13位取代苦参碱衍生物抗癌活性的定量构效关系研究

采用密度泛函理论B3LYP方法计算了13个13位取代苦参碱衍生物的电子结构,研究了化合物结构与抑制人肝癌细胞HepG2抗癌活性的定量构效关系(QSAR).结果表明:(1)13位取代的苦参碱类衍生物的最低空轨道能ELUMO越低,最低空轨道与最高占据轨道的能隙ΔE越小,化合物抗癌活性越高;(2)分子的能量Etotal、面积S以及体积V越大,其极化度P越大,活性越大;(3)分子的油水分配系数logP越大,活性越大,即分子的疏水性增大活性增强.综合得到了显著性较好的QSAR方程:-lgIC50=97.008-11.759ΔE+818.602QC2-2.132×10-4Etotal,可用于预测该类衍生物抑制人肝癌细胞HepG2的活性并进行分子设计.     

四[对-(羧基甲氧基)苯基]卟啉金属配合物(M=Zn,Cu,Ni)的π-π配合及其二丁基锡(Ⅳ)酯衍生物的抗癌活性

自 1 92 4年 Policard发现血卟啉在癌组织内聚集以来 ,人们对利用卟啉的荧光性质检测及治疗癌症进行了广泛的研究 [1,2 ] .卟啉及金属卟啉的自聚合及与配体的 π- π配合反应对理解卟啉的生物功能具有重要意义[3～ 6] .有机锡 ( )类化合物自被发现有抗癌活性以来一直受到极大的关注 [7～ 9] .Mirisola等 [9]研究了四 (对 -羧基苯基 )卟啉有机锡 ( )酯化合物的体内抗癌活性 .我们合成了四 [对 - (羧基甲氧基 )苯基 ]卟啉的 Zn2 + ,Cu2 + ,Ni2 + 配合物及其二丁基锡 ( )酯衍生物 ,测定了它们的体外抗肿瘤活性 ,并研究了四 [对 - (羧基甲…     

6-叠氮-6-脱氧凝聚多糖的选择性一步合成

由于含氨基或氨基衍生物的多糖对细胞表面及细胞之间的生理功能具有特殊的作用,在研究细胞之间有效作用的促进剂和抑制剂方面具有潜在的应用价值,因而叠氮化多糖作为制备氨基多糖及其衍生物的中间体受到人们的重视,含乙酰氨基的天然多糖（如Chitin）和氨基多糖（如Chitosan）,由于具有抗感染和医治创伤作用,广泛用于医疗领域,含氨基和硫酸酯的多糖肝素有很好的抗凝血作用和降血脂活性,已用于动脉硬化病的治疗,我们发现含乙酰氨基的硫酸化核聚糖具有很高的抗艾滋病毒活性,而且没有抗凝血的副作用。     

二苯乙烯衍生物的合成与抗癌活性的初步研究

以对硝基甲苯和3,4,5-三甲氧基苯甲醛或3,4-二甲氧基苯甲醛为起始原料,经过缩合、还原和酰化反应,合成了(E)-3,4,5-三甲氧基-4'-乙酰氨基二苯乙烯等4种二苯乙烯衍生物.4种化合物对HepG2和BGC-823两种细胞模型的体外抗癌活性测试结果表明,这些化合物具有良好的抗肿瘤活性且对正常细胞毒性较小.     

6,7-二甲氧基喹啉衍生物的合成及体外抗肿瘤活性研究

以3,4-二甲氧基苯胺和丙二酸为原料,经过多步反应合成得到一系列6,7-二甲氧基喹啉衍生物(3～7b),中间体及产物结构经~1H NMR和ESI-MS表征。并着重考察了Suzuki反应中,物料比对化合物5a和5b收率的影响,确定适宜物料比为n(化合物4)∶n(乙烯基硼酸频哪醇酯)=1∶2.0。在该反应条件下,化合物5a和5b收率分别为54.5%和33.8%。采用MTT法测定6,7-二甲氧基喹啉衍生物3～7b对人肝癌细胞HepG2及人非小细胞肺癌A549的体外抗肿瘤活性。结果表明,化合物7b对HepG2细胞的体外生长具有显著的抑制活性,IC_(50)为8.9±0.95μM·L~(-1)。     

微波辅助高效合成2-氮杂环丁酮类衍生物及其抗肿瘤活性研究

含氮杂环是非常重要的一类有机化合物,具有广泛的生物活性和药理活性,目前临床上正在使用或者处于研究开发的许多药物结构中都含有含氮杂环.因此,含氮杂环的快速高效合成及其生物活性研究一直都是有机化学和药物化学领域的研究热点之一.本文利用Ugi反应设计合成了两类具有潜在抗癌活性的2-氮杂环丁酮类衍生物,其结构均经核磁共振氢谱(~1H NMR)、碳谱(~13C NMR)和高分辨质谱(HRMS)确证.以人肺癌细胞A549、人胶质瘤细胞LN229、人乳腺癌细胞MDA-MB-453、人结肠癌细胞SW620和人前列腺癌细胞DU145等5种细胞株为活性筛选对象,采用噻唑蓝(MTT)法对目标分子进行了体外抗肿瘤活性研究,结果表明,所合成的目标分子具有一定的体外抗肿瘤活性,其中化合物7e和13e分别对LN229和DU145的抑制率达到了53%,具有可进一步深入研究的价值.     

斑蝥素衍生物的合成、抗肝癌活性及构效关系研究

斑蝥素衍生物具有结构多样性和良好的抗肝癌活性。本文以呋喃、顺丁烯二酸酐为原料,合成了35个斑蝥素衍生物。以顺铂为阳性对照药,经MTT法测试了所合成化合物对人肝癌HepG2细胞的体外抗肿瘤活性。结果表明,化合物6d、6f、6g、6h、6i的抗肝癌活性与顺铂相当,其中,斑蝥素酰亚胺类化合物具有较好的抗肝癌活性,且当取代基为吸电子基或含氮杂环时化合物显现出较强的抗肝癌活性,该类化合物具有潜在的抗肝癌应用价值。     

吴茱萸碱及其衍生物抗肿瘤活性的密度泛函理论研究

为了研究吴茱萸碱及其衍生物的抗肿瘤活性和分子结构之间的关系,运用密度泛函理论B3LYP方法,以6-311++G**为基组对吴茱萸碱、5-硫代吴茱萸碱和5-亚甲基吴茱萸碱进行了优化计算.从分子的几何构型、NBO电荷及前线轨道能等方面分析吴茱萸碱及其衍生物的抗肿瘤活性与结构之间的关系.结果表明,前线分子轨道对活性影响显著,ΔE_(LUMO-HOMO)越低,分子的抗肿瘤活性越强.由此得到的抗肿瘤活性大小为,5-硫代吴茱萸碱的抗肿瘤活性是最强的,吴茱萸碱次之,5-亚甲基吴茱萸碱的抗肿瘤活性最弱,计算结果与实验结果十分吻合.     

鬼臼及其羧酸酯类化合物2位立体异构体的EI MS质谱研究

鬼臼(podophyllotoxin)及其衍生物在抗癌方面表现出良好的活性。最近,Lopez-perez等人研究了合成的鬼臼羧酸酯类化合物的细胞活性,发现鬼臼的4位降冰片烯酯化合物在对P-388,A-549,HT-29和MEL-28有较母体鬼臼强3~5倍的活性[1],因此引起了人们对鬼臼酯类化合物抗癌活性与结构特点     

小檗碱与和厚朴酚及槲皮素缀合物的合成及其体外抗肝癌HepG2细胞活性评价（英文）

小檗碱、和厚朴酚、槲皮素都是具有良好抗肿瘤活性的先导化合物,以其为原料合成了三个新型化合物,通过~1H NMR、~(13)C NMR、2D NMR、HRMS、IR和UV等方法对目标化合物进行结构确证;体外抗HepG2肝癌细胞活性结果显示,两个化合物对Hep G2肝癌细胞的抑制作用远远优于原料药和厚朴酚与盐酸小檗碱,且活性与阳性对照药顺铂相当,有望成为潜在的抗肿瘤药物.     

Isolation,Purification and Bioactivities of Polysaccharides from Irpex lacteus

Irpex lacteus has been widely used for treating chronic glomerulonephritis as a traditional Chinese medicine.Seven water-soluble polysaccharide fractions(ILN Ⅰ,ILN Ⅱ,ILN Ⅲ,ILA Ⅰ,ILA Ⅱ,ILB Ⅰ and ILB Ⅱ)w...     

STRUCTURE, MOLECULAR WEIGHT AND BIOACTIVITIES OF （1→3）-β-D-GLUCANS AND ITS SULFATED DERIVATIVES FROM FOUR KINDS OF LENTINUS EDODES

Abstract Lentinan samples, (1→3)-β-D-glucans containing 4.6-15.2 wt% proteins, coded as L-I1. L-I2. L-I3 and L-I4 (L-I)were isolated from four kinds of Lentinus edodes. These glucans were treated with acetone to remove the protein in order to obtain free protein glucans coded as LNP-I1. LNP-I2, LNP-I3 and LNP-I4 (LNP-I). The free-protein polysaccharides were sulfated to give derivatives (S-LNP-I) with degree of substitution (DS) from 0.4-0.8. The structural features and weight- average molecular weight (Mw) of the samples were investigated by using infrared spectroscopy, elemental analysis,^13C-NMR, size exclusion chromatography combined with laser light scattering (SEC-LLS) and viscometry. The effects of structure and conformation of the polysaccharides on antitumor activities were assayed in vivo (Sarcoma 180 solid tumors)and in vitro (Sarcoma 180, HL-60, MCF-7 and Vero tumors). The results indicated that the predominant species of the samples L-I and LNP-I in 0.2 mol/L NaCl aqueous solution existed as triple-helical chains with high rigidity and in dimethyl sulfoxide (DMSO) as single-flexible chains. Interestingly, the antitumor activities of LNP-I are lower than those of the native glucans (L-I), whereas their sulfated derivatives have higher inhibition ratio against Sarcoma 180 than LNP-I. The results reveal that the binding of protein, sulfated modification and the triple helix conformation are important factors in the enhancement of the antitumor activities of polysaccharides on the whole.     

STRUCTURE, MOLECULAR WEIGHT AND BIOACTIVITIES OF (1→3)-β-D- GLUCANS AND ITS SULFATED DERIVATIVES FROM FOUR KINDS OF LENTINUS EDODES

Lentinan samples, (1→3)-β-D-glucans containing 4.6-15.2 wt% proteins, coded as L-I1, L-I2, L-I3 and L-I4 (L-I)were isolated from four kinds of Lentinus edodes. These glucans were treated with acetone to remove the protein in order to obtain free protein glucans coded as LNP-I1, LNP-I2, LNP-I3 and LNP-I4 (LNP-I). The free-protein polysaccharides were sulfated to give derivatives (S-LNP-I) with degree of substitution (DS) from 0.4-0.8. The structural features and weight- average molecular weight (Mw) of the samples were investigated by using infrared spectroscopy, elemental analysis,13C-NMR, size exclusion chromatography combined with laser light scattering (SEC-LLS) and viscometry. The effects of structure and conformation of the polysaccharides on antitumor activities were assayed in vivo (Sarcoma 180 solid tumors)and in vitro (Sarcoma 180, HL-60, MCF-7 and Vero tumors). The results indicated that the predominant species of the samples L-I and LNP-I in 0.2 mol/L NaCl aqueous solution existed as triple-helical chains with high rigidity and in dimethyl sulfoxide (DMSO) as single-flexible chains. Interestingly, the antitumor activities of LNP-I are lower than those of the native glucans (L-I), whereas their sulfated derivatives have higher inhibition ratio against Sarcoma 180 than LNP-I. The results reveal that the binding of protein, sulfated modification and the triple helix conformation are important factors in the enhancement of the antitumor activities of polysaccharides on the whole.     

Synthesis and Antitumor Activity of Capecitabine Derivatives

A series of capecitabine derivatives with a Boc group at the N⁴-position was synthesized and their in vitro antitumor activities against HepG2(liver hepatocellular carcinoma) were primarily evaluated. Some compounds were chosen for further evaluation of their in vivo efficacy on nude mice xenografted human hepatoma HepG2. The results showed that compounds 3 and 6 had considerable in vivo activity against HepG2, with tumor growth inhibition rates of 70% and 64% on day 21, respectively, and 56% and 55% on day 35, respectively, which are roughly comparable to capecitabine(74% and 59% on days 21 and 35, respectively).     

杜氏盐藻多糖的高效体积排阻色谱的保留特性及其分析方法的研究

通过对从杜氏盐藻中提取出的不同多糖级分在高效体积排阻色谱柱(Waters Ultrahydragel Linear,7.8 mm i.d.×300 mm,2根串联)上的保留特性的考察及其分离分析条件的优化,建立了高效体积排阻色谱分析盐藻多糖平均相对分子质量及其分布的方法。结果表明:流动相中盐的种类及其浓度、pH值对3种酸性多糖级分(特别是硫酸化多糖级分PD4a)的保留行为有显著影响;在柱温为45 ℃,流速为0.9 mL/min条件下,使用0.1 mol/L的NaAc水溶液作流动相基本上能消除非特异性吸附作用及分子间缔合等因素的干扰,使各多糖级分基本以非缔合状态按立体排除机制保留和分离。在优化的色谱条件下,测得的盐藻多糖5个级分的重均相对分子质量(Mw)分别为1548000,33000,67000,424000,10000;测得的硫酸化多糖级分PD4a的Mw和峰面积的相对标准偏差分别为1.7%和 0.88%(n=5)。     

氟代索拉非尼的合成及其抗肿瘤活性研究

以N-甲基-4-氯-2-吡啶甲酰胺为原料,经过4步共合成4个化合物(S-1,S-2,R-1和R-2),其中2个为新的化合物(S-1和R-2)。经过1H NMR,13C NMR,HR-MS等方法对其结构表征。最后通过CTG法,测试4种化合物对四种人肝癌细胞(PLC/PRF/5,Hep3B,HepG2,BEL-7402)的抑制活性。结果表明:S-1,S-2,R-1和R-2均表现较明显的对4种细胞的抑制活性,且呈现出浓度依赖关系。IC50值从1304nM到11228nM。其中化合物R-1(瑞格非尼)对PLC/PRF/5和HepG2细胞,S-1对Hep3B细胞的抑制活性,R-2对HepG2的细胞活性均较高于原药索拉非尼。     

Engineered bio-active polysaccharides from heparin

[Image: see text] Heparin, the well-known anticoagulant polysaccharide, is also active in many other biological systems owing to its structural similarity to HS, but usually lacks selectivity because it is more highly sulfated. A series of straightforward chemical reactions (de-O-sulfation, de-N-sulfation and re-N-acetylation), carried out to partial or complete extent, were combined, resulting in a number of modified heparin polysaccharide derivatives with altered properties. These exhibited a range of abilities to promote cell signalling through the FGF/FGFR tyrosine kinase signalling system, in an in vitro cell assay with combinations of FGF-1, -2, -3 and FGFR 1 and 3. One polysaccharide (N-acetylated, 6-O- and 2-O-sulfated heparin), with only a fraction (<10(-3)) of the anticoagulant activity of heparin (200 U . mg(-1)), promoted FGF-2-mediated angiogenesis (10-fold) and therefore had an improved ratio of pro-angiogenic activity to anticoagulant activity in excess of 10(4) compared to heparin. These results demonstrate that heparin-derived polysaccharides can be engineered for selected activities and have potential in a wide range of medical, biotechnological and tissue-engineering applications. Effect of selected engineered heparin polysaccharides on angiogenesis.     

Synthesis and anti-tumour activities of sulphated polysaccharide obtained from Momordica charantia

A native polysaccharide (MCP2) was extracted and isolated from Momordica charantia. Four sulphated derivatives of MCP2 were prepared by chlorosulphonic acid method. The structures of the sulphated derivatives were characterised by FT-IR spectra. Depending on the reaction conditions, the sulphated derivatives showed different degree of substitution (DS) ranging from 0.56 to 1.10, and different weight-average molecular mass (Mw) ranging from 7.2 to 9.3?KDa. It implied the efficient substitution of hydroxyl groups in the polysaccharides by sulphated groups with degradation. The effects of the sulphated derivatives on inhibiting the growth of HepG2 cells and Hela cells in?vitro were compared with taking non-modified MCP2 as control. The sulphated derivatives inhibited the growth of HepG2 cells and Hela cells in?vitro significantly, which indicated that sulphated modification could enhance the anti-tumour activity of MCP2.     

Synthesis and antitumor activities of glucan derivatives

A highly efficient and practical method for the preparation of β-d-Glc-(1→6)-[β-d-Glc-(1→3)]-β-d-Glc-(1→6)-β-d-Glc-(1→6)-[β-d-Glc-(1→3)]-d-Glc-OMe was described. A dendritic nonasaccharide was also synthesized. The antitumor activities of hexasaccharide, the dendrimer, their sulfated derivatives, together with the natural glucan-protein and the corresponding polysaccharide isolated from barmy mycelium of Grifola frondosa, were preliminarily investigated based on Sarcoma-180 studies in mice tests. Our results suggest that the sulfated branching oligosaccharide and natural glycoprotein have better antitumor activities comparing to the parent sugar residue (oligosaccharide or polysaccharide).     

Catalytic Properties of Mechanically Activated Humic Substances in Electroreduction of Oxygen

Effect of mechanical treatment of peat on the yield of the major fractions (polysaccharides, poly- phenols, water-soluble compounds, and humic acids) and catalytic activity of humic substances in oxidation processes is studied. Conditions of formation of substances with the maximal antioxidant and initiating activities are determined. The antioxidant and initiating activities of the polysaccharide and humic fractions is studied, in relation to the structure and iron content.