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。     

红树林来源黑曲霉Aspergillus niger ZHN2-20次级代谢产物的研究D

目的 研究红树林植物榄李Lumnitzera racemosa根泥来源黑曲霉Aspergillus niger ZHN2-20的抗肿瘤活性次级代谢产物。方法 利用硅胶柱层析、凝胶Sephadex LH-20柱层析、HPLC等常规化学手段对次级代谢产物进行了分离纯化;通过理化性质结合波谱学数据分析及文献对照,鉴定化合物的结构;分别以SRB和MTT法评价了化合物的细胞毒活性。结果 从黑曲霉Aspergillus niger ZHN2-20的次级代谢产物中,分离鉴定了5个甾类单体化合物,分别为：helvolic acid (1),methyl helvolic acid (2),(22E, 24R)-ergosta-7, 9 (11), 22-triene-3β, 5α, 6β-triol (3),cerevisterol (4),(22E, 24R)-ergosta-7, 9 (11), 22-triene-3β, 5α-diol (5)。化合物3、5对HL-60和K-562肿瘤细胞株均表现出一定的细胞增殖抑制作用,抑制率分别为78.10%,60.50%和62.36%,49.43%。 结论 化合物1-3、5为首次在黑曲霉Aspergillus niger中分离得到,其中化合物2为新结构化合物。首次测定了化合物1-5对Hela、A-549、MGC-803、HL-60和K-562五种肿瘤细胞株的细胞毒活性,其中化合物3、5对两株人白血病细胞显示出一定的抑制作用。     

南海柳珊瑚来源真菌Aspergillus hiratsukae SCSIO 7S2001的次生代谢产物及活性研究

目的 对一株采自南海柳珊瑚来源曲霉属真菌Aspergillus hiratsukae SCSIO 7S2001进行次级代谢产物及活性研究。方法 通过条件优化对菌株进行大规模发酵，采用硅胶柱层析、葡聚糖凝胶、半制备高效液相等色谱学方法对其大米发酵产物进行分离纯化，利用NMR、MS等波谱学技术，结合其理化性质及文献数据对比进行化合物的结构鉴定，并对化合物进行初步抗氧化和抗菌活性测试。结果 从菌株SCSIO 7S2001中分离鉴定9个单体化合物cristatumin F (1)，，neoechinulin B (2），，cyclo (Trp-Ana) (3)，，cyclo (D-Trp-L-Pro) (4)，，cyclo (D-Pro-D-Phe) (5)，，Phomoindene A(6)，，β-adenosine (7), ，E-6-hydroxy-3-(4-hydroxybenzylidene)-benzo[b]furan-2-one(8a8)，Z-6-hydroxy-3-(4-hydroxybenzylid-ene)-benzo[b]furan-2-one(8b9)，并对化合物进行抗菌活性、DPPH自由基清除活性以及乙酰胆碱酯酶抑制活性的测定。化合物1-89均为首次从该菌株中分离得到，化合物8和9为首次从海洋真菌中分离得到的新天然产物。所有化合物均无抗菌活性，化合物6表现出显著的DPPH自由基清除活性，其IC50为8.50 μM，几乎与阳性对照相当(阳性对照IC50=5.58 μM)。化合物1和2表现出微弱的乙酰胆碱酯酶抑制活性，在浓度为50 μg. /mL-1下，抑制率分别为16.44%和19.75%。     

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。     

深红虫草次级代谢产物的分离与鉴定

目的:对深红虫草的次级谢产物进行分离、鉴定,为进一步发掘深红虫草活性物质和丰富虫草类真菌天然产物库提供参考。方法:采用正相硅胶柱层析、C_(18)反相硅胶柱层析、Sephadex LH-20凝胶柱层析、薄层色谱等色谱技术对深红虫草发酵液中的化合物进行分离;通过核磁共振氢谱、核磁共振碳谱和质谱分析对分离的化合物进行结构鉴定。结果:从深红虫草发酵液的乙酸乙酯萃取部分共分离得到6个化合物,分别鉴定为5-甲基-1,3-苯二酚(化合物1)、4-hydroxy-17R-methylincisterol(化合物2)、5α,8α-氧桥-(22E,24R)-麦角甾-6,22-二烯-3β-醇(化合物3)、3β,5α,6β-三羟基-(22E,24R)-麦角甾-7,22-二烯(化合物4)、尿嘧啶核苷(化合物5)、卵孢菌素(化合物6)。结论:本研究从该属真菌中分离得到了6个化合物,其中化合物1和化合物2为首次分离得到。     

红树植物尖瓣海莲（Brguiera sexangula var. rhynchopetala）化学成分研究

目的 对红树植物尖瓣海莲（Brguiera sexangula var. rhynchopetala）化学成分及抗菌活性进行研究。方法 采用活性追踪分离的方法,利用硅胶柱层析、Sephadex LH-20 凝胶柱层析和半制备 HPLC 等手段对尖瓣海莲茎的化学成分进行了分离纯化;通过NMR, MS 等波谱方法并与文献对照,确定化合物的结构;利用微量稀释法评价化合物的抗菌活性。结果 从红树植物尖瓣海莲（Brguiera sexangula var. rhynchopetala）茎的石油醚提取物中分离鉴定了 6 个单体化合物,分别为: methylent-16β,17-dihydroxy-9(11)-kauren-19-oate (1), ceriopsin E (2), ent-kaur-16-en-13-hydroxy-19-al (3), 4α,5S,8α,9α,10S,13S-ent-17-hydroxy-16-oxobeyeran-19-al (4), 17-hydroxy-16-oxobeyer-9(11)-en-19-al (5) 和 4''-hydroxy-3''-methoxyphenol-β-D-[6-O-(4"-hydroxy-3",5"-dimeth-oxylbenzoate)]-glucopyranoside (6)。结论 化合物 2, 3 和 6 为首次从该植物中分离得到。酚苷类化合物 6 对溶藻弧菌(Vibrio alginolyticus) 和白色葡萄球菌 (Staphylococcus albus) 显示较强的抑制活性。     

西沙群岛来源真菌Pestalotiopsis sp.中脑苷脂类化合物及其生物活性研究

目的 研究中国南海西沙群岛来源真菌Pestalotiopsis sp.7-6中的活性次级代谢产物的化学结构及其生物活性。方法 利用现代波谱方法,鉴定脑苷脂类化合物cerebroside A (1)和(4E,8E)-N-D-2′-hydroxypalmitoyl-1-O-β-D –glycopyranosyl -9-methyl-4,8-sphingadienine (2)的化学结构;利用抗菌和抗病毒活性模型对其进行生物活性评价。结果 化合物1对痢疾志贺氏菌 (Shigellad ysenteriae) 显示一定的抗菌活性(MIC = 50 μM);化合物2对单纯疱疹病毒 (HSV-1) 和肠道病毒71 (EV71) 有较好的抗病毒活性。结论 从西沙群岛来源真菌Pestalotiopsis sp.7-6中分离获得两个具有抗菌和抗病毒活性的脑苷脂类化合物。     

枫杨化学成分及其抑制α-葡萄糖苷酶的活性研究

目的研究枫杨的化学成分及其抑制α-葡萄糖苷酶的活性。方法采用反复硅胶柱层析、葡聚糖凝胶(Sephadex LH-20)柱色谱、重结晶等分离纯化方法从枫杨乙酸乙酯部位分离单体化合物,依据主要理化性质和波谱数据鉴定化合物结构,运用96孔板测定化合物体外抑制α-葡萄糖苷酶活性。结果从乙酸乙酯部位分离鉴定了11个化合物,分别为β-胡萝卜苷(1)、水杨酸(2)、槲皮苷(3)、对香豆酸(4)、槲皮素(5)、5-羟基-2-甲氧基-1,4-萘醌(6)、β-谷甾醇(7)、没食子酸(8)、山柰酚(9)、槲皮素-3-O-β-D-半乳糖苷(10)、原儿茶酸(11)。体外α-葡萄糖苷酶抑制活性实验结果表明:在浓度为1mg·mL-1时,化合物5、9对α-葡萄糖苷酶的抑制率超过90%,与阿卡波糖相当;化合物2、3、10对α-葡萄糖苷酶的抑制活性一般(约40%)。结论化合物2～4和9～11为首次从枫杨属植物中分离得到,化合物5、9对α-葡萄糖苷酶具有较强的抑制活性。     

西沙软珊瑚Sarcophyton.sp.共附生青霉菌Penicillium citrinum次级代谢产物和生物活性研究

目的：对从软珊瑚Sarcophyton.sp.中发现的青霉菌Penicillium citrinum的次级代谢产物进行研究。方法：利用硅胶柱色谱、薄层色谱、Sephadex LH-20、ODS中压色谱、凝胶色谱、半制备HPLC等方法对该菌的次级代谢产物进行了分离纯化;通过NMR、MS等方法,并结合文献对照,鉴定化合物的结构。结果：从青霉菌Penicillium citrinum中一共发现了8个化合物：2,3-dihydrosorbicillin(1)、Citrinin (2)、Penicitol(3)、dimethyl-4,7- dihydroxy-9-oxo-9H-xanthene-3,5-dicarboxylate(4)、Emodin(5)、methyl-2,8- dihydroxy-6-methyl-9-oxo-9H-xanthene-1- dicarboxy(6)、8-hydroxy-6-methyl-9-oxo- 9H-xanthene-1- carboxylate(7)、ergostane(8)。生物活性显示化合物3对HCT-116和Hela细胞株有细胞毒性。     

１株海洋来源真菌Cladosporium halotolerans次级代谢产物的研究

摘 要：目的 对１株来源于中国西沙群岛的珊瑚Sarcophyton trocheliophorum共附生真菌Cladosporium halotolerans（18XS79ZP-2）进行次级代谢产物的化学成分研究。方法 利用薄层色谱、硅胶柱层析、高效液相色谱和中压制备液相色谱等分离手段对真菌Cladosporium halotolerans的次级代谢产物进行分离、纯化；运用核磁共振波谱、质谱等方法，并通过与报道的数据进行对比，对化合物的化学结构进行鉴定。结果 从真菌Cladosporium halotolerans的次级代谢产物中分离鉴定10个化合物，分别为1-Acetyl-β-carboline（1）、(K)-3a-hydroxyfuroindoline（2）、3-Hydroxyacetylindole（3）、(R)-3-Hydroxy-3-(2-hydroxyethyl)indolin-2-one（4）、(R)-3-hydroxy-3-( 2"-oxopro-pyl) indolin-2-one（5）、Nb-acetyltryptamine（6）、cyclo-(L-Pro-L-Leu)（7）、cyclo(L-Pro-L-Phe（8）、cyclo-(L-Val-L-Tyr)（9）、cyclo-(L-Val-L-Leu)（10）。结论 从真菌Cladosporium halotolerans的次级代谢产物中分离得到10个已知化合物，化学结构类型分别属于β-carboline类生物碱、吲哚类生物碱和二酮哌嗪类生物碱。化合物1~10均为首次从真菌Cladosporium halotolerans中得到。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.