大黄酸的结构修饰及其生物活性研究进展

大黄酸是大黄素型羟基蒽醌，主要存在于大黄等中药中。大黄酸具有抗癌、抗炎、抗菌、抗阿尔茨海默病等广泛的药理活性，但由于其水溶性差、生物利用度低等缺点，限制了其临床应用。为了克服这些缺点，研究者通过对其进行结构修饰研究，设计并合成了大量生物活性更为突出的大黄酸衍生物。本文综述了近年来大黄酸的结构修饰及其生物活性研究进展，为大黄酸类衍生物的进一步研究提供参考依据。     

大黄素衍生物的化学合成与抗肿瘤活性

目的设计合成一系列大黄素衍生物,以研究其构效关系.方法以天然产物大黄素为原料,通过不同的方法合成一系列大黄素的衍生物,并且通过MTT法测试它们对KLE细胞株的抗肿瘤活性.结果合成了11个大黄素衍生物并通过元素分析、IR、1H-NMR、13C-NMR和MS确证了它们的结构.活性试验显示某些化合物的活性强于大黄素.结论大黄素类化合物是一类很有希望的肿瘤抑制剂,值得进一步开发研究.     

查耳酮衍生物的结构修饰及生物活性研究进展

查耳酮类化合物广泛存在于天然植物中,具有抗癌、抗炎、抗氧化等多种药理活性。近年来,通过对大量具有查耳酮骨架的新型化合物的合成,查耳酮衍生物的生物活性也得到了深入研究。综述查耳酮衍生物的生物活性、结构修饰及构效关系的最新研究进展。     

大黄素10位希夫氏碱衍生物的合成与体外抗肿瘤活性初步研究

目的:合成大黄素10-位希夫氏碱衍生物并研究其抗肿瘤活性。方法:将大黄素与氨衍生物在无水乙醇中以醋酸催化而合成,用核磁共振氢谱、电子轰击质谱法进行结构表征;用四唑盐(MTT)比色法测定其对k562肿瘤细胞增殖抑制率并计算其IC50值。结果:合成了3个大黄素10-位希夫氏碱衍生物,对k562肿瘤细胞的IC50值分别是4.5,3.8,2.0μmol·L-1。结论:大黄素10位希夫氏碱衍生物提高了其母体化合物的抗肿瘤活性并增加了成药性,值得进一步研究。     

大黄素衍生物的合成研究

本文通过甲基化反应和NBS反应,对大黄素的6位进行了化学修饰工作．共合成得到14个大黄素衍生物．并测试了它们对白血病细胞K562和Jurkat的毒性实验。虽然这些衍生物的活性没有明显高于大黄素本身,但对大黄素进行化学修饰仍然是一个有益的研究。     

二硫代氨基甲酸酯及其衍生物在药物化学中的应用

二硫代氨基甲酸酯及其衍生物具有独特的分子结构,这使其具有广泛的生物活性,已经成为近年来化工和药学领域研究的重点。本文综述了二硫代氨基甲酸酯及其衍生物的结构、合成和其在抗氧化、抗病毒、抗菌、抗肿瘤和抗阿尔茨海默病方面的生物活性,并对其今后的发展做出了展望。     

长春西汀及其类似物的合成和构效关系研究进展

总结介绍了20世纪90年代以来长春西汀及其类似物的合成及构效关系研究成果。长春西汀是生物碱长春胺的合成衍生物,是目前临床治疗和预防缺血性脑血管疾病的一线药物,近年来研究人员展开了对其衍生物合成路线及生物活性的相关研究,以期进一步阐明该类化合物作用机制和发现活性更好的衍生物。     

岩白菜素:一种通用易得的生物活性修饰前体（英文）

岩白菜素是中药岩白菜的主要生物活性成分和许多植物家族的重要成分或次级代谢产物,岩白菜素及其衍生物因其独特的生物活性和药理性质引起了人们的极大兴趣。在过去的几十年中,大量岩白菜素衍生物合成出来并考察其生物活性,取得了许多积极的结果。这些研究有助于从岩白菜素衍生物中发现和鉴定新的候选药物治疗剂,了解它们的分子靶点和药理作用机制。本工作总结了岩白菜素半合成衍生物的零散信息及在生物活性修饰方面的最新进展。     

阿魏酸衍生物及其生物活性

阿魏酸具有抗血小板聚集、抗氧化、抗自由基、抗菌消炎、抗肿瘤、抗突变、增强免疫功能等多方面的生物活性。研究人员现已设计并合成了阿魏酸盐类修饰物及酯类、醚类、酰胺类等衍生物,并通过药效筛选发现了一些生物活性强于阿魏酸的化合物。综述阿魏酸结构改造与修饰及阿魏酸衍生物的生物活性方面的研究进展。     

大黄素三甲氧基衍生物合成及体外抗肿瘤活性试验

目的:以天然存在的大黄素为原料合成了甲基化衍生物三甲氧基大黄素,并进行体外抗肿瘤活性的研究。方法:利用硫酸二甲酯/丙酮甲基化组合合成目标化合物1,3,8-三甲氧基-6-甲基蒽醌;通过常规方法,对其理化性质进行鉴定。采用HPLC及ESI-MS对其结构进行表征;通过MTT比色法与流式细胞术检测其对K562细胞增殖及细胞周期分布的影响。结果:三甲氧基大黄素为淡黄色粉末,mp:226～227℃,溶于氯仿等有机溶剂。其结构经HPLC及ESI-MS检测得到确证;浓度依赖性地抑制K562细胞的增殖,并使G0/G1期的细胞比例增加。结论:以大黄素为原料,成功合成了其新的衍生物。三甲氧基大黄素具有抑制K562细胞增殖及阻滞细胞周期由G0/G1期向S期移行的抗肿瘤活性。     

大黄素衍生物抗肿瘤活性的定量构效关系

目的 建立大黄素衍生物抗肿瘤活性的构效关系模型.方法 采用量子化学的AM1算法计算了12个大黄素衍生物的分子结构参数,利用逐步回归分析建立构效关系模型.结果 成功建立了大黄素衍生物抗肿瘤活性的构效关系模型.结论 大黄素衍生物抗肿瘤活性与分子体积V、极化率α及C环上净电荷QC相关.     

In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives.

Anthraquinones and anthraquinone derivatives were characterized for their antiviral and virucidal activities against viruses representing several taxonomic groups. One of these compounds, hypericin, had activity against vesicular stomatitis virus, herpes simplex virus types 1 and 2, parainfluenza virus, and vaccinia virus (from 0.5 to 3.8 log10 reductions in infectivity) at concentrations of less than 1 microgram/ml as determined by a direct pre-infection incubation assay. Human rhinovirus was not sensitive to hypericin at concentrations up to 10 micrograms/ml. Addition of small amounts of Tween-80 to solutions containing hypericin enhanced, by up to 2.6 log10, hypericin's virucidal activity. Anthraquinones and anthraquinone derivatives with the hydroxyl and alkyl substitution pattern of emodin (i.e. emodin, emodin anthrone, emodin bianthrone and hypericin) were active against the enveloped viruses tested. The following general pattern of activity was found: hypericin greater than emodin bianthrone greater than emodin anthrone greater than emodin. Chrysophanic acid, aloe-emodin, and sennosides A and B did not possess activity against any of the viruses tested.     

Apoptosis-inducing activity of new pyrazole emodin derivatives in human hepatocellular carcinoma HepG2 cells

A series of new pyrazole derivatives from emodin synthesized in our lab have been shown to have much stronger cytotoxicity than emodin against various tumor cell lines. This study was to examine the apoptosis-inducing activity of these new emodin derivatives in human hepatocellular carcinoma HepG2 cell culture for a better understanding of their cytotoxic effects on the cancer cells. Several major events in the induction of cell apoptosis, nuclear chromatin condensation, DNA fragmentation, caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage were detected in the cells after treatment with the compounds at various concentrations. Of the seven emodin derivatives tested at a dose of 10 microM and within a treatment period of 24 h, only compounds 1 and 3 effectively induced all these apoptotic events in the cancer cells. The apoptosis-inducing activity of the compounds showed a positive correlation to their cytotoxic activity, suggesting a close connection between the growth inhibition and apoptosis induction of the cancer cells by these pyrazole emodin derivatives.     

大黄素衍生物对口腔底癌细胞活性的构效关系研究

目的探索建立大黄素衍生物抗口腔底癌细胞活性的构效关系模型。方法采用量子化学的AM1半经验算法,计算10个大黄素衍生物分子结构参数,并用逐步回归分析方法,拟定大黄素衍生物抗口腔底癌细胞活性的构效关系模型。结果建立了大黄素衍生物抗口腔底癌细胞活性的构效关系模型。结论大黄素衍生物抗口腔底癌细胞活性与此类化合物分子的疏水性参数、A环上的负电荷及第二条最低空轨道能量有关。     

Synthesis and Antitumor Activity of Natural Compound Aloe Emodin Derivatives

In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a–j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure–activity relationships. The structures of the compounds were determined by ¹H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI‐H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations.     

Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus.

A number of anthraquinones, anthrones and anthraquinone derivatives were evaluated for antiviral activity against human cytomegalovirus (HCMV) as well as for cytotoxicity. Of those compounds evaluated, quinalizarin, emodin, rhein, hypericin, protohypericin, alizarin, emodin bianthrone and emodin anthrone showed antiviral activity against a normal laboratory HCMV strain, AD-169. When tested against a ganciclovir-resistant strain of HCMV, the EC50 values for quinalizarin, rhein and alizarin were superior to the values obtained for the AD-169 strain of HCMV. These results suggest that these compounds will be useful as prototypes for synthesizing a class of anti-HCMV drugs that are effective against ganciclovir-sensitive and -resistant strains of HCMV.     

Antidyslipidemic effect and antioxidant activity of anthraquinone derivatives from Rheum emodi rhizomes in dyslipidemic rats

The aim of the present study was to evaluate the antidyslipidemic effect of ethanolic extract of Rheum emodi rhizomes and its constituents in Triton-WR-1339 and high-fat diet (HFD)-induced dyslipidemic rats. In preliminary screening, the ethanolic extract showed significant activity in Triton-treated rats. Bioassay-guided fractionation of the ethanolic extract resulted in the identification of four anthraquinone derivatives, viz. chrysophanol, emodin, chrysophanol 8-O-β-d-glucopyranoside and emodin 8-O-β-d-glucopyranoside as active constituents. All these compounds significantly reduced plasma lipid levels. The most active compound emodin showed significant lipid-lowering activity in the HFD-fed model. In addition, these compounds showed significant antioxidant activity. The effect of emodin on enzymes modulating lipid metabolism confirms and supports the efficiency of emodin as a potent antidyslipidemic agent.