丹皮酚的新法制备及其糖苷化衍生物的合成

丹皮酚(paeonol,1)可从中药材牡丹皮中提取得到,化学名为2-羟基-4-甲氧基苯乙酮,具有抑菌抗炎、解热镇痛、降压利尿、抗凝血、抗过敏、增强免疫功能等作用[1].目前,丹皮酚的生产主要从牡丹皮中提取,受植物资源限制产量较小,而且提取工艺复杂,产品纯度低;另外,由于水溶性差,无法直接制成水溶性注射剂以提高人体的吸收.所以,有文献报道了对丹皮酚的结构进行修饰,制成磺酸酯钠盐、胂化物、环糊精等衍生物以提高其水溶性[2-4].     

丹皮酚在石墨烯修饰电极上的电化学行为及应用研究

利用电化学还原法制备了还原氧化石墨烯修饰电极(rGO/GCE)。采用循环伏安法研究了丹皮酚在rGO/GCE上的电化学行为。结果表明,rGO/GCE对丹皮酚有较好的电催化活性。考察了缓冲溶液pH值、扫描圈数、富集时间、扫速等对丹皮酚电化学响应的影响,建立了检测丹皮酚的标准曲线。丹皮酚峰电流与丹皮酚浓度在4.0×10~(-6)～8.0×10~(-5) mol·L~(-1)范围内有良好线性关系:I_(pa)=0.49 c(μmol·L~(-1))+8.46(R~(2 )=0.9786),检出限为1.0×10~(-6) mol·L~(-1)。将此方法应用于丹皮酚软膏样品中丹皮酚含量的测定,回收率为90.0%～108.6%。     

微量热法研究丹皮酚及其一种同分异构体与β-环糊精的相互作用

在298.15K下,用微量热法研究了丹皮酚及其一种同分异构体与β-环糊精在水溶液中包结作用的热效应,并用核磁共振来表征包结物的形成。从丹皮酚及其同分异构体的结构出发讨论了主-客体的相互作用强弱以及热力学数据的差异。结果表明,β-环糊精对两种同分异构体具有明显的分子识别功能。     

几种天然植物提取物对酪氨酸酶活性的抑制作用

选择合适的溶剂体系,用维生素C(Vc)作为阳性对照物,采用分光光度法测定了不同浓度的茶多酚、丹皮酚及金银花叶子总黄酮提取物(乙酸乙酯相)对酪氨酸酶活性的抑制作用.结果表明:采用1%丙三醇和1%吐温-80(体积比1∶1)混合液作溶剂可显著增加丹皮酚和金银花叶子总黄酮提取物在水中的溶解度;茶多酚、丹皮酚、金银花叶子总黄酮提取物对酪氨酸酶的活性都有一定的抑制作用,其抑制作用从强到弱依次为Vc、Vc∶丹皮酚=1∶2(质量比)、Vc∶丹皮酚=1∶1(质量比)、茶多酚、茶多酚∶丹皮酚=2∶1(质量比)、丹皮酚、金银花叶子总黄酮提取物.     

乙嘧酚磺酸酯中杂质的GC-MS分析

嘧啶类化合物因具有不同的生物活性,如杀虫、杀菌、除草、抗病毒等[1-2],引起人们的广泛兴趣.乙嘧酚磺酸酯(bupirimate)属于嘧啶类内吸性杀菌剂,具有用量少、高效、低毒、对白粉病有特效等优点,因此取代了乙嘧酚和二甲嘧酚等农药.目前乙嘧酚磺酸酯的合成与生物活性研究已成为当今绿色农药创制的热点[3].     

去甲丹皮酚衍生物的合成及其抗炎活性

去甲丹皮酚或丹皮酚分别与非甾体抗炎药(NSAIDs)阿司匹林、布洛芬和双氯芬酸偶联,合成了5个新的去甲丹皮酚衍生物(3a～3c,4b)和丹皮酚衍生物(5b),其结构经1H NMR,IR和HR-MS表征.二甲苯致小鼠耳肿胀试验结果表明,3和5均有较强的抗炎活性,与阴性对照对CMC-Na相比,表现出显著性差异(P＜0.01).     

丹皮酚腙类化合物的合成及其抗菌活性

根据拼接原理将活性基团腙引入中药活性成分丹皮酚中对其结构进行修饰,以丹皮酚为原料,与80%水合肼在乙醇中反应得到中间体丹皮酚腙(2),然后与芳香醛反应合成了10个芳甲叉基丹皮酚腙(3a-3j),其结构经IR、~1H NMR、~(13)C NMR和ESI-MS表征。采用二倍稀释法测定目标化合物对金黄色葡萄球菌和大肠杆菌的最低抑菌浓度(MIC),结果表明:大部分化合物金黄色葡萄球菌和大肠杆菌表现出较好的抑菌活性,特别是化合物3i对金黄色葡萄球菌的的MIC为2μg·mL~(-1),优于阳性对照药环丙沙星。     

相溶解度法研究不同环糊精对丹皮酚的增溶作用

采用相溶解度法,通过测定丹皮酚在不同温度不同浓度的β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)、羟乙基-β-环糊精(HE-β-CD)、取代度为4的磺丁基醚-β-环糊精(SBE4-β-CD)以及取代度为7的磺丁基醚-β-环糊精(SBE7-β-CD)中的溶解度,绘制相溶解度曲线,丹皮酚的溶解度均随5种环糊精浓度的增加而成线性增加,相溶解度曲线为AL型,说明丹皮酚与环糊精以1∶1包合,实验结果表明,5种环糊精对丹皮酚均有增溶作用且SBE7-β-CD的增溶效果最佳.     

新型丹皮酚嘧啶类化合物的合成及抗肿瘤活性

以丹皮酚为原料与1,4-二溴丁烷反应合成中间产物2-(4-溴丁烷氧基)-4-甲氧基苯乙酮(2); 2与嘧啶类化合物反应合成了11新型个丹皮酚嘧啶类化合物(4a~4k)，其结构经¹HNMR, ¹³CNMR, IR和MS（ESI）表征。采用MTT法测定目标化合物对HepG2（人肝癌细胞）、MCF-7（人乳腺癌细胞）、HCT-116（人结肠癌细胞）、A549（人肺癌细胞）和LO2（人正常肝细胞）等5种细胞的抑制活性。结果表明：部分化合物表现出一定的抗肿瘤活性，其中6-(2-氟苯基)-5-氰基-4-羟基-2-丹皮酚丁巯基嘧啶(4c)以及6-甲基-4-羟基-2-丹皮酚丁巯基嘧啶(4i)对HCT-116的IC₅₀值分别为(9.22±1.80)μg/mL、(1.32±0.71)μg/mL，优于阳性对照药顺铂。     

双波长导数光谱法测定牡丹皮中丹皮酚的含量

1 引言 牡丹皮为毛茛科植物牡丹(Paeonia suffruticosa Andr.)的干燥根皮,是临床常用的一种中药,具有清热凉血、活血化瘀之功效。丹皮酚是其中主要的化学成分,其它成分尚有芍药甙、丹皮甙、挥发油和苯甲酸,植物甾醇等。丹皮酚的含量是评价牡丹皮质量的一个重要指标,中国药典采用水蒸汽蒸馏—紫外法测定其含量。我们采用双波长导数光谱法测定了牡丹皮中丹皮酚的含量,结果较为满意。     

丹皮酚与钙粘素相互作用的分析研究

丹皮酚对多种肿瘤细胞具有抑制作用,而钙粘素是与肿瘤产生和恶化密切相关的一类糖蛋白.本研究运用荧光光谱法和原子力显微技术探索了丹皮酚与钙粘素的相互作用.荧光光谱法研究结果表明,丹皮酚对钙粘素的荧光具有显著的猝灭作用,通过猝灭常数随温度变化趋势推断为静态猝灭过程.丹皮酚与钙粘素形成复合物的热力学参数分别为ΔH=-4.3×10.5 J/mol和ΔS=-1.3×10.3 J/(mol·K), 表明此结合过程以氢键和范德华力为主.原子力显微观察结果表明,钙粘素分子间可形成有序长链结构,丹皮酚加入后能显著破坏这种组装结构而形成短链结构,这是由于丹皮酚与钙粘素末端色氨酸残基的作用而影响相邻钙粘素分子结构域间的交错作用所致.本研究结果表明,钙粘素可能是丹皮酚体现其活性的一个重要作用靶点.     

丹皮酚苯磺酰腙类衍生物的合成及杀粘虫活性研究

丹皮酚可作用于乙酰胆碱酯酶、穿过血脑屏障,该作用机理为使其可能开发成为新型杀虫剂。鉴于此,本文合成了5个丹皮酚苯磺酰腙类衍生物(5a^5e),并评价了它们对威胁农作物的害虫的杀虫活性。在1mg/mL浓度下,以川楝素为阳性对照,采用小叶碟添加法测定化合物3和5a^5e的杀粘虫活性。其中,化合物5e杀虫活性显著,最终校正死亡率(FMR=50.0%)与商品化植物源杀虫剂川楝素等同。初步构效关系研究表明,丹皮酚羰基位修饰是可行的;中间体3的亚胺位磺化修饰可提高杀虫活性,且磺化取代基不同活性差异显著。此外,实验还发现试虫取食了附有供试化合物的叶片后在幼虫期、化蛹期和羽化期均出现不同程度、不同状况的非正常生长。     

用偶合反应化学发光法研究丹皮酚在兔体内的药物代谢动力学

为了研究丹皮酚的药物代谢动力学，采用高灵敏的偶合反应化学发光法，对兔血中的血药浓度进行监测，在ｐＨ为９．２的介质中，以Ｈ２Ｏ２氧化丹皮酚的反应与Ｌｕｍｉｎｏｌ－Ｈ２Ｏ２－ＣＯ＾２＋化学发光反应相偶合，测得牡丹皮和徐长卿中丹皮酚在兔体内的吸收速率分别为２．０７和０．４９９ｈ＾－１，消除半衰期分别为１１．７６和３．０４ｈ，相对而言牡丹皮所含丹皮酚具有吸收快、消除慢、生物利用度大的优点。     

Development of microwave-assisted extraction followed by headspace single-drop microextraction for fast determination of paeonol in traditional Chinese medicines

Paeonol is an important active component present in traditional Chinese medicines (TCMs), which was used for the treatment of many diseases such as eczema. In this work, microwave-assisted extraction (MAE) was firstly combined with headspace single-drop microextraction (HS-SDME), and applied to rapid determination of paeonol in two TCMs of Cynanchum paniculatum and Paeonia suffruticosa. In the proposed method, paeonol in TCMs was isolated by using MAE, followed by extraction and concentration by HS-SDME, and detected by gas chromatography-mass spectrometry (GC-MS). The experiment parameters of MAE and HS-SDME were discussed, and the method precision, recovery and detection limit were also studied. To further demonstrate the reliability of the quantification, both the proposed method and a standard method of steam distillation (SD) were simultaneously applied to quantitative analysis of paeonol in TCM samples from different growing areas. The experimental results show that MAE-HS-SDME is a simple and rapid method for the quantitative analysis of paeonol in TCMs, and is also a potential and alternative tool for quality monitoring for the two TCMs of C. paniculatum and P. suffruticosa.     

玫瑰花提取工艺、化学成分及其生物活性研究进展

玫瑰花具有重要的观赏和药用价值, 主要的化学成分有玫瑰精油、黄酮类、多糖类和酚酸类等, 具有心肌保护、抗氧化、抑菌、抗肿瘤、抗病毒、镇静催眠作用、调节血脂和降血糖等生物活性.玫瑰精油是高级香水、香料和化妆品不可取代的原料, 其提取工艺是工业研究的重点.对玫瑰花中的化学成分和生物活性进行了综述, 并重点总结了玫瑰精油的提取工艺、成分和生物活性, 为玫瑰花, 特别是玫瑰精油的研究和开发提供参考.     

Phytotoxic property of metabolites isolated from Garcinia gardneriana

Garcinia gardneriana is a medicinal tree species used in Brazil in the treatment of hepatitis and gastritis. This use is attributed to phenolic compounds, mainly 7-epiclusianone, guttiferone-A and fukugetin, which present several proven biological activities. However, to the best of our knowledge, no study on the phytotoxic activity of G. gardneriana extracts has been conducted until now. This research proposed to isolate and quantify by high-performance liquid chromatography (HPLC) the major compounds from G. gardneriana seed extracts in ethyl acetate and to evaluate their phytotoxic activities. The natural products 7-epiclusianone, guttiferone-A and fukugetin were quantified at concentrations varying from 0.46 to 1.13 mg mL⁻¹ and were isolated with yields ranging from 7% to 23% (w/w). The phytotoxic assay indicated that the crude extract showed no action on the dry matter of Sorghum bicolor plants, but the isolated compounds fukugetin and 7-epiclusianone had moderate activity. On the other hand, guttiferone-A displayed a greater herbicide activity than glyphosate, a positive control, even in almost three times lower concentrations, causing severe intoxication in the plants. This work is the first report on this activity by the extract of G. gardneriana and its isolated compounds. Besides that, guttiferone-A showed up as a scaffold for the development of new agrochemicals. Complementing these findings, computational studies suggested that this benzophenone can interact effectively with transferase enzymes type, in special caffeic acid O-methyltransferase from S. bicolor (PDB code: 4PGH), indicating a possible mechanism of action in this plant.     

One-pot enantioselective synthesis of functionalized pyranocoumarins and 2-amino-4H-chromenes: discovery of a type of potent antibacterial agent

Function-oriented design and synthesis of chiral small molecules with novel activity is a key goal in modern organic chemistry. As multiple antibiotic-resistant pathogens are emerging and causing serious diseases, the need for practical routes for the development of new types of antibacterial agents is very urgent. Herein, we present a highly efficient process for the synthesis of optically active pyranocoumarins and 2-amino-4H-chromenes through an organocatalytic Knoevenagel/Michael/cyclization sequence, and the preliminary biological studies of these new heterocyclic compounds revealed potent antibacterial activity. This study provides a novel strategy for further research and development of new types of antibacterial agents effective against human pathogens.     

LC Tissue Distribution Study of Paeonol in Rats after Oral Administration

Paeonol, an important constituent of the traditional Chinese medicine Cortex Moutan, has a variety of bioactivity. A simple and sensitive HPLC?CUV method has been developed for analysis of paeonol in different rat tissue (heart, liver, spleen, lung, kidney, and brain). Bio-samples were prepared by simple protein precipitation, and separation of paeonol was achieved on a C₁₈ column with methanol?C2% glacial acetic acid solution 70:30 (v/v) as mobile phase at a flow rate of 1.0 mL min^?1. UV detection was at 274 nm and the column temperature was 30 °C. Linearity was good between 0.025 and 5.0 ??g mL^?1 (r ² ?? 0.9990) for tissue samples. Inter-day and intra-day accuracy (as relative error, RE) and precision (as relative standard deviation, RSD) were <5.94 and 6.05%, respectively. The limit of detection was 0.025 ??g mL^?1 and extraction recovery for all samples was ??85.86%. The method was successfully applied to a tissue-distribution study after oral administration of 40 mg kg^?1 paeonol to healthy Sprague?CDawley rats. The study showed that paeonol was quickly distributed and eliminated after oral administration; liver and kidney were the major distribution tissues of paeonol in rats, and paeonol quickly passed through the blood?Cbrain barrier. It was also found there was no long-term accumulation of paeonol in rat tissues.     

Fast determination of paeonol in plasma by headspace solid-phase microextraction followed by gas chromatography-mass spectrometry

Paeonol is the active component in the traditional Chinese medicines (TCMs), such as Cynanchum paniculatum, which has been used to treat many diseases, such as eczema. In this work, a simple, rapid and sensitive method was developed for the determination of paeonol in rabbit plasma, which was based on headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). The extraction parameters of fiber coating, sample temperature, extraction time, stirring rate and ion strength were systemically optimized; the method linearity, detection limit and precision were also investigated. It was shown that the proposed method provided a good linearity (0.02-20 μg mL⁻¹, R² > 0.990), low detection limit (2.0 ng mL⁻¹) and good precision (R.S.D. value less than 8%). Finally, GC/MS following HS-SPME was applied to fast determination of paeonol in rabbit plasma at different time point after oral demonstration of Cynanchum paniculatum essential oil. The experimental results suggest that the proposed method provided an alternative and novel approach to the pharmacokinetics study of paeonol in the TCMs.     

一系列新型三环二萜的合成与抗肿瘤活性研究

对活性天然产物(+)-7-deoxynimbidiol非对映异构体的外消旋体cis-(±)-7-deoxynimbidiol进行了合成和衍生, 共得到了8个新型三环二萜化合物; 对合成的新化合物进行了抗肿瘤活性的实验研究, 其中化合物5d对人体乳腺癌瘤株MCF7表现出了较强的抑制作用(IC50=7.49 μg/mL), 可能作为新型抗肿瘤药物先导化合物.