氟代胆碱类化合物的合成及其抗肿瘤活性的研究

以甲二醇二对甲苯磺酸酯和重氮乙酸乙酯为起始原料 ,经取代、还原、甲基化、磷酸化反应合成了 5个氟代胆碱类化合物 ,经1H NMR及质谱确证了结构 ,并进行了抗肿瘤活性的细胞筛选实验。结果表明这 5个化合物均具有一定的抗肿瘤活性。其中FC 3对 4种癌细胞均具有较好的抑制作用 ,值得进一步进行活性筛选     

2-(4-三氟甲基苯基)-4-乙基-呋喃-3-酰胺衍生物的设计、合成及其抗肿瘤活性研究

目的 设计、合成新型抗肿瘤的2-（4-三氟甲基苯基）-4-乙基-呋喃-3-酰胺衍生物.方法 以对三氟甲基苯甲醛和丙二酸二乙酯为起始原料,经缩合、环合、酰氯化及胺解等4步反应,合成系列目标化合物.结果 设计合成了15个目标化合物,并对其进行了4种肿瘤细胞A549、QGY、HeLa和SW480的活性测试.结论 显示出较好的抗肿瘤活性,化合物5b显示出最优的高效、广谱抗肿瘤活性,值得深入研究.     

沙利度胺衍生物的设计合成及其抗肿瘤活性研究

目的设计合成1，3-二氢-1，3-二氧代．2H-异吲哚-N-取代沙利度胺衍生物。并对其进行体外抗肿瘤活性测试。方法以2．氨基-β-D-吡喃葡萄糖盐酸盐为原料，经过6步反应得到化合物N-（3’，4’，6＇-三乙酰-1’-溴代吡喃葡萄糖）-1,3-二氢-1，3-二氧代-2H-异吲哚，该化合物经过溴代、取代反应得到目标化合物。通过对4T1细胞存活率的测试测定20个目标化合物体外抗肿瘤活性。结果设计合成的20个目标化合物均未见文献报道。所有化合物均经过1H-NMR谱确证，部分化合物经IR、MS谱确证。结论所有目标化合物对4T1细胞均具有-定的抑制生长作用。表明所合成的沙利度胺衍生物均有-定的抗肿瘤活性。     

新型PARP-1抑制剂的合成及体外抗肿瘤活性研究

目的设计合成2个系列新型聚腺苷二磷酸核糖聚合酶-1(PARP-1)抑制剂并测定其体外抗肿瘤细胞增殖活性。方法以上市药物为先导化合物,设计合成了系列以6,8-二氟-2-硫代-2,3-二氢喹唑啉-4(1H)-酮及6-氟-2-硫代-2,3-二氢吡啶并[2,3-d]嘧啶-4(1H)-酮为母核结构的化合物。采用Alarm Blue法测定目标化合物对体外培养的人源乳腺癌细胞MDA-MB-436的增殖抑制作用。结果与结论合成了10个未见文献报道的新化合物,其结构经~1H-NMR、~(13)C-NMR、质谱确证。初步体外细胞活性结果表明,目标化合物对MDA-MB-436细胞具有一定的增殖抑制作用(IC_(50)值为14.1～1 246 nmol·L~(-1));具有6,8-二氟-2-硫代-2,3-二氢喹唑啉-4(1H)-酮母核的目标化合物16a～16e对MDA-MB-436细胞的抑制活性普遍高于目标物16f～16j,其中,化合物16c的抑制活性略低于阳性对照药奥拉帕尼;6,8-二氟-2-硫代-2,3-二氢喹唑啉-4(1H)-酮母核具有一定的抑制肿瘤增殖活性,可为化合物进一步的结构修饰提供参考依据。     

卟啉介导抗癌药物的合成及其活性研究

目的设计合成新型替加氟卟啉化合物及其金属络合物，并评价其抗肿瘤活性。方法根据卟啉对肿瘤组织的选择性滞留作用，设计了3个卟啉替加氟化合物及3个金属络合物，并以吡咯和取代苯甲醛为原料经4步反应以满意的收率得到目标化合物。采用MTT法，以替加氟为阳性对照药，评价目标化合物对人结肠癌Lovo细胞株和人肝癌SMCC-7721细胞株的抗肿瘤活性；同时通过裸鼠体内抗肿瘤实验进一步评价金属络合物4b的体内抗肿瘤活性。结果合成了6个未见文献报道的新化合物，其结构经IR、UV-vis、1^H-NMR、MS及元素分析确证；体外活性实验表明，3个卟啉替加氟化合物表现出与替加氟相似的抗肿瘤活性，而3个金属络合物的抗肿瘤活性却是替加氟的两倍；金属络合物4b的体内肿瘤抑制率达70．4％。结论通过金属卟啉结构单元的引入可明显提高替加氟的抗肿瘤活性。     

1,4-二［3-(氨基硫代甲酰硫基)丙酰基］哌嗪类化合物的合成及其抗肿瘤活性

目的　寻找并合成低毒、有较强抗肿瘤活性的哌嗪类化合物。方法和结果　以1,4-二(3-溴丙酰基)哌嗪为先导物,合成了一系列1,4-二［3-(氨基硫代甲酰硫基)丙酰基］哌嗪类新化合物,并测试了这些化合物(4a-j)对8种瘤细胞株的体外抗肿瘤活性。结论　体外抗肿瘤活性试验结果表明,大多数化合物显示一定的抗肿瘤活性,尤其是化合物4c,4d和4e,浓度在10μmol.L^-1时,对HL-60细胞抑制率分别为44%,90%和70%。     

3,4-二氢-4-芳基香豆素类化合物的合成及其生物活性研究

目的 设计合成一系列3,4-二氢4-芳基香豆素类化合物,并评价其抗氧化、抗肿瘤活性.方法 以取代苯甲醛为原料,经缩合及Ponndorf反应制得目标化合物.采用DPPH法测定目标化合物的抗氧化活性;采用MTT法以胃癌细胞BGC-823为测试细胞株对目标化合物进行体外抗肿瘤活性评价.结果 与结论合成了10个新的3,4-二氢...     

取代4-苯乙烯基香豆素的合成及其抗肿瘤活性

目的为寻找有抗肿瘤活性的物质,设计并合成了一系列取代4-苯乙烯基香豆素化合物。方法用相转移Wittig反应和Horner反应得目的物,用¹HNMR,MS和元素分析确证其结构;用HL-60,KB,HCT-8和Bel-7402进行体外细胞毒活性筛选。结果所合成的20个(1-20)4-苯乙烯基香豆素为新化合物。化合物18对KB细胞株有效。结论化合物18显示了抗肿瘤活性,值得进一步研究。     

葡萄糖苯丙苷类化合物的合成及其抗肿瘤活性

目的设计合成葡萄糖苯丙苷衍生物，并寻求具有抗肿瘤活性的新化合物。方法四乙酰基溴代葡萄糖与醇经过成苷、脱保护、与苯甲醛缩合3步反应得到目标化合物。以A431（人表皮鳞癌细胞）、A549（人肺腺癌细胞）、7721（人肝癌细胞）3种肿瘤细胞为测试细胞株，采用M1vr法评价了目标化合物的抗肿瘤活性。结果与结论合成了19个糖苷衍生物，其结构均经。H—NMR确证。体外抗肿瘤活性实验表明，4，6-O-亚苄基β－D－吡喃葡萄糖－3－（4－甲氧基苯基）丙苷（1j）显示出较好的抗肿瘤活性。     

4-芳胺基-6-烷氧基蝶啶类化合物的合成与抗肿瘤活性

目的合成一系列4-(N-芳基)胺基-6-烷氧基取代蝶啶类化合物,并测试其对A549、VX-2肿瘤细胞的增殖抑制作用。方法以3-氨基吡嗪-2-羧酸甲酯为起始底物,经氨化、卤代、合环、取代等反应合成目标化合物,采用系列波谱手段(IR、核磁共振氢谱、质谱)进行结构表征,并进行体外抗肿瘤活性实验。结果采用微波合成法进行芳胺化反应,合成16种目标化合物,其结构均未见文献报道。化合物7p对VX-2细胞的抑制活性最高(IC50值14. 28μmol·L~(-1)),活性与阳性对照物吉非替尼和伊马替尼相当。结论目标化合物7p显示出良好的抗肿瘤活性,值得进一步深入研究。     

Cancer chemopreventive activity of terpenoid coumarins from Ferula species

Several natural products have been found to have anti-tumor promoting activity. In the present study, we carried out a primary screening of ten terpenoid coumarins isolated from plants of the Ferula species, examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. Auraptene (7-geranyloxycoumarin, 1) and umbelliprenin (7-farnesyloxycoumarin, 2) were found to significantly inhibit EBV-EA activation and preserved the high viability of Raji cells, suggesting that they might be valuable anti-tumor-promoting agents (IC (50) 8.3 and 9.1 nM, respectively). Our findings revealed that the presence of a prenyl moiety in the terpenoid coumarins plays an important role in anti-tumor promoting activity as previously reported for xanthones, coumarins, flavonoids and phenylpropanoids.     

复方灵芝胶囊的抗肿瘤作用研究

目的:研究复方灵芝胶囊的抗肿瘤作用。方法:观察复方灵芝胶囊(9.00、4.50、2.25g·kg-1)对3种肿瘤细胞(S180肉瘤细胞、H22肝癌细胞与Lewis肺癌细胞)的抑制作用及与注射用环磷酰胺(CTX)、5-氟尿嘧啶(5-Fu)联合用药对S180肉瘤细胞的抑制作用。结果:9.00、4.50、2.25g·kg-1复方灵芝胶囊对小鼠S180肉瘤细胞、H22肝癌细胞与Lewis肺癌细胞生长均具有一定的抑制作用。9.00、4.50、2.25g·kg-1复方灵芝胶囊与0.01g·kg-1的CTX或5-Fu合用,与单用0.01g·kg-1CTX或5-Fu比较,对S180肿瘤的生长抑制作用更强。结论:复方灵芝胶囊对3种肿瘤的生长均有一定的抑制作用,与化疗药合用有协同作用。     

竹类植物化学成分及药理活性研究进展

竹类植物主要包含黄酮、萜、醇、醛、酚酸、木质素、挥发油、香豆素、生物碱、核苷类等多类别化学成分,药理活性主要表现为抗氧化、抗炎、抗菌、抗抑郁、抗疲劳、抗肿瘤等作用。竹类植物所含化学成分类别众多,药理活性多样,值得继续深入研究。     

Antimycotic drugs, IX: Fluorinated 2-benzylthiopyrimidines (author's transl)]

Antimycotic Drugs, IX: Fluorinated 2-Benzylthiopyrimidines By condensation of benzylisothiourea (1) with the fluorinated β-diketones 2a-g , the fluorinated 2-benzylthiopyrimidines 3a-g were obtained. Compound 3b exhibits antimycotic activity.     

Inhibitory effects of 1,3‐thiazine derivatives on melanogenesis

Objectives The aim of this study was to identify a novel skin‐depigmenting agent from synthetic 1,3‐thiazine derivatives. Methods We investigated the inhibitory effects of six kinds of 1,3‐thiazine derivative on melanogenesis by examining their effects on tyrosinase activity and melanin biosynthesis in melan‐a cells and the zebrafish model. Key findings Of the six compounds, 4‐hydroxy‐2,6‐dimethyl‐5,6‐dihydro‐4H‐1,3‐thiazine (TZ‐6) had the strongest anti‐melanogenic effects in cultured melan‐a cells (30.4% inhibition at 100 μM). In addition, TZ‐6 exhibited an inhibitory effect on mushroom and cellular tyrosinase. Based on the results of Western blotting, TZ‐6 reduced the expression of tyrosinase at 100 mM. Additionally, TZ‐6 reduced body pigmentation and inhibited tyrosinase activity in the zebrafish model. Conclusions The results have provided useful information for the development of a skin whitening agent.     

通光藤化学成分及抗肿瘤活性研究

目的 提取分离并筛选通光藤中具有抗肿瘤活性的化学成分,并研究其化学结构。方法 系统溶剂法对通光藤药材进行化学部位分离,并利用色谱法对正丁醇部位中的化学成分进行分离和纯化,利用波谱学方法鉴定其化学结构。MTT法筛选所得化学成分体外对8种人癌细胞增殖的抑制作用。结果 在通光藤正丁醇部位中得到3个化学成分单体分别为：牛奶菜醇（化合物1）、通光藤苷元B（化合物2）、大叶牛奶菜苷丁（化合物3）,化合物2对于MGC-803肿瘤细胞抑制作用较强,IC50为80.3μg.mL 1,而化合物3对于ISMMC-7721肿瘤细胞液表现出较强抑制作用,IC50为40.7μg.mL 1。结论 化合物2为首次在该植物中分离到的苷元成分。化合物2、3体外对肿瘤细胞具有显著的抑制活性。     

Blocking effect of anti-Dectin-1 antibodies on the anti-tumor activity of 1,3-beta-glucan and the binding of Dectin-1 to 1,3-beta-glucan

Schizophyllan (SPG) is used to treat cervical cancer in combination with irradiation to enhance the immunological surveillance system. Dectin-1 is a cell surface receptor for 1,3-beta-glucan. In this study, we prepared two anti-Dectin-1 monoclonal antibodies, 4B2 and SC30 having a K(D) of 7.04 x 10(-8) M and 1.55 x 10(-7) M, respectively, and evaluated the role of Dectin-1 in SPG-induced anti-tumor activity in mice. Expression of Dectin-1 on peritoneal macrophages and binding of SPG to the cells were decreased by administration of 4B2 and SC30. SPG-mediated anti-tumor activity was inhibited by 4B2 and SC30. 4B2 and SC30 inhibited the binding of SPG to splenocytes from mice. The binding of SPG-biotin to Dectin-1-transfected HEK293 cells was inhibited by 4B2, but not SC30. 4B2 and SC30 differ in their influence on Dectin-1 between primary cells and transduced cells, and Dectin-1 effects 1,3-beta-glucan-mediated anti-tumor activity in mice by binding to SPG.     

Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.     

Coumarinic derivatives show anti-inflammatory effects on alveolar macrophages, but their anti-elastase activity is essential to reduce lung inflammation in vivo

We have previously demonstrated the potency of coumarinic derivatives to inhibit human leukocyte elastase. Given the anti-inflammatory activities of some coumarins, we investigated the capacity of our coumarinic derivatives to inhibit inflammation and whether their anti-elastase activity was essential for their anti-inflammatory functions. All compounds studied were coumarinic derivatives displaying differential anti-proteinase activity. Coumarinic derivatives 1, 2, and 3 efficiently inhibited human leukocyte elastase in vitro, whereas the coumarinic derivative 4 did not show inhibitory activity. The anti-inflammatory effect of these compounds and a coumarin control, scopoletin, on interleukin-6 (IL-6), tumor necrosis factor (TNF), and macrophage chemotactic protein-1 (MCP-1) release was studied using lipopolysaccharide (LPS)-stimulated alveolar macrophages. The in vivo effect of compound 2, that inhibits elastase, and compound 4, that does not show proteinase inhibition, was investigated using a mouse model of LPS-induced lung inflammation and elastase-induced acute lung injury. All investigated coumarinic derivatives, regardless of their anti-proteinase activity, significantly inhibited IL-6 and TNF production by LPS-stimulated alveolar macrophages. However, only compounds 2, 3, and 4 significantly reduced MCP-1 release. Compound 2 attenuated LPS-induced leukocyte recruitment in bronchoalveolar lavage, whereas no inhibition was observed with compound 4 devoid of elastase inhibitory capacity. Interestingly, MCP-1 level was reduced in bronchoalveolar lavage of compound 4 treated mice, whereas TNF and IL-6 levels were not modulated by coumarins. Furthermore, compound 2, but not 4, reduced elastase induced lung injury. Our data suggest that although coumarinic derivatives have anti-inflammatory properties, their anti-elastase activity is essential to reduce lung inflammation in vivo.