Four new C-21 steroidal glycosides from the roots of Stephanotis mucronata and their immunological activities

Four new C-21 steroidal glycoside, stemucronatosides D (1), E (2), F (3), and G (4) were isolated from the roots of Stephanotis mucronata. Their structures were determined on the basis of chemical evidence and extensive spectroscopic methods including one-dimensional and two-dimensional NMR. These isolated compounds were assayed for their immunological activities in vitro against concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced proliferation of mice splenocytes. Compounds 1, 2, and 4 showed immunosuppressive activities in a dose-dependent manner, while compound 3 showed immunomodulating activities.     

Cholestane and spirostane glycosides from the rhizomes of Dioscorea septemloba

Cholestane glycosides, dioseptemlosides A (1) and B (2), together with six spirostane glycosides, dioseptemlosides C-H (3-8), were isolated from the rhizomes of Dioscorea septemloba. Their structures were established on the basis of physical data, spectroscopic analysis (HRESIMS, 1D and 2D NMR), and chemical methods. Spirostane aglcones containing hydroxyl group at C-7, as found in compounds 4-7, were reported in the family Dioscoreaceae for the first time. These compounds did not show considerable inhibitory anti-tumor activities at a concentration of 10 microM.     

A new ecdysteroid with unique 9beta-OH and four other ecdysteroids from Silene italica ssp. nemoralis

A new natural ecdysteroid, 9beta,20-dihydroxyecdysone (1) and four related compounds 5alpha-20-hydroxyecdysone (2), 5alpha-2-deoxy-integristerone A (3), integristerone A (4) and 22-deoxy-integristerone A (5) were isolated from the herb of Silene italica ssp. nemoralis. Compound 1 is the C-9 epimer of the known 9alpha,20-dihydroxyecdysone (6) and represents a peculiar steroid skeleton. The structures of the compounds were elucidated by 1D and 2D NMR, IR and MS spectroscopy.     

Potent inhibition of bacterial neuraminidase activity by pterocarpans isolated from the roots of Lespedeza bicolor

Bacterial neuraminidase has been highlighted as a key enzyme for pathogenic infection and sepsis. Six pterocarpans displaying significant levels of neuraminidase inhibitory activity were isolated from the root bark of Lespedeza bicolor. The isolated compounds were identified as three new pterocarpans (1-3) together with known compounds erythrabyssin II (4), lespebuergine G4 (5), and 1-methoxyerythrabyssin II (6). The new compounds were characterized as bicolosin A (1), bicolosin B (2), and bicolosin C (3). All compounds inhibited bacterial neuraminidase in a dose-dependent manner with significant inhibition (IC(50)=0.09-3.25 μM). All neuraminidase inhibitors screened were found to exhibit noncompetitive kinetics. The three most potent neuraminidase inhibitors (1, 3 and 6) feature a methoxy substitution on C-1.     

Biotransformation of betulinic and betulonic acids by fungi

Betulinic acid (1), a triterpenoid found in many plant species, has attracted attention due to its important pharmacological properties, such as anti-cancer and anti-HIV activities. The closely related, betulonic acid (2) also has similar properties. In order to obtain derivatives potentially useful for detailed pharmacological studies, both compounds were submitted to incubations with selected microorganisms. In this work, both were individually metabolized by the fungi Arthrobotrys, Chaetophoma and Dematium, isolated from the bark of Platanus orientalis as well as with Colletotrichum, obtained from corn leaves; such fungal transformations are quite rare in the scientific literature. Biotransformations with Arthrobotrys converted betulonic acid (2) into 3-oxo-7beta-hydroxylup-20(29)-en-28-oic acid (3), 3-oxo-7beta,15alpha-dihydroxylup-20(29)-en-28-oic acid (4) and 3-oxo-7beta,30-dihydroxylup-20(29)-en-28-oic acid (5); Colletotrichum converted betulinic acid (1) into 3-oxo-15alpha-hydroxylup-20(29)-en-28-oic (6) acid whereas betulonic acid (2) was converted into the same product and 3-oxo-7beta,15alpha-dihydroxylup-20(29)-en-28-oic acid (4); Chaetophoma converted betulonic acid (2) into 3-oxo-25-hydroxylup-20(29)-en-28-oic acid (7) and both Chaetophoma and Dematium converted betulinic acid (1) into betulonic acid (2). Those fungi, therefore, are useful for mild, selective oxidations of lupane substrates at positions C-3, C-7, C-15, C-25 and C-30.     

Effect of natural and synthetic benzyl benzoates on calmodulin

The present investigation describes the effect of the spasmolytic benzylbenzoates 1-9 from Brickellia veronicifolia on CaM using a functional in vitro enzymatic assay. Bovine brain PDE1 was used as a monitoring enzyme. The most active natural inhibitors of the system CaM-PDE1 were benzyl benzoates 3-5, which inhibited the activity of PDE1 in a concentration-dependent manner. In addition, three series of analogs of compound 4, compounds 10a-32a, were prepared and assayed. The benzyl benzoates from the first series, namely 10a-24a, possess no substituents on ring B but different number and position of hydroxyl or methoxy groups in ring A. The second group (25-32a), on the other hand, possesses an A ring identical to that on compound 4, but different substituents in Ring B. The most active compounds were 14a, 15a and 30a. These compounds were two to six times more potent than chlorpromazine, a well known CaM inhibitor. Benzyl benzoates 14a and 15a have methoxyl groups at C-2/C-4 and C-3/C-4 in ring A, respectively; while 30a, in addition to the methoxyl groups at C-2/C-6 of ring A, hold a benzoyloxy moiety at C-3' of ring B. Kinetic studies revealed that compounds 3, 4, 14a, 15a and 30a behave as competitive CaM antagonists.     

Chemistry and weak antimicrobial activities of phomopsins produced by mangrove endophytic fungus Phomopsis sp. ZSU-H76

Three metabolites named phomopsin A (1), B (2) and C (3), together with two known compounds cytosporone B (4) and C (5), were isolated from the mangrove endophytic fungus, Phomopsis sp. ZSU-H76 obtained from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly by 1D and 2D NMR spectroscopic techniques. The medium-sized cyclic phenol ether based on 1 or 2 is rare in natural products. In bioassays, compounds 1, 2, and 3 had no significant antibiotic activities, but compounds 4 and 5 inhibited two fungi Candida albicans and Fusarium oxysporum with an MIC ranging from 32 to 64 microg/ml.     

New bioactive sulfated alkenes from the sea cucumber Apostichopus japonicus

Two new alkene sulfates, (5Z)-dec-5-en-1-yl sulfate (4) and (3E)-dec-3-en-1-yl sulfate (5), together with three known sulfated alkanes, 2,6-dimethylheptyl sulfate (1), octyl sulfate (2), and decyl sulfate (3), were isolated from the sea cucumber Apostichopus japonicus. The structures of the new compounds 4 and 5 were elucidated by spectroscopic analysis, including 1H-, 13C-, and 2D-NMR, ESI-MS, and HR-ESI-MS. Compounds 2 and 3 were isolated from natural sources for the first time. In preliminary bioassays in vitro, compounds 4 and 5 showed antibacterial, antifungal, and cytotoxic activities.     

Three new 12-carbamoylated streptothricins from Streptomyces sp. I08A 1776

Two new streptothricins (1 and 2) and a new streptothricin acid derivative (3), all with the carbamoyl group substituted at C-12 of the gulosamine moiety, together with the known N(β)-acetylstreptothricin D acid (4), have been isolated from the culture broth of Streptomyces sp. I08A 1776. The structures of the new compounds were determined by MS, CD, and 1D and 2D NMR spectroscopic data analysis. The isolated compounds were evaluated for antibacterial and antifungal activities. Streptothricin E (6) showed potent activity against the clinically isolated extensively drug-resistant Mycobacterium tuberculosis with MIC values of 0.25-0.5μg/mL.     

Phenolic compounds from the fruit of Garcinia dulcis

Dulcinoside (1), dulcisisoflavone (2), dulcisxanthone A (3) and sphaerobioside acetate (6) together with 22 known compounds were isolated from the green fruit of G. dulcis. Dulcisflavan (4), dulcisxanthone B (5) and isonormangostin (7) together with 22 known compounds were isolated from the ripe fruit. Compounds 6 and 7 were synthetic known compounds. Their structures were determined by spectroscopic methods. The radical scavenging and antibacterial activities of some of the compounds were investigated.     

Glycon specificity profiling of alpha-glucosidases using monodeoxy and mono-O-methyl derivatives of p-nitrophenyl alpha-D-glucopyranoside

Hydrolysis of probe substrates, eight possible monodeoxy and mono-O-methyl analogs of p-nitrophenyl alpha-D-glucopyranoside (pNP alpha-D-Glc), modified at the C-2, C-3, C-4, and C-6 positions, was studied as part of investigations into the glycon specificities of seven alpha-glucosidases (EC 3.2.1.20) isolated from Saccharomyces cerevisiae, Bacillus stearothermophilus, honeybee (two enzymes), sugar beet, flint corn, and Aspergillus niger. The glucosidases from sugar beet, flint corn, and A. niger were found to hydrolyze the 2-deoxy analogs with substantially higher activities than against pNP alpha-D-Glc. Moreover, the flint corn and A. niger enzymes showed hydrolyzing activities, although low, for the 3-deoxy analog. The other four alpha-glucosidases did not exhibit any activities for either the 2- or the 3-deoxy analogs. None of the seven enzymes exhibited any activities toward the 4-deoxy, 6-deoxy, or any of the methoxy analogs. The hydrolysis results, with the deoxy substrate analogs, demonstrated that alpha-glucosidases having remarkably different glycon specificities exist in nature. Further insight into the hydrolysis of deoxyglycosides was obtained by determining the kinetic parameters (k(cat) and K(m)) for the reactions of sugar beet, flint corn, and A. niger enzymes.     

Anti-plasmodial and antioxidant activities of constituents of the seed shells of Symphonia globulifera Linn f

A xanthone derivative, named gaboxanthone (1), has been isolated from the seed shells of Symphonia globulifera, together with known compounds, symphonin (2), globuliferin (3), guttiferone A (4), sistosterol, oleanolic acid and methyl citrate. The structure of the compound was assigned as 5,10-dihydroxy-8,9-dimethoxy-2,2-dimethyl-12-(3-methylbut-2-enyl) pyrano [3,2-b]xanthen-6(2H)-one, by means of spectroscopic analysis. The anti-plasmodial and antioxidant activities of the phenolic compounds were evaluated, respectively, in culture against W2 strain of Plasmodium falciparum and using the free radical scavenging activity of the DPPH radical, respectively. Compounds 1-4 were found to be active against the Plasmodium parasites (IC(50) of 3.53, 1.29, 3.86 and 3.17 microM, respectively). Guttiferone A (4) showed a potent free radical scavenging activity compared to the well-known antioxidant caffeic acid.     

Immunosuppressive diacetylenes, ceramides and cerebrosides from Hydrocotyle leucocephala

Three C-17 diacetylenic compounds (1-3), one monoterpenoid (4), seven ceramides (leucoceramides A-G, 5a-g), six cerebrosides (leucocerebrosides A-F, 6a-f) and nine known compounds were isolated from the methanolic extract of Hydrocotyle leucocephala. Their structures were established by spectroscopic methods. The isolated compounds 1-3, 5a-g, 6a-f and 7 were shown to be active in the lipopolysaccharide (LPS) induced cytokine production assay for IL-10, IL-12, and TNF-alpha.     

Leishmanicidal cycloartane-type triterpene glycosides from Astragalus oleifolius

Two new cycloartane-type glycosides oleifoliosides A (1) and B (2) were isolated from the lower stem parts of Astragalus oleifolius. Their structures were identified as 3-O-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-O-beta-xylopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane and 3-O-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-O-beta-glucopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane, respectively, by means of spectroscopic methods (IR, 1D and 2D NMR, ESI-MS). Three known cycloartane glycosides cyclocanthoside E (3), astragaloside II (4) and astragaloside IV (5) were also isolated and characterized. All five compounds were evaluated for in vitro trypanocidal, leishmanicidal and antiplasmodial activities as well as their cytotoxic potential on primary mammalian (L6) cells. Except for the compound 5, all compounds showed notable growth inhibitory activity against Leishmania donovani with IC50 values ranging from 13.2 to 21.3 microg/ml. Only weak activity against Trypanosoma brucei rhodesiense was observed with the known compounds astragaloside II (4, IC50 66.6 microg/ml) and cyclocanthoside E (3, IC50 85.2 microg/ml), while all compounds were inactive against Trypanosoma cruzi and Plasmodium falciparum. None of the compounds were toxic to mammalian cells (IC50's > 90 microg/ml). This is the first report of leishmanicidal and trypanocidal activity of cycloartane-type triterpene glycosides.     

Compounds from Kadsura angustifolia with anti-HIV activity

Four new cycloartane triterpenoids, angustific acid A (1), angustific acid B (2), angustifodilactone A (3) and angustifodilactone B (4) were isolated from the branches of Kadsura angustifolia together with six known compounds, micranoic acid B (5), nigranoic acid (6), schisandrin (7), schisantherin D (8), interiotherin B (9), schisantherin B (10). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. Compound 1, characterized by the presence of a C-16/C-17, C-20/C-21 conjugated diene and a C-1/C-7 ester bridge formed in rings A and B, provided a novel structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, the anti-HIV activities of these compounds were determined in infected C8166 cells, and it was found that angustific acid A (1) exhibited the most potent anti-HIV activity with an EC₅₀ value of 6.1 μg/mL and a therapeutic index of more than 32.8.     

Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive activities from the marine-derived fungus Penicillium sp. SOF07

Three new mycophenolic acid derivatives, penicacids A-C (1-3), together with two known analogues, mycophenolic acid (MPA, 4) and 4'-hydroxy-MPA (5), were isolated from a fungus Penicillium sp. SOF07 derived from a South China Sea marine sediment. The structures of compounds 1-3 were elucidated on the basis of MS and NMR ((1)H, (13)C, HSQC and HMBC) data analyses and comparisons with the known compounds. Structure-activity relationship studies of compounds 1-5 focused on inosine-monophosphate dehydrogenase inhibition revealed that hydroxylation at C-4', methylation at C-7-OH, dual hydroxylation at C-2'/C-3' double bond of MPA diminished bioactivity whereas glucosyl hydroxylation at C-4' correlated to bioactivity comparable to that observed for MPA.     

Stereumin A-E, sesquiterpenoids from the fungus Stereum sp. CCTCC AF 207024

Five cadinane sesquiterpenoids, named stereumin A (1), B (2), C (3), D (4) and E (5) were isolated from the CHCl(3) extract of the culture broth of the fungal strain CCTCC AF 207024. Based on the sequences at the internal transcribed spacer (ITS) region and partial 28S rDNA, this fungus was identified as a Stereum sp. The structures of the five compounds were elucidated using spectroscopic data from 1D, 2D NMR and HRESIMS experiments, and the structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction analysis. Compounds 1-5 showed nematicidal activities against the nematode Panagrellus redivivus at 400 mg l(-1). Among these five compounds, compounds 3 and 4 killed 84.4% and 94.9% of P. redivivus, respectively in 48 h.     

海南大风子活性成分研究

用色谱技术对海南大风子(Hydnocarpus hainanensis (Merr.) Sleum.)枝条的乙醇提取物进行分离纯化,从中分离得到了6个化合物,经波谱数据分析与文献数据对照,分别鉴定为eoniferaldehyde (1)、mulberroside C(2)、mulberrofuran G(3)、mulb...     

Three new isoflavonoids with antioxidant properties from Ptycholobium contortum (N.E.Br.) Brummitt (Leguminosae)

Two new pterocarpans, seputhecarpan A (1) and B (2) and a new isoflavanone seputheisoflavone (3) were isolated from the roots of Ptycholobium contortum. Seputhecarpan A and B were identified respectively as 9-hydroxylated and 9,16-dihydroxylated pterocarpans possessing a linear (C-2/C-3) isopropenyldihydrofuran substituent and seputheisoflavone as 5′-α,α-dimethylallyl-4′,5,7-trihydroxy-2′-methoxyisoflavanone. In addition, four known compounds, genistein, isoliquiritigenin, thonningiol and (−)-medicarpin were isolated. Their structures were elucidated using intensive 1D and 2D NMR spectroscopies, CD and MS data. The new compounds were assayed for their antimicrobial, α-glucosidase and antioxidant activities. If the antimicrobial and α-glucosidase inhibitory properties were weak, all the tested compounds exhibited antioxidant activities and seputhecarpan A (1) was most effective as an antioxidant with an EC50 value of 0.030 mg/ml.     

Structure of a fucoidan from the brown seaweed Fucus serratus L

A fucoidan consisting of L-fucose, sulfate and acetate in a molar proportion of 1:1:0.1 and small amounts of xylose and galactose were isolated from the brown seaweed Fucus serratus L. The fucoidan structure was investigated by 1D and 2D 1H and 13C NMR spectroscopy of its desulfated and de-O-acetylated derivatives as well as by methylation analysis of the native and desulfated polysaccharides. A branched structure was suggested for the fucoidan with a backbone of alternating 3- and 4-linked alpha-L-fucopyranose residues, -->3)-alpha-L-Fucp-(1-->4)-alpha-L-Fucp-(1-->, about half of the 3-linked residues being substituted at C-4 by trifucoside units alpha-L-Fucp-(1-->4)-alpha-L-Fucp-(1-->3)-alpha-L-Fucp-(1-->. Minor chains built up of 4-linked alpha-fucopyranose and beta-xylose residues were also detected, but their location, as well as the position of galactose residues, remained unknown. Sulfate groups were shown to occupy mainly C-2 and sometimes C-4, although 3,4-diglycosylated and some terminal fucose residues may be nonsulfated. Acetate was found to occupy C-4 of 3-linked Fuc and C-3 of 4-linked Fuc in a ratio of about 7:3.