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1.
采用HZ818大孔吸附树脂对红豆杉浸膏中的紫杉醇成分进行吸附和洗脱试验,同时利用液质联用进行分析检测,确定了其最佳工艺参数。结果表明,HZ818树脂对紫杉醇有良好的吸附分离效果。优化工艺条件为:样品溶于体积分数40%甲醇,以1.5mL/min过柱,体积分数75%甲醇淋洗,体积分数85%甲醇以0.5mL/min洗脱,紫杉醇的质量分数从原浸膏中的1.02%提高到8.1%,回收率达98.6%。 相似文献
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3.
紫杉醇诱导HL—60细胞凋亡的研究 总被引:2,自引:0,他引:2
目的:观察抗微管药紫杉醇对急性白血病细胞株HL-60是否具有凋亡诱导作用,并进一步研究bcl-2基因在此过程中的作用。方法:(1)以紫杉醇处理HL-60细胞,观察细胞生长抑制作用的时间效应和剂量效应,在光镜和电镜下观察细胞形态变化;(2)用流式细胞仪检测药物孵育前后细胞凋亡率(AP)的变化;(3)用RT-PCR法检测药物孵育前后bcl-2基因的表达水平。结果:(1)在一定剂量和时间范围内紫杉醇能抑制HL-60细胞生长;(2)紫杉醇能诱导HL-60细胞凋亡,并显示剂量效应:(3)在紫杉醇诱导HL-609细胞凋亡过程中,bcl-2基因表达水平下调。结论:紫杉醇能诱导HL-60细胞凋亡;bcl-2基因参与了紫杉醇诱导HL-60细胞凋亡的调控。 相似文献
4.
A colorless, parallelepiped crystal of methyl (2R,3S)-N-benzoyl-3-phenylisoserinate belonging to the space group P2l with a = 5.414(4), b = 7.813(1), c = 17.802(7) , = 90.87(4)°, Z = 2, V = 752.9 3, D
calc = 1.32 g cm–3, and µcalc = 1.02 cm–1 was selected and the structure solved using direct methods. Refinement led to a final R = 0.079 for 819 [F
o 5(Fo)] reflections. Intermolecular hydrogen-bonding interactions are prevalent in the crystal lattice of this compound. 相似文献
5.
Thomas A. Krenitsky John Dillberger Elena Zotova Joseph C. Arezzo James B. Koprich Farzad Mortazavi Timothy A. Gates Gary L. Dunbar 《Drug development research》2004,62(1):60-70
In cultured cells, KP544 [2‐amino‐5‐(4‐chlorophenylethynyl)‐4‐(4‐trans‐hydroxycyclohexyl amino) pyrimidine] amplifies differentiation initiated by nerve growth factor (NGF) or cAMP. This report describes the pharmacokinetics, safety, and neuroprotective efficacy of KP544 in rats. After an oral dose of 10 mg/kg KP544 was 25% bioavailable with a plasma half‐life of 1.3 h and brain levels 6‐fold higher than plasma levels at 4 and 8 h post‐dose. In a safety study, daily oral dosing for 30 days at 10 and 100 mg/kg was well tolerated. The favorable pharmacokinetic and safety profiles, together with its amplification of NGF in vitro, prompted evaluation of KP544 in two models involving NGF deficiencies. In the first model, brains were lesioned with intrastriatal injections of quinolinic acid. KP544 at oral doses of 0.02 to 1.0 mg/kg/day almost completely prevented the resulting learning deficits as evaluated using a radial‐arm‐water maze. At the lowest dose, there was a slower onset of functional improvement. These effects were accompanied by reductions (16–34%) in the striatal lesion size that were greatest at the highest dose and comparable to those seen with NGF therapy. The second model involved a peripheral neuropathy induced by taxol that is associated with decreases in NGF. KP544 at oral doses of 0.1–10 mg/kg/day decreased the severity of the neuropathy as measured by caudal nerve conduction velocities (30–70% return to control values). In both models, KP544 had a large therapeutic index suggesting its potential as a new approach for treating clinical disorders involving deficiencies in NGF. Drug Dev. Res. 62:60–70, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
6.
双四氢呋喃型番荔枝内酯体内抗肿瘤作用 总被引:2,自引:2,他引:2
目的研究双四氢呋喃型番荔枝内酯的体内抗肿瘤作用。方法以紫杉醇为阳性对照,观察4个双四氢呋喃型番荔枝内酯单体番荔枝塔亭戊(squamostatin-E,1)、番荔枝塔亭甲(squamostatin-A,2)、去乙酰紫玉盘素(desacetyluvaricin,3)、泡番荔枝辛(bullatacin,4)对移植性肝癌Heps和肉瘤S180荷瘤小鼠的抑瘤作用及对小鼠体质量与肝、胸腺和脾指数的影响。结果与模型组比较,化合物1高剂量(60μg/kg)、化合物3和4低剂量(15μg/kg)对移植性肝癌Heps荷瘤小鼠肿瘤有极显著抑制作用(P<0.01),抑制率分别为51.6%、32.5%、63.4%;化合物2和3高剂量(60μg/kg)对移植性肝癌Heps荷瘤小鼠肿瘤有显著抑制作用(P<0.05),抑制率分别为31.2%、70.9%;紫杉醇40μg/kg的抑瘤率为62.2%。化合物3高剂量对移植性肉瘤S180荷瘤小鼠肿瘤有极显著抑制作用(P<0.01),抑制率为63.9%;紫杉醇40μg/kg的抑瘤率为48.9%。结论化合物1~4对移植性肝癌Heps荷瘤小鼠、肉瘤S180荷瘤小鼠均有明显抗肿瘤作用,部分化合物的抗肿瘤活性强于紫杉醇。 相似文献
7.
紫杉醇、三尖杉宁碱和7-表-10-去乙酰基紫杉醇的分离及7-表-紫杉醇的转化研究 总被引:1,自引:1,他引:1
目的 探索从云南红豆杉树皮提取物中分离紫杉醇、三尖杉宁碱和7-表-10-去乙酰基紫杉醇3种纯化合物以及7-表-紫杉醇转化成紫杉醇的高效方法。方法 用乙酸叔丁酯为单漉动相。硅胶为填充柱的正相色谱系统分离。使用碱性氧化铝,在40℃对7-表-紫杉醇进行催化而转化成紫杉醇。结果与结论 分离得到紫杉醇、三尖杉宁碱和7-表-10-去乙酰基紫杉醇3个纯化合物。7-表-紫杉醇转化率可达30%。 相似文献
8.
赖氨大黄酸和紫杉醇对肺癌细胞增殖的抑制作用和凋亡诱导作用 总被引:1,自引:0,他引:1
目的:研究赖氨大黄酸(RHL)、紫杉醇单独和两者联合对人肺癌H460细胞增殖和凋亡的影响,阐明其作用机制。方法:选取处于对数生长期肺癌细胞株H460,随机分为对照组(不加药物)、紫杉醇组(1 μmol•L-1紫杉醇)、RHL组(100 μmol•L-1 RHL)和紫杉醇联合RHL组,并设空白组。采用MTT法和流式细胞术分别检测各组处理后48 h的细胞增殖率和凋亡率;采用Western blotting 方法检测凋亡相关蛋白和MEK/ERK蛋白的表达水平。结果:细胞培养48 h后,联合用药组细胞增殖率显著低于对照组、紫杉醇组和RHL组 (P<0.05),联合用药组细胞凋亡率显著高于对照组、紫杉醇组和RHL组(P<0.05),联合用药组caspase-3和poly ADP-ribose polymerase (PARP)的切割片段蛋白表达强度明显高于对照组、紫杉醇组和RHL组,联合用药组Bcl-2和NF-κB蛋白表达强度明显低于对照组、紫杉醇组和RHL组,同时RHL组紫杉醇上调的MEK和ERK蛋白磷酸化强度降低。结论:紫杉醇和RHL均可抑制肺癌H460细胞增殖,诱导细胞凋亡;RHL通过降低ERK活性、上调caspase-3和PARP的切割片段蛋白表达,增强紫杉醇抑制肺癌细胞增殖和凋亡诱导作用。 相似文献
9.
《Expert review of anticancer therapy》2013,13(10):1433-1447
Microtubules and their component protein, tubulin, constitute a popular target for the treatment of cancer. Many drugs that are presently used in clinics or in clinical trials and drugs that show promise as anticancer drugs bind to tubulin and microtubules. There are three conventional binding sites on β-tubulin where many of these drugs bind. The binding properties, conformational changes upon binding, association constants and thermodynamic parameters for the drug–tubulin interaction on these three sites are discussed. The antiproliferative activities of these drugs and the possible correlation with the binding properties are also described. 相似文献
10.
《药学学报(英文版)》2020,10(2):327-343
Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer. 相似文献