6-或7-（取代苯乙烯基）香豆素类化合物的合成及其抗癌活性的研究

目的：设计合成一系列苯乙烯基香豆素类化合物,并通过药理筛选寻找具有抗肿瘤活性的药物。方法：通过相转移Wittig反应得到目的物,利用几种药理模型进行体外抗肿瘤活性筛选。结果：合成了30个（I₁～II_I6）新的苯乙烯基香豆素类化合物并确定其构型。结论：药理筛选结果表明,7个化合物(I₂,I_4,II_2,II_2c,III_1a,III_2a,III_5a)对L-1210,HL-60,HCT-8,KB和Bel-7402细胞株有效,显示了一定的抗肿瘤活性。     

硫酸化胆汁酸水解酶基因BSS H1克隆、表达及活性

目的 从铜绿假单胞菌克隆出硫酸化胆汁酸水解酶(BSS)基因,并表达蛋白产物、研究其活性.方法 通过序列比对确定铜绿假单胞菌中的目的序列BSS H1;通过PCR扩增获得BSS H1基冈全序列,将其插入pET30b(+)载体,并将重组表达载体转化到大肠杆菌BL21(DE3)中诱导表达.通过优化诱导表达条件,实现重组蛋白BSS H1的高效表达;通过BSS-HSD酶联法初步研究其酶活性质.结果 工程菌扩大培养3h、以终浓度为1 mmol/L IPTG诱导5h时蛋白表达量最高;研究发现BSS H1能催化底物生成3α和3β两种构型的羟基胆汁酸,在pH 8.5时,其活性分别是(632±65) U/L和(52±4) U/L.结论 成功构建BSS H1高效表达菌株.BSS H1能催化生成两种立体异构体的特性在其他BSS中未见报道,其机制尚不明确,值得深入研究.     

正相高效液相色谱-荧光检测法同时测定植物油中的四种维生素E异构体

目的:建立正相高效液相色谱-荧光检测法测定植物油中的四种维生素E异构体。方法:采用Waters Sunfire硅胶柱(4.6 mm×250 mm,5μm),流动相为正己烷∶叔丁基甲醚∶2-甲基环丙烷=92∶8∶0.8,流速1.2 ml/min,柱温25℃,荧光检测器检测。结果:该方法测定四种维生素E的线性范围均为0.5μg/ml～100.0μg/ml,四种维生素E的检出限均为0.1μg/ml,加标回收率为92%～98%。结论:该方法操作简单、灵敏度高、回收率和重现性良好,结果准确可靠。     

头孢哌酮的质量研究

本文报道了从头孢哌酮合成母液中分离得到的产物被证实为头孢哌酮Ｓ型异构体，该异构体对２１株金葡球菌抗菌作用很弱，对包括１９株绿脓假单胞菌在内的四种革兰氏阴性杆菌几乎没有抗菌活性。为了控制产品质量，本文还介绍了Ｓ型异构体的测定方法。     

Pygo2、M2BPGi在慢性乙型肝炎肝纤维化患者血清中的表达及联合诊断价值

目的研究人尾肢同源蛋白2(Pygo2)、Mac-2结合蛋白糖基化异构体(M2BPGi)在慢性乙型肝炎肝纤维化患者中的诊断效能。 方法选取345例慢性乙型肝炎患者,根据病理活检肝纤维化分期结果,将患者分别纳入S0组(n＝49)、S1组(n＝94)、S2组(n＝53)、S3组(n＝87)及S4组(n＝62)。应用全自动酶标仪酶联免疫法检测血清Pygo2和M2BPGi水平,应用ROC曲线分析血清Pygo2和M2BPGi单独及联合检测预测慢性乙型肝炎肝纤维化分期的诊断效能。 结果检测血清Pygo2诊断S1的临界值为62.35 μg/L,灵敏度为79.73%,特异度为79.76%,药时曲线下面积(AUC)为0.826(95%CI 0.774~0.877);检测血清M2BPGi诊断S1的临界值为0.74 g/L,灵敏度为79.39%,特异度为76.78%,AUC为0.784(95%CI 0.758~0.810)。平行联合检测诊断S1的灵敏度为90.20%,特异度为73.21%,AUC为0.903(95%CI 0.804~0.918)。检测血清Pygo2诊断S2的临界值为78.65 μg/L,灵敏度为82.67%,特异度为79.39%,AUC为0.829(95%CI 0.779~0.867);检测血清M2BPGi诊断S2的临界值为1.01 g/L,灵敏度为79.70%,特异度为78.62%,AUC为0.793(95%CI 0.763~0.815)。平行联合检测诊断S2的灵敏度为90.59%,特异度为77.48%,AUC为0.908(95%CI 0.799~0.919)。 结论血清Pygo2和M2BPGi单独检测对慢性乙型肝炎肝纤维化临床诊断具有重要意义,且平行联合检测可提高肝纤维化诊断效能。     

LC-MS法研究盐酸克林霉素中的有关物质

目的:建立LC-MS方法检测盐酸克林霉素中有关物质,并利用质谱对有关物质进行初步鉴定。方法:液相色谱条件:色谱柱为Diamonsil C18(250 mm×4.6 mm,5μm);流动相为乙腈-四氢呋喃-水-无水甲酸(18∶3∶79∶0.2),氨水调pH为5.45±0.02;流速:1.0 mL.min-1;检测波长:210 nm;柱温为室温;质谱条件:电喷雾电离源正离子检测;源温80℃;锥孔电压35 V。结果:检测出盐酸克林霉素原料中6个有关物质,分别为林可霉素异构体(1)、林可霉素(2)、克林霉素B(3)、7-表克林霉素(4)、克林霉素异构体(5)及去氢克林霉素(6)。除林可霉素、克林霉素B和7-表克林霉素外,其余均未被各国药典收载。结论:本文采用液质联用法,灵敏度高,分离度好,能用于盐酸克林霉素的质量控制及其代谢产物的研究。     

End‐Group Selectivity of Low‐Molecular‐Weight Polystyrenes on a Carbon‐Clad Zirconia Stationary Phase in Reversed‐Phase HPLC

The separation of isomers of polystyrene oligomers was demonstrated on a carbon‐clad zirconia stationary phase in an acetonitrile mobile phase. The carbon‐clad zirconia surface gave considerably better resolution of isomers than a C18 surface, and the separation was sensitive to the end group of the oligomer. Oligomers with sec‐butyl end groups displayed almost twice as many isomers as the corresponding n‐butyl oligomer on the carbon‐clad zirconia surface. These additional bands could be explained by the stereochemistry of the sec‐butyl end group. In addition, the migration rate of the polystyrene isomers was dependent upon the end group, with n‐butyl polystyrenes displaying significantly greater retention on the carbon‐clad zirconia stationary phase. In comparison, the selectivity of conventional C18 columns could not discriminate between the n‐butyl and sec‐butyl end groups.     

Cationic Monomer‐Isomerization Polymerization of Oxetanes Having an Ester Substituent,to Give Poly(orthoester) or Polyether

This study shows the cationic monomer‐isomerization polymerization of 3‐R¹‐oxetanes ( 1 ) having a 3‐ester substituent (—CH₂OCOR²) through two ring‐opening routes (R¹ = CH₃, Ph; R² = Pr, Ph). The polymerization of 1 with Lewis acids usually gave poly(orthoester) ( 3 ) or polyether ( 4 ), together with bicyclic orthoester ( 2 ) as the isomerization product. The isomerization took place prior to polymerization, because of the preferable nucleophilic attack of the intermolecular carbonyl oxygen. Subsequently, 2 polymerized in either a single‐ or double‐ring‐opening manner depending on temperature. The single‐ring‐opening polymerization of 2 below room temperature was an equilibrium polymerization through bicyclic oxonium ends leading to 3 , and the thermodynamic parameters were estimated according to Dainton's equation. Thus, Corey's orthoester synthesis from ester‐substituted oxetanes is regarded as a phenomenon in the equilibrium polymerization only around the ceiling temperature (T_c). Above T_c, 2 brought about the double‐ring‐opening polymerization through monocyclic diaoxacarbenium ends to afford 4 . Relatively bulky R¹ and R² such as the Ph group exerted a large steric effect on both polymerization routes. As a special case arising from this effect, the CF₃SO₃H‐catalyzed reaction of 1 c (R¹, R² = Ph) resulted in an unusual cyclodimerization accompanied by the elimination of benzoic acid, owing to the susceptibility of the neophyl skeleton to cation transfer.     

Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer

Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.     

氯喹异构体的分离和鉴别

从磷酸氯喹的粗品重结晶母液中，通过离解萃取法分离提纯得到其结构同分异构体５－氯－４－（４－二乙胺基－１－甲基丁胺基）喹啉。其结构经ＭＳ、１ＨＮＭＲ和１３ＣＮＭＲ验证。