银莲花的抗氧化、抑菌和抗肿瘤活性

为了有效利用野生银莲花资源,将银莲花的乙醇提取物进行石油醚-丙酮梯度洗脱,得到5个组分,分别采用DPPH法、琼脂孔扩散法、MTT法进行了抗氧化、抑菌和抗人乳腺肿瘤细胞(MDA-MB-231)活性研究.结果表明:5个组分均有氧自由基清除能力,其中组分工抗氧化活性最好,半数抑制质量浓度为30.58 μg/mL;5个组分均有抑菌活性,其中组分Ⅴ抑菌活性最好.各组分和单体化合物对人乳腺肿瘤细胞均有一定的抑制作用,组分Ⅱ对人乳腺肿瘤细胞的抑制率最高,达到50.32％.     

Cytotoxicity of Frutalin on Distinct Cancer Cells Is Independent of Its Glycosylation

Frutalin is a plant lectin with beneficial immunobiological action, although the access to its active form is still restricted. Moreover, there is a knowledge gap on isoform activity and glycosylation impact on its bioactivity, and recombinant production protocols were seen as ineffective. Here, a simpler and faster production and purification protocol was developed, attaining a yield of purified frutalin 3.3-fold higher than that obtained previously. Hemagglutination assays confirmed that this frutalin isoform could not agglutinate rabbit erythrocytes, while maintaining the native tetrameric structure, as indicated by DLS analysis, and strong interaction with methyl-alpha-galactose, in fluorescence spectroscopy studies. The cytotoxicity of the recombinant frutalin isoform was shown in a broad panel of human cancer cells: colon (HCT116), melanoma (A375), triple-negative breast cancer (MDA-MB-231), and ovarian (IGROV-1). Treatment with 8.5–11.8 μM TrxFTL reduced proliferation of all cancer cells to half in 48 h. This anti-proliferative effect encompasses the p53 pathway since it was significantly reduced in p53-null colon cancer cells (HCT116 p53^−/−; GI₅₀ of 25.0 ± 3.0 μM), when compared to the isogenic p53-positive cells (HCT116 p53^+/+; GI₅₀ of 8.7 ± 1.8 μM; p < 0.002). This recombinantly produced frutalin isoform has relevant cytotoxic effect and its biological activity is not dependent on glycosylation. The developed E. coli production and purification protocol generates high yield of non-glycosylated frutalin isoform with potent cytotoxic activity, enabling the development of novel anticancer p53-targeting therapies.     

Anticancer Agents from the Australian Tropical Rainforest: Spiroacetals EBC‐23, 24, 25, 72, 73, 75 and 76

EBC‐23, 24, 25, 72, 73, 75 and 76 were isolated from the fruit of Cinnamomum laubatii (family Lauraceae) in the Australian tropical rainforests. EBC‐23 ( 1 ) was synthesized stereoselectively, in nine linear steps in 8 % overall yield, to confirm the reported relative stereochemistry and determine the absolute stereochemistry. Key to the total synthesis was a series of Tietze–Smith linchpin reactions. The novel spiroacetal structural motif, exemplified by EBC‐23 ( 1 ), was found to inhibit the growth of the androgen‐independent prostate tumor cell line DU145 in the mouse model, indicating potential for the treatment of refractory solid tumors in adults.     

氧肟酸类组蛋白去乙酰化酶抑制剂的药效团模型研究

基于24个目前已知的氧肟酸类组蛋白去乙酰化酶抑制剂,我们运用Catalyst软件建立了一个三维药效团模型。其中,最好的药效团模型1,包含了四个化学特征（一个氢键供体,一个芳环和两个疏水基）,相关系数达到0.946,并由另外20个化合物进行了测试验证。我们第一次特征性描述了组蛋白去乙酰化酶的帽子（CAP）部分。我们的研究结果对于设计全新组蛋白去乙酰化酶抑制剂具有很好的指导作用。     

Peptidomimetics and metalloprotease inhibitors as anticancer drugs

Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the development of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeutic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity. Supported by the National High Technology Research and Development Program of China (863 Project) (Grant No. 2007AA02Z314), the National Natural Science Foundation of China (Grant Nos. 90713041 & 30772654), and the Doctoral Fund of Ministry of Education of China (Grant No. 20060422029)     

Review on supermolecules as chemical drugs

Supramolecular medicinal chemistry field has been a quite rapidly developing, increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceutical sciences, and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through non-covalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs, i.e. supramolecular chemical drugs or supramolecular drugs, which might have the excellences of lower cost, shorter period, higher potential as clinical drugs for their successful research and development, may possess higher bioavailability, better biocompatibility and drug-targeting, fewer multidrug-resistances, lower toxicity, less adverse effect, and better curative effects as well as safety, and therefore exhibit wide potential application. These overwhelming advantages have drawn enormous special attention. This paper gives the definition of supramolecular drugs, proposes the concept of supramolecular chemical drugs, and systematically reviews the recent advances in the research and development of supermolecules, including organic and inorganic complex ones as chemical drugs in the area of antitumor, anti-inflammatory, analgesic, antimalarial, antibacterial, antifungal, antivirus, anti-epileptic, cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented. Supported by the Southwest University (Grant Nos. SWUB2006018 & XSGX0602), the Natural Science Foundation of Chongqing (Grant Nos. 2007BB5369 & 2006BB4341) and the Key Project from the Personnel Department of China (Grant No. 2002-99)     

MTT法测定高三尖杉酯碱对人肝癌HepG2抑制作用

采用MTT法检测高三尖杉酯碱对HepG2细胞体外培养的抑制作用.将常规用96孔板培养的HepG2细胞作为空白组,其余分11个剂量的给药组,相应处理24、48、72 h.与空白组对照后,HepG2细胞的增殖被各给药组不同程度的抑制,并随着给药剂量的增加其抑制率也增加.高三尖杉酯碱在体外可有效的抑制人肝癌细胞的活性和细胞增殖.     

红树林内生真菌Paecilomyces sp．（treel—7）蒽醌类代谢产物研究

红树林内生真菌Paecilomyces sp．（treel-7）采自红树植物秋茄树皮,在实验室150L规模下静置培养．反复进行硅胶,Sephadex LH-20柱层析．通过1D,2DNMR和EI—MS等手段鉴定5个蒽醌类化合物和2个甾体类代谢产物的结构．通过MTT法测试5个蒽醌类化合物有抑制鼻咽癌细胞（KB,KBv）的活性,结果显示葸醌类化合物1-5对鼻咽癌细胞有不同程度的抑制活性．     

基于冬虫夏草制剂的药物设计研究进展

近年来,各种中药制剂的研发取得了较大的进展,冬虫夏草作为名贵中药因其疗效独特而倍受青睐。总结了冬虫夏草各种制剂的设计原理、制备方法、制剂特点和目前存在的一些问题,并对其中活性成分的药理作用、生物利用度等进行了分析;提出未来发展应重视下列方面:1单一活性成分的分离与提纯;2基于药物分子机制对其抗癌活性成分的合理设计;3利用缓控释和靶向控制释放等提高其活性成分的生物利用度;4人工替代品的研制与开发。     

轴向嘧啶衍生物修饰硅酞菁的光谱性质、光动力抗癌活性及与白蛋白相互作用的研究

研究了一种新型轴向修饰硅酞菁,即二(2-氨基-6-三氟甲基-4-嘧啶氧基)硅酞菁(SiPcF)的光物理光化学性质、离体光动力抗癌活性以及与白蛋白的相互作用。结果表明,SiPcF的Q带最大吸收峰波长686 nm,摩尔吸光系数为2.3×105 mol-1·L ·cm-1,荧光发射峰694 nm,荧光量子产率为0.46,光敏化产生单线态氧的量子产率为0.38,是有效的1O₂光敏剂。SiPcF与牛血清白蛋白(BSA)具有较强的相互作用,两者的结合常数为4.33×105mol·L-1,结合位点数为1。离体细胞实验表明,SiPcF具有较高的光动力抗癌活性,对人肝癌细胞HepG2的IC₅₀值为5×10-7mol·L-1。