1株红树来源真菌Daldinia eschscholtzii HJ001 的活性次级代谢产物研究

目的 研究1株红树尖瓣海莲来源内生真菌Daldinia eschscholtzii HJ001的次级代谢产物及其生物活性。方法 综合运用硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备HPLC等色谱分离技术对菌株的发酵产物进行分离纯化,通过NMR、MS、旋光等多种现代波谱技术以及与文献数据对照,确定化合物的结构,对化合物进行抗氧化活性和α-葡萄糖苷酶测试。结果 从红树来源内生真菌D. eschscholtzii HJ001中分离得到8个化合物（1~8）,结构分别确定为sulochrin（1）、(4R)-O-methylsclerone（2）、(R)-(-)-mellein methyl ether（3）、helicascolide A（4）、kojic acid（5）、uracil（6）、cyclo（L-4-Hyp-L-pro）（7）、?ethyl β-D-xylopyranoside（8）,除化合物4外,其余化合物均首次从Daldinia属中分离得到。?结论 化合物5显示强的抗氧化活性,IC50值为11.9 μmol·L?1,强于阳性对照Trolox（IC50 = 26.6 μmol·L?1）。     

长柱金丝桃的化学成分研究

目的研究长柱金丝桃的化学成分。方法利用硅胶柱色谱、高效液相色谱等技术对长柱金丝桃甲醇提取物进行分离纯化,通过波谱数据分析鉴定其化学结构,利用噻唑蓝(MTT)法测试化合物抗肿瘤活性。结果从长柱金丝桃中共分离出10个化合物,均无抗肿瘤活性,分别鉴定为:isodauc-6-ene-10β,14-diol(1)、10-oxoisodauc-3-en-15-al(2)、10β-hydroxyisodauc-6-en-14-al(3)、artabotrol(4)、saniculamoid B(5)、1β-6α-dihydroxy-4(15)endesmene(6)、5-epi-eudesm-4(15)-eno-1β,6β-diol(7)、15-hydroxu-T-muurolol(8)、oplopanone(9)、larixol(10)。结论化合物1~10均为首次从该属植物中分离得到。     

圆滑番荔枝树皮中的化学成分

目的对番荔枝科植物圆滑番荔枝(Annona glabraLinn.)树皮的化学成分进行分离、鉴定。方法采用硅胶柱、色谱等分离手段;利用理化性质与波谱技术对化合物进行鉴定。结果分得7个化合物,经鉴定为:ent-kauran-16α,17-diol(1),16-αH-ent-kauran-17-oic acid(2),19-hydroxy-16-α(-)-kauran-17-oic acid(3),16-αhydro-19-acetoxy-ent-kauran-17-oic acid(4),liriodenine(5),β-谷甾醇(-βsitosterol,6)和胡萝卜苷(daucosterol,7)。结论化合物26、、7为首次从该植物中分离得到。     

一株红树内生真菌Phomopsis sp. MGF222次级代谢产物及其活性研究

目的 研究一株红树植物木果楝（Xylocarpus granatum Koenig）来源内生真菌Phomopsis sp. MGF222的次级代谢产物及其生物活性。方法 利用硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备HPLC等色谱分离方法，对该菌发酵产物的乙酸乙酯浸膏的次级代谢产物进行分离纯化；综合利用NMR、MS等波谱解析方法以及与文献数据对照，鉴定化合物的结构；并对化合物进行抗菌和α-葡萄糖苷酶抑制活性评价。结果 从内生真菌Phomopsis sp. MGF222中分离鉴定9个化合物(1~9)，结构分别为12-epicitreoisocoumarinol (1)，5-hydroxy-7methoxy-4methylphthalide (2)，5-hydroxy-7-methoxy-4,6-dimethylphthalide (3)，(2-(2"-hydroxypropyl)-5-methyl-7-hydroxychromone (4)，tyrosol (5)，2-hydroxy-benzaldehyde (6)，5-hydroxymethyl-pyrrole-2-carbaldehyde (7)，(2S,2"R,3R,4E,8E,3"E)-2-(2"-hydroxy-3"-octadecenoylamino)-9-methyl-4,8-octadecadiene-l,3-diol (8)，(22E,24S)-5,8-epidioxy-24-methyl-cholesta-6,9(11),22-trien-3-ol (9)；其中化合物9对白色念珠菌Canidia albicans显示抗菌活性；化合物2, 5和8具有α-葡萄糖苷酶抑制活性。结论 发现1个具有抗菌活性和3个具有α-葡萄糖苷酶抑制活性的化合物，具有重要的研究和应用价值。     

圆滑番荔枝的化学成分研究

目的从番荔枝科植物圆滑番荔枝(annona glabra linn)树皮中分离其化学成分并进行成分分析.方法采用柱层析和红外、核磁共振、质谱仪等进行结构分析.结果分离到6个化合物,其中5个为贝壳杉烷型二萜,1个为生物碱.根据理化性质和波谱特征鉴定其为萜Ⅰ、Ⅱ分别为ent-19-carbomethoxykauran-17-oic acid、19-hydroxy-16α-(-)-kauran-17-oic acid,生物碱Ⅰ、Ⅱ分别为liriodenine、oxoglaucine.结论其中萜Ⅰ ent-19-carbomethoxykauran-17-oic acid、萜Ⅱ19-hydroxy-16α-(一)-kauran-17-oic acid和生物碱Ⅱoxoglaucine为首次从该植物中分得.     

一株红树内生真菌Penicillium sp. JY246次级代谢产物及其活性研究

目的 研究一株红树角果木来源内生真菌Penicillium sp. JY246的次级代谢产物及其生物活性。方法 利用硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备HPLC等方法,对该菌发酵产物的乙酸乙酯浸膏进行分离纯化;利用NMR、MS等波谱解析方法以及与文献数据对照,鉴定化合物的结构;通过抗菌和抗虫活性模型对化合物的生物活性进行评价。结果 从内生真菌Penicillium sp. JY246中分离得到12个化合物,分别为7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (1),(2′S)-2-(propan-2′-ol)-5-hydroxy-benzopyran-4-one (2),2, 3-dihydro-5-hydroxy-2(S)-methyl-4H-1-benzopyran-4-one (3),(11S)-diaprothin (4),questin (5),4-hydroxy-3-prenylbenzoic acid (6),4-methoxy-6-styryl-pyran-2-one (7),(R) 4-hydroxy-2-oxo-1-pyrrolidineacetamide (8),p-hydroxy-benzaldehyde (9),4-hydroxyacetophenone (10),apocynin (11)和1-(2,6-dihydroxyphenyl) ethan-1-one (12)。结论 从内生真菌Penicillium sp. JY246的次级代谢产物中分离得到12个单体化合物,并对所有化合物进行抗菌和抗虫活性测试。结果表明,化合物1, 2, 4和5显示抗细菌活性;化合物4, 5和8对棉铃虫幼虫显示了生长抑制活性。     

紫丁香叶三萜类化学成分研究

目的研究木犀科丁香属植物紫丁香(Syringa oblata Lindl.)叶的化学成分。方法利用硅胶柱色谱法、Sephadex LH-20凝胶柱色谱法、中压柱层析及半制备高效液相色谱等方法分离纯化;通过核磁共振谱、质谱等光谱数据鉴定化合物结构。结果分离得到8个三萜类化合物,分别鉴定为Maslinic acid(1),3β-O-trans-p-coumaroyl maslinic acid(2),3β-O-cis-p-coumaroyl maslinic acid(3),2α-Hydroxy ursolic acid(4),3β-O-trans-p-coumaroyloxy-2α-hydroxyurs-12-en-28-oic acid(5),3β-O-cis-p-coumaroyloxy-2α-hydroxyurs-12-en-28-oic acid(6),3β-O-trans-p-coumaroyl tormentic acid(7),3β-O-cis-p-coumaroyl tormentic acid(8)。结论化合物1～8均为首次从丁香属植物中分离得到。     

红树植物拟海桑(Sonneratia paracaseolaris)化学成分研究

目的研究红树植物拟海桑Sonneratia paracaseolaris的化学成分。方法利用硅胶柱层析、凝胶Sephadex LH-20柱层析、HPLC等手段对化学成分进行了分离纯化;通过理化性质,结合波谱数据分析并与文献对照,鉴定化合物的结构,分别以MTT和SRB法评价化合物的抗肿瘤活性。结果从红树植物拟海桑Sonneratia paracaseolaris的甲醇提取物中,分离鉴定了9个单体化合物:9-氧橙花叔酮(1),3,7,11-三甲基-1,7(E),10-十二碳三烯-3-羟基-9-酮(2),(22E,24R)-5α,8α-过氧化麦角甾-23-甲基-6,22-二烯-3β-醇(3),(22...     

中国南海侧扁软柳珊瑚Subergorgia suberosa次级代谢产物

目的研究中国南海侧扁软柳珊瑚Subergorgia suberosa的次级代谢产物。方法利用硅胶柱层析、Sephadex LH-20凝胶柱层析、HPLC等方法对化合物进行分离纯化;利用NMR,MS等波谱方法,并与文献对照,鉴定化合物的结构;利用抗菌活性模型和卤虫致死活性模型评价化合物的生物活性。结果从侧扁软柳珊瑚中分离鉴定了6个单体化合物,分别为:倍半萜化合物subergorgic acid(1),2-β-hydroxysubergorgic acid(2)和2-β-acetoxysubergorgic acid(3);甾体化合物3β-hydroxy-5α-pregnan-20-one(4),5α-pregnane-3,20-di-one(5)和胆甾醇(6)。结论化合物1～3对白色葡萄球菌Staphylococcus albus均显示出较强的抑制活性,化合物4对蜡状芽孢杆菌Bacillus cereus显示出较强的抑制活性,而化合物4和5显示出较强的卤虫致死活性。     

绿舒筋化学成分研究

目的 分离、鉴定绿舒筋活性化学成分。方法 采用反复硅胶柱色谱和Sephadex LH 20凝胶柱色谱对绿舒筋中化合物进行分离得到单体,应用理化常数测定和现代波谱方法鉴定其化学结构。结果 从绿舒筋中分离并鉴定了6个化合物：雷公藤内酯甲（wilforlide A , I）,雷公藤内酯乙（wilforlide B, II）, 齐墩果-12-烯-3,29-二醇(olean-12-en-3,29-diol, III),3-羟基-2-氧代-无羁萜烯-29-酸(3-hydroxy-2-oxo-3-fridelen-20α-carboxylic acid, IV),3β,22α-二羟基-△12-齐墩果烯-29-羧酸(3β,22α-dihydroxy-olean-12-en-29-oic-acid, V),β-谷甾醇 (β-sitosterol, VI)。结论化合物V为首次从该植物中分离得到。     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

血管内皮生长因子的异常与子(癎)前期发病的关系

目的:研究血浆可溶性细胞间黏附分子-1(sICAM-1)浓度和胎盘组织血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)及其血管内皮生长因子受体1(VEGFR1,Flt-1)、可溶性血管内皮生长因子受体1(sVEGFR1,sFlt-1)mRNA的表达与子前期的关系.方法:采用酶联免疫吸附测定法(ELISA)检测45例子前期患者和45例健康产妇血清sICAM-1的浓度,逆转录-聚合酶链反应(RT-PCR)方法检测胎盘组织中VEGF、PLGF、Flt-1、sFlt-1 mRNA的表达.结果:(1)子前期组sICAM-1水平为(218.45±29.93) μg/L,显著高于对照组的(168.84±19.39) μg/L(P < 0.01).(2)子前期患者胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量显著高于对照组(均P < 0.01).(3)血清sICAM-1浓度与胎盘组织中sFlt-1mRNA的相对表达量呈正相关(r = 0.90,P < 0.01).结论:子前期患者血清sICAM-1浓度升高,其胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量也升高.胎盘组织sFlt-1mRNA的高表达与子前期内皮损伤等有密切关系.     

Antiparasitic protozoan vaccines

Parasitic infections caused by pathogenic protozoa affect over 1 billion people worldwide and impose a substantial health and economic burden, particularly on inter-tropical less-developed countries where they are more prevalent. Despite encouraging progress in vaccine development, chemotherapy remains the single most effective, efficient and inexpensive means to control most parasitic infections [1]. However, day to day parasites are becoming increasingly resistant to drugs currently in use, such as Plasmodium towards chloroquine, lending to the start of a promising future for vaccines. Patent applications regarding vaccines for the prevention, control and diagnosis of parasitic protozoan infections are reviewed for the period December 1996 - October 2000. However, vaccines for some of the protozoan infections do not appear in the literature in the period reviewed; only, vaccines against malaria, leishmaniasis, trypanosomiasis, cryptosporidiosis, pneumocystosis, eimeriosis, toxoplasmosis and neosporosis, as well as Babesia microti infections have been found.     

Binding affinity in drug design: experimental and computational techniques

ABSTRACT

Introduction: In pharmaceutical design where future drugs are developed by targeting a specific chosen protein, the evaluation of ligand affinity is crucial. For this very purpose are a multitude of diverse methods which are continuously being improved, which, in turn, makes it difficult to choose which techniques to use in practice.

Areas covered: In this review, the authors discuss both experimental and computational approaches for affinity evaluation. Basic principles, general limitations and advantages, as well as main areas of application in drug discovery, are overviewed for some of the most popular ligand binding assays. The authors further provide a guide to affinity predictions, collectively covering several techniques that are used in the first stages of rational drug design.

Expert opinion: All affinity estimation methods have limitations and advantages that partially overlap and complement one another. Some of the suggested best practices include cross-verification of data using at least two different techniques and careful data interpretation.