Resin glycosides from the roots of Ipomoea tyrianthina and their biological activity

Seven new tetrasaccharide glycosides, tyrianthins 1-7 (1-7), along with six known glycolipids were isolated from the roots of Ipomoea tyrianthina, and their structures were elucidated by spectroscopic and chemical methods. The content of resin glycosides in samples collected in three different regions was analyzed and compared, and the results showed that the flowering or dry season did not have any effect on the chemical composition for the same locality, but the growing location itself did affect the chemical composition of resin glycosides. Intraperitoneal administration to mice of tyrianthin 6 (6) resulted in antidepressant activity. Tyrianthin 6 (6), scammonin 1 (8), and scammonin 2 (9) exhibited dose-dependent protective effects against pentylenetetrazole-induced seizures. Also, tyrianthin 6 (6) and scammonin 2 (9) produced relaxant effects on spontaneous contractions in the isolated rat ileum.     

Phenolic compounds from Brazilian propolis with pharmacological activities

Four compounds were isolated from Brazilian propolis. They are identified as: (1) 3-prenyl-4-hydroxycinnamic acid (PHCA), (2) 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyrane (DCBEN), (3) 3,5-diprenyl-4-hydroxycinnamic acid (DHCA), and (4) 2,2-dimethyl-6-carboxyethenyl-8-prenyl-2H-1-benzopyran (DPB). The structures of the compounds were determined by MS and NMR techniques. All compounds were assayed against Trypanosoma cruzi and the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis. Compounds (1) to (4) were active against T. cruzi. Except (1), all compounds presented activity against the bacteria tested. When compounds (1)-(3) were tested in the guinea pig isolated trachea, all induced a relaxant effect similar to propolis extract.     

红大戟中的非蒽醌类化学成分

运用硅胶、Sephadex LH-20柱色谱和HPLC制备色谱等方法进行分离和纯化,从茜草科红芽大戟属植物红大戟根的乙醇提取物中首次分离得到21个非蒽醌类成分;通过NMR和MS等波谱数据鉴定了化合物的结构,包括10个三萜:乌苏酸(1),齐墩果酸(2),3β,19α-二羟基-2-氧-乌苏-12-烯-28-酸(3),坡模酸(4),马斯里酸(5),3β,19α,24-三羟基-乌苏-12-烯-28-酸(6),委陵菜酸(7),救必应酸-3,23-缩丙酮(8),2α,3β,19α,23-四羟基-齐墩果-12-烯-28-酸(9),2α,3β,19α,23-四羟基-乌苏-12-烯-28-酸(10);4个豆甾酮:(24R)-24-豆甾-4,22-二烯-3-酮(11),(24R)-24-豆甾-4-烯-3-酮(12),(24R)-24-豆甾-3β-羟基-5,22-二烯-7-酮(13),(24R)-24-豆甾-3β-羟基-5-烯-7-酮(14);2个木脂素:桉脂素(15),刺五加酮(16);1个香豆素:8-甲氧基异欧前胡素(17);4个简单芳香类化合物:5-羟甲基呋喃醛(18),3-羟基-4-甲氧基苯甲酸(19),苯甲酸(20),2-羟基-5-甲氧基-苯丙烯醛(21)。在肿瘤细胞毒(MTT法,HCT-8,Bel7402,BGC-823,A549和A2780),神经细胞保护(去血清和谷氨酸损伤模型),抗氧化(Fe2+-Cys诱导大鼠肝微粒体丙二醛生成模型),抗炎(小鼠腹腔巨噬细胞分泌NO模型),抗HIV(VS-VG/HIV-luc模型)和抗糖尿病(PTP1B酶抑制模型)药理模型上筛选结果显示,在1.0×10-5mol.L-1浓度下,这些化合物均未表现出活性。     

Antitumor agents, 118. The isolation and characterization of bruceanic acid A, its methyl ester, and the new bruceanic acids B, C, and D, from Brucea antidysenterica

The known bruceanic acid A [1] and its methyl ester 2, as well as the new bruceanic acids B [3], C [4], and D [5], have been isolated from Brucea antidysenterica. The structures of 1-5 were elucidated by spectral data. Compound 1 demonstrated cytotoxicity against KB and TE671 tumor cells. Compound 5 was cytotoxic against P-388 lymphocytic leukemia cells.     

Verrucamides A-D, antibacterial cyclopeptides from Myrothecium verrucaria

Four new cyclic tetradecapeptides, verrucamides A-D (1-4), have been isolated from the solid-substrate fermentation culture of the ascomycete fungus Myrothecium verrucaria. The structures of these compounds, each featuring six N-methylated amino acid residues, were elucidated primarily by NMR and MS methods. The absolute configurations of 1-4 were assigned by application of Marfey's method on their acid hydrolysates. Compounds 1-4 showed antimicrobial activity against the Gram-positive bacterium Staphylococcus aureus.     

Isolation,characterization and biological activity of betulinic acid and ursolic acid from Vitex negundo L

Two pentacyclic triterpenoids, betulinic acid (3beta-hydroxylup-20-(29)-en-28-oic acid) (3), and ursolic acid (2beta-hydroxyurs-12-en-28-oic acid) (4), were isolated for the first time from leaves of Vitex negundo L. along with three other compounds; an aliphatic alcohol n-hentriacontanol (1), beta-sitosterol (2) and p-hydroxybenzoic acid (5). Their antifeedant activity against the larvae of an agricultural pest, the castor semilooper (Achoea janata), in a no-choice laboratory assay and their antibacterial activity against Bacillus subtilis and Escherichia coli, by the paper disc method, were tested. Ursolic acid (4) showed more effective antifeedant activity than the betulinic acid (3). However, both these compounds have shown a very mild antibacterial activity. The other three compounds; n-hentriacontanol (1), beta-sitosterol (2) and p-hydroxybenzoic acid (5) have shown a little antifeedant activity against the larvae and did not show any antibacterial activity.     

Usimines A-C, bioactive usnic acid derivatives from the Antarctic lichen Stereocaulon alpinum

Usimines A-C ( 1- 3), three new usnic acid derivatives, have been isolated from a MeOH extract of the Antarctic lichen Stereocaulon alpinum by various chromatographic methods. The structures of 1- 3 were determined by analysis of their spectroscopic data (NMR, UV, MS) and by chemical methods. The known compound usnic acid ( 4) was also obtained. Compounds 1- 4 showed moderate inhibitory activity against therapeutically targeted protein tyrosine phosphatase 1B (PTP1B).     

Minutissamides A-D, antiproliferative cyclic decapeptides from the cultured cyanobacterium Anabaena minutissima

Four cyclic decapeptides, minutissamides A-D (1-4), were isolated from the cultured cyanobacterium Anabaena minutissima (UTEX 1613). The planar structures were determined using various spectroscopic techniques including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the α-amino acid residues were assigned using Marfey's method after acid hydrolysis. The absolute configuration of a β-amino acid residue was assigned by a combination of the advanced Marfey's method, J-based configurational analysis, and ROE spectroscopic analysis. The structures of minutissamides A-D (1-4) were characterized by the presence of three nonstandard α-amino acid residues (two α,β-dehydro-α-aminobutyric acids and one N-methylated Asn) and one β-amino acid residue (2-hydroxy-3-amino-4-methyldodecanoic acid or 2-hydroxy-3-amino-4-methylhexadecanoic acid). Minutissamides A-D (1-4) exhibited antiproliferative activity against the HT-29 human colon cancer cell line with IC?? values of 2.0, 20.0, 11.8, and 22.7 μM, respectively.     

Triterpene acids from Poria cocos and their anti-tumor-promoting effects

The structures of six new lanostane-type triterpene acids isolated from the epidermis of the sclerotia of Poria cocos were established to be 15alpha-hydroxydehydrotumulosic acid (5), 16alpha,25-dihydroxydehydroeburicoic acid (9), 5alpha,8alpha-peroxydehydrotumulosic acid (10), 25-hydroxyporicoic acid H (11), 16-deoxyporicoic acid B (12), and poricoic acid CM (16) on the basis of spectroscopic methods. On evaluation of these six and 11 other known triterpene acids isolated from the sclerotium, 1-4, 6-8, 13-15, and 17, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds except for 1, 3, 4, and 8 exhibited inhibitory effects with IC50 values of 195-340 mol ratio/32 pmol TPA. Compound 12 and poricoic acid C (13) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.     

Anti-inflammatory and potential cancer chemopreventive constituents of the fruits of Morinda citrifolia (Noni)

A new anthraquinone, 1,5,15-tri-O-methylmorindol (1), and two new saccharide fatty acid esters, 2-O-(beta-D-glucopyranosyl)-1-O-hexanoyl-beta-D-gluropyranose (4) and 2-O-(beta-D-glucopyranosyl)-1-O-octanoyl-beta-D-gluropyranose (5), have been isolated from a methanol extract of the fruits of Morinda citrifolia (noni) along with 10 known compounds, namely, two anthraquinones (2, 3), six saccharide fatty acid esters (6-11), an iridoid glycoside (12), and a flavanol glycoside (13). Upon evaluation of six compounds (5-7, 9, 10, and 13) for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, four saccharide fatty acid esters, 5-7 and 9, exhibited potent anti-inflammatory activity, with ID50 values of 0.46-0.79 mg per ear. In addition, when compounds 1-13 were evaluated against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA, all of the compounds exhibited moderate inhibitory effects (IC50 values of 386-578 mol ratio/32 pmol TPA).     

Homosecoiridoids from the flower buds of Lonicera japonica

Homosecoiridoids (1-15) were isolated from the flower buds of Lonicera japonica. Compounds 1-4, designated as loniphenyruviridosides A-D, possess unprecedented skeletons featuring phenylpyruvic acid derived moieties coupled with an iridoid or a secoiridoid nucleus. Compounds 5-15 (lonijaposides D-N) are additional examples of the unusual pyridinium alkaloid-coupled secoiridoids (lonijaposides A-C). The validity of the CD data to determine the configuration of the secoiridoid derivatives is discussed on the basis of detailed CD data analysis and semisynthesis of 2 and 3 with the co-occurring secologanic acid. The configuration of secologanic acid was determined by a single-crystal X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Biosynthetic pathways of the homosecoiridoids were postulated. Compounds 1-4 inhibited STAT-3 activity of HELF cells, and lonijaposides F (7), H (9), I (10), and K (12) showed activity against the release of glucuronidase in rat polymorphonuclear leukocytes induced by platelet-activating factor.     

Isolation and pharmacological characterization of vernolepin

Vernolepin, a sesquiterpene lactone, was isolated from the dried fruit of Vernonia amygdalina Del. The different steps used during the extraction were: continuous extraction with chloroform, partition of the chloroform-extract between pertroleum ether and 10% aqueous methanol, column chromatography of the methanol extract, isolation of the active fractions by pharmacological and chemical characterization. Vernolepine was obtained as colorless prisms and identified by melting point, uv, ir, 1H nmr, optical rotation, and mass spectrometry. The total content of the dried fruit was 0.09% vernolepin. The first pharmacological characterization of vernolepin revealed: (1) a competitive antagonism against histamine in guinea pig ileum (pA2 = 5.61; 15 min incubation); (2) a biphasic enhancement/inhibition of coaxial stimulation of guinea pig ileum; (3) an antiaggregating and disaggregating activity against rabbit platelet aggregation induced by arachidonic acid (1 X 10(-4) g/ml; 3.3 X 10(-4)M) or ADP (4 X 10(-6) g/ml; 1 X 10(-5)M) without inhibition of cyclo-oxygenase or lipoxygenase. All these reactions were time dependent and occurred at concentrations of 5 X 10(-6) to 1 X 10(-5) g/ml vernolepin (1.8 to 3.5 X 10(-5)M).     

别嘌醇、丙磺舒以及两者联用对马兜铃酸肝肾损害保护作用研究

目的：探讨别嘌醇（A）、丙磺舒（P）以及两者联用对马兜铃酸肝肾毒性的防治作用,并初步探讨其作用机制。方法：将雄性ICR小鼠随机分为5组：正常对照组（C组）、关木通模型组（M组）、别嘌醇组（A组）、丙磺舒组（P组）、剐嘌醇＋丙磺舒组（A-FP组）。C组灌胃等体积饮用水,后4组灌胃给予7g·kg-1·d-1的关木通水煎剂。给药4天后停药3天,持续4周;各给药组从第3周起在给予造模药的同时灌胃给予相应药物即A（70rag·kg·d。）、P（360rag·kg-1·d-1）、A（70mg·kg-1·d-1）＋P（360mg·kg-1·d-1）。实验结束时,测定小鼠血清肌酐（Cr）、尿素氮（BUN）、谷丙转氨酶（ALT）、谷草转氨酶（AST）水平,并记录左肾、左睾系数。结果：与M组相比,各给药组均能显著降低血清Cr、BUN、ALT、AST水平,其中A＋P组各指标改善作用最为显著。结论：A和P对马兜铃酸所致肝肾损伤都具有保护作用。且两药联用的效果优于两药单独应用。     

Fatty acid synthase inhibitors from plants: isolation,structure elucidation,and SAR studies

Fatty acid synthase (FAS) has been identified as a potential antifungal target. FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1-13), including three new natural products (1, 4, 12), were isolated and their structures identified by spectroscopic interpretation. They represented five chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin-related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4-O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56) analogues of the five chemotypes from our natural product repository and commercial sources were tested for their FAS inhibitory activity. Structure-activity relationships for some chemotypes were investigated. All these compounds were further evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. Although there were several antifungal compounds in the set, correlation between the FAS inhibitory activity and antifungal activity could not be defined.     

Complex C-glycosyl flavonoid phytoalexins from Cucumis sativus

Extraction of cucumber leaf tissue expressing induced resistance against powdery mildew fungi revealed the presence of two new major C-glycosyl flavonoid products: vitexin-6-(4-hydroxy-1-ethylbenzene) (cucumerin A, 1) and isovitexin-8-(4-hydroxy-1-ethylbenzene) (cucumerin B, 2). In addition, the known C-glycosyl flavonoids apigenin-8-C-beta-D-glucopyranoside (vitexin, 3), apigenin-6-C-beta-D-glucopyranoside (isovitexin, 4), luteolin-8-C-beta-D-glucopyranoside (orientin, 5), and luteolin-6-C-beta-D-glucopyranoside (isoorientin, 6), as well as 4-hydroxycinnamic acid (p-coumaric acid, 7) and its methyl ester (p-came, 8), were found in higher quantities within resistant plants. The structures of 1-8 were elucidated using spectroscopic methods and unambiguously confirmed for 3-8 using co-chromatography experiments with authentic standards. On the basis of the results of this study and the reported biological activities of C-glycosyl flavonoids, these compounds would play a vital role in the defense strategy of this species by acting as phytoalexins.     

Isolation of an antiviral polysaccharide, nostoflan, from a terrestrial cyanobacterium, Nostoc flagelliforme

A novel acidic polysaccharide, nostoflan, was isolated from a terrestrial cyanobacterium, Nostoc flagelliforme. Nostoflan exhibited a potent anti-herpes simplex virus type 1 (HSV-1) activity with a selectivity index (50% cytotoxic concentration/50% inhibitory concentration against viral replication) of 13,000. Sugar composition and methylation analyses revealed that it was mainly composed of -->4)-D-Glcp-(1-->, -->6,4)-D-Glcp-(1-->, -->4)-D-Galp-(1-->, -->4)-D-Xylp-(1-->, D-GlcAp-(1-->, D-Manp-(1--> with a ratio of ca. 1:1:1:1:0.8:0.2. Two pyridylaminated oligosaccharides were prepared by partial acid hydrolysis and pyridylamination. On the basis of MALDI-TOF-MS and NMR analyses, they were found to be beta-D-Glcp-(1-->4)-D-Xyl-PA and beta-D-GlcAp-(1-->6)-beta-D-Glcp-(1-->4)-D-Gal-PA. From these results, nostoflan might be mainly composed of the following two types of sugar sequence: -->4)-beta-D-Glcp-(1-->4)-D-Xylp-(1--> and -->4)-[beta-D-GlcAp-(1-->6)-]-beta-D-Glcp-(1-->4)-D-Galp-(1-->. Besides anti-HSV-1 activity, nostoflan showed potent antiviral activities against HSV-2, human cytomegalovirus, and influenza A virus, but no activity against adenovirus and coxsackie virus was observed. Therefore, nostoflan has a broad antiviral spectrum against enveloped viruses whose cellular receptors are carbohydrates. Furthermore, nostoflan showed no antithrombin activity, unlike sulfated polysaccharides.     

Triterpenes from Garcia parviflora. Cytotoxic evaluation of natural and semisynthetic friedelanes

Three new friedelane-type triterpenes, 1,2-dehydro-2,3-secofriedelan-3-oic acid (1), 1β-hydroxyfriedelin (2), and 3β-hydroxyfriedelan-23-oic acid (3), and the known compounds friedelin-3,4-lactone (4), acetyl aleuritolic acid (5), 4-hydroxy-5-propionyl-1,3-di-O-methylpyrogallol, elemicin, and (-)-syringaresinol were isolated from the leaves of Garcia parviflora. The structures of 1-3 were elucidated by spectroscopic methods, including 1D and 2D NMR, HREIMS, X-ray, and CD analysis. Some derivatives of 2 (6-14) were prepared via oxidation, reduction, and esterification. The natural triterpenes and the semisynthetic friedelane derivatives were tested for cytotoxic activity against human cancer cell lines U251, PC-3, K562, HCT-15, MCF-7, and SKLU-1. Compound 5 was cytotoxic against U251 cells.     

Malyngamide 3 and cocosamides A and B from the marine cyanobacterium Lyngbya majuscula from Cocos Lagoon, Guam

Malyngamide 3 (1) and cocosamides A (2) and B (3) were isolated from the lipophilic extract of a collection of Lyngbya majuscula from Cocos Lagoon, Guam. The planar structures of compounds 1-3 were determined by spectroscopic methods. The absolute configuration of 1 was determined by modified Mosher's method, NOESY data, and comparison with lyngbic acid (4). The absolute configurations of 2 and 3 were assigned by enantioselective HPLC analysis and comparison with the closely related compound pitipeptolide A (5). Compounds 1-3 showed weak cytotoxicity against MCF7 breast cancer and HT-29 colon cancer cells.     

Pursaethosides A-E, triterpene saponins from Entada pursaetha

Five new triterpenoid saponins, pursaethosides A-E (1-5), were isolated from the n-BuOH extract of the seed kernels of Entada pursaetha along with the known phaseoloidin. The structures of 1-5 were elucidated mainly by spectroscopic data interpretation and chemical degradation. Pursaethosides C-E (3-5) possess as a common structural feature entagenic acid as aglycon, which is rare among triterpene saponins. Compounds 2-4 and phaesolidin were found to be not cytotoxic when tested against HCT 116 and HT-29 human colon cancer cells.     

Antifungal substances against pathogenic fungi, talaroconvolutins, from talaromyces convolutus

The dichloromethane extract of Talaromyces convolutus cultivated on barley exhibited antifungal activity against Candida albicans. In the course of a search for the active compounds, four new tetramic acid derivatives, talaroconvolutins A (1), B (2), C (3), and D (4), were isolated along with ZG-1494alpha (5), and mitorubrin derivatives. The structures of talaroconvolutins A-D (1-4) were established on the basis of spectroscopic and chemical investigations and chemical correlations. The antifungal activity of the talaroconvolutins against the pathogenic fungi Aspergillus fumigates, Aspergillus niger, C. albicans, and Cryptococcus neoformans was determined.