Cerebrosides and terpene glycosides from the root of<Emphasis Type="Italic">aster scaber</Emphasis>

Three cerebrosides 2, 3, and 5 and two terpene glycosides 1 and 4 have been isolated from the methanol extract of the root of Aster scaber. Their structures were determined as 3-O-beta-D-glucuronopyranosyl-oleanolic acid methyl ester (1), (2S, 3S, 4R, 2'R, 8Z, 15'Z)-N-2'-hydroxy-15'-tetracosenoyl-1-O-beta-D-glucopyranosyl-4-hydroxy-8-sphingenine (2), (2S, 3S, 4R, 8Z)-N-octadecanoyl-1-O-beta-D-glucopyranosyl-4-hydroxy-8-sphingenine (3), 1alpha-hydroxy-6beta-O-beta-D-glucosyl-eudesm-3-ene (4), and (2S, 3S, 4R, 2'R, 8Z)-N-2'-hydroxy-hexadecanoyl-1-O-beta-D-glucopyranosyl-4-hydroxy-8-sphingenine (5) on the basis of spectroscopic methods.     

Selaginellin M, a new selaginellin derivative from Selaginella pulvinata

A new selaginellin derivative, selaginellin M (1), together with one known compound, selaginellin E (2), was isolated from Selaginella pulvinata. The structure of the new compound was elucidated and named as (R,S)-4-((4'-hydroxy-4-((2-hydroxyethoxy)methyl))-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone on the basis of the spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS analysis.     

Hydroxymethoxybenzoylmethylecgonines: new metabolites of cocaine from human urine

4'-Hydroxy-3'-methoxybenzoylecgonine methyl ester (IIIe) and 3'-hydroxy-4'-methoxybenzoylecgonine methyl ester (IIId) were identified as cocaine metabolites in the urine of an admitted habitual polydrug user. The mass spectra and relative gas-liquid chromatography retention times of these metabolites were compared with those of five synthesized hydroxymethoxycocaine positional isomers. IIIe was also identified by mass chromatography in the urine of three patients who received emergency treatment for cocaine abuse.     

New dihydrochalcones and anti-platelet aggregation constituents from the leaves of Muntingia calabura

Two new dihydrochalcones, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone (1) and 4,2',4'-trihydroxy-3'-methoxydihydrochalcone (2), and a new flavanone, (2R,3R)-(-)-3,5-dihydroxy-6,7-dimethoxyflavanone (3), together with nineteen known compounds have been isolated from the leaves of Muntingia calabura. The structures of three new compounds were determined through spectral analyses including extensive 2D-NMR data. Among the isolates, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone, 5,7-dihydroxy-3-methoxyflavone, 5,7-dihydroxy-6-methoxyflavone, 5,4'-dihydroxy-3,7-dimethoxyflavone, (2S)-7,8,3',4',5'-pentamethoxyflavan, (2S)-5'-hydroxy-7,8,3',4'-tetramethoxyflavan, and methyl gallate exhibited significant anti-platelet aggregation activity in vitro.     

Synthesis of biologically active 1'-(2-oxo-2H-benzopyran-6-yl)- 5'-hydroxy-2'-methylindole-3'-amido-2"-phenyl-thiazolidene-4"-ones

6-Aminocoumarins on refluxing with ethyl acetoacetate in 1,2-dichloroethane gave two products: 3'-(2-oxo-2H-benzopyran-6-yl-amino)-but-2'-enoic acid ethyl ester 2a-c and N-(-2-oxo-2H-benzopyran-6-yl)-3'-oxo-butyramide 3a-c. Compounds 2a-c on treatment with 1,4-benzoquinone in N2-atmosphere yielded 1'-( 2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methyl-3'-carbethoxyindoles 4a-c, which on further treatment with hydrazine hydrate gave 1'-(2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methylindole-3'-acid hydrazides 5a-c. These acid hydrazides were treated with benzaldehyde to give 1'-(2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methylindole-3'-benzylidene hydrazides 6a-c, which on further treatment with mercaptoacetic acid in 1,4-dioxane yielded 1'-(2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methylindole-3'-amido-2"-phenylthiazolidene-4"-ones 7a-c. The structures of the compounds have been established on the basis of spectral and analytical data. All compounds have been screened for their antimicrobial activity and have been found to exhibit significant antibacterial and antifungal activities.     

Metabolism of [6]-shogaol in mice and in cancer cells

Ginger has received extensive attention because of its antioxidant, anti-inflammatory, and antitumor activities. However, the metabolic fate of its major components is still unclear. In the present study, the metabolism of [6]-shogaol, one of the major active components in ginger, was examined for the first time in mice and in cancer cells. Thirteen metabolites were detected and identified, seven of which were purified from fecal samples collected from [6]-shogaol-treated mice. Their structures were elucidated as 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 5-methoxy-1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M7), 3',4'-dihydroxyphenyl-decan-3-one (M8), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9), 5-methylthio-1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M10), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), and 5-methylthio-1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M12) on the basis of detailed analysis of their (1)H, (13)C, and two-dimensional NMR data. The rest of the metabolites were identified as 5-cysteinyl-M6 (M1), 5-cysteinyl-[6]-shogaol (M2), 5-cysteinylglycinyl-M6 (M3), 5-N-acetylcysteinyl-M6 (M4), 5-N-acetylcysteinyl-[6]-shogaol (M5), and 5-glutathiol-[6]-shogaol (M13) by analysis of the MS(n) (n = 1-3) spectra and comparison to authentic standards. Among the metabolites, M1 through M5, M10, M12, and M13 were identified as the thiol conjugates of [6]-shogaol and its metabolite M6. M9 and M11 were identified as the major metabolites in four different cancer cell lines (HCT-116, HT-29, H-1299, and CL-13), and M13 was detected as a major metabolite in HCT-116 human colon cancer cells. We further showed that M9 and M11 are bioactive compounds that can inhibit cancer cell growth and induce apoptosis in human cancer cells. Our results suggest that 1) [6]-shogaol is extensively metabolized in these two models, 2) its metabolites are bioactive compounds, and 3) the mercapturic acid pathway is one of the major biotransformation pathways of [6]-shogaol.     

Isolation of chlorphenoxamine metabolites in human urine and their identification

After the administration of chlorphenoxamine (2-[1-(4-chlorophenyl)-1-phenylethoxy]-N,N-dimethylethanamine++ +, Systral) (I) the following compounds have been detected in human urine. They were identified as chlorphenoxamine (I), N-demethyl-chlorphenoxamine (II), chlorphenoxamine-N-oxide (III), 1-(4-chlorophenyl)-l-phenylethanol (IV), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethanol (V), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethene (VI), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethanol (VII), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethene (VIII), 2-[1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethoxy]-N-methyl-ethanamine (IX) and 2-[1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl-ethoxy]- N-methylethanamine (X). The compounds IV, V, VI, VII, VIII, IX and X were also found to be excreted as conjugates. It cannot be excluded that the compounds VI and VIII are artefacts.     

Synthesis and antimicrobial activity of 3-(4'-hydroxy-3'-methylphenyl)-5-[(substuted) phenyl]-4,5-dihydro-1H-1-pyrazolyl-4-pyridylmethanone derivatives

A series of 3-(4'-hydroxy-3'-methylphenyl)-5-[(substituted) phenyl]-4,5-dihydro-1H-1-pyrazolyl-4-pyridylmethanone derivatives were synthesized by the reaction between isoniazid (INH) and various chalcones and were tested for their antimicrobial activity in vitro against Staphylococcus aureus 209p, Escherichia coli ESS 2231, Aspergillus fumigatus, Candida albicans, Candida albicans ATCC 10231, Candida krusei GO3 and Candida glabrata HO5. Among the synthesized compounds, all the compounds possess the significant antibacterial activity. Compounds I(III) and I(x), i.e. 3-(4'-hydroxy-3'-methylphenyl)-5-(4"-dimethylaminophenyl)-4,5-dihydro-1H-1-pyrazolyl-4-pyridyl methanone and 3-(4'-hydroxy-3'-methylphenyl)-5-(2",6"-dichlorophenyl)-4,5-dihydro-1H-1-pyrazolyl-4-pyridylmethanone were found to be the most active agents against used bacterial and fungal strains with minimum inhibitory concentration of less than 0.5 microg/mL and were equally active as standard drugs Ofloxacin and Fluconazole.     

Antiproliferative constituents in plants 14. Coumarins and acridone alkaloids from Boenninghausenia japonica NAKAI

The MeOH extracts of the ground part and the root of Boenninghausenia japonica NAKAI showed inhibitory activity against tumor cell growth. Fractionation of the extracts has resulted in isolation of 1,3-dihydroxy-4-(2'-hydroxy-3'-hydroxymethyl-3',4'-epoxy-butyl)-N-methylacridone, 1,3-dihydroxy-4-[(Z)-3'-hydroxy-3'-methyl-buten-1'-yl]-N-methylacridone, 3-(1',1'-dimethylallyl)-7-hydroxy-8-methoxy-2H-1-benzopyran-2-one, casegravol, cis-casegravol, and edgeworin in addition to 9 compounds reported from B. japonica and B. albiflora. The isolates from this plant and some related compounds were tested for antiproliferative activity against human gastric adenocarcinoma (MK-1), human uterus carcinoma (HeLa), and murine melanoma (B16F10) cells.     

Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura

Two new dihydrochalcones, 2',4'-dihydroxy-3'-methoxydihydrochalcone, (-)-3'-methoxy-2',4',beta-trihydroxydihydrochalcone, a new flavanone, (2 S)-(-)-5'-hydroxy-7,3',4'-trimethoxyflavanone, and a new flavonol derivative, muntingone, along with sixteen known compounds, were isolated from the leaves of Muntingia calabura. The structures of these new compounds were determined using spectral analyses including extensive 2D NMR data. Among the isolates, (2 S)-5'-hydroxy-7,3',4'-trimethoxyflavanone, 4'-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, and 2',4'-dihydroxy-3'-methoxychalcone exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.     

New prenylchalcones from the hops of Humulus lupulus

Two new prenylchalcones, xanthohumol C and D, together with two known prenylchalcone derivatives, xanthohumol (1) and 5'-(2'-hydroxyisopropyl)-dihydrofurano-[2',3'-b]-4,4'-dihydroxy-6'-methoxy-chalcone (4) were isolated and identified from the hops of Humulus lupulus L. The structures of xanhohumol C and D were elucidated as 5'-hydroxy-6',6'-dimethyl-dihydropyrano-[2',3'-b]-4,4'-dihydroxy-6'-methoxy-chalcone (2) and 5'-hydroxy-6',6'-dimethyl-dihydropyrano-[2',3'-b]-4',6'-dimethoxy-4-hydroxy-chalcone (3) on the basis of HRFAB-MS, 1D and 2D NMR (HMQC, HMBC) spectroscopic data. Among the new prenylchalcones, compound 2 showed marginal cytotoxic activity against human stomach carcinoma BGC-823 and human hepatic carcinoma HepG2 cells.     

The structure of inducing factors for virginiamycin production in Streptomyces virginiae

Virginiamycin inducing factors (inducing material or inducing factor) of Streptomyces virginiae were isolated from the culture broth of this microbe and separated into three closely related compounds. They were named virginiae butanolides A, B and C and their structures were determined as 2-(1'-hydroxy-5'-methylhexyl)-3-(hydroxymethyl)butanolide (6), 2-(1'-hydroxy-4'-methylhexyl)-3-(hydroxymethyl)butanolide (7) and 2-(1'-hydroxyhexyl)-3-(hydroxymethyl)butanolide (8), respectively. Part of their stereochemistry was also determined. Racemic virginiae butanolide C was synthesized to confirm their structures.     

Dihydrochalcones from Piper longicaudatum

Bioactivity-guided fractionation of an ethanolic extract of the leaves and twigs of Piper longicaudatum Trelease & Yunker (Piperaceae) resulted in the isolation of one new (1) and three known (2-4) dihydrochalcones. The known compounds are: 2',6'-dihydroxy-4'-methoxydihydrochalcone (2), 2',6',4-trihydroxy-4'-methoxydihydrochalcone (asebogenin) (3), and 2'-hydroxy-4'-methoxy-2'-[1-hydroxy-1-methylethyl]-2",3"-dihy- drofurano[4",5":5',6"]-3"-[2-hydroxy-5-methoxycarbonylphe- nyl]dihydrochalcone (piperaduncin B) (4). The new compound is 2'-hydroxy-4'-methoxy-2"-[2-hydroxy-5-methoxycarbonyl- phenyl]-furano[4",5":5',6']-dihydrochalcone (longicaudatin) (1). Compounds 1-4 were tested for antibacterial activity against S. aureus and methicillin-resistant S. aureus (MRSA); only compound 3 showed inhibitory activity (IC50 of 10 and 4.5 micrograms/ml, respectively).     

2-氨基异黄酮化合物的合成

本文报道了一系列2-氨基-3′-胺甲基-4′-羟基-6-取代异黄酮化合物(Ⅱ)的合成。中间体2-甲氧基-5-取代苯甲酸甲酯(Ⅲ)系用相转移催化技术同时进行醚化和酯化得到。Claisen缩合产物用三溴化硼脱甲基同时环化成2-氨基异黄酮化合物(Ⅵ)。利用Mannich反应在4′-羟基的邻位引入胺甲基制得目的物。药理筛选结果显示Ⅱbb′对小鼠具有明显的耐缺氧作用。     

Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra

Isoflavan derivatives, glabridin (1), hispaglabridin A (2), hispaglabridin B (3), 4'-Omethylglabridin (4) and 3'-hydroxy-4'-O-methylglabridin (5), isolated from Glycyrrhiza glabra, were investigated for their ability to protect liver mitochondria against oxidative stresses. Mitochondrial lipid peroxidation linked to respiratory electron transport and that induced non-enzymatically were inhibited by these isoflavans. Hispaglabridin A (2) strongly inhibited both peroxidations and 3'-hydroxy-4'-O-methylglabridin (5) was the most effective at preventing NADH-dependent peroxidation. 3'-Hydroxy-4'-O-methylglabridin (5) protected mitochondrial respiratory enzyme activities against NADPH-dependent peroxidation injury. Dihydroxyfumarate-induced mitochondrial peroxidation was also prevented by this isoflavan. Isoflavans from G. glabra were shown to be effective in protecting mitochondrial function against oxidative stresses.     

Neuroprotective dibenzylbutyrolactone lignans of Torreya nucifera

The methanolic extract of the bark of Torreya nucifera Sieb. et Zucc. (Taxaceae) significantly protected primary cultures of rat cortical cells exposed to the excitotoxic amino acid, L-glutamate. (-)-Arctigenin (1), (-)-traxillagenin (2), arctiin (4), traxillaside (5), and a newly-reported compound 3 (-)-4'-demethyltraxillagenin [(2R,3R)-2-(4'-hydroxy-3'-methoxybenzyl)-3-(4'-hydroxy-3',5'-dimethoxybenzyl)-butyrolactone] were isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. These lignans and their glycosides had significant neuroprotective activities against glutamate-induced toxicity in primary cultures of rat cortical cells at concentrations ranging from 0.01 microM to 10.0 microM.     

In silico and in vitro immunomodulatory studies on compounds of Lindelofia stylosa

Lindolefia stylosa (Kar. and Kir.) is an important medicinal plant in Central and West Asia. Compounds 1 (ethyl lithospermate), 2 (methyl lithospermate), 3 (lithospermate B), 4 (rosmarinic acid), 5 (methyl rosmarinate), 6 (ethyl rosmarinate), 7 (3-O-feruloyl-6'-O-coumaroyl sucrose), 8 (3-O-feruloyl-6'-O-caffeoyl sucrose), 9 (3,6'-O-diferuloyl sucrose), 10 (3,6'-O-diferuloyl-1-kestose), 11 (3-O-feruloyl-6'-O-coumaroyl-1-kestose), 12 (3,6'-O-diferuloyl nystose), 13 (3-O-Feruloyl-6'-O-coumaroyl nystose), 14 (p-coumaric acid), 15 (ferulic acid), 16 (naphthalene glycoside (8-O-β-D-glucopyranoside)), and 17 (4'-hydroxy-5-methoxy-6,7-methylenedioxyisoflavone), isolated from this plant, were evaluated for their ability to modulate the immune response. Studies included monitoring the effect on reactive oxygen species (ROS) production, T-lymphocyte proliferation, and inhibition of four cytokines (IL-2, TNFα, IL-1β, and IL-4). These cytokines play a major role in immune response modulation. Molecular docking studies on selected compounds were also conducted, which predict a potent activity of compounds 5 and 6 and moderate activity of compounds 1 and 2 as inhibitors of IL-2. Correlation between the predicted binding scores and the experimental results was found to be valid. Compound 5 was identified as the most potent IL-2 inhibitor in the series.     

Abiotic transformations and decomposition kinetics of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)-bis(pyridin ium chloride) in aqueous phosphate buffers

The rate of disappearance of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene) bis (pyridinium chloride) (HI-6) from aqueous phosphate buffers (pH 3.0-9.1) was both pH and temperature sensitive. In midrange buffers (pH 6.0-9.1, mu = 0.2 M) at 37, 25, or 4 degrees C the decomposition followed first-order kinetics consistent with hydroxide-promoted decomposition of the un-ionized drug or with hydrolysis of the ionized oxime anion to result in 4-carbamoyl-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 1). The subsequent conversion of intermediate 1 to 4-carboxy-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 2) followed higher order kinetics which were consistent with either acid- or base-promoted hydrolysis of the B-ring amide functionality. After approximately 138 days in the dark, the sum of the residual HI-6, intermediate 1, and intermediate 2 in the crude decomposition mixture accounted for 89.9 +/- 10.0% of the initial substrate. Minor byproducts included 4-carbamoyl-2'-carboxy-1,1'-(oxydimethylene)bis(pyridinium) cation, 2-pyridinealdoxime, 2-pyridinecarboxaldehyde, 2-hydroxypyridine, isonicotinamide, isonicotinic acid, and traces of cyanide. In addition, 2-cyanopyridine appeared to be a transient intermediate in more alkaline media. In total, this drug resembles other mono- and bis(pyridinium) aldoximes in terms of the decomposition routes in aqueous solutions at intermediate pHs.     

Phenolic glycosides from Exostema mexicanum leaves

Phytochemical investigation of the leaves of Exostema mexicanum led to the isolation of two novel acylated flavonol glycosides 6, 7 and three glycosides 1-4 structurally belonging to the group of 4-phenylcoumarins. One of them, 5-O-beta-D-glucopyranosyl-4'-hydroxy-7-methoxy-4-phenylcoumarin (2), turned out to be new. Furthermore, the 4-phenylcoumarin aglycone 3'-hydroxy-4',5,7-trimethoxy-4-phenylcoumarin (5) was obtained. The in vitro cytotoxicity of 3-5 against the cell line ECV-304 was evaluated; the aglycone 5 was highly cytotoxic, whereas the glycosidic compounds 3 and 4 were inactive.     

Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by 2'-hydroxychalcone derivatives in RAW 264.7 cells

In cultures of the murine macrophage cell line RAW 264.7, effects of four 2'-hydroxychalcone derivatives, 2'-hydroxy-4'-methoxychalcone (compound 1), 2',4-dihydroxy-4'-methoxychalcone (compound 2), 2',4-dihydroxy-6'-methoxychalcone (compound 3) and 2'-hydroxy-4,4'-dimethoxychalcone (compound 4), on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined. Compounds 1, 2 and 3 at 3-30microM inhibited the production with almost the same potency. Compound 4 showed no inhibitory activity. Compounds 1, 2 and 3 at 3-30microM inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha mRNA. To clarify the mechanism involved, effects of compounds 1, 2 and 3 on the activation of nuclear factor (NF)-kappaB and activator protein-1 (AP-1) were examined. Both the LPS-induced activation of NF-kappaB and AP-1 were blocked by compounds 1, 2 and 3 at 3-30microM. Moreover, the three compounds at such concentrations inhibited the LPS-induced IkappaB degradation and the phosphorylation of c-jun N-terminal kinase (JNK) and c-jun. These findings suggest that the inhibition of the LPS-induced production of NO and TNF-alpha by the 2'-hydroxychalcone derivatives is due to the inhibition of NF-kappaB and AP-1 activations.