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41.
CNDO分子轨道法研究靛玉红及其衍生物的定量构效关系 总被引:5,自引:0,他引:5
用CNDO分子轨道法计算了中药青黛的抗肿瘤有效成分靛玉红及其衍生物的全部分子轨道指数。经过全面系统地搜索,发现其3位净电荷与抗肿瘤活性显著相关,并将3位净电荷与两组疏水参数进行多元逐步回归处理,从而建立了Hansch回归方程,为寻找抗肿瘤活性更高的靛玉红衍生物提供了有效的理论指导。还对该回归方程预测未知的靛玉红衍生物抗肿瘤活性的能力,3位净电荷在药物与受体相互络合中所起的关键性作用以及疏水参数的计算方法等进行了较为深入的探讨。 相似文献
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目的 探究复方板蓝根喷雾剂的制备工艺,建立质量控制的方法.方法 利用交叉对比试验探究复方板蓝根喷雾剂的制备工艺,以DiamonsiTMC18 (250mm×4.6mm,5um),流动相:甲醇一0.1%乙酸铵一乙酸(80:20:1),流速:1.0ml/min,检测波长:286nm为定量方法.结果 用65%乙醇渗漉法提取效率较高.靛玉红的进样量在0.0812~0.9745ug/m1 (r2=0.999945,n=7)范围内与峰面积积分值呈良好的线性关系.平均加样回收率为99.12%,RSD为1.94%(n=6).结论 本法可作为复方板蓝根喷雾剂的制备工艺,检测方法简便、快捷、分离度高、重现性好,可用于复方板蓝根喷雾剂的质量控制. 相似文献
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目的:建立测定大鼠肝微粒体孵育液中靛玉红含量的方法。方法:采用液相色谱-电喷雾串联质谱法。肝微粒体孵育液样品处理采用液-液提取,提取物以甲醇-10mmol·L-1乙酸铵溶液(氨水调pH值至7.40)=90:10为流动相进行分离,以选择性反应离子监测(SRM)方式进行定量分析,用于监测的离子为m/z262.9→219.0(靛玉红)和m/z531.0→82.1(酮康唑,内标)。结果:5min内完成靛玉红的检测,工作曲线线性范围为1~100ng·mL-1,日内、日间精密度分别<3.6%、<13.4%,平均回收率为94.0%~104.4%,检测限为0.5ng·mL-1。结论:本方法灵敏度高、特异性好,可以用于肝微粒体孵育液样品中靛玉红的检测。 相似文献
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板蓝根含片中靛玉红的含量测定研究 总被引:7,自引:0,他引:7
目的:建立板蓝根含片的含量测定方法。方法:采用薄层扫描法测定板蓝根含片中靛玉红的含量。结果:板蓝根含片中靛玉红含量测定线性范围为0.1-0.5μg,平均回收率95.6%,RSD为1.6%。结论:用薄层扫描法测定板蓝根含片中靛玉红的含量是可行的,该法有效控制了产品的质量。 相似文献
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Simone Braig Fabian Bischoff Behnaz A. Abhari Laurent Meijer Simone Fulda Leandros Skaltsounis Angelika M. Vollmar 《Biochemical pharmacology》2014
TRAIL (TNFα-related apoptosis-inducing factor) has been promoted as a promising anti-cancer agent. Unfortunately many tumor cells develop resistance towards TRAIL due to numerous defects in apoptotic signaling. To handle this problem combination therapy with compounds affecting as many different anti-apoptotic targets as possible might be a feasible approach. The bromo-substituted indirubin derivative 6BIO meets this challenge: Treatment of breast cancer and bladder carcinoma cell lines with micromolar concentrations of 6BIO abrogates cellular growth and induces apoptosis. Combination of subtoxic amounts of 6BIO with ineffective doses of TRAIL completely abolishes proliferation and long-term survival of cancer cells. As shown in two-dimensional as well as three-dimensional cell culture models, 6BIO potently augments TRAIL-induced apoptosis in cancer cell lines. The potent chemosensitizing effect of 6BIO to TRAIL-mediated cell death is due to the pleiotropic inhibitory profile of 6BIO. As shown previously, 6BIO abrogates STAT3, PDK1 as well as GSK3 signaling and moreover, inhibits the expression of the anti-apoptotic Bcl-2 family members Bcl-xL and Mcl-1 on mRNA as well as on protein level, as demonstrated in this study. Moreover, the expression of cFLIP and cIAP1 is significantly downregulated in 6BIO treated cancer cell lines. 相似文献
49.
Anja Berger Sandra-Annika Quast Michael Plötz Martin Hein Manfred Kunz Peter Langer Jürgen Eberle 《Biochemical pharmacology》2011,(1):71
Until today effective therapies are lacking for metastatic melanoma. The death ligand TRAIL appears as promising in cancer treatment; however, melanoma cells reveal both preexisting and inducible TRAIL resistance. Here, we present evidence that the recently described indirubin derivative 8-Rha-β enhances melanoma cell sensitivity for death ligands and overcomes resistance to TRAIL and CD95 agonists. Indirubin is known from traditional Chinese medicine and is a potent kinase inhibitor. Unraveling of apoptotic signaling pathways revealed that TRAIL resulted in a quick (within 8 h) downregulation of both agonistic TRAIL receptors DR4 and DR5, in a kind of negative feed-back loop. Treatment with indirubin, however, mediated upregulation of both receptors, thus compensating this negative feed-back loop by TRAIL. Furthermore, indirubin activated intrinsic apoptosis pathways, seen in loss of mitochondrial membrane potential and release of cytochrome c. The mitochondrial response appeared as related to upregulation of Bax and Bad and to downregulation of Mcl-1. Remarkably, indirubin in combination with TRAIL was also able to overcome apoptosis resistance due to ectopic Bcl-2 overexpression. The tumor suppressor p53 appeared as master regulator of these propapoptotic changes and is the transactivator of proapoptotic proteins which was upregulated by indirubin. Taking into account the physiological role of death ligands in immune surveillance, sensitization of melanoma cells for death ligands may be supportive for an anti-tumor immune response. Furthermore, combinations with kinase inhibitors, such as indirubin 8-Rha-β may help for a breakthrough of TRAIL-mediated strategies in melanoma. 相似文献
50.
Molecular mechanisms of indirubin and its derivatives: novel anticancer molecules with their origin in traditional Chinese phytomedicine 总被引:9,自引:0,他引:9
Eisenbrand G Hippe F Jakobs S Muehlbeyer S 《Journal of cancer research and clinical oncology》2004,130(11):627-635
Indirubin, a 3, 2 bisindole isomer of indigo, has originally been identified as the active principle of a traditional Chinese preparation and has been proven to exhibit antileukemic effectiveness in chronic myelocytic leukemia. Indirubin was detected to represent a novel lead structure with potent inhibitory potential towards cyclin-dependent kinases (CDKs) resulting from high affinity binding into the enzymes ATP binding site. This seminal finding triggered our research to improve the pharmacological activities of the parent molecule within comprehensive structure-activity studies. Molecular modifications made novel anticancer compounds accessible with strongly improved CDK inhibitory potential and with broad spectrum antitumour activity. This novel family of compounds holds strong promise for clinical anticancer activity and might be useful also in several important noncancer indications, including Alzheimers disease or diabetes. 相似文献