青霉属真菌Penicillium sp. CPCC 400786的抗病毒活性成分

采用抗艾滋病毒抑制剂筛选模型对一株青霉属真菌Penicillium sp. CPCC 400786发酵产物的乙酸乙酯提取物进行活性评价,结果显示,其对艾滋病毒有较强的抑制活性。采用正相硅胶柱、Sephadex LH-20凝胶柱和半制备HPLC等色谱技术对乙酸乙酯提取物进行分离纯化,从中分离得到8个化合物。通过波谱数据分析,分别鉴定为：oxalicine A（1）、oxalicine B（2）、cis-4,6-dihydroxymellein（3）、亚油酸（4）、十八烯酸（5）、肉豆蔻酸（6）、尿嘧啶（7）、胸腺嘧啶（8）。化合物1和2为杂萜类化合物。对化合物1-6进行了抗艾滋病毒（HIV-1）和抗甲型流感病毒（H1N1）的活性评价。结果显示,化合物1具有良好的抗H1N1活性,其IC₅₀值为38.5μmol/L,比阳性对照药利巴韦林稍弱（IC₅₀=20.5μmol/L）;化合物1和2具有抗HIV-1的活性,其IC₅₀值分别为22.4、67.8μmol/L;其他化合物未显示抗病毒活性。本研究为从青霉属中发现更多抗病毒活性杂萜分子提供了依据。     

南极适冷菌Pseudomonassp．C抑菌活性物质的分离纯化与结构鉴定北大核心CSCD

本文对南极适冷菌Pseudomonassp．c发酵液上清中的抗植物病原菌活性物质进行了研究,结果表明在温度40-70℃和pH5—9的范围内发酵液上清的抑菌活性稳定。根据活性追踪,通过硅胶柱层析和高效液相色谱对发酵液上清中的抑菌活性物质进行了分离纯化,得到了3个对常见植物病原真菌尖孢镰刀菌具有抑菌活性的化合物,并对其中的两个化合物进行了结构鉴定。化合物1为环二肽类（环（苯丙氨酸-脯氨酸））,化合物2为壬基酚聚氧乙烯醚类（14-壬基苯氧基．3,6,9,12．四氧十四烷-1-醇）,两者对枯草芽孢杆菌也具有一定的抑菌活性。     

螺卷毛壳霉代谢产物的抗菌活性研究(英文)

采用管碟法首次对螺卷毛壳霉（Chaetomium cochloides）的含硫次生代谢产物（1—5）进行了体外抗细菌和抗真菌活性测定,并对其构效关系进行了研究。活性测定显示化合物1—5对革兰氏阳性细菌（Staphylococcus aureus）具有较强的抑制活性,其中化合物1的抑菌活性最强。构效关系研究表明位于C-3’和C-6’之间的二硫桥为化合物的抑菌活性中心,C-3与C-11a之间的二硫桥和N-6与O—3’之间的大环结构能够增强活性。     

源于一株青霉菌的4,5-环氧环己烯类次生代谢产物研究

从一株青霉菌Penicillium sp.（XZ075）的发酵粗提物中分离了4个4,5-环氧环己烯类新结构次生代谢产物penoxides A－D（1－4）和同类型的已知化合物eupenoxide（5）,并采用质谱和核磁共振技术确定了新化合物的结构。化合物1的绝对构型是通过与已知化合物5比对核磁数据确定的,而2－4的绝对构型是通过与化合物1比对CD谱图确定的。活性测试结果表明化合物1,2及4对宫颈癌细胞（HeLa）具有中等的细胞毒活性。     

黄皮根和茎中一个新的木脂体

从黄皮（Clausenalansium）根和茎中分离得到8个化合物,其中化合物claulignan（1）为一个新的木脂体类化合物,通过1D-、2D—NMR和高分辨质谱确定其结构。化合物2-8首次从黄皮属（Clausena）植物中分离得到。活性筛选结果表明,化合物1和6显示一定的细胞毒活性,对人宫颈癌HeLa细胞株的,c50分别为25．03和53．99μM;化合物3具有一定的抗氧化活性,在DPPH实验中的EC50为268．96g·kg-1。     

多炔类化合物对美洲大蠊的触杀活性及对乙酰胆碱酯酶和腺苷三磷酸酶活性的影响

采用药膜法测定了人工合成的11个多炔类化合物对美洲大蠊Periplaneta americana初孵若虫的触杀活性。结果表明,当化合物处理浓度为20 μg/cm²时,致死率达70%以上的有: 化合物2 (1-叔丁基-4-羟甲基-丁二炔)、化合物9 (1-苯甲基-4-甲基-丁二炔)和化合物10 (O-炔丙基硫代磷酸二乙酯)。经毒力测定,化合物9和化合物10的LC₅₀分别为3.91 μg/cm²和1.50 μg/cm²。化合物2、化合物7 (1-苯基-4-邻硝基苯基-丁二炔)和化合物10对美洲大蠊乙酰胆碱酯酶(AChE)具有抑制活性,抑制率分别为12.00%、27.24%和62.22%。化合物2和化合物10对Na⁺-K⁺-ATPase具有抑制活性,抑制率分别为44.55%和31.44%;而化合物5 (1-苯基-4-（3,4-亚甲基二氧）苯基-丁二炔)和化合物6 (1-苯基-4-间硝基苯基-丁二炔)对该酶具有激活活性,激活率分别为24.98%和20.99%。化合物2、化合物4 （1-苯基-4-对甲氧基苯基-丁二炔）和化合物7对Ca²⁺-Mg²⁺-ATPase具有抑制活性,抑制率分别为49.02%、38.53%和35.32%, 其他化合物对该酶具有激活活性,其中激活活性最高的为化合物5,激活率达81.12%。     

蝉虫草（蝉花）来源的化合物鉴定与抗菌活性检测

蝉虫草（蝉花）是我国重要的传统中药材之一,用于治疗慢性肾炎等,但对其活性成分的研究仍不充分。本文采用硅胶柱、凝胶柱、ODS柱分离,以及HPLC等色谱技术,对蝉虫草子实体样品的乙酸乙酯提取物进行分离纯化,得到3个化合物。根据波谱学数据,化合物1-3分别鉴定为(E,E)-9-酮-10,12-十八碳二烯酸(E,E)-9-oxooctadeca-10,12-dienoic acid（1）、麦角甾醇ergosterol（2）和白僵菌酮bassiatin（3）,其中化合物1为首次从蝉虫草中分离获得。抑菌实验表明,3个化合物均对革兰氏阴性大肠杆菌Escherichia coli和革兰氏阳性枯草芽孢杆菌Bacillus subtilis有显著的抑菌活性,化合物1和3还对条件致病真菌白色念珠菌Candida albicans有明显的抑菌活性。本文的研究结果丰富了蝉虫草的活性化合物组成。     

来自普哥滨珊瑚的一株Talaromyces sp.真菌的活性次生代谢产物

利用硅胶柱层析、制备型HPLC和重结晶等手段从普哥滨珊瑚分离的一株Talaromyces sp.真菌C21-1中筛选得到2个活性化合物,运用核磁共振、质谱和圆二色谱等技术鉴定这两个化合物分别为(R)-(-)-hydroxysydonic acid（1）和homodimeric WIN 64821（2）,补充完善了化合物2的核磁共振信号归属,并对化合物进行抗菌活性和乙酰胆碱酯酶抑制活性的测定,发现化合物1对白色假丝酵母Canidia albicans和耐甲氧基青霉素的金黄色葡萄球菌Methicillin-resistant Staphylococcus aureus（MRSA）具有一定的抑制作用,其最低抑菌浓度（MIC）分别为0.075mmol/L和0.2mmol/L,对副溶血弧菌Vibrio parahemolyticus的抑制活性较弱,在0.2mmol/L浓度下的抑制率为17%;化合物2最大浓度0.2mmol/L条件下对这3种菌均没有明显的抑制效果。化合物2表现出剂量依赖的乙酰胆碱酯酶抑制活性,0.5mmol/L时抑制率达到35.1%。     

株特殊生境荒漠植物雾冰藜内生真菌Stagonospora sp.的次级代谢产物

本文通过对1株特殊生境荒漠植物雾冰藜内生真菌Stagonospora sp.的次级代谢产物进行研究,首次分离得到4个松萝酸结构类似物,包括1个新化合物stagonone（1）和3个已知化合物：松萝酸（2）,cercosporamide（3）和usnic acid amide（4）。通过高分辨质谱和NMR实验解析了新化合物1的平面结构,采用圆二色谱（CD）方法确定了其绝对构型;本文还报道了松萝酸（2）的单晶结构以及松萝酸（2）的CD谱,为确定该同类化合物的绝对构型提供了支持;活性试验结果证实化合物1-4具有选择性抗肿瘤细胞活性。基于化合物1-4的结构特征,推测了其可能的生物合成途径。     

蛹虫草子实体活性成分的分离鉴定

蛹虫草具有悠久的食药用历史,但关于其活性成分的种类仍知甚少。本文采用大孔树脂、硅胶柱、HPLC等色谱技术对蛹虫草Cordyceps militaris子实体粗提物进行分离纯化,从中得到3个化合物。通过波谱数据分析,化合物1–3分别被鉴定为：虫草素（3’-脱氧腺苷）（1）,色氨酸（2）和5,5’-dibuthoxy-2,2’-bifuran（3）,杂环化合物3为首次从蛹虫草子实体中获得。对化合物进行抗菌活性测定发现,虫草素和5,5’-dibuthoxy-2,2’-bifuran对枯草芽孢杆菌和大肠杆菌都有显著的抑菌活性,但是它们对酿酒酵母均未表现出明显抑菌活性。     

Ursolic acid induces ER stress response to activate ASK1–JNK signaling and induce apoptosis in human bladder cancer T24 cells

Here we studied the cellular mechanisms of ursolic acid's anti-bladder cancer ability by focusing on endoplasmic reticulum stress (ER stress) signaling. We show that ursolic acid induces a significant ER stress response in cultured human bladder cancer T24 cells. ER stress inhibitor salubrinal, or PERK silencing, diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits ursolic acid-induced CHOP expression, Bim ER accumulation and caspase-3 activation in T24 cells. Ursolic acid induces IRE1–TRAF2–ASK1 signaling complex formation to activate pro-apoptotic ASK1–JNK signaling. We suggest that ER stress contributes to ursolic acid's effects against bladder cancer cells.     

New ursolic and betulinic derivatives as potential cytotoxic agents

Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhibitory activity for three of them. Beta-D-Glucopyranosyl-3beta-hydroxyurs-12(13)-en-28-oate 1c, 3beta-3-(3-pyridyl)-prop-2-enoyloxyurs-12(13)-en-28-oic acid 1i and the potassium salt of 3beta-cinnamoyloxylup-20(29)-en-28-oic acid 2d demonstrated cytotoxic activity in the micromolar range: 8.0, 45.0 and 8.0 microM, respectively.     

Pentacyclic triterpenoids from the aerial parts of Lantana camara and their nematicidal activity

Two new olean-12-ene triterpenoids, camarolic acid (1) and lantrigloylic acid (2), have been isolated from the aerial parts of Lantana camara, along with ten known triterpenes, namely, camaric acid, lantanolic acid, lantanilic acid, pomolic acid, camarinic acid, lantoic acid, camarin, lantacin, camarinin, and ursolic acid. The new compounds have been characterized as 3,25-epoxy-3alpha-hydroxy-22beta-{[(S)-3-hydroxy-2-methylidenebutanoyl]oxy}olean-12-en-28-oic acid (1) and 3,25-epoxy-3alpha-hydroxy-22beta-[(3-methylbut-2-enoyl)oxy]olea-9(11),12-dien-28-oic acid (2) through spectroscopic studies and a chemical transformation. Seven of the constituents, namely pomolic acid, lantanolic acid, lantoic acid, camarin, lantacin, camarinin, and ursolic acid, were tested for nematicidal activity against root-knot nematode Meloidogyne incognita. Pomolic acid, lantanolic acid, and lantoic acid showed 100% mortality at 1 mg/ml concentration after 24 h, while camarin, lantacin, camarinin, and ursolic acid exhibited 100% mortality at this concentration after 48 h. These results are comparable to those obtained with the conventional nematicide furadan (100% mortality at 1 mg/ml concentration after 24 h).     

Differential gene expression for investigation of Escherichia coli biofilm inhibition by plant extract ursolic acid

After 13,000 samples of compounds purified from plants were screened, a new biofilm inhibitor, ursolic acid, has been discovered and identified. Using both 96-well microtiter plates and a continuous flow chamber with COMSTAT analysis, 10 microg of ursolic acid/ml inhibited Escherichia coli biofilm formation 6- to 20-fold when added upon inoculation and when added to a 24-h biofilm; however, ursolic acid was not toxic to E. coli, Pseudomonas aeruginosa, Vibrio harveyi, and hepatocytes. Similarly, 10 microg of ursolic acid/ml inhibited biofilm formation by >87% for P. aeruginosa in both complex and minimal medium and by 57% for V. harveyi in minimal medium. To investigate the mechanism of this nontoxic inhibition on a global genetic basis, DNA microarrays were used to study the gene expression profiles of E. coli K-12 grown with or without ursolic acid. Ursolic acid at 10 and 30 microg/ml induced significantly (P < 0.05) 32 and 61 genes, respectively, and 19 genes were consistently induced. The consistently induced genes have functions for chemotaxis and mobility (cheA, tap, tar, and motAB), heat shock response (hslSTV and mopAB), and unknown functions (such as b1566 and yrfHI). There were 31 and 17 genes repressed by 10 and 30 microg of ursolic acid/ml, respectively, and 12 genes were consistently repressed that have functions in cysteine synthesis (cysK) and sulfur metabolism (cysD), as well as unknown functions (such as hdeAB and yhaDFG). Ursolic acid inhibited biofilms without interfering with quorum sensing, as shown with the V. harveyi AI-1 and AI-2 reporter systems. As predicted by the differential gene expression, deleting motAB counteracts ursolic acid inhibition (the paralyzed cells no longer become too motile). Based on the differential gene expression, it was also discovered that sulfur metabolism (through cysB) affects biofilm formation (in the absence of ursolic acid).     

熊果酸衍生物的合成及其对肺癌细胞活性抑制的研究

目的：探讨合成的熊果酸衍生物对肺癌LTEP-α-2肿瘤细胞增殖的抑制作用。方法：熊果酸经氧化、肟化和腙化合成为3-氧代熊果酸、3-肟基熊果酸和3-（2＇,4＇-二硝基）-苯腙熊果酸。采用MTT法检测熊果酸及其衍生物对肺癌LTEP-α-2细胞的体外抗肿瘤活性。结果：熊果酸及其衍生物对肺癌LTEP-α-2细胞有抑制作用,且3-肟基熊果酸对肺癌LTEP-α-2细胞抑制作用高于其他化合物,其抑制率为90.0%,IC50为7.4μg/m L。结论：熊果酸衍生物3-肟基熊果酸抗肺癌LTEP-α-2肿瘤细胞活性高于熊果酸的活性。     

海芒果叶中三萜类成分的研究

采用多种柱色谱等分离纯化手段对海芒果叶中的三萜类成分进行分离,得到7个化合物,通过理化性质和波谱方法鉴定化合物为熊果醇(1),(23Z)-9,19-cycloart-25-ene-3β,24-diol(2),大戟醇(3),乌苏酸(4),2α-羟基乌苏酸(5),乙酰乌苏酸(6),α-香树脂醇(7)。化合物1～6均为首次从该属植物中分离得到。     

熊果酸在肿瘤治疗中的研究进展

熊果酸(ursolic acid)是广泛存在于自然界植物中的一种五环三萜类化合物,具有广泛的生物学活性,主要经肝脏代谢。传统临床治疗中熊果酸多用于抗炎、抗病毒、调节免疫功能以及保肝治疗等。近年来的研究表明,在体外和体内实验中,熊果酸能够对不同肿瘤细胞产生杀伤作用,抑制恶性肿瘤组织的生长,具有广谱的抗肿瘤活性。此外,熊果酸联合放化疗能够提高肿瘤细胞对治疗的敏感性,产生辅助增强放化疗疗效的作用,并且在放疗中可保护受照射机体的正常组织,促进免疫机能的恢复。熊果酸的抗肿瘤作用机制与下调促肿瘤生长、侵袭和转移相关基因的水平,增强凋亡基因的表达有关,并且能够通过调节多种细胞信号转导通路,杀灭肿瘤细胞,延缓肿瘤组织生长。同时,熊果酸可影响肿瘤细胞周期的分布,导致细胞的G1/S期阻滞,从而抑制肿瘤细胞的有丝分裂,诱导细胞凋亡。因此,熊果酸是一种极具潜力的天然抗肿瘤药物。本文对熊果酸在肿瘤治疗中的研究结果进行整合,阐述了熊果酸的抗肿瘤分子机制及其疗效,为熊果酸今后在临床中的进一步应用提供指导思路。     

Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer cells

A series of new heterocyclic derivatives of ursolic acid 1 were synthesized and evaluated for their antiproliferative activity against AsPC-1 pancreatic cancer cells. Compounds 24–32, with an α,β unsaturated ketone in conjugation with an heterocyclic ring in ring A have improved antiproliferative activities. Compound 32 is the most active compound with an IC₅₀ of 1.9 μM which is sevenfold more active than ursolic acid 1. Compound 32 arrests cell cycle in G1 phase and induces apoptosis in AsPC-1 cells with upregulation of p53, p21^waf1 and NOXA protein levels.     

Apoptotic action of ursolic acid isolated from Corni fructus in RC-58T/h/SA#4 primary human prostate cancer cells

Ursolic acid (3β-hydroxy-urs-12-en-28-oic acid) is a major biological active component of Corni fructus that is known to induce apoptosis. However, the apoptotic mechanism of ursolic acid using primary malignant tumor (RC-58T/h/SA#4)-derived human prostate cells is not known. In the present study, ursolic acid significantly inhibited the growth of RC-58T/h/SA#4 cells in dose- and time-dependent manners. Ursolic acid induced cell death as evidenced by an increased proportion of cells in sub-G1 phase, the formation of apoptotic bodies, nuclear condensation, and DNA fragmentation. After ursolic acid treatment at concentrations above 40 μM, the activities of caspase-3, -8, and -9 were significantly increased compared that of control. Ursolic acid modulated the upregulation of Bax (pro-apoptotic) as well as the downregulation of Bcl-2 (anti-apoptotic). Ursolic acid also stimulated Bid cleavage, which indicates that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Thus, the apoptotic effect of ursolic acid was involved in extrinsic and intrinsic signaling pathways. In addition, ursolic acid increased the expression of the caspase-independent mitochondrial apoptosis factor (AIF) in RC-58T/h/SA#4 cells. The present results suggest that ursolic acid from Corni fructus activated apoptosis in RC-58T/h/SA#4 cells via both caspase-dependent and -independent pathways.