Synthesis and antiviral activity of novel thioether derivatives containing 1,3,4-oxadiazole/thiadiazole and emodin moieties

A series of novel thioether derivatives containing 1,3,4-oxadiazole/thiadiazole and emodin moieties were designed and synthesized. The structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR, Infrared, and elemental analysis. The results of bioactivity analysis showed that most of the target compounds exhibited moderate to good antiviral activity against tobacco mosaic virus at a concentration of 500 mg/L. Especially, among the title compounds, Y2, Y8, and Y10 possessed appreciable curative activity in vivo, with inhibition rates of 50.51, 52.08, and 54.62%, respectively, which were similar to that of Ningnanmycin (53.40%).     

Simultaneous determination and pharmacokinetic studies of aloe emodin and chrysophanol in rats after oral administration of Da-Cheng-Qi decoction by high-performance liquid chromatography

A validated high-performance liquid chromatography (HPLC) method was developed for simultaneous determination and pharmacokinetic study of aloe emodin and chrysophanol in rats. It was performed on a reverse-phase C(18) column and a mobile phase made up of methanol and 0.2% acetic acid (83:17, v/v). The ultraviolet detection was 254 nm. 1,8-dihydroxyanthraquinone was used as the internal standard. The assay was linear over the range 28-2800 ng/mL (r(2) = 0.9993) for aloe emodin and 25.6-2560 ng/mL (r(2) = 0.9991) for chrysophanol. The average percentage recoveries of three spiked plasmas were 98.8-104.8% and 97.7-103.2% for aloe emodin and chrysophanol, respectively. Their RSD of intra-day and inter-day precision at concentrations of 56, 280 and 1400 ng/mL for aloe emodin and 51.6, 258 and 1290 ng/mL for chrysophanol were less than 3.5%. This method was applied for the first time to simultaneously determinate aloe emodin and chrysophanol in rats following oral administration of traditional Chinese medicine of Da-Cheng-Qi decoction. The pharmacokinetic parameters showed that chrysophanol was better absorbed with higher concentrations in plasma than aloe emodin did. They both eliminated slowly in male rats. The assay is suitable for identifying the plasma and tissue levels of aloe emodin and chrysophanol in preclinical investigations.     

大黄素键合硅胶高效液相色谱柱的制备和应用

采用中间体法,先将大黄素配体与γ-[（2,3）-环氧丙氧]丙基三甲氧基硅烷（KH-560）偶联剂反应制备含配体的硅氧烷试剂,然后再与硅胶键合,最终制得大黄素键合硅胶液相色谱固定相（以下简称ESP）。通过红外光谱、元素分析和热重分析表征固定相的结构。以萘作为溶质探针,甲醇-水（60：40,v/v）为流动相,流速为0.8 mL/min,测得ESP柱的柱效。采用传统的反相C₁₈和苯基柱作参比,将ESP应用于系列中性、碱性和酸性芳香族化合物以及实际样品风油精的分离分析,并探讨相关的色谱分离机理。结果表明,配体大黄素被成功地键合到球形硅胶表面,测得配体键合量为0.23 mmol/g,ESP柱理论塔板数约为19874 N/m。ESP的偶联剂链和蒽醌环提供了疏水性的结构基础,大黄素配体还能为溶质提供π-π或p-π、电荷转移、氢键、偶极-偶极等作用点。多位点的协同作用使得ESP柱具有独特和优秀的色谱分离选择性,并且无需调节pH值,采用简单而廉价的甲醇-水流动相就能实现胺类、酚类等极性样品的基线分离,实验条件简单、方便。     

金丝桃素的合成工艺改进

以大黄素为原料,经还原,Aldol缩合和光照反应合成了金丝桃素,总收率58.6%,其结构经1H NMR, IR和MS表征.     

毛细管胶束电动色谱-质谱联用法同时测定心脑康胶囊中3种成分含量

采用胶束电动色谱-质谱联用法同时测定心脑康胶囊中的芍药苷、葛根素、大黄素含量。该方法以未涂层石英毛细管(80cm×50μm)为分离通道,以30 mmol/L月桂酸-90 mmol/L氨水(pH值9.0)为缓冲溶液,50%异丙醇(含1 mmol/L乙酸)为鞘液,工作电压为25kV。测定结果:各组分在18 min内达到完全分离,芍药苷、葛根素、大黄素的线性范围分别为0.20～200mg/L、0.50～500mg/L、0.020～300 mg/L,检出限分别为0.020mg/L、0.050mg/L、0.0060 mg/L。样品的加标回收率在96.5%～102%之间,相对标准偏差均小于3.1%。该方法简便、快速、准确可靠,已成功应用于心脑康胶囊中芍药苷、葛根素、大黄素的含量测定。     

分光光度法测定大黄中大黄素的含量

建立了10倍量90%乙醇回流提取、15倍量乙酸乙脂二次回流提取,最后用碱提酸沉法制备高纯度大黄素的方法。用改进的分光光度法对纯化后产品进行测定,大黄素含量达85.41%。显色剂为5mol/L的NaOH溶液,检测波长为530nm,该显色体系的线性范围为1~400μg/mL,相关系数为0.9993,平均回收率为99.57%,RSD为1.31%(n=4)。     

大黄素衍生物的合成及细胞毒性研究

以天然大黄素为母体, 经化学修饰得到一系列新的含氮衍生物6～14. 通过¹H NMR, IR, MS和元素分析确定了结构. 选择口腔底癌(KB)和乳腺癌(MFC-7)两种人癌细胞株, 采用标准MTT法测定了这类大黄素衍生物的细胞毒性. 研究表明大多数衍生物都有较强的抗癌活性, 其中位置异构体7a和7b的混合物表现出最强的活性, 与母体大黄素相比较, 活性分别提高了174倍(KB)和133倍(MFC-7).     

Identification and determination of active anthraquinones in Chinese teas by micellar electrokinetic capillary chromatography

The simultaneous determination of emodin, aloe-emodin and rhein, in Semen Cassiae, Qinghai Wild Dahuang tea, Ningxia Juemingzi tea, Lanzhou Juemingzi tea and Surong Juemingzi tea, has been investigated by micellar electrokinetic capillary chromatography for the fi rst time. With an electrolyte containing 15 mm borax, 30 mm SDS, 10% (v/v) ethanol, at pH 9.60 and 20 kV applied voltage, the three analytes were completely separated within 12 min. The effects of the concentration of borax, electrolyte pH, the concentrations of SDS and organic modifier and the applied voltage on electropheoretic behavior and separation were studied. The linear calibration range was 4-120 micro g/mL (r = 0.9921) for emodin, 10-200 micro g/mL (r = 0.9970) for aloe-emodin and 2-100 micro g/mL (r = 0.9971) for rhein, respectively. Under the optimum conditions, the relative standard deviation (RSD) values (n = 6) of the migration time and the peak area of each peak was 0.59-0.80% and 1.30-3.22%, respectively. The contents of the analytes in Rheum, Qinghai Wild Dahuang tea, Semen Cassiae and three other kinds of teas were easily determined with recoveries ranging from 95.3 to 104.4%.     

大黄素/Mg-Al-LDHs纳米杂化物的制备及缓释性能研究

以Mg-Al型层状双金属氢氧化物(Mg-Al-LDHs)为载体,将大黄素分子通过二次组装法成功插入其层间,得到大黄素/Mg-Al-LDHs纳米杂化物。XRD结果显示,Mg-Al-LDHs粒子层间距由0.48 nm增大到3.35 nm。差热曲线(DTA曲线)分析结果表明,该纳米杂化物分子中大黄素的分解温度比纯大黄素的分解温度高50℃。分别在pH 4.8和pH 7.5的缓冲溶液中测定了大黄素/LDHs的缓释性能,结果表明大黄素/LDHs的药品释放速率明显低于二者的物理混合物,并探讨了释放机理。     

Bioguided Isolation of Active Compounds from Rhamnus alaternus against Methicillin-Resistant Staphylococcus aureus (MRSA) and Panton-Valentine Leucocidin Positive Strains (MSSA-PVL)

Despite intensified efforts to develop an effective antibiotic, S. aureus is still a major cause of mortality and morbidity worldwide. The multidrug resistance of bacteria has considerably increased the difficulties of scientific research and the concomitant emergence of resistance is to be expected. In this study we have investigated the in vitro activity of 15 ethanol extracts prepared from Moroccan medicinal plants traditionally used for treatment of skin infections. Among the tested species I. viscosa, C. oxyacantha, R. tinctorum, A. herba alba, and B. hispanica showed moderate anti-staphylococcal activity. However, R. alaternus showed promising growth-inhibitory effects against specific pathogenic bacteria especially methicillin-susceptible Staphylococcus aureus Panton-Valentine leucocidin positive (MSSA-PVL) and methicillin-resistant S. aureus (MRSA). The bioguided fractionation of this plant using successive chromatographic separations followed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) including EIMS and HREIMS analysis yielded the emodin (1) and kaempferol (2). Emodin being the most active with MICs ranging between 15.62 and 1.95 µg/mL and showing higher activity against the tested strains in comparison with the crude extract, its mechanism of action and the structure-activity relationship were interestingly discussed. The active compound has not displayed toxicity toward murine macrophage cells. The results obtained in the current study support the traditional uses of R. alaternus and suggest that this species could be a good source for the development of new anti-staphylococcal agents.