熊果酸衍生物的合成及抗肿瘤血管生成活性

对熊果酸C28位与C3位进行结构修饰得到了24个衍生物, 并利用 1H NMR, 13C NMR, MS及HR-MS对这些化合物进行了结构表征. 进一步通过MTT法, 以内皮细胞HUVEC为主要模型, 研究了24个衍生物抗肿瘤血管生成的活性, 同时以A549, Bel-7402及MCF-7细胞为模型研究了上述衍生物对肿瘤细胞的抑制活性. 研究结果表明, 与熊果酸相比, 化合物5, 9, 12e和14e对HUVEC细胞有较好的选择性, 化合物12a和13h比熊果酸的抗肿瘤血管生成活性略高, 因此通过适当改变熊果酸C28位的结构可以提高其对内皮细胞HUVEC的选择性, 增强抗肿瘤血管生成活性. 本文结果表明, 熊果酸及其衍生物是潜在的具有抗肿瘤血管生成作用的先导化合物, 通过有效的结构优化可能得到新型的抗肿瘤血管生成的化合物.     

有机-无机杂化材料[Na2(H2O)4]2[γ-Mo8O26·(Gly-Gly)2]·4H2O的合成及晶体结构

多金属氧酸盐因其独特的结构而具有较高的抗肿瘤及抗病毒活性,蛋白质和肽是氨基酸的聚合体,氨基酸侧链官能团能与多金属氧酸盐形成新型配合物.了解氨基酸和肽与多金属氧酸盐的相互作用对于深入研究多金属氧酸盐抗肿瘤及抗病毒机理很有意义.我们曾报道了赖氨酸、丙氨酸及甘氨酸二肽与钼磷酸所形成化合物的晶体结构.     

微管菌素类似物的合成及抗肿瘤活性

以微管菌素为先导化合物, 设计合成了一系列类似物; 所有化合物的结构均经¹H NMR, ¹³C NMR及HRMS确证, 均为新化合物. 采用噻唑蓝(MTT)法对其抗肿瘤活性进行了初步筛选, 结果表明, 化合物Ⅱb具有一定的抗肿瘤活性.     

NO供体型苦参碱衍生物的合成及抗肿瘤活性

以苦参碱为原料, 设计合成了13个NO供体型苦参碱衍生物, 衍生物的结构经EI-MS, ¹H NMR, IR和元素分析确证. 采用 MTT法测试所合成化合物的体外抗肿瘤活性, 结果表明, 所合成的化合物均有一定的抗肿瘤作用, 其中化合物11a~11c, 11h, 11i对肝癌细胞HepG2的抑制活性优于5-氟尿嘧啶.     

大黄酸-缬氨酸加合物的合成及初步抗肿瘤活性

以大黄酸为原料,经酯化、烷基化、水解及缩合等反应步骤合成了12个大黄酸-缬氨酸加合物.目标化合物经1H NMR,~(13)C NMR和HRMS进行了结构确证.以顺铂和阿霉素为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物的体外抗肿瘤(Hela,MCF-7,HepG2,KB和HEK293T等5株细胞)活性.结果表明,化合物5l显示出较好的抗肿瘤活性,其IC50值在1.6~9.4μmol/L之间.作用机制研究结果表明,化合物5l能够与DNA发生较强的结合作用.     

基于苯丙氨酸衍生物的小分子肽合成及抗肿瘤活性的研究

为了寻找更高效、更经济的抗肿瘤药物,以L-苯丙氨酸为起始原料,经氨基保护、酰胺缩合、脱保护、再缩合、再脱保护、再缩合等多步反应,设计并合成了8种新型苯丙氨酸衍生物的小分子肽,并采用FTIR、1H NMR、I3C NMR、HRMS和元素分析等测试方法对其结构进行确认.采用溴化噻唑蓝四氮唑法(MTT)比色法对所有目标化合物进行了抗肿瘤活性测试,测试结果表明,所有化合物对肝癌细胞SMC7721均有一定的抑制作用,其中化合物5e和8b对肝癌细胞的抑制作用最强.     

熊果酸-3’-取代丙醇酯衍生物的合成及抗肿瘤活性研究

熊果酸与1,3-二溴丙烷反应制得中间体熊果酸-3’-溴代丙醇酯(1),含溴醇酯1与含氮化合物反应,合成了系列熊果酸含氮衍生物2a～2j,均未见文献报道,其结构经1H NMR,13C NMR,IR,MS确认.初步的抗肿瘤生物活性研究表明,部分化合物的抗肿瘤活性与熊果酸相比均有提高,其中化合物2e具有更强的抑制活性.     

2-取代苯氨基喹唑啉衍生物的合成及抗肿瘤活性研究

以2,4-喹唑啉二酮为起始原料,通过氯代、Suzuki偶联和芳环亲核取代反应得到一系列2-取代苯氨基喹唑啉衍生物,并经~1H NMR,~(13)C NMR和HRMS进行结构确证.应用溴化噻唑蓝四氮唑(MTT)法对目标化合物进行了初步体外抗肿瘤细胞增殖活性研究.结果表明,部分化合物具有较好的体外抗肿瘤细胞增殖活性,其中活性化合物4u和4v对Hela,A549和MCF-7三种肿瘤细胞株的增殖均有明显抑制作用.     

氯硝柳胺衍生物的合成及抗肿瘤活性研究

以氯硝柳胺为起始原料,经醚化、亲核取代反应得到目标化合物,采用MTT法考察所合成化合物对人类乳腺癌细胞(MDA-MB-231)和人类胰腺癌细胞(ASPC-1)的体外抗肿瘤活性。合成了5个氯硝柳胺衍生物,其结构均经IR、1H-NMR、13C-NMR和MS确证。初步的体外抗肿瘤活性结果显示目标化合物9b和9c的抗肿瘤活性强于阳性对照药,其中化合物9b的活性对所测两种肿瘤株的抑制活性均强于阳性对照药,展现出较强的应用前景。     

17-(2′,5′-二取代噁唑基)-雄甾-4,16-二烯-3-酮的合成及抗肿瘤活性研究

以4-雄烯二酮1为原料,用金催化甾炔法设计并合成了一系列17-(2′,5′-二取代噁唑基)-雄甾-4,16-二烯-3-酮衍生物4a~4k.所合成产物通过1H NMR,13C NMR,IR和HRMS方法进行了结构表征.以阿比特龙为阳性对照,通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法测试了目标化合物对MCF-7(人乳腺癌细胞)、A549(人肺癌细胞)、Bel-7402(人肝癌细胞)、Hela(人宫颈癌细胞)和PC-3M-1E8(人前列腺癌细胞)的体外抗肿瘤活性.结果表明大多数化合物表现出了较好的抗肿瘤活性,其中化合物4c,4g,4i和4j的抗肿瘤活性与阳性对照物阿比特龙相当,且所测化合物对MCF-7有较好选择性作用,其IC50值在3.0~25.5μmol/L之间.     

Total Synthesis of Phakellistatin 13 by Solution Method

Since George R. Pettit’s group isolated cycloheptapeptide phakellistatin 1 from sponge1, over ten similar cyclic peptides have been obtained2-5. Phakellistatin 134 (Figure 1) is a cycloheptapeptide isolated from the brown snubby sponge from the South Chi…     

Total synthesis and modification of proline-rich cyclopeptides Phakellistatins 17 and 18 isolated from marine sponge

The Phakellistatins 17 and 18, two naturally occurring cyclic proline-rich peptides from marine sponge, were synthesized by utilizing a two-step solid-phase/solution synthesis strategy for the first time. Phakellistatin 18 exhibited a weak inhibitory activity against human lung carcinoma cell (A549) and human hepatoma (BEL-7042). In order to improve the activity of Phakellistatin 18, two of its analogues which contain sulfonyl fluoride group (P18-1) and arginine substituted derivative (P18-2) were also synthesized respectively. The spectral data of Phakellistatins 17 and 18 were identical to that reported for the natural products. Analogues P18-1 and P18-2 were identified by means of HR-QTOF-MS, ¹H NMR and ¹³C NMR. More importantly, analogue P18-1 exhibited significantly enhanced cytotoxicity against BEL-7042 cancer cells compared with Phakellistatin 18, suggesting that the sulfonyl fluoride group in the parent peptide may contribute to the improvement of antitumor activity. This strategy provides a reference method for improving the activity of natural peptides. reserved.     

Synthesis of phakellistatin 13 and oxidation to phakellistatin 3 and isophakellistatin 3

The natural product phakellistatin 13 cyclo-(TrpProPheGlyProThrLeu) was synthesized. Photosensitized oxidation of phakellistatin 13 gave the natural products phakellistatin 3 and isophakellistatin 3, demonstrating for the first time that a tryptophan residue can be directly converted to the corresponding 3a-hydroxypyrrolo[2,3-b]indoline in a full length peptide. Competitive oxidation of the indoline product was identified as the cause of low mass balance and is probably the source of low mass balance in the oxidative cyclization of all tryptamine derivatives. [reaction--see text]     

Two distinct conformers of the cyclic heptapeptide phakellistatin 2 isolated from the fijian marine sponge stylotellaaurantium

The isolation, structure determination, and solution conformation of two conformers of the cyclic heptapeptide phakellistatin 2 (cyclo-[Phe1-cis-Pro2-Ile3-Ile4-cis-Pro5-Tyr6-cis-Pro7]) isolated from the Fijian marine sponge Stylotella aurantium are reported. The conformers can be isolated separately by HPLC and are stable in methanol solution over a period of weeks as determined by NMR. Their NMR spectra and mass spectral fragmentation patterns differ significantly. Their solution conformations were determined by NOE-restrained molecular dynamics calculations and indicated that the two conformers had different folds, hydrogen bonding patterns, and solvent accessible surfaces. These factors may contribute to the independent stability of the two conformers, and may explain the variable biological activity previously reported for phakellistatin 2.     

Automated structure elucidation of organic molecules from (13)c NMR spectra using genetic algorithms and neural networks.

The automated structure elucidation of organic molecules from experimentally obtained properties is extended by an entirely new approach. A genetic algorithm is implemented that uses molecular constitution structures as individuals. With this approach, the structure of organic molecules can be optimized to meet experimental criteria, if in addition a fast and accurate method for the prediction of the used physical or chemical features is available. This is demonstrated using (13)C NMR spectrum as readily obtainable information. (13)C NMR chemical shift, intensity, and multiplicity information is available from (13)C NMR DEPT spectra. By means of artificial neural networks a fast and accurate method for calculating the (13)C NMR spectrum of the generated structures exists. The approach is limited by the size of the constitutional space that has to be searched and by the accuracy of the shift prediction for the unknown substance. The method is implemented and tested successfully for organic molecules with up to 20 non-hydrogen atoms.     

光谱法分析乙丙共聚物的序列结构及链节比

用FTIR, 1 H NMR和 13 C NMR分析乙丙共聚物的序列结构与链节比. 通过对乙丙共聚物 1 H NMR, 13 C NMR和 13 C-1 H二维核磁共振谱的综合分析, 提出了与前人不同的归属, 并提出了不同位置碳原子积分面积相关性分析方法, 该方法避免了烦琐的理论计算, 可简便地得到乙丙共聚物的主要序列结构. 通过比较 1 H NMR和 13 C NMR计算乙丙共聚物中乙烯、 丙烯链节比, 表明可以用 1 H NMR代替 13 C NMR完成对乙丙共聚物中乙烯、 丙烯链节比的定量计算.     

原位制备8-氘代奥美拉唑钠

奥美拉唑分子中的氮原子质子化,对邻近的碳核产生有效的电四极矩驰豫,使邻近碳核信号加宽或消失,以致奥美拉唑在DMSO-d6或DMSO-d6/D2O溶液中的碳谱(13CNMR、DEPT-90、DEPT-135)及碳-氢相关谱(HMQC、HMBC)具有非典型的特征,即部分碳原子不出峰且峰形很差,以致无法确定具体的碳数,延长脉冲重复时间无改观。本实验通过将奥美拉唑与NaOH的D2O溶液反应原位制备8-氘代奥美拉唑钠,使吡啶氮原子去质子化,从而使部分不出峰的碳核信号变窄或重又出现,顺利地完成了8-氘代奥美拉唑钠上述谱图的采集,间接地解决了奥美拉唑的碳谱分析,因而提供了一种可通用的测试苯骈咪唑类质子泵抑制剂碳谱及其二维相关谱的方法。     

Evidence of graphitic AB stacking order of graphite oxides

Graphite oxide (GO) samples were prepared by a simplified Brodie method. Hydroxyl, epoxide, carboxyl, and some alkyl functional groups are present in the GO, as identified by solid-state 13C NMR, Fourier-transform infrared spectroscopy, and X-ray photoemission spectroscopy. Starting with pyrolytic graphite (interlayer separation 3.36 A), the average interlayer distance after 1 h of reaction, as determined by X-ray diffraction, increased to 5.62 A and then increased with further oxidation to 7.37 A after 24 h. A smaller signal in 13C CPMAS NMR compared to that in 13C NMR suggests that carboxyl and alkyl groups are at the edges of the flakes of graphite oxide. Other aspects of the chemical bonding were assessed from the NMR and XPS data and are discussed. AB stacking of the layers in the GO was inferred from an electron diffraction study. The elemental composition of GO prepared using this simplified Brodie method is further discussed.     

Artarborol, a nor-caryophyllane sesquiterpene alcohol from Artemisia arborescens. stereostructure assignment through concurrence of NMR data and computational analysis

A nor-caryophyllane derivative, artarborol, has been isolated from wormwood (Artemisia arborescens) and its stereostructure established by using a combination of chemical derivatization, NMR data, molecular modeling, and quantum-mechanical calculations. In particular, comparison of experimental 13C NMR data with a Boltzmann-weighed average of 13C NMR chemical shifts, calculated by ab initio DFT method, supported the stereochemical assignment.     

Structure determination of a membrane protein in proteoliposomes

An NMR method for determining the three-dimensional structures of membrane proteins in proteoliposomes is demonstrated by determining the structure of MerFt, the 60-residue helix-loop-helix integral membrane core of the 81-residue mercury transporter MerF. The method merges elements of oriented sample (OS) solid-state NMR and magic angle spinning (MAS) solid-state NMR techniques to measure orientation restraints relative to a single external axis (the bilayer normal) from individual residues in a uniformly (13)C/(15)N labeled protein in unoriented liquid crystalline phospholipid bilayers. The method relies on the fast (>10(5) Hz) rotational diffusion of membrane proteins in bilayers to average the static chemical shift anisotropy and heteronuclear dipole-dipole coupling powder patterns to axially symmetric powder patterns with reduced frequency spans. The frequency associated with the parallel edge of such motionally averaged powder patterns is exactly the same as that measured from the single line resonance in the spectrum of a stationary sample that is macroscopically aligned parallel to the direction of the applied magnetic field. All data are collected on unoriented samples undergoing MAS. Averaging of the homonuclear (13)C/(13)C dipolar couplings, by MAS of the sample, enables the use of uniformly (13)C/(15)N labeled proteins, which provides enhanced sensitivity through direct (13)C detection as well as the use of multidimensional MAS solid-state NMR methods for resolving and assigning resonances. The unique feature of this method is the measurement of orientation restraints that enable the protein structure and orientation to be determined in unoriented proteoliposomes.