海绵Dysideidae sp.中的两个溴代酚类化合物

利用各种层析手段,从海绵Dysideidae sp.的正丁醇部分纯化了两个溴代酚类化合物,通过各种波谱数据鉴定为3,4,5-三溴-2-(2,′4′-二溴-苯氧基)-苯酚(1)和3,4,5,6-四溴-2-(2,′4′-二溴-苯氧基)-苯酚(2)。     

锡尾矿链霉菌AE21985代谢产物的分离与鉴定

采用硅胶柱、凝胶柱层析、高效液相制备等方法从分离自云南锡尾矿土壤的链霉菌AE21985发酵液中分离到19个化合物,通过波谱学方法鉴定为11个环二肽类化合物:3-(4-羟基苄基)-6-(1H-吲哚-3-基甲基)哌嗪-2,5-二酮(1)、(3S,6S)-3-((R)-仲-丁基)-6-甲基哌嗪-2,5-二酮(2)、(3S)-3-苄基哌嗪-2,5-二酮(3)、(3S,6S)-3-(2-甲基丙基)-6-(丙-2-基)哌嗪-2,5-二酮(4)、3-异丁基六吡咯并[1,2-α]吡嗪-1,4-二酮(5)、(3S,6S)-3-((R)-仲-丁基)-6-甲基哌嗪-2,5-二酮(6)、(3S,6S)-3-异丙基-6-甲基哌嗪-2,5-二酮(7)、(3S,7R,9S)-7-羟基-3-异丁基六吡咯并[1,2-α]吡嗪-1,4-二酮(8)、3-(1H-吲哚-3-基甲基)-6-(丙-2-基)哌嗪-2,5-二酮(9)、(3S,8a S)-3-(丙-2-基)六氢吡咯并[1,2-α]吡嗪-1,4-二酮(10)及(3S,6S)-3-苄基-6-甲基哌嗪-2,5-二酮(11);5个酰胺类化合物:(2E)-3-苯基丙-2-烯酰胺(12)、3-苯基丙酰胺(13)、2-苯基乙酰胺(14)、苯甲酰胺(15)及3-(1H-吲哚-3-基)丙酰胺(16);1个生物碱类物质:1H-吲哚-5-甲醛(17);2个核苷类物质:尿苷(18)及胸腺嘧啶(19)。这些化合物均为首次从该菌株中发现。     

买麻藤化学成分的研究

从买麻藤(Gnetum montanum Markgr)的藤茎中分离鉴定出4个新化合物:2-羟基(?)甲氧基-4-甲氧羰基吡咯(1),2-羟基-3-甲氧甲基-4-甲氧羰基吡咯(2),3,4-二羟基-4-(?)氧基二苄醚(3)和3,3',4'-三羟基-4-甲氧基二苄醚(4)以及两个已知化合物2,3-二苯基吡咯(5)和胺甲基甲醇(6)。化合物(1)、(2)和(6)是以盐酸盐形式分离得到。     

细花线纹香茶菜的化学成分研究

用色谱技术对细花线纹香茶菜(Isodon lophanthoides var.graciliflora)全草水提物进行分离纯化,获得了11种单体化合物。通过光谱分析及与文献数据对照,分别鉴定为牡荆素(vitexin,1)、藿香黄酮醇(pachypodol,2)、猫眼草黄素(chrysoplenetin,3)、9-羟基-5,7-豆甾二烯-4-酮(9-hydroxy-5,7-megastigmadien-4-one,4)、3,9-二羟基-5,7-豆甾二烯-4-酮(3,9-dihydroxy-5,7-megastigmadien-4-one,5)、黑麦草内酯(loliolide,6)、4-乙酰-5-甲基二氢呋喃-2-酮(4-acetyl-5-methyldihydrofuran-2-one,7)、5-羟甲基糠醛(5-hydroxymethylfuraldehyde,8)、5-甲氧甲基-1H-吡咯-2-甲醛(5-methoxymethyl-1H-pyrrole-2-carbaldehyde,9)、3-吲哚甲醛(indole-3-aldehyde,10)和丁二酸单丁酯(succini cacid monobutyl ester,11)。这些化合物均为首次从线纹香茶菜中分离得到。     

IQGAP1高表达抑制食管鳞癌细胞对顺铂化疗的敏感性

本文旨在研究含IQ模序的GTP酶激活蛋白1(IQ motif containing GTPase-activating protein 1,IQGAP1)过表达或基因干扰是否影响食管鳞癌细胞对顺铂化疗的敏感性。质粒转染构建IQGAP1高表达和基因干扰的稳定细胞系,并采用Western blot进行鉴定。然后,采用不同浓度(2.5μmol/L、5μmol/L、10μmol/L、20μmol/L、40μmol/L)的顺铂处理细胞,通过3-(4,5-二甲基-2-噻唑)-2,5-二苯基溴化四氮唑噻唑蓝[3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide,MTT]法检测IQGAP1高表达、IQGAP1基因干扰和相应对照细胞的活力,通过4′,6-二脒基-2-苯基吲哚(4′,6-Diamidino-2-phenylindole,DAPI)染色和流式细胞技术检测细胞凋亡率,Western blot检测凋亡相关蛋白的表达。结果显示,IQGAP1高表达和基因干扰的稳定细胞系成功建立。在不同浓度的顺铂处理后,MTT结果表明,IQGAP1...     

二硫吡咯酮类抗生素的生物合成与代谢工程应用北大核心CSCD

二硫吡咯酮类抗生素是一类具有独特的吡咯酮二硫杂环戊二烯(4H-[1,2]二硫[4,3-b]吡咯-5-酮)骨架的化合物的总称。基于N-7位酰基侧链的不同以及N-4位是否含有甲基,可分为N-methyl-Nacylpyrrothine、N-acylpyrrothine和thiomarinols等类别。迄今为止,已有27种该类化合物被报道,重要代表包括全霉素(holomycin)、硫藤黄菌素(thiolutin)、金霉素(aureothricin)以及最近发现的thiomarinols。就生物活性而言,二硫吡咯酮类抗生素具有广谱的抗细菌活性,对多种微生物,包括革兰氏阴性菌、革兰氏阳性菌以及寄生虫都有较好的杀灭活性。甚至一些二硫吡咯酮衍生物表现出较强的抗肿瘤活性。近几年来,多个二硫吡咯酮类抗生素的生物合成基因簇相继被报道,其生物合成机理也逐步被阐明。本文将针对目前国内外二硫吡咯酮类抗生素的生物合成研究进展,以及在组合生物合成与代谢工程领域所取得的成果进行综述,旨在为通过合成生物学的方法创造结构新颖、高效低毒的"非天然"二硫吡咯酮类化合物提供理论借鉴。     

虫类中药蛴螬中含氮化合物研究

从虫类中药蛴螬Holotrichia diomphalia Bates的乙醇提取物中分离得到13个化合物,其结构经谱学数据和与已知化合物比较,分别鉴定为N-[2-(4-羟苯基)-乙基]乙酰胺(1)、环(酪氨酸-脯氨酸)(2)、吡啶-3-甲酰胺(3)、胸苷(4)、戊内酰胺(5)、5-(羟甲基)-1H-吡咯-2-醛(6)、环(脯氨酸-缬氨酸)(7)、环(脯氨酸-丙氨酸)(8)、羟吲哚(9)、1,2,3,4-四氢-1,3,4-三氧-β-咔啉(10)、吲哚-3-醛(11)、黄苷(12)和苯基丙氨酸(13)。化合物1～13均为首次从该种动物药中分离得到。     

假蒟叶的生物碱类成分研究

研究假蒟(Piper sarmentosum)叶的化学成分及其对金黄色葡萄球菌的抑菌活性。采用正相硅胶柱、Sephadex LH-20凝胶柱和半制备高效液相色谱等分离技术,从假蒟叶的总生物碱部位分离得到7个生物碱类成分,结合化合物的理化性质和波谱学数据,分别鉴定为chaplupyrrolidone C(1)、chaplupyrrolidone A(2)、chaplupyrrolidone B(3)、假蒟酰胺A(4)、N-3-苯丙酰胺吡咯(5)、3-(4-羟基-3,5-二甲氧基苯基)丙酰胺吡咯(6)、3-(3,4,5-三甲氧基苯基)丙酰胺吡咯(7)。其中,化合物1为新的酰胺类生物碱,化合物7为首次从假蒟中分离得到。采用微量二倍稀释法测试所有分离化合物的抑菌活性,结果表明化合物1～4对金黄色葡萄球菌均具有不同程度的抑制作用。     

新疆甘草化学成分研究

从新疆甘草(GlycyrrhizauralensisFisch.)根中分离得到5个化合物,分别鉴定为:槲皮素(1)、甘草次酸(2)、阿魏酸(3)、5,7,3′,4′-四羟基-7-葡萄糖基二氢黄酮醇(4)、8,5′-二羟基3′α-鼠李糖黄酮(5)。其中化合物4,5为首次从该植物中分离得到。     

燕山山脉一种香料型乳菇的香味成分分析

利用固相微萃取技术（SPME）偶联气相色谱-质谱（GC-MS）分析燕山山脉一种香料型乳菇——香亚环乳菇Lactarius subzonarius的挥发性成分。共检出25种挥发性成分,其中氧杂环化合物3种、醛类1种、酯类13种、烯烃类3种、芳香族化合物2种和烷烃类3种。具有葫芦巴感官气味的挥发性组分3-羟基-4,5-二甲基-2(5H)-呋喃酮的相对含量35.76%,该成分是其近缘种Lactarius helvus的主要香味化合物,故推测3-羟基-4,5-二甲基-2(5H)-呋喃酮是其关键香味成分。     

Biocatalytic ammonolysis of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester: preparation of an intermediate to the dipeptidyl peptidase IV inhibitor Saxagliptin

An efficient biocatalytic method has been developed for the conversion of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester (1) into the corresponding amide (5S)-5-aminocarbonyl-4,5-dihydro-1H-pyrrole-1-carboxylic acid, 1-(1,1-dimethylethyl)ester (2), which is a critical intermediate in the synthesis of the dipeptidyl peptidase IV (DPP4) inhibitor Saxagliptin (3). Candida antartica lipase B mediates ammonolysis of the ester with ammonium carbamate as ammonia donor to yield up to 71% of the amide. The inclusion of Ascarite and calcium chloride as adsorbents for carbon dioxide and ethanol byproducts, respectively, increases the yield to 98%, thereby offering an efficient and practical alternative to chemical routes which yield 57-64%.     

Antifouling activity of sponge-derived polybrominated diphenyl ethers and synthetic analogues

The antifouling (AF) activity of 2-hydroxy-4-(3-hydroxy-5-methylphenoxy)- 6-methylbenozoic acid methyl ester (1), 3,5-dibromo-2-(2',4'-dibromophenoxy)phenol (2); 3,4,5-tribromo-2-(2',4'-dibromophenoxy)phenol (3), 3,4,5-tribromo-2-(2'-bromophenoxy)phenol (4), 3,5-dibromo-2(2',4'-dibromophenoxy)phenol (5), 3,4,5,6-tetrabromo-2-(2'-bromophenoxy)phenol (6); 4-phenoxyphenol (7), 4-phenoxyaniline (9), 1-chloro-4-phenoxybenzene (10); 1-bromo-4-phenoxybenzene (13) was investigated against marine bacteria, a diatom, barnacle larvae and mussel juveniles. The naturally occurring compound 2 showed the strongest AF activity in all bioassays but lacked toxicity. It inhibited the growth of all tested bacterial strains (MIC = 0.02 - 1.52 microM) and its 50% effective concentrations (EC(50)) were 0.24 microM (diatom test), 0.66 microM (mussel test) and 1.26 microM (barnacle test). Among the commercially available derivates, compound 7 was the most active in bacterial and diatom bioassays but its activity was lower than that of compound 2. Overall, the naturally occurring compounds showed stronger activity than the commercially available analogues and could be possible future non-toxic AF candidates.     

<Emphasis Type="Italic">Hymeniacidon perleve</Emphasis> associated bioactive bacterium <Emphasis Type="Italic">Pseudomonas</Emphasis> sp. NJ6-3-1

Among marine bacteria isolated from the cytotoxic sponge Hymeniacidon perleve, one strain NJ6-3-1 classified as Pseudomonas sp. showed both cytotoxic and antimicrobial activities. Fatty acid analysis indicated that the bacterial strain consists mainly of C16:1, C16:0, C18:1, C18:0, C15:0, C14:0. One unusual 9,10-cyclopropane-C17:0 fatty acid and C26:0 also constitute major components, as well as the existence of squalene, the precursor of triterpenoids. The major metabolites in the culture broth were identified as alkaloids, including diketopiperazines and indole compounds, namely 3,6-diisopropylpiperazine-2,5-dione, 3-benzyl-3-isopropylpiperazine-2,5-dione, 3,6-bis-(2-methylpropyl)-piperazine-2,5-dione, indole-3-carboxaldehyde, indole-3-carboxylic acid methyl ester, indole-3-ethanol, and quinazoline-2,4-dione.From Prikladnaya Biokhimiya i Mikrobiologiya, Vol. 41, No. 1, 2005, pp. 35–39.Original English Text Copyright © 2005 by Li Zheng, Xiaojun Yan, Jilin Xu, Haimin Chen, Wei Lin.This article was submitted by the authors in English.     

Novel isomarabarican triterpenes, exhibiting selective anti-proliferative activity against vascular endothelial cells, from marine sponge Rhabdastrella globostellata

Four novel globostellatic acid X methyl esters (1-4) having isomarabarican-type triterpenoidal skeleton and three related new compounds (5-7) were isolated from the marine sponge Rhabdastrella globostellata, as selective anti-proliferative agents against human umbilical vein endothelial cells (HUVECs). Those chemical structures were elucidated by the detailed 2D NMR analysis. Two globostellatic acid X methyl esters (3 and 4) having 13E-geometry were found to inhibit proliferation of HUVECs, 80- to 250-fold selectively in comparison with several other cell lines. 13E,17E-Globostellatic acid X methyl ester (4) also inhibited bFGF-induced tubular formation and VEGF-induced migration of HUVECs. Moreover, 4 induced apoptosis of HUVECs, whereas it exhibited no effect on VEGF-induced phosphorylation of ERK1/2 in HUVECs.     

Antifungal and antiviral products of marine organisms

Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of employing them in clinical practice are promising in view of the wealth of these compounds from marine organisms. The compounds may also be used in agriculture and the food industry.     

Hymeniacidon perleve associated bioactive bacterium pseudomonas sp. NJ6-3-1

Among the marine bacteria isolated from cytotoxic sponge Hymeniacidon perleve, one strain NJ6-3-1 classified as Pseudomonas sp. showed both cytotoxic and antimicrobial activities. Fatty acid analysis indicated that the bacterial strain consists mainly of C16:1, C16:0, C18:1, C18:0, C15:0, C14:0. One unusual 9,10-cyclopropane-C17:0 fatty acid, and C26:0 also constitute as major component as well as the existence of squalene, the precursor of triterpenoids. The major metabolites in the culture broth were identified as alkaloids, including diketopiperazines and indole compounds, namely 3,6-diisopropylpiperazin-2,5-dione, 3-benzyl-3-isopropylpiperazin-2,5-dione, 3,6-bis-(2-methylpropyl)-piperazin-2,5-dione, indole-3-carboxaldehyde, indole-3-caroxylic acid methyl ester, indole-3-ethanol, and quinazoline-2,4-dione.     

Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity

Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for 18 polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 cells and calculated free energies of binding following docking the compounds into models of alphabeta-tubulin. These docking calculations coupled with HINT interaction analyses are able to represent the complex structures and the binding modes of inhibitors such that calculated and measured free energies of binding correlate with an r(2) of 0.76. Structural analysis of the binding pocket identifies important intermolecular contacts that mediate binding. As seen experimentally, the complex with JG-03-14 (3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester) is the most stable. These results illuminate the binding process and should be valuable in the design of new pyrrole-based colchicine site inhibitors as these compounds have very accessible syntheses.     

5-Hydroxyindole-type alkaloids,as Candida albicans isocitrate lyase inhibitors,from the tropical sponge Hyrtios sp.

Chemical investigations of the tropical marine sponge Hyrtios sp. have resulted in the isolation of a new alkaloid, 1-carboxy-6-hydroxy-3,4-dihydro-β-carboline (1) together with the known metabolites, 6-hydroxy-3,4-dihydro-1-oxo-β-carboline (2), 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3), serotonin (4), hyrtiosin A (5), 5-hydroxyindole-3-carbaldehyde (6), and hyrtiosin B (7). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. Hyrtiosin B (7) displayed a potent inhibitory activity against isocitrate lyase (ICL) of Candida albicans with an IC₅₀ value of 89.0 μM.     

Synthesis of BC-ring model of globostellatic acid X methyl ester, an anti-angiogenic substance from marine sponge

Concise synthesis of BC-ring model compounds of 13E,17E-globostellatic acid X methyl ester, an anti-angiogenic triterpene derivative from Indonesian marine sponge, was achieved through ynolate olefination and allylic oxidation as key steps. The model compound 5, which was synthesized within 10 reaction steps from commercially available Hajos-Parrish ketone, showed anti-proliferative activity against HUVECs with moderate selectivity.     

Indole alkaloids from a culture of the fungus Aporpium caryae

In a screening for antifungal metabolites, two indole compounds of mixed biogenesis, 1H-indole-3-carboxylic acid, 1-(1,1-dimethyl-2-propenyl) methyl ester and 1H-indole-3-carboxylic acid, 1-(2,3-dihydroxy-1,1-dimethylpropyl) methyl ester were isolated from a culture of the basidiomycete Aporpiums caryae. The structural elucidation of these compounds was accomplished by spectroscopic methods.