetramers can proceed via a decarboxylation reaction that regenerates this reactive moiety. Lastly, this study investigates the reactivity of other phenolic compounds: stilbene dimers, a dihydro-stilbene, a 4-O-methyl-stilbene and a simple phenol with the enzymatic secretome of B. cinerea. The observed efficient dimerization reactions consistently correlate with the presence of a para-phenol conjugated to an exocyclic double bond. The absence of this structural feature leads to variable results, with some compounds showing low conversion or no reaction at all. This research has allowed the development of a controlled method for the synthesis of specific dimers and tetramers of phenylpropanoid derivatives and novel stilbene derivatives, as well as an understanding of features that can promote efficient radical coupling reactions.
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  • 文章类型: Journal Article
    背景:对(聚)酚暴露的见解代表了一种可调节慢性胰腺炎(CP)炎症的可变因素,然而,摄入量特征不佳,评估方法不发达。
    目的:目的是使用Phenol-Explorer数据库开发和测试一种从90天食物频率问卷(FFQ)中估算(聚)酚摄入量的方法,并通过分析先前收集的横截面数据来确定CP患者与对照组的饮食模式。
    方法:从大型门诊诊所招募了52名CP患者和48名对照,学术机构。为了评估估计膳食(聚)酚暴露的拟议方法的可行性,我们完成了对FFQ数据的回顾性分析.Mann-WhitneyU检验用于按组比较(聚)酚摄入量;Spearman相关性和多变量调整的对数线性关联用于比较(聚)酚摄入量与样本中的饮食评分。
    结果:从FFQs中估算(聚)酚摄入量是可行的,并且在先前报告的摄入量范围内得出了估算值。CP与对照组相比,总(聚)酚摄入量显着降低(463与567mg/1000kcal;p=0.041)。在调整后的分析中,较高的总(聚)酚摄入量与较高的HEI-2015相关(r=0.34,p<0.001),aMED(r=0.22,p=0.007),EDIH(r=0.29,p<0.001),和EDIP评分(r=0.35,p<0.001),代表较高的整体饮食质量和较低的胰岛素和抗炎饮食潜力,分别。
    结论:使用增强方法从FFQ获得总(聚)酚摄入量是可行的。CP患者的总(聚)酚摄入量较低,膳食模式指数较差,因此支持未来在这一人群中进行量身定制的饮食干预研究。
    BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped.
    OBJECTIVE: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data.
    METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample.
    RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively.
    CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.
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  • 文章类型: Journal Article
    末端[NiII-OH]配合物1,由三氟胺官能化的NHC配体支持,对砜与醇的反应表现出不同的反应性,视基地集中度而定,温度,和时间。使用一当量实现了醇与砜的Julia型烯基化。的基础,而将基本载荷降低到0.5当量。得到α-烷基化砜。除了优异的底物范围和选择性,具有生物活性的二苯乙烯衍生物DMU-212,pinosylvin,白藜芦醇,在Julia型烯烃化条件下,以高产率合成了piceatannol。大量的受控实验和DFT计算提供了对反应途径的宝贵见解。
    A terminal [NiII-OH] complex 1, supported by triflamide-functionalized NHC ligands, showed divergent reactivity for the reaction of sulfone with alcohol, contingent on base concentration, temperature, and time. Julia-type olefination of alcohols with sulfones was achieved using one equiv. of base, whereas lowering base loading to 0.5 equiv. afforded α-alkylated sulfones. Besides excellent substrate scope and selectivity, biologically active stilbene derivatives DMU-212, pinosylvin, resveratrol, and piceatannol were synthesized in high yield under Julia-type olefination conditions. An extensive array of controlled experiments and DFT calculations provide valuable insight on the reaction pathway.
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  • 文章类型: Journal Article
    细胞色素P450(CYP)通过产生不同的初级和次级代谢产物来调节植物的生长和胁迫反应。然而,许多植物CYP的功能仍然未知,因为,尽管它们的结构相似,预测CYPs的酶活性是困难的。在这项研究中,从番茄中分离出CYP736A亚家族(CYP736A61)的一个成员,并表征了其酶功能。通过与分子伴侣共表达,CYP736A61在大肠杆菌中成功表达。纯化的CYP736A61对7-乙氧基香豆素显示出羟基化活性,产生7-羟基香豆素或3-羟基7-乙氧基香豆素。进一步的底物筛选表明,二氢查耳酮和二苯乙烯衍生物(白藜芦醇和虎杖苷)是CYP736A61的底物。CYP736A61还介导白藜芦醇和虎杖苷的羟基化,尽管活动较低。重要的是,CYP736A61介导白藜芦醇和虎杖苷以及pinostilbene和pterostilbene的裂解。有趣的是,CY736A61还将根皮素转化为柚皮素查尔酮。这些结果表明CYP736A61是一种具有二苯乙烯切割活性的新型CYP酶。
    Cytochrome P450s (CYPs) regulate plant growth and stress responses by producing diverse primary and secondary metabolites. However, the function of many plant CYPs remains unknown because, despite their structural similarity, predicting the enzymatic activity of CYPs is difficult. In this study, one member of the CYP736A subfamily (CYP736A61) from tomatoes was isolated and characterized its enzymatic functions. CYP736A61 was successfully expressed in Escherichia coli through co-expression with molecular chaperones. The purified CYP736A61 showed hydroxylation activity toward 7-ethoxycoumarin, producing 7-hydroxycoumarin or 3-hydroxy 7-ethoxycoumarin. Further substrate screening revealed that dihydrochalcone and stilbene derivates (resveratrol and polydatin) are the substrates of CYP736A61. CYP736A61 also mediated the hydroxylation of resveratrol and polydatin, albeit with low activity. Importantly, CYP736A61 mediated the cleavage of resveratrol and polydatin as well as pinostilbene and pterostilbene. Interestingly, CY736A61 also converted phloretin to naringenin chalcone. These results suggest that CYP736A61 is a novel CYP enzyme with stilbene cleavage activity.
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  • 文章类型: Journal Article
    除了先前描述的碳萘和碳联苯,从二苯乙烯母体中设想了一种新型的双-碳-苯分子。合成,结构,在互补的实验和计算DFT水平上描述了两种这样的碳-二苯乙烯的光谱和电化学性质。在选定的目标中,碳-二苯乙烯裸露的骨架碳体由8或10个苯基装饰,0或2个叔丁基,和2个正辛基链,后来的取代基被引入以补偿预期的溶解度问题。就像在母二苯乙烯系列中一样,表征了苯基化的碳-二苯乙烯的异构体。顺式和反式异构体以几乎相等的量形成并且不能通过色谱法或结晶分离。然而,由于在NMR时间尺度(高达55°C)下的缓慢相互转化,可以暂时确定两种碳二苯乙烯的两种异构体的1HNMR信号。顺式异构体的计算结构表现出螺旋形状,与观察到的存在于面对的C18环的屏蔽锥内部的苯基p-CH核的磁屏蔽一致。光谱学,电化学和DFT计算导致对异构体及其取代基的重要性的正确表征。
    Beyond previously described carbo-naphthalene and carbo-biphenyl, a novel type of bis-carbo-benzenic molecules is envisaged from the stilbene parent. The synthesis, structure, spectroscopic and electrochemical properties of two such carbo-stilbenes are described at complementary experimental and computational DFT levels. In the selected targets, the bare skeletal carbo-mer of carbo-stilbene is decorated by 8 or 10 phenyl groups, 0 or 2 tert-butyl groups, and 2 n-octyl chains, the later substituents being introduced to compensate anticipated solubility issues. As in the parent stilbene series, isomers of the phenylated carbo-stilbenes are characterized. The cis- and trans-isomers are, however, formed in almost equal amounts and could not be separated by either chromatography or crystallization. Nevertheless, due to a slow interconversion at the NMR time scale (up to 55 °C) the 1H NMR signals of both isomers of the two carbo-stilbenes could be tentatively assigned. The calculated structure of the cis-isomer exhibits a helical shape, consistent with the observed magnetic shielding of phenyl p-CH nuclei residing inside the shielding cone of the facing C18 ring. The presence of the two isomers in solution also gives rise to quite broad UV-vis absorption spectra with main bands at ca 460, 560 and 710 nm, and a significant bathochromic shift for the decaphenylated carbo-stilbene vs the di-tert-butyl-octaphenylated counterpart. Square wave voltammograms do not show any resolution of the two isomers, giving a reversible reduction wave at -0.65 or -0.58 V/SCE, and an irreversible oxidation peak at 1.11 V/SCE, those values being classical for most carbo-benzene derivatives. Calculated NICS values (NICS(1)=-12.5±0.2 ppm) also indicate that the aromatic nature of the C18 rings is not markedly affected by the dialkynylbutatriene (DAB) connector between them.
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  • 文章类型: Journal Article
    对Gnetumlatifolium树干的植物化学研究导致了一种新型的酚类葡萄糖苷的分离,2E-2,4-二-(3,4-二羟基苯基)丁-2-烯-1-基-O-β-D-吡喃葡萄糖苷(1),以及五种已知的二苯乙烯衍生物(2-6)。它们的结构主要使用高分辨率电喷雾电离质谱和核磁共振光谱分析来确定,然后将观察到的光谱数据与报告值进行比较。发现G.latifolium中的新型化合物1可用作化学分类学标记。生物学评价显示化合物6对一氧化氮的产生有显著的抑制作用,半最大抑制浓度(IC50)值为4.85±0.20µM,远高于阳性对照地塞米松(IC50=14.20±0.54µM)。
    Phytochemical investigation of the trunks from Gnetum latifolium led to the isolation of a novel phenolic glucoside, 2E-2,4-di-(3,4-dihydroxyphenyl)but-2-en-1-yl-O-β-D-glucopyranoside (1), along with five known stilbene derivatives (2-6). Their structures were determined mainly using high-resolution electrospray ionisation mass spectrometry and nuclear magnetic resonance spectroscopic analyses, followed by comparisons of observed spectral data with reported values. The novel compound 1 in G. latifolium was found to be useful as a chemotaxonomic marker. Biological evaluation revealed that compound 6 had remarkable inhibitory effects on nitric oxide production, with a half-maximal inhibitory concentration (IC50) value of 4.85 ± 0.20 µM, which was much higher than that of the positive control dexamethasone (IC50 = 14.20 ± 0.54 µM).
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  • 文章类型: Journal Article
    利用双重Heck偶联反应合成了噻吩核V形转子-二苯乙烯衍生物。这些化合物是在稀溶液中具有中等量子产率的蓝色发射体。合成的二苯乙烯的转子性质支持聚集诱导的发射(AIE)行为,并且它们在聚集状态下显示出依赖于取代基的发射行为。在存在捐赠团体的情况下(例如,叔丁基,甲氧基,二苯胺基团)在二苯乙烯中,他们展示AIE财产。但随着吸电子基团(硝基)的引入,它们显示出聚集引起的猝灭(ACQ)行为。在聚集状态下观察到不同类型的纳米聚集体形成。动态光散射(DLS)和扫描电子显微镜(SEM)研究证实了这一点。细节光物理(吸收,荧光,和终身),研究了电化学性能(循环伏安法)和热稳定性。优化的结构,通过理论计算研究了分子轨道的能量和电子分布。
    Thiophene core V-shaped rotor-stilbene derivatives have been synthesized utilizing two-fold Heck coupling reaction. These compounds are blue emitters with moderate quantum yield in dilute solution. Rotor nature of the synthesized stilbenes supports aggregation induced emission (AIE) behaviour and they show substituent dependent emission behavior in aggregate state. In presence of donating groups (e.g., tert-butyl, methoxy, diphenylamine group) in stilbenes, they exhibit AIE property. But with the introduction of electron withdrawing group (nitro group), they shows aggregation caused quenching (ACQ) behavior. Different types of nano-aggregates formation is observed in aggregated state, which was confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM) studies. The details photophysical (absorption, fluorescence, and lifetime), electrochemical property (cyclic voltammetry) and thermal stability have been investigated. Optimized structure, energy and electronic distribution of molecular orbitals have been studied by theoretical calculation.
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