Antiproliferative and apoptotic activities of tosylcyclonovobiocic acids as potent heat shock protein 90 inhibitors in human cancer cells

We evaluated whether inhibition of heat shock protein 90 (hsp90) function by novobiocin derivatives could induce the degradation of signal transducers that drive cancer cell growth and thereby promote apoptosis. Removal of the noviose moiety in novobiocin and introduction of a tosyl substituent at C-4 or C-7 coumarin nucleus provided derivatives 4TCNA and 7TCNA which compared favourably with novobiocin in MCF-7 breast cancer cells. Here we extend the antiproliferative and apoptotic properties of these analogues to a panel of cancer cell lines. Destabilization of hsp90 client proteins Raf-1, HER2, and cdk4 suggests inhibition of hsp90 chaperoning function. In HT29 colon and IGROV1 ovarian cancer cells, the growth inhibiting effect of 4TCNA and 7TCNA was consistent with the stimulation of cell death as assessed by the processing and activation of caspase 9, 8, 7 and 3 and the subsequent cleavage of poly(ADP-ribose) polymerase (PARP). In Ishikawa endometrial adenocarcinoma cells, 4TCNA also promoted apoptosis and the processing of PARP. These derivatives impacting multiple pathways involved in the neoplastic process may represent promising drugs for cancer therapy.     

旱前胡的化学成分及体外抗菌活性研究

目的 对云南大理旱前胡干燥根部的化学成分及抗菌活性进行研究,以期发现新的具有抗菌活性的化学成分.方法 用硅胶柱层析、Sephadex LH-20凝胶柱层析、Rp-18反相柱层析、半制备HPLC方法对旱前胡根部的甲醇提取物进行分离、纯化,用肉汤稀释法测定单体化合物对大肠杆菌和金黄色葡萄球菌的抗菌作用.结果 从旱前胡根部获得9个单体化合物,其中8个化合物为香豆素化合物.结论 旱前胡含有丰富的香豆素成分,经体外抗菌活性的初步筛选,化合物阿魏酸对金黄色葡萄球菌具有明显的抑菌效果,最低抑菌浓度2.5mg/mL,最低杀菌浓度为5.0 mg/mL.     

Coumarin anticoagulants and co-trimoxazole: avoid the combination rather than manage the interaction

Objective The objective of our study was to examine the management of the interaction between acenocoumarol or phenprocoumon and several antibiotics by anticoagulation clinics and to compare the consequences of this interaction on users of co-trimoxazole with those for users of other antibiotics. Methods A follow-up study was conducted at four anticoagulation clinics in The Netherlands. Data on measurements of the International Normalised Ratio (INR), application of a preventive dose reduction (PDR) of the coumarin anticoagulant, fever and time within or outside the therapeutic INR range were collected. Results The study cohort consisted of 326 subjects. A PDR was given more often to users of co-trimoxazole PDR than to users of other antibiotics. The PDR in co-trimoxazole users resulted in a significantly reduced risk of both moderate overanticoagulation (INR >4.5) and severe overanticoagulation (INR >6.0) compared with no PDR, with odds ratios (ORs) of 0.06 [95% confidence interval (CI): 0.01–0.51] and 0.09 (95% CI: 0.01–0.92), respectively. In co-trimoxazole users without PDR, the risk of overanticoagulation was significantly increased compared with users of other antibiotics. All co-trimoxazole users spent significantly more time under the therapeutic INR range during the first 6 weeks after the course than users of other antibiotics. Conclusion PDR is effective in preventing overanticoagulation in co-trimoxazole users, but results in a significantly prolonged period of underanticoagulation after the course. Avoidance of concomitant use of co-trimoxazole with acenocoumarol or phenprocoumon seems to be a safer approach than management of the interaction between these drugs.     

Coumarins from Coriaria nepalensis

Two new coumarins (1) and (2), along with seven known coumarins 3-9, were isolated from the leaves and stems of Coriaria nepalensis Wall. The two new compounds were established as 7-hydroxy-6-methoxy-3,8-bis(3-methyl-2-butenyl) coumarin (1) and 7-hydroxy-6-methoxy-3-(3-methyl-2-butenyl) coumarin (2), on the basis of 1D and 2D NMR techniques. The known compounds 3, 6-9 were isolated from this plant for the first time.     

Inhibitory activity of monoamine oxidase by coumarins fromPeucedanum japonicum

Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods. The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.     

不同基原八爪金龙药材中黄酮、香豆素类化学成分分析

目的:鉴定并分析不同基原八爪金龙药材中黄酮及香豆素类成分。方法:采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱法(UPLC-QE-HF-MS/MS)。色谱柱为Zorbax Eclipse-C18,流动相为乙腈-0.1%甲酸水溶液(梯度洗脱),柱温为30℃,流速为0.3 mL/min,自动进样器温度为4℃,进样量为2μL。离子源为电喷雾离子源,扫描模式为正、负离子模式,加热器温度为325℃,鞘气压力为45 arb,辅助气压力为15 arb,吹扫气压力为1 arb,电喷雾电压为3.5 kV,毛细管温度为330℃,透镜电压为55%,扫描模式为一级全扫描(m/z 100~1500)、数据依赖性二级质谱扫描(dd-MS2,Top N=10),分辨率为70000(一级质谱)、17500(二级质谱),碰撞模式为高能量碰撞解离。通过参考ChemSpider、mzCloud、mzVault、PubChem等国内外专业数据库,同时结合相关文献和对照品数据对化合物结构进行鉴定并比较含量。结果与结论:从朱砂根、百两金、红凉伞等3种不同基原的八爪金龙药材中共分离47个成分,鉴定出17个黄酮类化合物,包括9个黄酮醇类(槲皮素3-O-鼠李糖苷7-O-葡糖苷、杨梅素、芦丁、毛里求斯排草素、山柰酚、槲皮素、异鼠李素、槲皮苷、美恩西汀)、3个黄烷-3-醇类(表棓儿茶素、儿茶素、表没食子儿茶素没食子酸酯)、2个二氢黄酮类(黄颜木素、圣草酚)及3个其他类{3-(2,3-二氢苯并[1,4]二噁英-6-基)-7-羟基-2-三氟甲基-4-酮、墨沙酮、Oriciacridone F},10个香豆素类化合物{岩白菜素、[(7-羟基-4-甲基-2-氧代-2H-色烯-6-基)氧基]乙酸、[7-(羧基甲氧基)-4-甲基-2-氧-2-羟色基-3-基]乙酸、4,9-二羟基7H-呋喃并[3,2-g]色烯-7-酮、6,7-二羟基-4-甲基香豆素、七叶内酯、秦皮素、7,8-二羟基-4-甲基香豆素、4-甲基伞形酮葡萄糖醛酸、二十烷酮}。含量分析结果显示,黄酮、香豆素类化合物中,3种不同基原八爪金龙药材中共有5个共有成分,分别为岩白菜素(2号峰)、[7-(羧基甲氧基)-4-甲基-2-氧-2-羟色基-3-基]乙酸(5号峰)、墨沙酮(16号峰)、槲皮素(18号峰)、Oriciacridone F(26号峰),且共有成分的含量存在明显差异。除5个共有成分外,其余22个成分均为差异化学成分,分别为1、3、4、6~15、17、19~25、27号峰对应的化合物,其中3、6、8、23号峰对应的化合物仅存在于红凉伞中;12~15、19号峰对应的化合物仅存在于百两金中。UPLC-QE-HF-MS/MS法可高效、精确、快速地鉴别不同基原八爪金龙药材中黄酮类、香豆素类化学成分。     

香豆素对实验性大鼠草酸钙结石形成的影响

应用偏光显微镜和解剖镜观察ＶｉｔａｍｉｎＫ（Ｖｉｔ－Ｋ）拮抗剂香豆素对大鼠草酸钙结石形成影响，观察到香豆素显著地增加大鼠肾内草酸钙结晶数目，肾组织匀浆中草酸含量（１．１４±０．７３ｍｇ／ｇ）也显著高于对照组（０．０３６±０．１５ｍｇ／ｇ，Ｐ＜０．０５）。当停用香豆素后，肾内草酸钙结晶数又可减少。推测香豆素可拮抗Ｖｉｔ－Ｋ使得肾内依赖Ｖｉｔ－Ｋ的羧化作用减弱，肾内草酸钙抑制物Ｎｅｐｈｒｏｃａｌｃｉｎ（Ｎｃ）中谷氨酸转化成γ－羧基谷氨酸（Ｇｌａ）减少，Ｎｃ与钙结合减少，对草酸钙结晶抑制活性降低，易发生草酸钙结石。提示Ｖｉｔ－Ｋ缺乏可促进肾结石形成。     

重齿毛当归(独活)中异当归醇、毛当归醇及其它香豆素的分离与鉴定

Nine coumarins were isolated from dichloromethane extract of the roots of Angelica pubescens Maxim. Seven of them were identified as osthol (Ⅰ), columbianetin acetate (Ⅱ), columbianetin (Ⅲ), bergapten (Ⅳ), angelol (Ⅴ),xanthotoxin (Ⅵ) and isoimperatorin (Ⅶ). (Ⅵ) and (Ⅶ) were isolated for the first time from this plant. Two new coumarins were elucidated as isoangelol (Ⅷ), a geometric isomer of angelol C₂₀H₂₄O₇ [α]_D²⁰-133.5 and anpubesol C₂₀H₂₆O₇ [α]_D²⁰ -72.5 on the basis of spectral evidences.     

促渗剂对祖师麻总香豆素体外经皮渗透的影响

目的:研究几种常用促渗剂对祖师麻总香豆素体外经皮渗透的影响.方法:采用Tp-5智能扩散仪,离体SD大鼠腹部皮肤为渗透屏障,以累计渗透量为指标,用HPLC法测定有效成分祖师麻甲素的浓度.结果:氮酮、冰片合用丙二醇可作为促渗剂,用于祖师麻总香豆素经皮吸收制剂,且氮酮合用丙二醇效果最好.结论:为研发祖师麻经皮给药制剂提供了实验依据.     

渗漉法提取白芷总香豆素的工艺研究

目的优化渗漉法提取白芷香豆素的提取工艺。方法采用单因素和正交实验设计，以白芷总香豆素的含量为评价指标，对白芷香豆素类化合物进行渗漉提取。结果渗漉法提取总香豆素含量高达10．144mg／g，其最佳工艺条件为：8倍量75％乙醇，浸泡8h，渗漉速度0．5mL／min。结论建立的数学模型和优化结果合理，渗漉法提取白芷香豆素可行。