酰胺类NO供体熊果酸衍生物的合成

为提高五环三萜类天然产物熊果酸的抗肿瘤活性,以熊果酸为母核引入具有广泛生物活性的酰胺结构以及具有抗肿瘤作用的NO供体支链形成酰胺类NO供体型熊果酸衍生物。采用熊果酸为原料,经氧化、亲核取代等多步反应合成8个酰胺类NO供体熊果酸衍生物2、12～18,所有化合物采用IR、~1H NMR、~(13)C NMR、HR MS进行表征。     

熊果酸类似物的结构改造及其体外抗肿瘤活性研究

以熊果酸为先导化合物,设计并合成其衍生物并检测体外抗肿瘤活性。利用熊果酸与各种芳香醛的缩合反应,采用计算机辅助设计,对设计的化合物进行筛选;合成分子对接分最高的的12个化合物。对其C-2位ClaisenSchmidt缩合反应,C-3位以及C-28位羧基进行结构改造;采用MTT法测试目标化合物对人肝癌细胞(HepG2)和人肺癌细胞(A549)的体外抗肿瘤活性。目标化合物对这两种细胞株的抑制活性均优于母体熊果酸,其中化合物Ⅰ_6和Ⅱ_4表现出较强的抗肿瘤活性。经结构改造后的熊果酸衍生物具有一定的抗肿瘤活性,值得进一步研究。     

车前草根茎叶中熊果酸含量的测定

车前草是一种传统药草,具有利尿、清热、明目、祛痰药理作用的功效。其根茎叶中含有熊果酸,熊果酸具有较强的抗肿瘤活性,对多种致癌、促癌物有抵抗作用。笔者将通过测定车前草根茎叶中熊果酸的含量,发挥车前草最大的药用价值。     

新型熊果酸喹啉衍生物抗肿瘤活性研究

原料为五环三萜类天然产物熊果酸,合成新型熊果酸喹啉衍生物。使用元素分析法、ESIMS、13C NMR等,分析1,3,4-噁二唑衍生物4a-4f,以及熊果酸喹啉酰肼衍生物3a-3f。采用MTT法,对4a-4f、3a-3f进行测试,分析对三种肿瘤细胞株的增殖抑制活性。结果显示,对三种肿瘤细胞株,包括SMMC-77213、HeL、MDA-MB-231,3a-3c都有明显的抑制活性。比对照依托泊苷更强,对SMMC-77213、HeL、MDA-MB-231的IC50值,分别是17.49～19.43μmol/L、0.84～1.19μμmol/L、1.17～1.85μμmol/L。根据抗肿瘤活性结果显示,喹啉基引入熊果酸分子中,羧基修饰为1,3,4-噁二唑基、酰肼基,抗肿瘤活性能够明显增强,酰肼的衍生物为侧链,相比噁二唑的衍生物活性更佳。因此,能够进一步优化熊果酸结构,提升抗肿瘤活性。     

泡桐叶中熊果酸的超声波提取与分离研究(摘要)

<正>泡桐作为一种广泛分布的树种,其叶中含有多种生物活性物质,其中熊果酸具有保肝、抗炎、抑菌、抗肿瘤、增强免疫、降血糖血脂等一系列重要的药理功能,在医药保健、日用化工、功能食品等方面具有广泛应用。本文以泡桐叶为原料,研究了其中熊果酸的超声波提取、分离工艺。同时,建立了泡桐叶中熊果酸和齐墩果酸的HPLC分析方法,从泡桐种属、原料存储方法和采集时间等方面对泡桐叶原料选取进行了研究。     

熊果酸衍生物的研究现状和展望

熊果酸(UA,3β-羟基-乌苏烷型-12-烯-28-羧酸),五环三萜化合物,作为药草的主要成分,存在于丰富的植物王国中.据报道,UA具有广谱的生物活性,调控和控制肿瘤细胞形成.UA多效件的抗肿瘤活性激发了专家们在这方面的积极研究,现综合国内外文献报道.对熊果酸结构修饰物及其药理活性进行综述.     

熊果酸提取方法及其功能应用的研究

综述了常见的几种提取熊果酸的优化方法,并介绍了熊果酸的主要功能作用。重点概述了熊果酸有保持湿润、美白肌肤、抗氧化性等护肤功效,并介绍了熊果酸的相关应用研究,尤其是在护肤品、化妆品领域的应用研究发展。     

熊果酸衍生物的合成

设计合成了熊果酸衍生物.对熊果酸的3-位、28-位进行结构修饰,通过一系列的酰化反应制备其衍生物,并通过红外、核磁对其结构进行鉴定.制备了8个熊果酸衍生物,其中4个化合物为新化合物.这些化合物结构正确,其中合成的熊果酸钠盐比熊果酸具有更好的水溶性,从而改善了制剂质量.     

超声波辅助提取石榴皮中熊果酸工艺研究

以石榴皮为原料,以熊果酸得率为指标,采用超声波辅助提取了石榴皮中熊果酸。分别研究了提取剂乙醇浓度、料液比、超声时间、超声温度对熊果酸提取的影响,通过正交试验优化了提取工艺。结果表明,熊果酸提取的最佳工艺条件是:乙醇体积分数50%、固液比1∶20、超声时间30 min、超声温度60℃,在最佳条件下,熊果酸得率可达1.1142%。     

微波法合成熊果酸衍生物

以熊果酸为原料,分别通过常规方法及微波法合成3-O-乙酰基熊果酸和熊果酸丁酯,并经核磁共振氢谱确证其化学结构。结果表明,微波法大大缩短了反应时间,提高了收率。     

二氯荧光素二丙烯酸酯的合成与抗肿瘤活性研究

合成了化合物二氯荧光素二丙烯酸酯(Ⅰ),用元素分析、IR、1HNMR、UV、荧光光谱对它进行了表征。测试了Ⅰ对小鼠白血病L1210细胞生长曲线的影响和对人体胃腺癌SGC-7901的抗肿瘤活性。结果表明,Ⅰ对体外培养肿瘤细胞L1210有很强的瞬时杀伤作用〔在ρ(Ⅰ)=0 1μg mL时,24h对其杀死率几乎为100%〕;对人体胃腺癌SGC-7901有很强的细胞增殖的抑制作用〔在ρ(Ⅰ)=0 1μg mL时,克隆数约为(3±1.1)%,集落形成率=0 15%,存活率=0 4%〕。是有希望的脂溶性、带荧光的抗肿瘤药学化合物。     

Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects

We have previously demonstrated a high antitumor potential of NOS inhibitor T1023 (1-isobutanoyl-2-isopropylisothiourea hydrobromide): antitumor antiangiogenic activity in several animal tumor models and its ability to synergistically enhance the antitumor effects of bevacizumab, cyclophosphamide and γ-radiation. At the same time, rather rapid adaptation of experimental neoplasias to T1023 treatment was often observed. We attempted to enhance the antitumor activity of this NOS inhibitor by supplementing its molecular structure with a PDK-inhibiting fragment, dichloroacetate (DCA), which is capable of hypoxia-oriented toxic effects. We synthesized compound T1084 (1-isobutanoyl-2-isopropylisothiourea dichloroacetate). Its toxic properties, NOS-inhibiting and PDK-inhibiting activity in vivo, and antitumor activity on the mouse Ehrlich carcinoma model (SEC) were investigated in compare with T1023 and Na-DCA. We found that the change of the salt-forming acid from HBr to DCA does not increase the toxicity of 1-isobutanoyl-2-isopropylisothiourea salts, but significantly expands the biochemical and anti-tumor activity. New compound T1084 realizes in vivo NOS-inhibiting and PDK-inhibiting activity, quantitatively, at the level of the previous compounds, T1023 and Na-DCA. In two independent experiments on SEC model, a pronounced synergistic antitumor effect of T1084 was observed in compare with T1023 and Na-DCA at equimolar doses. There were no signs of SEC adaptation to T1084 treatment, while experimental neoplasia rapidly desensitized to the separate treatment of both T1023 and Na-DCA. The totality of the data obtained indicates that the combination of antiangiogenic and hypoxia-oriented toxic effects (in this case, within the molecular structure of the active substance) can increase the antitumor effect and suppress the development of hypoxic resistance of neoplasias. In general, the proposed approach can be used for the design of new anticancer agents.     

云南产五味子科药用植物化学成分研究进展

五味子科药用植物中的主要生物活性成分为木脂素、羊毛甾烯型三萜酸及内酯 ,具有抗肝炎、抗癌、抗爱滋病毒、PAF拮抗及保护中枢神经系统等多方面的药理作用。为促进进一步的研究与开发利用 ,本文结合自己的工作 ,对云南产五味子科药用植物化学成分研究进展进行了综述。     

甘草甜素残液化学成分及含量的研究

对甘草提取甘草甜素后的残液进行了研究，经溶剂提取、硅胶柱层析分离，共分离鉴定了２１种化合物，其中五环三萜类化合物８种，黄酮类化合物１２种，脂肪化合物１种，并地各化合物的含量进行了研究。     

7-对氟苯甲酰基喜树碱的合成及其抗癌活性研究

为提高天然喜树碱的活性并降低其毒性,在它的7位引进了含氟的亲脂基团。以对氟苯甲醛、20(S)-喜树碱等为原料,经Fenton自由基取代反应,合成了7-对氟苯甲酰基-20(S)-喜树碱,产率38.5%,合成的新化合物结构经MS、1HNMR和IR确证,并对FeSO4.7H2O?过氧化氢?对氟苯甲醛?浓硫酸的投料量等反应条件进行了初步优化。目标产物经北京大学药学院天然药物及仿生药物国家重点实验室用磺酰罗丹明B(SRB)法在体外对人癌细胞增殖的抑制作用进行了测定,结果表明,在20μmol/L时,该化合物对人白血病(HL-60)、人胃癌(BGC-823)、人肝癌(Bel-7402)3种人癌细胞增殖都有抑制作用。     

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid Derivatives Conjugated with Acyl-Thiourea Peptide Moiety as Antitumor Agents

A series of dehydroabietic acid (DHAA) acyl-thiourea derivatives were designed and synthesized as potent antitumor agents. The in vitro pharmacological screening results revealed that the target compounds exhibited potent cytotoxicity against HeLa, SK-OV-3 and MGC-803 tumor cell lines, while they showed lower cytotoxicity against HL-7702 normal human river cells. Compound 9n (IC₅₀ = 6.58 ± 1.11 μM) exhibited the best antitumor activity against the HeLa cell line and even displayed more potent inhibitory activity than commercial antitumor drug 5-FU (IC₅₀ = 36.58 ± 1.55 μM). The mechanism of representative compound 9n was then studied by acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay and flow cytometry, which illustrated that this compound could induce apoptosis in HeLa cells. Cell cycle analysis indicated that compound 9n mainly arrested HeLa cells in the S phase stage. Further investigation demonstrated that compound 9n induced apoptosis of HeLa cells through a mitochondrial pathway.     

京尼平及其衍生物抗阿尔兹海默病作用的研究进展

京尼平(Genipin)是具有环烯醚萜结构的化合物,具有抗血栓、降血糖、抗肿瘤、抗炎和抗老年痴呆等多种药理活性.近年来,人们通过对其结构进行修饰改造,获得了一系列具有抗阿尔兹海默病(AD)活性的京尼平衍生物.对京尼平及其衍生物抗阿尔兹海默病作用的研究进展进行综述,为京尼平的开发利用提供依据.     

Synthesis of novel poly 2‐vinylpyridine‐mixed metal complexes and studying their effect as antitumor chemotherapeutic agents,part 2

The poly2‐vinylpyridine and cationic polymer‐mixed metal complexes (P2VPMC) have been prepared and characterized by analytical measurement such as: molecular weight, elemental analysis, IR‐spectroscopy, NMR‐spectroscopy, XRD, and UV. The degree of N‐alkylation of poly vinyl pyridine (P‐2VP) was 10% determined by chlorine content according to elemental microanalysis. Through ICP instrument the complexation between P‐2VPC and the mixed metal chlorides was proven. The structure of the samples was characterized using X‐ray diffraction. It was found that the complexes have amorphous properties. The antitumor activity of this compound was examined in vitro on cell lines. The results reflect pronounced cytotoxicity of P‐2VPMC against animal experimental EAC cells line, and human, HeLa, HCT116 and Hep‐G2, cell lines. Antitumor activity of the novel compound as applied on mice bearing Ehrlich solid carcinoma, revealed delays tumor growth compared with untreated animals and decreases tumor volume. The antitumor activity of the P2VPMC might be due to its ability to pass through the membrane and interact with, DNA causing cross‐linking action which might be the key factor for great antitumor activity of the P2VPMC compound. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells.     

Aristoforin, a novel stable derivative of hyperforin, is a potent anticancer agent

Hyperforin, a natural product of St. John's wort (Hypericum perforatum L.), has a number of pharmacological activities, including antidepressive and antibacterial properties. Furthermore, hyperforin has pronounced antitumor properties against different tumor cell lines, both in vitro and in vivo. Despite being a promising novel anticancer agent, the poor solubility and stability of hyperforin in aqueous solution limits its potential clinical application. In this study, we present the synthesis of hyperforin derivatives with improved pharmacological activity. The synthesized compounds were tested for their solubility and stability properties. They were also investigated for their antitumor properties, both in vitro and in vivo. One of these hyperforin derivatives, Aristoforin, is more soluble in aqueous solution than hyperforin and is additionally highly stable. Importantly, it retains the antitumor properties of the parental compound without inducing toxicity in experimental animals. These data strongly suggest that Aristoforin has potential as an anticancer drug.