Design,synthesis, and cytotoxic evaluation of novel scopoletin derivatives

A series of scopoletin derivatives were designed and synthesized by introducing α‐aminoacetamide, acrylamide and β‐aminopropamide, respectively, to 3‐position of scopoletin, and their chemical structures were confirmed by ESI‐MS, IR, ¹H NMR, and ¹³C NMR spectra. All target compounds were evaluated in vitro against four human cancer cell lines (MDA‐MB‐231, MCF‐7, HepG2, and A549) by MTT method. Cytotoxic assay showed that compounds 7a , 7b , 7e , 7f , 8a , and 8e exhibited more potent cytotoxicities compared to scopoletin. Besides, we have further evaluated the growth inhibitory activities of these selected compounds against normal tissue cell lines HFL‐1. Although compound 8a showed the strongest antiproliferative activity in vitro, it exhibited strong cytotoxicity on normal cells HFL‐1, which limited its further study. Compound 7a and 7b exhibited higher antiproliferative activity against MDA‐MB‐231 and HepG2 cells and weak cytotoxicity on HFL‐1, which suggested that 7a and 7b might be ideal anticancer candidates. The SARs showed that the introduction of the acrylamide and its analogues β‐aminopropamide could significantly improve activity, while the α‐aminoacetamide failed to enhance potency obviously. Therefore, the mechanism of compound 7a and 7b is worthy of further research and the structure of compound 8a should be further optimized.     

基于血清药物化学的厚藤治疗急性痛风性关节炎质量标志物研究

目的基于中药质量标志物(qualitymarker,Q-Marker)的概念,研究厚藤提取物对急性痛风性关节炎(acutegouty arthritis,AGA)大鼠的治疗作用,并分析厚藤提取物在正常大鼠及AGA大鼠的血中移行成分,为厚藤Q-Marker的确定提供依据。方法采用尿酸钠建立AGA大鼠模型,考察厚藤提取物对AGA大鼠关节肿胀指数、足垫肿胀程度和滑膜组织病理变化的影响,考察厚藤提取物对AGA大鼠血清中白细胞介素-1β(interleukin-1β,IL-1β)、巨噬细胞炎性蛋白-1α(macrophage inflammatory protein-1α,MIP-1α)和MIP-2水平的影响。采用液相色谱-四级杆-飞行时间串联质谱(LC-Q-TOF-MS/MS)技术对厚藤提取物进行定性分析,探寻正常大鼠和AGA大鼠ig厚藤提取物后的入血成分。结果与模型组比较,厚藤提取物组大鼠关节肿胀指数和足垫厚度均显著降低(P0.05、0.01),厚藤提取物高、中剂量组大鼠血清中IL-1β、MIP-1α和MIP-2水平均显著降低(P0.05),厚藤提取物高、中剂量组大鼠滑膜组织炎性细胞浸润减轻。从厚藤提取物中鉴定出树脂糖苷类、黄酮类、有机酸类、香豆素类、核苷类、木脂素类等53个成分,其中有机酸类和黄酮类为其主要成分,并推测了树脂糖苷类、黄酮类、有机酸类、香豆素类部分成分的裂解规律;正常大鼠含药血浆中鉴定出苹果酸、咖啡酸、咖啡酸甲酯和对羟基苯甲酸4个成分,AGA大鼠含药血浆中鉴定出莨菪亭、咖啡酸、咖啡酸甲酯和对羟基苯甲酸4个成分。结论厚藤提取物能够明显改善AGA大鼠关节肿胀,抑制血清中IL-1β、MIP-1α及MIP-2水平,并抑制炎症反应;采用LC-Q-TOF-MS/MS技术可快速鉴定厚藤水提物的主要成分为有机酸类和黄酮类,莨菪亭、咖啡酸、绿原酸及其异构体(新绿原酸、隐绿原酸、异绿原酸B、异绿原酸A、异绿原酸C)和原儿茶酸在AGA大鼠中以原型成分或代谢物形式入血,可作为厚藤治疗AGA的Q-Marker。     

Antimicrobial activities of some Thai traditional medical longevity formulations from plants and antibacterial compounds from Ficus foveolata

Context: Medicinal plants involved in traditional Thai longevity formulations are potential sources of antimicrobial compounds.

Objective: To evaluate the antimicrobial activities of some extracts from medicinal plants used in traditional Thai longevity formulations against some oral pathogens, including Streptococcus pyogenes, Streptococcus mitis, Streptococcus mutans, and Candida albicans. An extract that possessed the strongest antimicrobial activity was fractionated to isolate and identify the active compounds.

Materials and methods: Methanol and ethyl acetate extracts of 25 medicinal plants used as Thai longevity formulations were evaluated for their antimicrobial activity using disc diffusion (5?mg/disc) and broth microdilution (1.2–2500?µg/mL) methods. The ethyl acetate extract of Ficus foveolata Wall. (Moraceae) stems that exhibited the strongest antibacterial activity was fractionated to isolate the active compounds by an antibacterial assay-guided isolation process.

Results and discussion: The ethyl acetate extract of F. foveolata showed the strongest antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 19.5–39.0 and 39.0–156.2?µg/mL, respectively. On the basis of an antibacterial assay-guided isolation, seven antibacterial compounds, including 2,6-dimethoxy-1,4-benzoquinone (1), syringaldehyde (2), sinapaldehyde (3), coniferaldehyde (4), 3β-hydroxystigmast-5-en-7-one (5), umbelliferone (6), and scopoletin (7), were purified. Among these isolated compounds, 2,6-dimethoxy-1,4-benzoquinone (1) exhibited the strongest antibacterial activities against S. pyogenes, S. mitis, and S. mutans with MIC values of 7.8, 7.8, and 15.6?µg/mL, and MBC values of 7.8, 7.8, and 31.2?µg/mL, respectively. In addition, this is the first report of these antibacterial compounds in the stems of F. foveolata.     

新乌檀化学成分研究

目的为了探明新乌檀化学成分,寻找新药目标分子或先导化合物.方法利用现代分离方法和1H-13CNMR、EI-MS等分析方法研究新乌檀(N.griffithii merr)化学成分.结果从新乌檀(N.griffithii merr)枝干部分分离得到23个化合物,鉴定其中4个化合物结构,分别为:苯甲酰胺、苯丙烯酰胺、原儿茶酸、东莨菪亭内酯.结论以上4个化物均为首次从该属植物中分离得到.     

双波长薄层扫描法测定地骨皮中莨菪亭含量

本文用双波长薄层扫描法首次测定了５种商品地骨皮药材中莨菪亭的含量，以山西２产地骨皮的含量最高。     

不同来源桑白皮东莨菪内酯含量测定

目的研究不同来源桑白皮东莨菪内酯含量和测定方法.方法采用HPLC法,以MeOH-H2O-HAc(40600.25)为流动相,345 nm为检测波长.结果东莨菪内酯平均回收率为98.88%,RSD为1.91%,线性范围为0.025 6～0.128 μg.不同来源最高含量为0.017 3%,最低含量为0.002%.结论HPLC测定法简便,稳定可靠,重复性好,灵敏度高.     

络石藤化学成分的研究

目的 研究络石藤Trachelosperomum jasminoides的化学成分。方法 采用色谱技术进行分离纯化,根据波谱学数据鉴定结构。 结果 从络石藤中分离得到4个单体化合物,分别鉴定为4-二甲基庚二酸(1)、东莨菪素(2)、去甲络石苷元-8-O-β-D-葡萄糖苷(3)及芹菜素-7-O-新橙皮糖苷(4)。 结论 化合物1为新化合物,化合物2为首次从该植物中分得。     

HPLC法测定雪隆胶囊中东莨菪素和伞形花内酯的含量

目的 测定雪隆胶囊中东莨菪内酯和伞型花内酯的含量.方法 采用高效液相色谱法,色谱柱为Phenomenex C18(250 mm×4.6 mm,5μm),流动相为甲醇-四氢呋喃水溶液进行梯度洗脱,检测波长为346nm.结果 东莨菪内酯平均回收率为99.3%,RSD为0.81%,伞型花内酯的平均回收率为99.6%,RSD为1.03%.结论 本法简便、准确、精密度高、重现性好,可用于该制剂的质量控制.     

Anti‐angiogenic potential of scopoletin is associated with the inhibition of ERK1/2 activation

Angiogenesis plays an important role in many diseases, such as cancer, rheumatoid arthritis, and diabetic retinopathy. Specific inhibitors of angiogenesis are therefore expected to be potential candidate therapeutics for these disorders. Recently, several naturally occurring coumarins and synthetic analogues have proved to hinder new vessel formation. The present study was undertaken to investigate the effects of scopoletin, a phenolic coumarin compound with various biological activities on endothelial cell activation and resultant angiogenesis. Scopoletin had no cytotoxic effect on endothelial cells at the concentrations tested but suppressed the endothelial cell migration and disrupted rat tail collagen tube formation at concentrations of 62.5, 125, 250, and 500 µM, whereas it only moderately inhibited the proliferation and adhesion of endothelial cells. Notably, scopoletin (500 µM) selectively downregulated serum‐induced ERK1/2 phosphorylation, without affecting endothelial cell p38 MAPK or JNK phosphorylation. These findings demonstrate that scopoletin has anti‐angiogenic properties that are manifest mainly through inhibiting migration and tube formation of endothelial cells via downregulating ERK1/2 activation. Scopoletin may potentially be useful for the treatment of angiogenesis‐mediated diseases and could serve as a structural basis for screening for more potent synthetic analogues. Drug Dev Res 2009. © 2009 Wiley‐Liss, Inc.