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Sample records for 17-hydroxygeranyllinalool diterpene glycosides

  1. Using the knowns to discover the unknowns: MS-based dereplication uncovers structural diversity in 17-hydroxygeranyllinalool diterpene glycoside production in the Solanaceae.

    PubMed

    Heiling, Sven; Khanal, Santosh; Barsch, Aiko; Zurek, Gabriela; Baldwin, Ian T; Gaquerel, Emmanuel

    2016-02-01

    Exploring the diversity of plant secondary metabolism requires efficient methods to obtain sufficient structural insights to discriminate previously known from unknown metabolites. De novo structure elucidation and confirmation of known metabolites (dereplication) remain a major bottleneck for mass spectrometry-based metabolomic workflows, and few systematic dereplication strategies have been developed for the analysis of entire compound classes across plant families, partly due to the complexity of plant metabolic profiles that complicates cross-species comparisons. 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) are abundant defensive secondary metabolites whose malonyl and glycosyl decorations are induced by jasmonate signaling in the ecological model plant Nicotiana attenuata. The multiple labile glycosidic bonds of HGL-DTGs result in extensive in-source fragmentation (IS-CID) during ionization. To reconstruct these IS-CID clusters from profiling data and identify precursor ions, we applied a deconvolution algorithm and created an MS/MS library from positive-ion spectra of purified HGL-DTGs. From this library, 251 non-redundant fragments were annotated, and a workflow to characterize leaf, flower and fruit extracts of 35 solanaceous species was established. These analyses predicted 105 novel HGL-DTGs that were restricted to Nicotiana, Capsicum and Lycium species. Interestingly, malonylation is a highly conserved step in HGL-DTG metabolism, but is differentially affected by jasmonate signaling among Nicotiana species. This MS-based workflow is readily applicable for cross-species re-identification/annotation of other compound classes with sufficient fragmentation knowledge, and therefore has the potential to support hypotheses regarding secondary metabolism diversification.

  2. Jasmonate and ppHsystemin Regulate Key Malonylation Steps in the Biosynthesis of 17-Hydroxygeranyllinalool Diterpene Glycosides, an Abundant and Effective Direct Defense against Herbivores in Nicotiana attenuata[W

    PubMed Central

    Heiling, Sven; Schuman, Meredith C.; Schoettner, Matthias; Mukerjee, Purba; Berger, Beatrice; Schneider, Bernd; Jassbi, Amir R.; Baldwin, Ian T.

    2010-01-01

    We identified 11 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) that occur in concentrations equivalent to starch (mg/g fresh mass) in aboveground tissues of coyote tobacco (Nicotiana attenuata) and differ in their sugar moieties and malonyl sugar esters (0-2). Concentrations of HGL-DTGs, particularly malonylated compounds, are highest in young and reproductive tissues. Within a tissue, herbivore elicitation changes concentrations and biosynthetic kinetics of individual compounds. Using stably transformed N. attenuata plants silenced in jasmonate production and perception, or production of N. attenuata Hyp-rich glycopeptide systemin precursor by RNA interference, we identified malonylation as the key biosynthetic step regulated by herbivory and jasmonate signaling. We stably silenced N. attenuata geranylgeranyl diphosphate synthase (ggpps) to reduce precursors for the HGL-DTG skeleton, resulting in reduced total HGL-DTGs and greater vulnerability to native herbivores in the field. Larvae of the specialist tobacco hornworm (Manduca sexta) grew up to 10 times as large on ggpps silenced plants, and silenced plants suffered significantly more damage from herbivores in N. attenuata's native habitat than did wild-type plants. We propose that high concentrations of HGL-DTGs effectively defend valuable tissues against herbivores and that malonylation may play an important role in regulating the distribution and storage of HGL-DTGs in plants. PMID:20081114

  3. Diterpene glycosides from Stevia phlebophylla A. Gray.

    PubMed

    Ceunen, Stijn; Wim, De Borggraeve; Compernolle, Frans; Mai, Anh Hung; Geuns, Jan M C

    2013-09-20

    The rare Mexican species Stevia phlebophylla A. Gray was long considered to be the only known Stevia species, beside the well-known S. rebaudiana, containing the highly sweet diterpenoid steviol glycosides. We report a re-evaluation of this claim after phytochemically screening leaves obtained from two herbarium specimens of S. phlebophylla for the presence of steviol glycosides. Despite extensive MS analyses, no steviol glycosides could be unambiguously verified. Instead, the main chromatographic peak eluting at retention times similar to those of steviol glycosides was identified as a new compound, namely 16β-hydroxy-17-acetoxy-ent-kauran-19-oic acid-(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl) ester (1) on the basis of extensive NMR and MS data as well as the characterization of its acid hydrolysate. Seven more compounds were detected by ESIMS which are possibly structurally related to 1. It can therefore be concluded that S. phlebophylla is unlikely to contain significant amounts of steviol glycosides, if any.

  4. Minor diterpene glycosides from the leaves of Stevia rebaudiana.

    PubMed

    Ibrahim, Mohamed A; Rodenburg, Douglas L; Alves, Kamilla; Fronczek, Frank R; McChesney, James D; Wu, Chongming; Nettles, Brian J; Venkataraman, Sylesh K; Jaksch, Frank

    2014-05-23

    Two new diterpene glycosides in addition to five known glycosides have been isolated from a commercial extract of the leaves of Stevia rebaudiana. Compound 1 (rebaudioside KA) was shown to be 13-[(O-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid 2-O-β-d-glucopyranosyl-β-d-glucopyranosyl ester and compound 2, 12-α-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester. Five additional known compounds were identified, rebaudioside E, rebaudioside M, rebaudioside N, rebaudioside O, and stevioside, respectively. Enzymatic hydrolysis of stevioside afforded the known ent-kaurane aglycone 13-hydroxy-ent-kaur-16-en-19-oic acid (steviol) (3). The isolated metabolite 1 possesses the ent-kaurane aglycone steviol (3), while compound 2 represents the first example of the isomeric diterpene 12-α-hydroxy-ent-kaur-16-en-19-oic acid existing as a glycoside in S. rebaudiana. The structures of the isolated metabolites 1 and 2 were determined based on comprehensive 1D- and 2D-NMR (COSY, HSQC, and HMBC) studies. A high-quality crystal of compound 3 has formed, which allowed the acquisition of X-ray diffraction data that confirmed its structure. The structural similarities between the new metabolites and the commercially available stevioside sweeteners suggest the newly isolated metabolites should be examined for their organoleptic properties. Accordingly rebaudiosides E, M, N, O, and KA have been isolated in greater than gram quantities.

  5. Diterpene glycosides from the ethanol extract of Diplopterygium rufopilosum.

    PubMed

    Hu, Jiang; Song, Yan; Li, Hui; Mao, Xia; Shi, Xiao-Dong

    2015-01-01

    A phytochemical investigation on the 70% EtOH extract from the dry fronds of Diplopterygium rufopilosum afforded two new labdane-type diterpene glycosides, (3β,13S)-3-O-β-d-glucopyranosyl-13-O-α-l-rhamnopyranosyl-labda-8(17),14-diene (1) and (3β,13S)-3-O-α-l-rhamnopyranosyl-13-O-[6-O-acetyl-β-d-glucopyranosyl-(1 → 4)-2-O-acetyl-α-l-rhamnopyranosyl]-labda-8(17),14-diene (2). Their structures were determined on the basis of chemical method and spectroscopic analyses, including 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and HR-ESI-MS analyses.

  6. Clerodane and Ent-kaurane Diterpene Glycosyl and Glycoside Derivatives from the Leaves of Casearia sylvestris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five new clerodane diterpene glycosides caseariasides A-E (1-4) and three new ent-kaurane diterpene glucosides sylvestrisides C-E (6-8) were isolated from the leaves of Casearia sylvestris. Their structures were determined on the basis of chemical and spectroscopic analyses....

  7. New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha.

    PubMed

    Wu, La-Bin; Xiao, Chao-Jiang; Jiang, Xue; Qiu, Lin; Dong, Xiang; Jiang, Bei

    2015-08-01

    Two new labdane-type diterpenes (adenanthic acids A and B; 1 and 2, resp.) and three new labdane diterpene glycosides (adenanthosides A-C; 3-5, resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids (6-12), eight triterpenoids (13-20), one lignan glycoside (21), six steroids (22-27), and one ceramide (28). Their structures were elucidated by spectroscopic methods including extensive 2D-NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities.

  8. Cordifolide A, a Sulfur-containing Clerodane Diterpene Glycoside from Tinospora cordifolia

    PubMed Central

    Pan, Li; Terrazas, Cesar; Lezama-Davila, Claudio M.; Rege, Nirmala; Gallucci, Judith C.; Satoskar, Abhay R.; Kinghorn, A. Douglas

    2012-01-01

    Cordifolide A (1), a novel unprecedented sulfur-containing clerodane diterpene glycoside, together with other two new diterpene glycosides, cordifolides B (2) and C (3), and four known analogues, was isolated from a methanol-soluble extract of the stems of Tinospora cordifolia. The structures of the new compounds were determined on the basis of spectroscopic data interpretation, with that of cordifolide A (1) confirmed by a single-crystal X-ray crystallographic analysis. All isolates were evaluated for their in vitro immunomodulatory activity using mouse bone marrow-derived dentritic cells (BMDCs). PMID:22497272

  9. A New Diterpene Glycoside: 15α-Hydroxy-Rebaudioside M Isolated from Stevia rebaudiana.

    PubMed

    Prakash, Indra; Ma, Gil; Bunders, Cynthia; Devkota, Krishna P; Charan, Romila D; Ramirez, Catherine; Snyder, Tara M; Priedemann, Christopher

    2015-07-01

    In a continued search for novel diterpenoid glycosides, we recently isolated and characterized a Rebaudioside M derivative with a hydroxyl group at position 15 in the central diterpene core from an extract of Stevia rebaudiana Bertoni. Here we report the complete structure elucidation of 15α-hydroxy-Rebaudioside M (2) on the basis of NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY, NOESY) and mass spectral data. Steviol glycoside with a hydroxyl group at C-15 in the central diterpene core has not been previously reported.

  10. A New Diterpene Glycoside: 15α-Hydroxy-Rebaudioside M Isolated from Stevia rebaudiana.

    PubMed

    Prakash, Indra; Ma, Gil; Bunders, Cynthia; Devkota, Krishna P; Charan, Romila D; Ramirez, Catherine; Snyder, Tara M; Priedemann, Christopher

    2015-07-01

    In a continued search for novel diterpenoid glycosides, we recently isolated and characterized a Rebaudioside M derivative with a hydroxyl group at position 15 in the central diterpene core from an extract of Stevia rebaudiana Bertoni. Here we report the complete structure elucidation of 15α-hydroxy-Rebaudioside M (2) on the basis of NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY, NOESY) and mass spectral data. Steviol glycoside with a hydroxyl group at C-15 in the central diterpene core has not been previously reported. PMID:26410999

  11. New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha.

    PubMed

    Wu, La-Bin; Xiao, Chao-Jiang; Jiang, Xue; Qiu, Lin; Dong, Xiang; Jiang, Bei

    2015-08-01

    Two new labdane-type diterpenes (adenanthic acids A and B; 1 and 2, resp.) and three new labdane diterpene glycosides (adenanthosides A-C; 3-5, resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids (6-12), eight triterpenoids (13-20), one lignan glycoside (21), six steroids (22-27), and one ceramide (28). Their structures were elucidated by spectroscopic methods including extensive 2D-NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities. PMID:26265575

  12. Two new ent-kaurane-type diterpene glycosides from zucchini (Cucurbita pepo L.) seeds.

    PubMed

    Kikuchi, Takashi; Ando, Hiromi; Maekawa, Ken-Ichiro; Arie, Hiroki; Yamada, Takeshi; Tanaka, Reiko

    2015-12-01

    Two new ent-kaurane diterpene glycosides; 12α-(β-d-glucopyranosyloxy)-7β-hydroxykaurenolide (1) and 7β-(β-d-glucopyranosyloxy)-12α-hydroxykaurenolide (2), a new steroid; (24S)-stigmasta-7,22E,25-trien-3-one (12), and known compounds (3-11, 13-14) were isolated from zucchini (Cucurbita pepo L.) seeds. The absolute structures of 1 and 2 were determined by acid hydrolysis and application of a modified Moscher's method. Furthermore, isolated compounds (1-14), and a derivative, 1a, were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production.

  13. Two new ent-kaurane-type diterpene glycosides from zucchini (Cucurbita pepo L.) seeds.

    PubMed

    Kikuchi, Takashi; Ando, Hiromi; Maekawa, Ken-Ichiro; Arie, Hiroki; Yamada, Takeshi; Tanaka, Reiko

    2015-12-01

    Two new ent-kaurane diterpene glycosides; 12α-(β-d-glucopyranosyloxy)-7β-hydroxykaurenolide (1) and 7β-(β-d-glucopyranosyloxy)-12α-hydroxykaurenolide (2), a new steroid; (24S)-stigmasta-7,22E,25-trien-3-one (12), and known compounds (3-11, 13-14) were isolated from zucchini (Cucurbita pepo L.) seeds. The absolute structures of 1 and 2 were determined by acid hydrolysis and application of a modified Moscher's method. Furthermore, isolated compounds (1-14), and a derivative, 1a, were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. PMID:26420344

  14. New Ent-Kaurane-Type Diterpene Glycosides and Benzophenone from Ranunculus muricatus Linn.

    PubMed

    Wu, Bi-Ling; Zou, Hui-Liang; Qin, Fang-Min; Li, Hong-Yu; Zhou, Guang-Xiong

    2015-12-15

    Two new ent-kaurane diterpene glycosides, ranunculosides A (1) and B (2), and a new benzophenone, ranunculone C (3), were isolated from the aerial part of Ranunculus muricatus Linn. The chemical structures of compounds 1-3 were established to be (2S)-ent-kauran-2β-ol-15-en-14-O-β-d-glucopyranoside, (2S,4S)-ent-kauran-2β,18-diol-15-en-14-O-β-d-glucopyranoside, and (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxy-phenyl]-2-hydroxylpropanoic acid, respectively, by spectroscopic data and chemical methods. The absolute configuration of 1 was determined by the combinational application of RP-HPLC analysis and Mosher's method.

  15. Isolation and structural characterization of a new minor diterpene glycoside from Stevia rebaudiana.

    PubMed

    Chaturvedula, Venkata Sai Prakash; Zamora, Julian

    2014-12-01

    From the commercial extract of the leaves of the sweet plant Stevia rebaudiana Bertoni obtained from Sinochem Qingdao Co. Ltd., a new diterpene glycoside having three β-D-glucopyranosyl units of which two of them were connected in a relatively rare linkage of 3-β-D-glucobiosyl substitution at C-19 position of the aglycone steviol. The structure of the new compound has been characterized as 13-β-D-glucopyranosyloxy ent-kaur-16-en-19-oic acid-[(3-O-β-D- glucopyranosyl-β-D-glucopyranosyl) ester (1) on the basis of extensive 1D (1H and 13C) and 2D NMR (TOCSY, HMQC, and HMBC), and High Resolution mass spectroscopic data as well as hydrolysis studies. PMID:25632456

  16. Isolation and structural characterization of a new minor diterpene glycoside from Stevia rebaudiana.

    PubMed

    Chaturvedula, Venkata Sai Prakash; Zamora, Julian

    2014-12-01

    From the commercial extract of the leaves of the sweet plant Stevia rebaudiana Bertoni obtained from Sinochem Qingdao Co. Ltd., a new diterpene glycoside having three β-D-glucopyranosyl units of which two of them were connected in a relatively rare linkage of 3-β-D-glucobiosyl substitution at C-19 position of the aglycone steviol. The structure of the new compound has been characterized as 13-β-D-glucopyranosyloxy ent-kaur-16-en-19-oic acid-[(3-O-β-D- glucopyranosyl-β-D-glucopyranosyl) ester (1) on the basis of extensive 1D (1H and 13C) and 2D NMR (TOCSY, HMQC, and HMBC), and High Resolution mass spectroscopic data as well as hydrolysis studies.

  17. Rebaudiosides R and S, Minor Diterpene Glycosides from the Leaves of Stevia rebaudiana.

    PubMed

    Ibrahim, Mohamed A; Rodenburg, Douglas L; Alves, Kamilla; Perera, Wilmer H; Fronczek, Frank R; Bowling, John; McChesney, James D

    2016-05-27

    Two new diterpene glycosides have been isolated from a commercial extract of the leaves of Stevia rebaudiana. Compound 1 was shown to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-xylopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (rebaudioside R), while compound 2 was determined to be 13-[(2-O-α-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid 2-O-α-l-rhamnopyranosyl-β-d-glucopyranosyl ester (rebaudioside S). Six additional known compounds were identified, dulcoside B, 13-[(2-O-β-d-xylopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester, eugenol diglucoside, rebaudioside G, 13-[(2-O-6-deoxy-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester, and rebaudioside D (3), respectively. The structures of 1 and 2 were determined based on comprehensive 1D and 2D NMR (COSY, HSQC, and HMBC) studies. A high-quality crystal of compound 3 allowed confirmation of its structure by X-ray diffraction.

  18. Rebaudiosides R and S, Minor Diterpene Glycosides from the Leaves of Stevia rebaudiana.

    PubMed

    Ibrahim, Mohamed A; Rodenburg, Douglas L; Alves, Kamilla; Perera, Wilmer H; Fronczek, Frank R; Bowling, John; McChesney, James D

    2016-05-27

    Two new diterpene glycosides have been isolated from a commercial extract of the leaves of Stevia rebaudiana. Compound 1 was shown to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-xylopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (rebaudioside R), while compound 2 was determined to be 13-[(2-O-α-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid 2-O-α-l-rhamnopyranosyl-β-d-glucopyranosyl ester (rebaudioside S). Six additional known compounds were identified, dulcoside B, 13-[(2-O-β-d-xylopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester, eugenol diglucoside, rebaudioside G, 13-[(2-O-6-deoxy-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester, and rebaudioside D (3), respectively. The structures of 1 and 2 were determined based on comprehensive 1D and 2D NMR (COSY, HSQC, and HMBC) studies. A high-quality crystal of compound 3 allowed confirmation of its structure by X-ray diffraction. PMID:27119206

  19. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    PubMed

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  20. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    PubMed

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract. PMID:27071804

  1. A New ent-Labdane Diterpene Glycoside form the Leaves of Casearia sylvestris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sylvestin (1), a new ent-labdane glycoside, was isolated from the leaves of Casearia sylvestris. The structure was determined on the basis of 1D and 2 D NMR and HR-ESI-MS analyses. The diterpenoid of ent-labdane type was isolated for the first time from C. sylvestris....

  2. Hydrogenation of the Exocyclic Olefinic Bond at C-16/C-17 Position of ent-Kaurane Diterpene Glycosides of Stevia rebaudiana Using Various Catalysts

    PubMed Central

    Chaturvedula, Venkata Sai Prakash; Prakash, Indra

    2013-01-01

    Catalytic hydrogenation of the exocyclic double bond present between C16 and C17 carbons of the four ent-kaurane diterpene glycosides namely rebaudioside A, rebaudioside B, rebaudioside C, and rebaudioside D isolated from Stevia rebaudiana has been carried out using Pt/C, Pd(OH)2, Rh/C, Raney Ni, PtO2, and 5% Pd/BaCO3 to their corresponding dihydro derivatives with 17α and 17β methyl group isomers. Reactions were performed using the above-mentioned catalysts with the solvents methanol, water, and ethanol/water (8:2) under various conditions. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data, including a comparison with reported spectral data. PMID:23896597

  3. Acyclic diterpene glycosides, capsianosides VIII, IX, X, XIII, XV and XVI from the fruits of Paprika Capsicum annuum L. var. grossum BAILEY and Jalapeño Capsicum annuum L. var. annuum.

    PubMed

    Lee, Jong-Hyun; Kiyota, Naoko; Ikeda, Tsuyoshi; Nohara, Toshihiro

    2006-10-01

    Paprika and Jalapeño are used as vegetables and spices. We have obtained six new acyclic diterpene glycosides, called capsianosides XIII (2), XV (3), IX (4), XVI (5), X (6) and VIII (7) together with known capsianoside II (1) from the fruits of the Paprika and Jalapeño. The structures of these compounds have been elucidated by the (1)H- and (13)C-NMR spectra and two-dimensional NMR methods.

  4. Three new labdane-type diterpene glycosides from fruits of Rubus chingii and their cytotoxic activities against five humor cell lines.

    PubMed

    Zhong, Ruijian; Guo, Qing; Zhou, Guoping; Fu, Huizheng; Wan, Kaihua

    2015-04-01

    Three new labdane-type diterpene glycosides, 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-7(8),13(14)-diene-3β,15,18-triol (1), 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (2), and 15-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranosyl-18-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (3), were isolated from the fruits of Rubus chingii. Their structures were elucidated on the basis of spectroscopic data and chemical methods. The cytotoxic activities of compounds 1-3 were evaluated against five human tumor cell lines (HCT-8, BGC-823, A549, and A2780). Compounds 3 showed cytotoxic activity against A549 with an IC50 value of 2.32μM.

  5. Isolation, NMR Spectral Analysis and Hydrolysis Studies of a Hepta Pyranosyl Diterpene Glycoside from Stevia rebaudiana Bertoni

    PubMed Central

    Chaturvedula, Venkata Sai Prakash; Chen, Steven; Yu, Oliver; Mao, Guohong

    2013-01-01

    From the commercial extract of the leaves of Stevia rebaudiana Bertoni, a minor steviol glycoside, 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(2-O-(3-O-β-d-glucopyranosyl-α-l-rhamnopyranosyl)-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl) ester] (1); also known as rebaudioside O having seven sugar units has been isolated. Its structural characterization has been achieved by the extensive 1D (1H and 13C), and 2D NMR (COSY, HMQC, HMBC) as well as mass spectral data. Further, hydrolysis studies were performed on rebaudioside O using acid and enzymatic methods to identify aglycone and sugar residues in its structure as well as their configurations. PMID:24970189

  6. Effect of harvest timing on leaf production and yield of diterpene glycosides in Stevia rebaudiana Bert: a specialty perennial crop for Mississippi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stevia rebaundiana (Bertoni), a perennial shrub of the Asteraceae, is one of the most important sources of non-caloric natural sweeteners. Stevia’s plant extracts and glycosides have been used for several years in Paraguay and Brazil. Several studies suggest that Stevia and its glycosides exert ben...

  7. Synthesis of ent-kaurane diterpene monoglycosides.

    PubMed

    Chaturvedula, Venkata Sai Prakash; Klucik, Josef; Upreti, Mani; Prakash, Indra

    2011-01-01

    Synthesis of two ent-kaurane diterpene glycosides, steviol 19-O-β-D-glucopyranosiduronic acid (steviol glucuronide, 5), and 13-hydroxy ent-kaur-16-en-19-oic acid-β-D-glucopyranosyl ester (7) has been achieved from a common starting material, steviol, using phase transfer catalyst. Also, synthesis of an additional 17-nor-ent-kaurane glycoside, namely 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-β-D-glucopyranosyl ester (10) was performed using the starting material isosteviol and similar synthetic methodology. Synthesis of all three steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR as well as mass spectral (MS) data. PMID:21968534

  8. Leaf Ests from Stevia rebaudiana: a resource for gene discovery in diterpene synthesis.

    PubMed

    Brandle, J E; Richman, A; Swanson, A K; Chapman, B P

    2002-11-01

    Expressed sequence tags (ESTs) are providing a new approach to gene discovery in plant secondary metabolism. Stevia rebaudiana Bert. leaves produce high concentrations of diterpene steviol glycosides and should be a rich source of transcripts involved in diterpene synthesis. In order to create a resource for gene discovery and increase our understanding of steviol glycoside biosynthesis, we sequenced 5,548 ESTs from a S. rebaudiana leaf cDNA library. The EST collection was fully annotated based on database search results. ESTs involved in diterpene synthesis were identified using published sequences as electronic probes, by keyword searches of search results, and by differential representation. A significant portion of the ESTs were specific for standard leaf metabolic pathways; energy and primary metabolism represented 17.6% and 13.1% of total transcripts respectively. Diterpene metabolism in S. rebaudiana represented 1.1% of total transcripts. This study identified candidate genes for 70% of the known steps in the steviol glycoside pathway. One candidate, kaurene oxidase, was the 8th most abundant EST in the collection. Identification of many candidate genes specific to the I -deoxyxylulose 5-phosphate pathway suggests that the primary source of isopentenyl diphosphate, a precursor of geranylgeranyl diphosphate, is via the non-mevalonic acid pathway. The use of ESTs has greatly facilitated the identification of candidate genes and increased our understanding of diterpene metabolism.

  9. Geranyllinalool Synthases in Solanaceae and Other Angiosperms Constitute an Ancient Branch of Diterpene Synthases Involved in the Synthesis of Defensive Compounds1[C][W][OPEN

    PubMed Central

    Falara, Vasiliki; Alba, Juan M.; Kant, Merijn R.; Schuurink, Robert C.; Pichersky, Eran

    2014-01-01

    Many angiosperm plants, including basal dicots, eudicots, and monocots, emit (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene, which is derived from geranyllinalool, in response to biotic challenge. An Arabidopsis (Arabidopsis thaliana) geranyllinalool synthase (GLS) belonging to the e/f clade of the terpene synthase (TPS) family and two Fabaceae GLSs that belong to the TPS-g clade have been reported, making it unclear which is the main route to geranyllinalool in plants. We characterized a tomato (Solanum lycopersicum) TPS-e/f gene, TPS46, encoding GLS (SlGLS) and its homolog (NaGLS) from Nicotiana attenuata. The Km value of SlGLS for geranylgeranyl diphosphate was 18.7 µm, with a turnover rate value of 6.85 s–1. In leaves and flowers of N. attenuata, which constitutively synthesize 17-hydroxygeranyllinalool glycosides, NaGLS is expressed constitutively, but the gene can be induced in leaves with methyl jasmonate. In tomato, SlGLS is not expressed in any tissue under normal growth but is induced in leaves by alamethicin and methyl jasmonate treatments. SlGLS, NaGLS, AtGLSs, and several other GLSs characterized only in vitro come from four different eudicot families and constitute a separate branch of the TPS-e/f clade that diverged from kaurene synthases, also in the TPS-e/f clade, before the gymnosperm-angiosperm split. The early divergence of this branch and the GLS activity of genes in this branch in diverse eudicot families suggest that GLS activity encoded by these genes predates the angiosperm-gymnosperm split. However, although a TPS sequence belonging to this GLS lineage was recently reported from a basal dicot, no representative sequences have yet been found in monocot or nonangiospermous plants. PMID:25052853

  10. Erythroxan diterpenes from Fagonia glutinosa.

    PubMed

    Abdel-Kader, M S; Omar, A A; Stermitz, F R

    1997-08-01

    Further investigation of the ether extract of the aerial parts of Fagonia glutinosa utilizing the brine shrimp bioassay resulted in the isolation of two new cytotoxic erythroxan diterpenes: 1 alpha, 10 alpha-epoxy-2-oxofagonene (1) and 1 beta, 10 beta-epoxy-2-oxofagonene (2). In addition, two inactive diterpenes, 2-oxofagonene (3) and its previously reported isomer 2-oxo-5-epi-fagonene (4), were also isolated. PMID:9270385

  11. Diterpene production in Mycobacterium tuberculosis

    PubMed Central

    Prach, Lisa; Kirby, James; Keasling, Jay D.; Alber, Tom

    2011-01-01

    Diterpenes are a structurally diverse class of molecules common in plants, although they are very rarely found in bacteria. We report the identification in Mycobacterium tuberculosis (Mtb) of three diterpenes proposed to promote phagolysosome maturation arrest. MS analysis reveals that these diterpenes are novel compounds not previously identified in other organisms. The diterpene with highest abundance in Mtb has a mass fragmentation pattern identical to edaxadiene, which is produced in vitro from geranylgeranyl diphosphate by the enzymes Rv3377c and Rv3378c [Mann FM et al. (2009) J Am Chem Soc 131, 17526–17527]. A second diterpene found in Mtb has a similar mass spectrum, and is always observed in the same proportion relative to edaxadiene, indicating that it is a side product of the Rv3378c reaction in vivo. We name this second diterpene olefin edaxadiene B. The least abundant of the three diterpenes in Mtb extracts is tuberculosinol, a dephosphorylated side-product of the edaxadiene pathway intermediate produced by Rv3377c [Nakano C et al. (2009) Chembiochem 10, 2060–2071; Nakano C et al. (2005) Chem Commun (Camb) 8, 1016–1018]. A frameshift in Rv3377c in Mtb completely eliminates diterpene production, whereas expression of Rv3377c and Rv3378c in the nonpathogenic M. smegmatis is sufficient to produce edaxadiene and edaxadiene B. These studies define the pathway of edaxadiene and edaxadiene B biosynthesis in vivo. Rv3377c and Rv3378c are unique to Mtb and M. bovis, making them candidates for selective therapeutics and diagnostics. PMID:20670276

  12. Isolation, characterization and sensory evaluation of a Hexa beta-D-glucopyranosyl diterpene from Stevia rebaudiana.

    PubMed

    Prakash, Indra; Chaturvedula, Venkata Sai Prakash; Markosyan, Avetik

    2013-11-01

    From the extract of the leaves of Stevia rebaudiana Bertoni, a diterpene glycoside was isolated which was identified as 13-[(2-O-beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-(2-O-beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl-D-glucopyranosyl) ester (1). The complete 1H and 13C NMR assignment of 1 is reported for the first time, from extensive NMR (1H and 13C, COSY, HSQC, and HMBC) and mass spectral data. Also, we report the sensory evaluation of 1 against sucrose for the sweetness property of this molecule.

  13. A new labdane diterpene from Leonurus heterophyllus.

    PubMed

    Cai, X-H; Che, C-T; Lam, C-K; Mak, T C W; Wu, L-J

    2006-01-01

    A new labdane diterpene, heteronone B (1), together with a known labdane diterpene, heteronone A (2), have been isolated from the aerial part of Leonurus heterophyllus. Their structures were established mainly by 1D and 2D NMR analysis and the stereochemistry of 2 was confirmed by single-crystal X-ray diffraction analysis.

  14. Cardiac glycoside overdose

    MedlinePlus

    ... found in the leaves of the digitalis (foxglove) plant. This plant is the original source of this medicine. People ... Digitoxin (Crystodigin) Digoxin (Lanoxicaps, Lanoxin) Besides the foxglove plant, cardiac glycosides also occur naturally in plants such ...

  15. Labdane diterpenes of Leonurus sibiricus.

    PubMed

    Boalino, Dionne M; McLean, Stewart; Reynolds, William F; Tinto, Winston F

    2004-04-01

    Seven new labdane diterpenes, sibiricinones A-E (1-4, 6) and 15-epi-sibiricinones D and E (5 and 7), and the flavone genkwanin were isolated from the aerial parts of Leonurus sibiricus. Sibiricinone D (4) and 15-epi-sibiricinone D (5), and sibiricinone E (6) and 15-epi-sibiricinone E (7), respectively, were isolated as C-15 epimeric pairs. These secondary metabolites were identified on the basis of 1D and 2D NMR including (1)H-(1)H COSY, HSQC, and HMBC spectroscopic techniques. The stereochemical configurations of compounds 4-7 were assigned through 2D T-ROESY and selective NOE experiments.

  16. Seasonal Variation of Cistus ladanifer L. Diterpenes

    PubMed Central

    Alías, Juan Carlos; Sosa, Teresa; Valares, Cristina; Escudero, José Carlos; Chaves, Natividad

    2012-01-01

    The exudate of Cistus ladanifer L. consists mainly of two families of secondary metabolites: flavonoids and diterpenes. The amount of flavonoids present in the leaves has a marked seasonal variation, being maximum in summer and minimum in winter. In the present study, we demonstrate that the amount of diterpenes varies seasonally, but with a different pattern: maximum concentration in winter and minimum in spring-summer. The experiments under controlled conditions have shown that temperature influences diterpene production, and in particular, low temperatures. Given this pattern, the functions that these compounds perform in C. ladanifer are probably different. PMID:27137636

  17. Anxiolytic Activity of Diterpene Alkaloid Songorine.

    PubMed

    Nesterova, Yu V; Povet'eva, T N; Suslov, N I; Shults, E E; Ziuz'kov, G N; Aksinenko, S G; Afanas'eva, O G; Krapivin, A V; Kharina, T G

    2015-09-01

    Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect.

  18. Anxiolytic Activity of Diterpene Alkaloid Songorine.

    PubMed

    Nesterova, Yu V; Povet'eva, T N; Suslov, N I; Shults, E E; Ziuz'kov, G N; Aksinenko, S G; Afanas'eva, O G; Krapivin, A V; Kharina, T G

    2015-09-01

    Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect. PMID:26468026

  19. Diterpenes inhibiting NO production from Euphorbia helioscopia.

    PubMed

    Chen, Hongqiang; Wang, Hao; Yang, Bo; Jin, Da-Qing; Yang, Shuliang; Wang, Meicheng; Xu, Jing; Ohizumi, Yasushi; Guo, Yuanqiang

    2014-06-01

    Three new jatrophane diterpenes (1-3), an unreported spectroscopic data jatrophane diterpenene (4), and nine known analogues (5-13) have been isolated from the whole plants of Euphorbia helioscopia. Their structures were established by detailed spectroscopic data analyses (IR, ESIMS, HR-ESIMS, and 1D and 2D NMR), and the structure of 1 was confirmed by X-ray crystallography. The diterpenes showed inhibitory activities on LPS-induced NO production in murine microglial BV-2 cells.

  20. New diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.

    PubMed

    Kuo, Y H; Chen, C H; Huang, S L

    1998-06-26

    An abietane diterpene, 11,14-dihydroxy-8,11,13-abietatrien-7-one (1); a seco-abietane diterpene, obtuanhydride (2); and an isopimarane diterpene, 18,19-O-isopropylidene-18, 19-dihydroxyisopimara-8(14),15-diene (3) were isolated from the heartwood of Chamaecyparis obtusa var. formosana. The structures of these new compounds were elucidated by spectroscopic methods. PMID:9644078

  1. Spatial organisation of four enzymes from Stevia rebaudiana that are involved in steviol glycoside synthesis.

    PubMed

    Humphrey, Tania V; Richman, Alex S; Menassa, Rima; Brandle, Jim E

    2006-05-01

    The sweet steviol glycosides found in the leaves of Stevia rebaudiana Bert. are derived from the diterpene steviol which is produced from a branch of the gibberellic acid (GA) biosynthetic pathway. An understanding of the spatial organisation of the two pathways including subcellular compartmentation provides important insight for the metabolic engineering of steviol glycosides as well as other secondary metabolites in plants. The final step of GA biosynthesis, before the branch point for steviol production, is the formation of (-)-kaurenoic acid from (-)-kaurene, catalysed by kaurene oxidase (KO). Downstream of this, the first committed step in steviol glycoside synthesis is the hydroxylation of kaurenoic acid to form steviol which is then sequentially glucosylated by a series of UDP-glucosyltransferases (UGTs) to produce the variety of steviol glycosides. The subcellular location of KO and three of the UGTs involved in steviol glycoside biosynthesis was investigated by expression of GFP fusions and cell fractionation which revealed KO to be associated with the endoplasmic reticulum and the UGTs in the cytoplasm. It has also been shown by expressing the Stevia UGTs in Arabidopsis that the pathway can be partially reconstituted by recruitment of a native Arabidopsis glucosyltransferase. PMID:16786291

  2. Variants of glycoside hydrolases

    DOEpatents

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung

    2011-04-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  3. Variants of glycoside hydrolases

    SciTech Connect

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung

    2013-02-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  4. Methylerythritol and mevalonate pathway contributions to biosynthesis of mono-, sesqui-, and diterpenes in glandular trichomes and leaves of Stevia rebaudiana Bertoni.

    PubMed

    Wölwer-Rieck, Ursula; May, Bianca; Lankes, Christa; Wüst, Matthias

    2014-03-19

    The biosynthesis of the diterpenoid steviol glycosides rebaudioside A and stevioside in nonrooted cuttings of Stevia rebaudiana was investigated by feeding experiments using the labeled key precursors [5,5-(2)H2]-mevalonic acid lactone (d2-MVL) and [5,5-(2)H2]-1-deoxy-d-xylulose (d2-DOX). Labeled glycosides were extracted from the leaves and stems and were directly analyzed by LC-(-ESI)-MS/MS and by GC-MS after hydrolysis and derivatization of the resulting isosteviol to the corresponding TMS-ester. Additionally, the incorporation of the proffered d2-MVL and d2-DOX into volatile monoterpenes, sesquiterpenes, and diterpenes in glandular trichomes on leaves and stems was investigated by headspace-solid phase microextraction-GC-MS (HS-SPME-GC-MS). Incorporation of the labeled precursors indicated that diterpenes in leaves and monoterpenes and diterpenes in glandular trichomes are predominately biosynthesized via the methylerythritol phosphate (MEP) pathway, whereas both the MEP and mevalonate (MVA) pathways contribute to the biosynthesis of sesquiterpenes at equal rates in glandular trichomes. These findings give evidence for a transport of MEP pathway derived farnesyl diphosphate precursors from plastids to the cytosol. Contrarily, the transport of MVA pathway derived geranyl diphosphate and geranylgeranyl diphosphate precursors from the cytosol to the plastid is limited.

  5. A new casbane diterpene from Euphorbia pekinensis.

    PubMed

    Wang, Kuilong; Yu, Hongli; Wu, Hao; Wang, Xinzhi; Pan, Yaozong; Chen, Yeqing; Liu, Liping; Jin, Yangping; Zhang, Chenchao

    2015-01-01

    A new casbane diterpenoid, referred to as pekinenin G, together with one cembrane diterpene and four known casbane diterpenoids were isolated from the roots of Euphorbia pekinensis. Their structures were elucidated on the basis of spectroscopic studies and comparison with related known compounds. The six compounds showed different cytotoxic activities against four human cancer cell lines.

  6. Glycoside vs. Aglycon: The Role of Glycosidic Residue in Biological Activity

    NASA Astrophysics Data System (ADS)

    Křen, Vladimír

    A large number of biologically active compounds are glycosides. Sometimes the glycosidic residue is crucial for their activity, in other cases glycosylation only improves pharmacokinetic parameters. Recent developments in molecular glycobiology brought better understanding of aglycon vs. glycoside activities, and made possible the development of new, more active or more effective glycodrugs based on these findings - a very illustrative recent example is vancomycin. The new enzymatic methodology "glycorandomization" enabled preparation of glycoside libraries and opened up paths to the preparation of optimized or entirely novel glycoside antibiotics. This chapter deals with an array of glycosidic compounds currently used in medicine but also covers the biological activity of some glycosidic metabolites of known drugs. The chapter discusses glycosides of vitamins, polyphenolic glycosides (flavonoids), alkaloid glycosides, glycosides of antibiotics, glycopeptides, cardiac glycosides, steroid and terpenoid glycosides etc. The physiological role of the glycosyl moiety and structure-activity relations (SAR) in the glycosidic moiety (-ies) are also discussed.

  7. Miltiorins A-D, diterpenes from Radix Salviae miltiorrhizae.

    PubMed

    Hirata, Ai; Kim, Sang-Yong; Kobayakawa, Natsuki; Tanaka, Naonobu; Kashiwada, Yoshiki

    2015-04-01

    Constituents of the anti-influenza A neuraminidase (NA) active extract from Radix Salviae miltiorrhizae were investigated, resulting in the isolation of four new diterpenes, miltiorins A-D (1-4), together with eight known diterpenes. The structures of 1-4 were assigned by spectroscopic analysis. Miltiorins A-C (1-3) were abietane diterpenes possessing a 2α-acetoxy group and a 12-hydroxy group in common, while miltiorin D (4) was a 11,12-seco-abietane diterpene with a γ-lactone ring. Miltiorin D (4) is the first example of a 11,12-seco-abietane diterpene from natural sources. Anti-NA activities of the isolated diterpenes were evaluated.

  8. Isoleojaponin, a new Halimane diterpene isolated from Leonurus japonicus.

    PubMed

    Wu, Hankui; Wang, Sensheng; Xu, Zhiyong; Sun, Shanshan; Liu, Haijuan; Wang, Jinjin; E, Yan; Lv, Yanyan; Dong, Xuelin; Li, Gang; Zhang, Liping; Shi, Yunfeng

    2015-01-07

    Leojaponin (2), a labdane diterpene, was isolated from the EtOH extract of the herb of Leonurus japonicus together with a new halimane diterpene named isoleojaponin (1). Isoleojaponin has a new diterpene skeleton with a unique cross-conjugated α,β-unsaturated ketone system, Their structures were elucidated by physical and spectroscopic analysis, and the relative configuration of the chiral C-9 carbon was determined by a computational method, and analysis of its possible biogenesis pathways.

  9. Gene discovery of modular diterpene metabolism in nonmodel systems.

    PubMed

    Zerbe, Philipp; Hamberger, Björn; Yuen, Macaire M S; Chiang, Angela; Sandhu, Harpreet K; Madilao, Lina L; Nguyen, Anh; Hamberger, Britta; Bach, Søren Spanner; Bohlmann, Jörg

    2013-06-01

    Plants produce over 10,000 different diterpenes of specialized (secondary) metabolism, and fewer diterpenes of general (primary) metabolism. Specialized diterpenes may have functions in ecological interactions of plants with other organisms and also benefit humanity as pharmaceuticals, fragrances, resins, and other industrial bioproducts. Examples of high-value diterpenes are taxol and forskolin pharmaceuticals or ambroxide fragrances. Yields and purity of diterpenes obtained from natural sources or by chemical synthesis are often insufficient for large-volume or high-end applications. Improvement of agricultural or biotechnological diterpene production requires knowledge of biosynthetic genes and enzymes. However, specialized diterpene pathways are extremely diverse across the plant kingdom, and most specialized diterpenes are taxonomically restricted to a few plant species, genera, or families. Consequently, there is no single reference system to guide gene discovery and rapid annotation of specialized diterpene pathways. Functional diversification of genes and plasticity of enzyme functions of these pathways further complicate correct annotation. To address this challenge, we used a set of 10 different plant species to develop a general strategy for diterpene gene discovery in nonmodel systems. The approach combines metabolite-guided transcriptome resources, custom diterpene synthase (diTPS) and cytochrome P450 reference gene databases, phylogenies, and, as shown for select diTPSs, single and coupled enzyme assays using microbial and plant expression systems. In the 10 species, we identified 46 new diTPS candidates and over 400 putatively terpenoid-related P450s in a resource of nearly 1 million predicted transcripts of diterpene-accumulating tissues. Phylogenetic patterns of lineage-specific blooms of genes guided functional characterization. PMID:23613273

  10. Gene discovery of modular diterpene metabolism in nonmodel systems.

    PubMed

    Zerbe, Philipp; Hamberger, Björn; Yuen, Macaire M S; Chiang, Angela; Sandhu, Harpreet K; Madilao, Lina L; Nguyen, Anh; Hamberger, Britta; Bach, Søren Spanner; Bohlmann, Jörg

    2013-06-01

    Plants produce over 10,000 different diterpenes of specialized (secondary) metabolism, and fewer diterpenes of general (primary) metabolism. Specialized diterpenes may have functions in ecological interactions of plants with other organisms and also benefit humanity as pharmaceuticals, fragrances, resins, and other industrial bioproducts. Examples of high-value diterpenes are taxol and forskolin pharmaceuticals or ambroxide fragrances. Yields and purity of diterpenes obtained from natural sources or by chemical synthesis are often insufficient for large-volume or high-end applications. Improvement of agricultural or biotechnological diterpene production requires knowledge of biosynthetic genes and enzymes. However, specialized diterpene pathways are extremely diverse across the plant kingdom, and most specialized diterpenes are taxonomically restricted to a few plant species, genera, or families. Consequently, there is no single reference system to guide gene discovery and rapid annotation of specialized diterpene pathways. Functional diversification of genes and plasticity of enzyme functions of these pathways further complicate correct annotation. To address this challenge, we used a set of 10 different plant species to develop a general strategy for diterpene gene discovery in nonmodel systems. The approach combines metabolite-guided transcriptome resources, custom diterpene synthase (diTPS) and cytochrome P450 reference gene databases, phylogenies, and, as shown for select diTPSs, single and coupled enzyme assays using microbial and plant expression systems. In the 10 species, we identified 46 new diTPS candidates and over 400 putatively terpenoid-related P450s in a resource of nearly 1 million predicted transcripts of diterpene-accumulating tissues. Phylogenetic patterns of lineage-specific blooms of genes guided functional characterization.

  11. Therapeutic Potential of Essential Oils Focusing on Diterpenes.

    PubMed

    Islam, Md Torequl; da Mata, Ana Maria Oliveira Ferreira; de Aguiar, Raí Pablo Sousa; Paz, Marcia Fernanda Correia Jardim; de Alencar, Marcus Vinícius Oliveira Barros; Ferreira, Paulo Michel Pinheiro; de Carvalho Melo-Cavalcante, Ana Amélia

    2016-09-01

    Among all plant derivates, essential oils (EOs) have gained the attention of many scientists. Diterpenes, a family of components present in some EO, are becoming a milestone in the EOs world. The goal of this review is to describe a scenario of diterpenes taking into health-consumption deportment. Previous studies revealed that diterpenes have antioxidant, antimicrobial, antiviral, antiprotozoal, cytotoxic, anticancer, antigenotoxic, antimutagenic, chemopreventive, antiinflammatory, antinociceptive, immunostimulatory, organoprotective, antidiabetic, lipid-lowering, antiallergic, antiplatelet, antithrombotic, and antitoxin activities. In conclusion, diterpenes may be an immense featuring concern in pharmaceutical consumption from a drug discovery point of view. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27307034

  12. Diterpenes from the endangered goldenrod Solidago shortii.

    PubMed

    Williams, Russell B; Du, Lin; Norman, Vanessa L; Goering, Matt G; O'Neil-Johnson, Mark; Woodbury, Scott; Albrecht, Matthew A; Powell, Douglas R; Cichewicz, Robert H; Eldridge, Gary R; Starks, Courtney M

    2014-06-27

    Species extinction is tantamount to loss of chemical diversity, and so it is important to seize all opportunities to study species on the brink of extinction. Such studies are often hampered by the limited material available, but that obstacle is surmountable through collaboration with botanical gardens and advances in instrumentation. The goldenrod Solidago shortii is one example of an endangered species native to the United States. From S. shortii, one known diterpene (1), two new diterpenes (2 and 3), and three new hydrolysis products (4-6) are described. This work was made possible through collaboration with the Missouri Botanical Garden and with the use of highly sensitive microcryoprobe NMR technology for structure elucidation and VCD spectroscopy for the determination of absolute configuration.

  13. Cytotoxic clerodane diterpenes from Zuelania guidonia.

    PubMed

    Calderón, Carlos; De Ford, Christian; Castro, Victor; Merfort, Irmgard; Murillo, Renato

    2014-03-28

    The leaves of Zuelania guidonia yielded eight new clerodane diterpenes, namely, zuelaguidins A-H (1-8), and the known clerodane diterpene esculentin A (9). Some of these structures contained a 3,6-dihydro-1,2-dioxin moiety. The new compounds were isolated and identified using 1D- and 2D-NMR experiments. All compounds were evaluated for cytotoxicity against the CCRF-CEM (human acute lymphocytic leukemia), CEM-ADR5000 (human acute lymphocytic leukemia resistant to doxorubicin), and MIA-PaCa-2 (human pancreatic carcinoma) cell lines as well as for their selectivity against peripheral blood mononuclear cells from healthy human subjects. Zuelaguidins B, C, and E were the most potent compounds against the CCRF-CEM cell line, with IC50 values ranging from 1.6 to 2.5 μM. PMID:24484281

  14. Diterpenes from the endangered goldenrod Solidago shortii.

    PubMed

    Williams, Russell B; Du, Lin; Norman, Vanessa L; Goering, Matt G; O'Neil-Johnson, Mark; Woodbury, Scott; Albrecht, Matthew A; Powell, Douglas R; Cichewicz, Robert H; Eldridge, Gary R; Starks, Courtney M

    2014-06-27

    Species extinction is tantamount to loss of chemical diversity, and so it is important to seize all opportunities to study species on the brink of extinction. Such studies are often hampered by the limited material available, but that obstacle is surmountable through collaboration with botanical gardens and advances in instrumentation. The goldenrod Solidago shortii is one example of an endangered species native to the United States. From S. shortii, one known diterpene (1), two new diterpenes (2 and 3), and three new hydrolysis products (4-6) are described. This work was made possible through collaboration with the Missouri Botanical Garden and with the use of highly sensitive microcryoprobe NMR technology for structure elucidation and VCD spectroscopy for the determination of absolute configuration. PMID:24922615

  15. A New Bioactive Diterpene Glycoside from Molinaea retusa from the Madagascar Dry Forest

    PubMed Central

    Eaton, Alexander L.; Harinantenaina, Liva; Brodie, Peggy J.; Cassera, Maria B.; Bowman, Jessica D.; Callmander, Martin W.; Randrianaivo, Richard; Rakotondrajaona, Roland; Rakotobe, Etienne; Rasamison, Vincent E.; Kingston, David G. I.

    2014-01-01

    In a continuing collaboration in a search for new antiproliferative compounds in Madagascar as part of an International Cooperative Biodiversity Group (ICBG), an ethanol extract of Molinaea retusa Radlk. (Sapindaceae) was investigated on the basis of its moderate antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 16 μg/mL). One new compound, 2″,3″,4″,6′-de-O-acetylcupacinoside (1, IC50 15.4 μM) and two known compounds, cupacinoside (2, IC50 9.5 μM) and 6-de-O-acetylcupacinoside (3, IC50 10.9 μM), were isolated by bioassay-directed fractionation using liquid-liquid partitioning, column chromatography, and HPLC. Compounds 2 and 3 also had moderate antiplasmodial activities, with IC50 values of 4.0 and 6.4 μM, respectively, against Plasmodium falciparum, Dd2 strain. The structures were determined using spectroscopic methods. PMID:24273845

  16. Detoxification of hostplant's chemical defence rather than its anti-predator co-option drives β-glucosidase-mediated lepidopteran counteradaptation.

    PubMed

    Poreddy, Spoorthi; Mitra, Sirsha; Schöttner, Matthias; Chandran, Jima; Schneider, Bernd; Baldwin, Ian T; Kumar, Pavan; Pandit, Sagar S

    2015-01-01

    The evolutionary plant-herbivore arms race sometimes gives rise to remarkably unique adaptation strategies. Here we report one such strategy in the lepidopteran herbivore Manduca sexta against its hostplant Nicotiana attenuata's major phytotoxins, 17-hydroxygeranyllinalool diterpene glycoside, lyciumoside IV and its malonylated forms. We show that alkalinity of larval regurgitant non-enzymatically demalonylates the malonylated forms to lyciumoside IV. Lyciumoside IV is then detoxified in the midgut by β-glucosidase 1-catalysed deglycosylation, which is unusual, as typically the deglycosylation of glycosylated phytochemicals by insects results in the opposite: toxin activation. Suppression of deglucosylation by silencing larval β-glucosidase 1 by plant-mediated RNAi causes moulting impairments and mortality. In the native habitat of N. attenuata, β-glucosidase 1 silencing also increases larval unpalatability to native predatory spiders, suggesting that the defensive co-option of lyciumoside IV may be ecologically advantageous. We infer that M. sexta detoxifies this allelochemical to avoid its deleterious effects, rather than co-opting it against predators. PMID:26443324

  17. Detoxification of hostplant's chemical defence rather than its anti-predator co-option drives β-glucosidase-mediated lepidopteran counteradaptation

    PubMed Central

    Poreddy, Spoorthi; Mitra, Sirsha; Schöttner, Matthias; Chandran, Jima; Schneider, Bernd; Baldwin, Ian T.; Kumar, Pavan; Pandit, Sagar S.

    2015-01-01

    The evolutionary plant–herbivore arms race sometimes gives rise to remarkably unique adaptation strategies. Here we report one such strategy in the lepidopteran herbivore Manduca sexta against its hostplant Nicotiana attenuata's major phytotoxins, 17-hydroxygeranyllinalool diterpene glycoside, lyciumoside IV and its malonylated forms. We show that alkalinity of larval regurgitant non-enzymatically demalonylates the malonylated forms to lyciumoside IV. Lyciumoside IV is then detoxified in the midgut by β-glucosidase 1-catalysed deglycosylation, which is unusual, as typically the deglycosylation of glycosylated phytochemicals by insects results in the opposite: toxin activation. Suppression of deglucosylation by silencing larval β-glucosidase 1 by plant-mediated RNAi causes moulting impairments and mortality. In the native habitat of N. attenuata, β-glucosidase 1 silencing also increases larval unpalatability to native predatory spiders, suggesting that the defensive co-option of lyciumoside IV may be ecologically advantageous. We infer that M. sexta detoxifies this allelochemical to avoid its deleterious effects, rather than co-opting it against predators. PMID:26443324

  18. Detoxification of hostplant's chemical defence rather than its anti-predator co-option drives β-glucosidase-mediated lepidopteran counteradaptation.

    PubMed

    Poreddy, Spoorthi; Mitra, Sirsha; Schöttner, Matthias; Chandran, Jima; Schneider, Bernd; Baldwin, Ian T; Kumar, Pavan; Pandit, Sagar S

    2015-10-07

    The evolutionary plant-herbivore arms race sometimes gives rise to remarkably unique adaptation strategies. Here we report one such strategy in the lepidopteran herbivore Manduca sexta against its hostplant Nicotiana attenuata's major phytotoxins, 17-hydroxygeranyllinalool diterpene glycoside, lyciumoside IV and its malonylated forms. We show that alkalinity of larval regurgitant non-enzymatically demalonylates the malonylated forms to lyciumoside IV. Lyciumoside IV is then detoxified in the midgut by β-glucosidase 1-catalysed deglycosylation, which is unusual, as typically the deglycosylation of glycosylated phytochemicals by insects results in the opposite: toxin activation. Suppression of deglucosylation by silencing larval β-glucosidase 1 by plant-mediated RNAi causes moulting impairments and mortality. In the native habitat of N. attenuata, β-glucosidase 1 silencing also increases larval unpalatability to native predatory spiders, suggesting that the defensive co-option of lyciumoside IV may be ecologically advantageous. We infer that M. sexta detoxifies this allelochemical to avoid its deleterious effects, rather than co-opting it against predators.

  19. New labdane diterpenes from Leonurus cardiaca.

    PubMed

    Agnihotri, Vijai K; Elsohly, Hala N; Smillie, Troy J; Khan, Ikhlas A; Walker, Larry A

    2008-08-01

    Leonurus cardiaca L. has been used in oriental medicine against several types of disorders. The ethanolic extract of leaves of Leonurus cardiaca yielded three new labdane-type diterpenes: 15- O-ethylleopersin C (1), 15- O-methylleopersin C (2), and 15- EPI- O-methylleopersin C (3). Their structures were determined using 1 D and 2 D NMR including 1H-1H COSY, HMQC, HMBC, and ROESY spectroscopic techniques. Compounds (1 - 3) were evaluated for in vitro antiplasmodial activity (D6 and W2 clones) and cytotoxicity (Vero cells).

  20. Labdane diterpenes from Leonurus japonicus leaves.

    PubMed

    Romero-González, Román R; Avila-Núñez, Jorge L; Aubert, Lianne; Alonso-Amelot, Miguel E

    2006-05-01

    Three labdane diterpenes 15,16-epoxy-6-hydroxylabda-5,8,13(16),14-tretraen-7-one (leojaponin), (9alpha,13S);15,16-diepoxy-7beta-hydroxylabd-14-en-6-one (13-epi-preleoheterin), and (9alpha,13R);15,16-diepoxy-6beta-hydroxylabd-14-en-7-one (iso-preleoheterin) were isolated from the leaves of Leonurus japonicus, in addition to the previously reported preleoheterin. The structure elucidations were made based on analysis of their spectroscopic data.

  1. Flavonol Glycosides from Gaura Biennis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytochemical investigation of the native American plant Gaura biennis led to the isolation of three new flavonol glycosides (1-3), along with eight known ones. Their structures were established primarily by spectroscopic data as quercetin 3-O-(2"-O-a-L-rhamnopyranosyl-6"-O-E-p-coumaroyl)-ß-D- gluco...

  2. Diterpene alkaloids and diterpenes from Spiraea japonica and their anti-tobacco mosaic virus activity.

    PubMed

    Ma, Yuan; Mao, Xin-Ying; Huang, Lie-Jun; Fan, Yi-Min; Gu, Wei; Yan, Chen; Huang, Tao; Zhang, Jian-Xin; Yuan, Chun-Mao; Hao, Xiao-Jiang

    2016-03-01

    Five new naturally occurring natural products, including two atisine-type diterpene alkaloids (1 and 2), two atisane-type diterpenes (3 and 4), and a new natural product spiramine C2 (5), along with nine known ones (6-14), were isolated from the ethanolic extracts of the whole plant of Spiraea japonica var. acuminata Franch. Their structures were elucidated by extensive spectroscopic analysis. The anti-tobacco mosaic virus (TMV) activities of all the compounds were evaluated by the conventional half-leaf method. Six compounds (2, 3, 6, 7, 11, and 12) exhibited moderate activities at 100 μg/mL with inhibition rates in the range of 69.4-92.9%, which were higher than that of the positive control, ningnanmycin. Their preliminary structure-activity relationships were also discussed.

  3. Trocheliolide A, a Hydroperoxycembranoidal Diterpene from the Octocoral Sarcophyton trocheliophorum.

    PubMed

    Liu, Kuan-Ming; Cheng, Ching-Hsiao; Chen, Wu-Fu; Lu, Mei-Chin; Fang, Lee-Shing; Wen, Zhi-Hong; Su, Jui-Hsin; Wu, Yang-Chang; Sung, Ping-Jyun

    2015-07-01

    A new hydroperoxycembranoidal diterpene, trocheliolide A (1), was isolated from the octocoral Sarcophyton trocheliophorum. The structure of 1 was elucidated on the basis of spectroscopic and mass spectrometric methods.

  4. Plant diterpene synthases: exploring modularity and metabolic diversity for bioengineering.

    PubMed

    Zerbe, Philipp; Bohlmann, Jörg

    2015-07-01

    Plants produce thousands of diterpenoid natural products; some of which are of significant industrial value as biobased pharmaceuticals (taxol), fragrances (sclareol), food additives (steviosides), and commodity chemicals (diterpene resin acids). In nature, diterpene synthase (diTPS) enzymes are essential for generating diverse diterpene hydrocarbon scaffolds. While some diTPSs also form oxygenated compounds, more commonly, oxygenation is achieved by cytochrome P450-dependent mono-oxygenases. Recent genome-, transcriptome-, and metabolome-guided gene discovery and enzyme characterization identified novel diTPS functions that form the core of complex modular pathway systems. Insights into diterpene metabolism may translate into the development of new bioengineered microbial and plant-based production systems.

  5. Edaxadiene: A New Bioactive Diterpene from Mycobacterium tuberculosis

    PubMed Central

    2009-01-01

    Mycobacterium tuberculosis remains a widespread and devastating human pathogen. Presented here is the characterization of an atypical class I diterpene cyclase from M. tuberculosis that catalyzes an unusual cyclization reaction in converting the known M. tuberculosis metabolite halimadienyl diphosphate to a further cyclized novel diterpene, which we have termed edaxadiene, as it directly inhibits maturation of the phagosomal compartment in which the bacterium is taken up during infection. PMID:19583202

  6. New clerodane diterpenoid glycosides from the aerial parts of Nannoglottis carpesioides.

    PubMed

    Meng, Xian-Hua; Zou, Chuan-Zong; Jin, Xiao-Jie; Huang, Guo-Du; Yang, Yong-Jin; Zou, Xi-Ying; Yao, Xiao-Jun; Zhu, Ying

    2014-03-01

    Three new clerodane diterpenoid glycosides with L-arabinose (1-3), together with ten known compounds including phytol-type diterpenes, cycloartane-type, ursane-type, and oleanane-type triterpenes, were isolated from the aerial parts of Nannoglottis carpesioides which a Chinese endemic genus. The structures of the new compounds 1-3 were identified based on chemical and spectroscopic studies, including one- and two-dimensional NMR, HRESIMS, UV, and IR results. Their absolute configurations were determined by the application of theory calculations of optical rotation, which were compared with the experimental data. New aglycone 1a and L-arabinose were obtained by acid hydrolysis of 1 and GC-MS analysis. The cytotoxicities of some isolated compounds against a panel of human cancer cell lines were evaluated by the MTT assay. Clerodane diterpenoides are the characteristic chemical constituents and may be used as chemical markers of the genus Nannoglottis.

  7. New Antiplasmodial Diterpenes from Gutierrezia sarothrae.

    PubMed

    Su, Qingxi; Dalal, Seema; Goetz, Michael; Cassera, Maria B; Kingston, David G I

    2016-06-01

    Bioassay guided fractionation of the MeOH extract of the plant Gutierrezia sarothrae (Asteraceae) using an assay for antiplasmodial activity against the drug-resistant Dd2 strain of Plasmodium falciparum led to the isolation of the two new diterpenes 3α-angeloyloxy-15-hydroxylabda-7,13-dien-16,15-olid-18-oic acid (1) and 3α-angeloyloxy-15-methoxylabda-7,13-dien-16,15-olid-18-oic acid (2). The structures of 1 and 2 were elucidated by interpretation of 1D and 2D NMR spectroscopic data, mass spectrometry, and comparison with the data of related compounds reported in the literature. Compound 1 exhibited moderate antiplasmodial activity with an IC50 values of 10.4 ± 4.3 μM. PMID:27534100

  8. Defensive Diterpene from the Aeolidoidean Phyllodesmium longicirrum.

    PubMed

    Bogdanov, Alexander; Hertzer, Cora; Kehraus, Stefan; Nietzer, Samuel; Rohde, Sven; Schupp, Peter J; Wägele, Heike; König, Gabriele M

    2016-03-25

    Phyllodesmium is a tropical marine slug genus with about 30 described species. None of them have a protective shell, and all of them feed on octocorals that are generally known to provide defensive compounds and thus help to defend the naked slugs against sympatric predators, such as fish, crabs, cephalopods, and echinoderms. Phyllodesmium longicirrum is the species that grows the biggest and that is least protected by camouflage on its respective food, usually a soft coral of the genus Sarcophyton. Investigation of the lipophilic extract of a single specimen of P. longicirrum from the Great Barrier Reef (Australia) led to the isolation of four new polycyclic diterpenes. Compound 1 showed significant deterrent activity in a fish feeding assay. PMID:26649919

  9. Defensive Diterpene from the Aeolidoidean Phyllodesmium longicirrum.

    PubMed

    Bogdanov, Alexander; Hertzer, Cora; Kehraus, Stefan; Nietzer, Samuel; Rohde, Sven; Schupp, Peter J; Wägele, Heike; König, Gabriele M

    2016-03-25

    Phyllodesmium is a tropical marine slug genus with about 30 described species. None of them have a protective shell, and all of them feed on octocorals that are generally known to provide defensive compounds and thus help to defend the naked slugs against sympatric predators, such as fish, crabs, cephalopods, and echinoderms. Phyllodesmium longicirrum is the species that grows the biggest and that is least protected by camouflage on its respective food, usually a soft coral of the genus Sarcophyton. Investigation of the lipophilic extract of a single specimen of P. longicirrum from the Great Barrier Reef (Australia) led to the isolation of four new polycyclic diterpenes. Compound 1 showed significant deterrent activity in a fish feeding assay.

  10. The total synthesis of Isodon diterpenes.

    PubMed

    Lazarski, Kiel E; Moritz, Benjamin J; Thomson, Regan J

    2014-09-26

    Families of structurally related molecules often provide stimulating targets for organic chemists that are engaged in the development of new methods and strategies for natural product synthesis. While typically focused on specific molecules, these synthetic investigations often lead to generalizable concepts and significant opportunities for learning in a greater sense. Historically well-investigated families of natural products, such as the prostanoids, indole alkaloids, and macrolide antibiotics, provide ample evidence for the enduring value of these collective activities. In this Minireview, we turn our attention to the polycyclic family of diterpenes isolated from the Isodon genus of plants and provide an account of the recent methods and strategies utilized for their total synthesis. PMID:25159338

  11. Trichodermaerin: a diterpene lactone from Trichoderma asperellum

    PubMed Central

    Chantrapromma, Suchada; Jeerapong, Chotika; Phupong, Worrapong; Quah, Ching Kheng; Fun, Hoong-Kun

    2014-01-01

    The title compound, C20H28O3, known as ‘trichodermaerin’ [systematic name: (4E)-4,9,15,16,16-penta­methyl-6-oxa­tetra­cyclo­[10.3.1.01,10.05,9]hexa­dec-4-ene-7,13-dione], is a diterpene lactone which was isolated from Trichoderma asperellum. The structure has a tetra­cycic 6–5–7–5 ring system, with the cyclo­hexa­none ring adopting a twisted half-chair conformation and the cyclo­pentane ring adopting a half-chair conformation, whereas the cyclo­heptene and tetra­hydro­furan­anone rings are in chair and envelope (with the methyl-substituted C atom as the flap) conformations, respectively. The three-dimensional architecture is stabilized by C—H⋯O inter­actions. PMID:24826124

  12. Triterpenoid glycosides from Bacopa monnieri.

    PubMed

    Sivaramakrishna, Chillara; Rao, Chirravuri V; Trimurtulu, Golakoti; Vanisree, Mulabagal; Subbaraju, Gottumukkala V

    2005-12-01

    Two triterpenoid glycosides have been isolated along with 10 known saponins from Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high resolution NMR spectral data and chemical correlations. Further, the chemical compositions of bacosides A and B have been delineated.

  13. Iridoid glycosides from Gmelina arborea.

    PubMed

    Tiwari, Neerja; Yadav, Akhilesh K; Srivastava, Pooja; Shanker, Karuna; Verma, Ram K; Gupta, Madan M

    2008-09-01

    Three iridoid glycosides 6-O-(3''-O-benzoyl)-alpha-L-rhamnopyranosylcatalpol (1a), 6-O-(3''-O-trans-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (2a) and 6-O-(3''-O-cis-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (3a) were isolated from aerial parts of Gmelina arborea and structures were elucidated by spectral analysis. Additionally a known iridoid 6-O-(3'', 4''-O-dibenzoyl)-alpha-L-rhamnopyranosylcatalpol (4) was also isolated and identified. PMID:18684476

  14. Bioconversion of steroid glycosides by Nocardia restricta.

    PubMed

    Belic, I; Kastelic-Suhadolc, T; Kralj, B

    1985-09-01

    The bioconversion of steroid alkaloid tomatine by Nocardia restricta yields the conjugate with lactic acid. We studied the bioconversion of some steroid glycosides without a nitrogen atom in the molecule to determine the effect of the nitrogen atom. The glycosides were of three different types: sterol glycosides, bufadienolide rhamnoside and steroid saponine. The results of bioconversions showed that Nocardia restricta converts steroid glycosides differently according to the sugar bound to the steroid aglycone. It can be concluded that in the absence of a nitrogen atom in the steroid molecule no conjugation with lactic acid by Nocardia restricta occurs. PMID:4046605

  15. Lipoxygenase-inhibiting phenolic glycosides and monoterpene glycosides from Paeonia lactiflora.

    PubMed

    Zou, Liang; Hu, Lin-Feng; Guo, Yi-Dong; Song, Yu; Fu, Qiang

    2015-01-01

    The EtOH extract of the roots of Paeonia lactiflora afforded a new phenolic glycoside paenoside A (1) and a new monoterpene glycoside paeonin D (2), and five known monoterpene glycosides. Their structures were elucidated on the basis of spectroscopic means and hydrolysis products. All compounds displayed inhibitory potential against enzyme lipoxygenase.

  16. Lipoxygenase-inhibiting phenolic glycosides and monoterpene glycosides from Paeonia lactiflora.

    PubMed

    Zou, Liang; Hu, Lin-Feng; Guo, Yi-Dong; Song, Yu; Fu, Qiang

    2015-01-01

    The EtOH extract of the roots of Paeonia lactiflora afforded a new phenolic glycoside paenoside A (1) and a new monoterpene glycoside paeonin D (2), and five known monoterpene glycosides. Their structures were elucidated on the basis of spectroscopic means and hydrolysis products. All compounds displayed inhibitory potential against enzyme lipoxygenase. PMID:25798791

  17. Diterpene Constituents of Euphorbia exigua L. and Multidrug Resistance Reversing Activity of the Isolated Diterpenes.

    PubMed

    Rédei, Dóra; Boros, Klára; Forgo, Peter; Molnár, Joseph; Kele, Zoltán; Pálinkó, István; Pinke, Gyula; Hohmann, Judit

    2015-08-01

    Phytochemical investigation of the MeOH extract obtained from the aerial parts of the annual weed Euphorbia exigua L. resulted in the isolation of two novel (1, 2) and one known (3) jatrophane diterpenes. Their structures were established by extensive 1D- and 2D-NMR spectroscopy and HR-ESI-MS. The isolated compounds were evaluated for multidrug resistance (MDR) reversing activity on human MDR gene-transfected L5178 mouse lymphoma cells; and all three compounds were found to modulate the intracellular drug accumulation.

  18. Diterpene Cyclases and the Nature of the Isoprene Fold

    PubMed Central

    Cao, Rong; Zhang, Yonghui; Mann, Francis M.; Huang, Cancan; Mukkamala, Dushyant; Hudock, Michael P.; Mead, Matthew; Prisic, Sladjana; Wang, Ke; Lin, Fu-Yang; Chang, Ting-Kai; Peters, Reuben; Oldfield, Eric

    2013-01-01

    The structures and mechanism of action of many terpene cyclases are known, but there are no structures of diterpene cyclases. Here, we propose structural models based on bioinformatics, site-directed mutagenesis, domain swapping, enzyme inhibition and spectroscopy that help explain the nature of diterpene cyclase structure, function, and evolution. Bacterial diterpene cyclases contain ∼20 α-helices and the same conserved “QW” and DxDD motifs as in triterpene cyclases, indicating the presence of a βγ barrel structure. Plant diterpene cyclases have a similar catalytic motif and βγ-domain structure together with a third, α-domain, forming an αβγ structure, and in H+-initiated cyclases, there is an EDxxD-like Mg2+/diphosphate binding motif located in the γ-domain. The results support a new view of terpene cyclase structure and function and suggest evolution from ancient (βγ) bacterial triterpene cyclases to (βγ) bacterial and thence to (αβγ) plant diterpene cyclases. PMID:20602361

  19. Accumulation of furanic labdane diterpenes in Marrubium vulgare and Leonurus cardiaca.

    PubMed

    Knöss, W; Zapp, J

    1998-05-01

    Accumulation of furanic labdane diterpenes has been investigated in different parts of field-grown plants of MARRUBIUM VULGARE (Lamiaceae) and LEONURUS CARDIACA (Lamiaceae). Furanic labdane diterpenes were produced and accumulated only in the aerial parts. Greatest amounts were measured in leaves and flowers. Up to 4 mg furanic labdane diterpenes per g fresh weight were found. Accumulation of furanic labdane diterpenes in plantlets seemingly depends on a developmental programme. No furanic labdane diterpenes were detected in plantlets during the first four to five weeks following germination. At this time the leaves became more differentiated and the number of trichomes on leaves was obviously increasing. Young leaves and buds contained most furanic labdane diterpenes. It was proven that at least a part of the non-volatile furanic labdane diterpenes is stored in peltate glandular trichomes. NMR signals of marrubiin were investigated with correlated spectra. Some (1)H- and (13)C-NMR assignments reported in literature were revised.

  20. Interaction of coffee compounds with serum albumins. Part II: Diterpenes.

    PubMed

    Guercia, Elena; Forzato, Cristina; Navarini, Luciano; Berti, Federico

    2016-05-15

    Cafestol and 16-O-methylcafestol are diterpenes present in coffee, but whilst cafestol is found in both Coffea canephora and Coffea arabica, 16-O-methylcafestol (16-OMC) was reported to be specific of only C. canephora. The interactions of such compounds, with serum albumins, have been studied. Three albumins have been considered, namely human serum albumin (HSA), fatty acid free HSA (ffHSA) and bovine serum albumin (BSA). The proteins interact with the diterpenes at the interface between Sudlow site I and the fatty acid binding site 6 in a very peculiar way, leading to a significant change in the secondary structure. The diterpenes do not displace reference binding drugs of site 2, but rather they enhance the affinity of the site for the drugs. They, therefore, may alter the pharmacokinetic profile of albumin - bound drugs.

  1. A new tigliane-type diterpene from Euphorbia dracunculoides Lam.

    PubMed

    Dai, Lin-Feng; Liang, Qian; Liu, Tie; He, Ming-Yu; Zhao, Ping; Xu, Wen-Hui

    2016-07-01

    One new tigliane-type diterpene, 4-deoxy-4(β)H-8-hydroperoxyphorbol-12-benzoate-13-isobutyrate (1), together with two known diterpenoids, 3-acetyl-5,8-dibenzoyl-14α-propanoyl-13,17-epoxy-7-myrsinaone diterpene with C9-C10 cyclised to form an additional lactone ring (2), Euphodendriane A (3) have been isolated from the whole plants of Euphorbia dracunculoides Lam. Their structures were elucidated by means of extensive spectroscopic analysis (NMR and HR-ESI-MS) and comparison with data reported in the literature. This is the first isolation of 8-hydroperoxy tigliane diterpene (1) from the genus of Euphorbia. All compounds were evaluated for their antifungal activities.

  2. Two New Triterpene Glycosides from Centella asiatica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytochemical investigation of the leaves of Centella asiatica resulted in the isolation and characterization of one new ursane type triterpene glycoside; asiaticoside G along with nine known compounds, that were characterized as ursane type triterpenes and /or their glycoside; asiatic acid (2), mad...

  3. Novel diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.

    PubMed

    Kuo, Yueh-Hsiung; Chen, Chia-Hsien; Chien, Shih-Chang; Lin, Hsiu-Chuan

    2004-06-01

    Two novel diterpenes, obtusanal B (1) and obtusadione (2), along with obtusanal A (3), obtunone (4), 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial, 8,12-dihydroxydielmentha-5,9-diene-7,11-dione and myrcene, isolated from the heartwood of Chamaecyparis obtusa var. formosana, were characterized by spectroscopic means, including 2D-NMR techniques. Compounds 1 and 2 are 7(6-->2)abeoabietane and 14(8-->9)abeoabietane type diterpenes, respectively. Their biosyntheses were proposed. PMID:15187404

  4. Novel neoclerodane diterpene derivatives from the smoke of salvinorin A

    PubMed Central

    Ma, Zhongze; Deng, Gang; Lee, David Y. W.

    2010-01-01

    Salvinorin A is a naturally-occurring potent and selective kappa opioid receptor agonist, and smoking salvinorin A produces the most intense hallucinogenic effects in human. Eight neoclerodane diterpene derivatives were isolated from the smoke of salvinorin A, and their structures were identified by spectroscopic methods. The major structural changes include epimerizations, eliminations, and rearrangements. PMID:20936100

  5. Methyl carnosate, an antibacterial diterpene isolated from Salvia officinalis leaves.

    PubMed

    Climati, Elisa; Mastrogiovanni, Fabio; Valeri, Maria; Salvini, Laura; Bonechi, Claudia; Mamadalieva, Nilufar Zokirzhonovna; Egamberdieva, Dilfuza; Taddei, Anna Rita; Tiezzi, Antonio

    2013-04-01

    Ethanolic extracts of Salvia officinalis leaves demonstrated antibacterial activity against Bacillus cereus. Fractionation of the extracts led to the isolation of the most active antibacterial compound, which, from spectroscopic and LC-MS evidence, was proved to be the diterpene, methyl carnosate.

  6. Total synthesis of the Isodon diterpene sculponeatin N.

    PubMed

    Moritz, Benjamin J; Mack, Daniel J; Tong, Liuchuan; Thomson, Regan J

    2014-03-10

    The total synthesis of sculponeatin N, a bioactive polycyclic diterpene isolated from Isodon sculponeatus, is reported. Key features of the synthesis include diastereoselective Nazarov and ring-closing metathesis reactions, and a highly efficient formation of the bicyclo[3.2.1]octane ring system by a reductive radical cyclization. PMID:24519748

  7. Bioactive clerodane diterpenes from roots of Carex distachya.

    PubMed

    Fiorentino, Antonio; D'Abrosca, Brigida; Pacifico, Severina; Izzo, Angelina; D'Angelo, Grazia; Monaco, Pietro

    2010-10-01

    Two new clerodane diterpenes were isolated from roots of Carex distachya Desf., a perennial plant widely distributed in the coastal area of the Mediterranean basin. Chemical characterization of the metabolites was carried out mainly by 1D and 2D NMR spectroscopy. The isolated compounds influenced either positively or negatively the plant growth (root and shoot elongation) of three coexisting herbaceous species.

  8. A new furostanol glycoside from Tribulus terrestris.

    PubMed

    Xu, Yajuan; Liu, Yonghong; Xu, Tunhai; Xie, Shengxu; Si, Yunshan; Liu, Yue; Zhou, Haiou; Liu, Tonghua; Xu, Dongming

    2010-01-27

    Besides two known glycosides, a new furostanol glycoside was isolated from the Fruits of Tribulus terrestris L. The structure of the new furostanol glycoside was established as 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furostane-20(22)-en-12-one-3beta, 26-diol-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-beta-D-galactopyranoside (1) on the basis of 1D and 2D-NMR techniques, including COSY, HMBC, and HMQC correlations.

  9. Hepatoprotective glycosides from Leonurus japonicus Houtt.

    PubMed

    Li, Yixiu; Chen, Zhong; Feng, Ziming; Yang, Yanan; Jiang, Jianshuang; Zhang, Peicheng

    2012-02-01

    Two new phenylethanoid glycosides 1 and 2 named leonoside E and leonoside F, and one new sesquiterpene glycoside (3) identified as 7α (H)-eudesmane-4,11 (12)-diene-3-one-2β-hydroxy-13-β-d-glucopyranoside, together with seven known glycosides (4-10), were isolated from the aerial part of Leonurus japonicus Houtt. Their structures were elucidated on the basis of spectroscopic data and chemical evidence. When tested in in vitro assays, compounds 1, 2, 4, and 6 exhibited potent hepatoprotective activity against d-galactosamine-induced toxicity in HL-7702 cells at concentration of 1×10(-5) M.

  10. Evolution of conifer diterpene synthases: diterpene resin acid biosynthesis in lodgepole pine and jack pine involves monofunctional and bifunctional diterpene synthases.

    PubMed

    Hall, Dawn E; Zerbe, Philipp; Jancsik, Sharon; Quesada, Alfonso Lara; Dullat, Harpreet; Madilao, Lina L; Yuen, Macaire; Bohlmann, Jörg

    2013-02-01

    Diterpene resin acids (DRAs) are major components of pine (Pinus spp.) oleoresin. They play critical roles in conifer defense against insects and pathogens and as a renewable resource for industrial bioproducts. The core structures of DRAs are formed in secondary (i.e. specialized) metabolism via cycloisomerization of geranylgeranyl diphosphate (GGPP) by diterpene synthases (diTPSs). Previously described gymnosperm diTPSs of DRA biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of GGPP followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. In contrast, similar diterpenes of gibberellin primary (i.e. general) metabolism are produced by the consecutive activity of two monofunctional class II and class I diTPSs. Using high-throughput transcriptome sequencing, we discovered 11 diTPS from jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta). Three of these were orthologous to known conifer bifunctional levopimaradiene/abietadiene synthases. Surprisingly, two sets of orthologous PbdiTPSs and PcdiTPSs were monofunctional class I enzymes that lacked functional class II active sites and converted (+)-copalyl diphosphate, but not GGPP, into isopimaradiene and pimaradiene as major products. Diterpene profiles and transcriptome sequences of lodgepole pine and jack pine are consistent with roles for these diTPSs in DRA biosynthesis. The monofunctional class I diTPSs of DRA biosynthesis form a new clade within the gymnosperm-specific TPS-d3 subfamily that evolved from bifunctional diTPS rather than monofunctional enzymes (TPS-c and TPS-e) of gibberellin metabolism. Homology modeling suggested alterations in the class I active site that may have contributed to their functional specialization relative to other conifer diTPSs. PMID:23370714

  11. Evolution of Conifer Diterpene Synthases: Diterpene Resin Acid Biosynthesis in Lodgepole Pine and Jack Pine Involves Monofunctional and Bifunctional Diterpene Synthases1[W][OA

    PubMed Central

    Hall, Dawn E.; Zerbe, Philipp; Jancsik, Sharon; Quesada, Alfonso Lara; Dullat, Harpreet; Madilao, Lina L.; Yuen, Macaire; Bohlmann, Jörg

    2013-01-01

    Diterpene resin acids (DRAs) are major components of pine (Pinus spp.) oleoresin. They play critical roles in conifer defense against insects and pathogens and as a renewable resource for industrial bioproducts. The core structures of DRAs are formed in secondary (i.e. specialized) metabolism via cycloisomerization of geranylgeranyl diphosphate (GGPP) by diterpene synthases (diTPSs). Previously described gymnosperm diTPSs of DRA biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of GGPP followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. In contrast, similar diterpenes of gibberellin primary (i.e. general) metabolism are produced by the consecutive activity of two monofunctional class II and class I diTPSs. Using high-throughput transcriptome sequencing, we discovered 11 diTPS from jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta). Three of these were orthologous to known conifer bifunctional levopimaradiene/abietadiene synthases. Surprisingly, two sets of orthologous PbdiTPSs and PcdiTPSs were monofunctional class I enzymes that lacked functional class II active sites and converted (+)-copalyl diphosphate, but not GGPP, into isopimaradiene and pimaradiene as major products. Diterpene profiles and transcriptome sequences of lodgepole pine and jack pine are consistent with roles for these diTPSs in DRA biosynthesis. The monofunctional class I diTPSs of DRA biosynthesis form a new clade within the gymnosperm-specific TPS-d3 subfamily that evolved from bifunctional diTPS rather than monofunctional enzymes (TPS-c and TPS-e) of gibberellin metabolism. Homology modeling suggested alterations in the class I active site that may have contributed to their functional specialization relative to other conifer diTPSs. PMID:23370714

  12. Biological activities and cytotoxicity of diterpenes from Copaifera spp. Oleoresins.

    PubMed

    de S Vargas, Fabiano; D O de Almeida, Patrícia; Aranha, Elenn Suzany P; de A Boleti, Ana Paula; Newton, Peter; de Vasconcellos, Marne C; Junior, Valdir F Veiga; Lima, Emerson S

    2015-04-09

    Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity and in vitro anti-inflammatory effects of six diterpene acids: copalic, 3-hydroxy-copalic, 3-acetoxy-copalic, hardwickiic, kolavic-15-metyl ester, and kaurenoic, isolated from the oleoresins of Copaifera spp. The diterpenes did not show cytotoxicity in normal cell lines, nor did they show significant changes in viability of tumoral line cells. The 3-hydroxy-copalic was able to inhibit the enzyme tyrosinase (64% ± 1.5%) at 250 µM. The kolavic-15-metyl ester at 200 µM showed high inhibitory effect on lipoxygenase (89.5% ± 1.2%). Among the diterpenes tested, only kaurenoic and copalic acids showed significant hemolytic activities with 61.7% and 38.4% at 100 µM, respectively. In addition, it was observed that only the copalic acid (98.5% ± 1.3%) and hardwickiic acid (92.7% ± 4.9%) at 100 mM inhibited nitric oxide production in macrophages activated by lipopolysaccharide. In this assay, the diterpenes did not inhibit tumor necrosis factor-α production. The acids inhibited the production of IL-6, 3-acetoxy-copalic (23.8% ± 8.2%), kaurenoic (11.2% ± 5.7%), kolavic-15-methyl ester (17.3% ± 4.2%), and copalic (4.2% ± 1.8%), respectively, at 25 µM. The kaurenoic, 3-acetoxy-copalic and copalic acids increased IL-10 production. This study may provide a basis for future studies on the therapeutic role of diterpenic acids in treating acute injuries such as inflammation or skin disorders.

  13. Gene Discovery of Modular Diterpene Metabolism in Nonmodel Systems1[W][OA

    PubMed Central

    Zerbe, Philipp; Hamberger, Björn; Yuen, Macaire M.S.; Chiang, Angela; Sandhu, Harpreet K.; Madilao, Lina L.; Nguyen, Anh; Hamberger, Britta; Bach, Søren Spanner; Bohlmann, Jörg

    2013-01-01

    Plants produce over 10,000 different diterpenes of specialized (secondary) metabolism, and fewer diterpenes of general (primary) metabolism. Specialized diterpenes may have functions in ecological interactions of plants with other organisms and also benefit humanity as pharmaceuticals, fragrances, resins, and other industrial bioproducts. Examples of high-value diterpenes are taxol and forskolin pharmaceuticals or ambroxide fragrances. Yields and purity of diterpenes obtained from natural sources or by chemical synthesis are often insufficient for large-volume or high-end applications. Improvement of agricultural or biotechnological diterpene production requires knowledge of biosynthetic genes and enzymes. However, specialized diterpene pathways are extremely diverse across the plant kingdom, and most specialized diterpenes are taxonomically restricted to a few plant species, genera, or families. Consequently, there is no single reference system to guide gene discovery and rapid annotation of specialized diterpene pathways. Functional diversification of genes and plasticity of enzyme functions of these pathways further complicate correct annotation. To address this challenge, we used a set of 10 different plant species to develop a general strategy for diterpene gene discovery in nonmodel systems. The approach combines metabolite-guided transcriptome resources, custom diterpene synthase (diTPS) and cytochrome P450 reference gene databases, phylogenies, and, as shown for select diTPSs, single and coupled enzyme assays using microbial and plant expression systems. In the 10 species, we identified 46 new diTPS candidates and over 400 putatively terpenoid-related P450s in a resource of nearly 1 million predicted transcripts of diterpene-accumulating tissues. Phylogenetic patterns of lineage-specific blooms of genes guided functional characterization. PMID:23613273

  14. Synthesis and antiproliferative activity of new tonantzitlolone-derived diterpene derivatives.

    PubMed

    Busch, Torsten; Dräger, Gerald; Kunst, Eike; Benson, Hannah; Sasse, Florenz; Siems, Karsten; Kirschning, Andreas

    2016-10-14

    The synthesis of the diterpene (+)-tonantzitlolone A and a series of derivatives is reported. The study includes the determination of their antiproliferative activities against selected cancer cell lines.

  15. New pimarane diterpenes and other antimycobacterial metabolites from Anisochilus verticillatus.

    PubMed

    Kulkarni, Roshan R; Shurpali, Ketaki; Khedkar, Vijay M; Puranik, Vedavati G; Sarkar, Dhiman; Joshi, Swati P

    2016-01-01

    Phytochemical investigation of the acetone extract of the aerial parts of Anisochilus verticillatus afforded a new 8,9-secopimarane diterpene (1), two new isopimarane diterpenes (2, 3) and the known ursolic acid (4), α-amyrin (5), β-amyrin (6), stigmast-5-en-3-one (7) and hydroxychavicol (8). Structures of the new compounds were elucidated with the help of 1D and 2D nuclear magnetic resonance spectroscopic data, and single crystal X-ray crystallography of compound 3. Compounds 2 and 8 inhibited Mycobacterium tuberculosis H37Ra with an IC50 of 11.3 (IC90 of 20.0 μg/mL) and 12.5 μg/mL, respectively. Correspondingly, molecular docking studies with Extra Precision Glide revealed a correlation between score and biological activity for these compounds to describe the molecular basis for the most significant SAR results.

  16. Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

    NASA Astrophysics Data System (ADS)

    Lovell, Kimberly M.; Prevatt-Smith, Katherine M.; Lozama, Anthony; Prisinzano, Thomas E.

    Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a basic nitrogen. There have been several total synthesis approaches to salvinorin A, and these will be detailed within this chapter. Additionally, research efforts have concentrated on structure modification of the salvinorin A scaffold through semi-synthetic methods. Most modifications have focused on the manipulation of the acetate at C-2 and the furan ring. However, chemistry has also been developed to generate analogs at the C-1 ketone, the C-4 methyl ester, and the C-17 lactone. The synthetic methodologies developed for the salvinorin A scaffold will be described, as well as specific analogs with interesting biological activities.

  17. Two new diterpenes from the seeds of Caesalpinia minax Hance.

    PubMed

    Lian, Lian; Li, Xiao-Bin; Yuan, Jiu-Zhi; Cheng, Li; Wu, Zhao-Hua; Gao, Hui-Yuan

    2015-01-01

    Molecules with diterpene skeletons often possess valuable medicinal properties. Two new diterpenes 1α,6α,7β-triacetoxy-5α-hydroxy-14β-ethyl-O-vouacapane (1) and 2α-acetoxy-14,15-cyclopimara-7β,16-diol (2) were isolated from the seeds of Caesalpinia minax Hance. Their structures were established on the basis of extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR (HSQC, HMBC, NOESY) methods. The stereochemical structure of 1 was confirmed via the circular dichroism spectrum and calculated ECD experiment. The inhibitory activity of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide of compounds 1 and 2 was evaluated, and compound 1 was found to show significant inhibitory effect.

  18. Biologically active diterpenes from Aspilia mossambicensis, a chimpanzee medicinal plant.

    PubMed

    Page, J E; Balza, F; Nishida, T; Towers, G H

    1992-10-01

    Two potent stimulators of uterine contraction, the diterpenes kaurenoic and grandiflorenic acids, were isolated from leaves of Aspilia mossambicensis. Their presence supports a hypothesis that wild chimpanzees consume Aspilia species for their pharmacological properties and may explain why female chimpanzees consume Aspilia leaves more frequently than do males. Thiarubrines were not present in any of the leaf samples collected in Mahale or Gombe National Parks, Tanzania, although these antifungal and nematocidal dithianes were found in significant amounts in roots.

  19. New clerodane diterpenes from Tinospora sagittata var. yunnanensis.

    PubMed

    Jiang, Zhi-Yong; Li, Wen-Juan; Jiao, Li-Xiang; Guo, Jun-Ming; Tian, Kai; Yang, Chun-Tao; Huang, Xiang-Zhong

    2014-03-01

    Four new clerodane diterpenes, namely sagittatayunnanosides A-D (1-4), were isolated from the roots of Tinospora sagittata var. yunnanensis, together with two known compounds, tinospinoside C (5) and tinospinoside E (6). The structures of the four new compounds were well elucidated by extensive analyses of the MS, IR, and 1D and 2D NMR data. The cytotoxic and antifouling activities of compounds 1-6 were evaluated. PMID:24634023

  20. Cassane diterpenes from the seed kernels of Caesalpinia sappan.

    PubMed

    Nguyen, Hai Xuan; Nguyen, Nhan Trung; Dang, Phu Hoang; Thi Ho, Phuoc; Nguyen, Mai Thanh Thi; Van Can, Mao; Dibwe, Dya Fita; Ueda, Jun-Ya; Awale, Suresh

    2016-02-01

    Eight structurally diverse cassane diterpenes named tomocins A-H were isolated from the seed kernels of Vietnamese Caesalpinia sappan Linn. Their structures were determined by extensive NMR and CD spectroscopic analysis. Among the isolated compounds, tomocin A, phanginin A, F, and H exhibited mild preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived condition without causing toxicity in normal nutrient-rich conditions.

  1. Antimalarial diterpene alkaloids from the seeds of Caesalpinia minax.

    PubMed

    Ma, Guoxu; Sun, Zhaocui; Sun, Zhonghao; Yuan, Jingquan; Wei, Hua; Yang, Junshan; Wu, Haifeng; Xu, Xudong

    2014-06-01

    Two new diterpene alkaloids, caesalminines A (1) and B (2), possessing a tetracyclic cassane-type furanoditerpenoid skeleton with γ-lactam ring, were isolated from the seeds of Caesalpinia minax. Their structures were determined by different spectroscopic methods and ECD calculation. The plausible biosynthetic pathway of caesalminines A and B was proposed. The anti-malarial activity of compounds 1 and 2 is presented with IC50 values of 0.42 and 0.79 μM, respectively.

  2. A New Cytotoxic Clerodane Diterpene from Casearia graveolens Twigs.

    PubMed

    Meesakul, Pornphimol; Ritthiwigrom, Thunwadee; Cheenpracha, Sarot; Sripisut, Tawanun; Maneerat, Wisanu; Machan, Theeraphan; Laphookhieo, Surat

    2016-01-01

    The first phytochemical investigation of Casearia graveolens twigs led to the isolation and identification of a new clerodane diterpene, caseariagraveolin (1), together with six known compounds (2-7). Their structures were elucidated by intensive analysis of their spectroscopic data. Compound 1 showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC₅₀ values of 2.48 and 6.63 µM, respectively.

  3. Casbane Diterpenes from Red Sea Coral Sinularia polydactyla.

    PubMed

    Hegazy, Mohamed-Elamir F; Mohamed, Tarik A; Elshamy, Abdelsamed I; Al-Hammady, Montaser A; Ohta, Shinji; Paré, Paul W

    2016-01-01

    The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O (3); in addition, known metabolites (4-5) were isolated. Compounds were elucidated on the basis of spectroscopic analyses; the absolute configuration was confirmed by X-ray analysis. PMID:27011161

  4. Casbane Diterpenes from Red Sea Coral Sinularia polydactyla.

    PubMed

    Hegazy, Mohamed-Elamir F; Mohamed, Tarik A; Elshamy, Abdelsamed I; Al-Hammady, Montaser A; Ohta, Shinji; Paré, Paul W

    2016-01-01

    The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O (3); in addition, known metabolites (4-5) were isolated. Compounds were elucidated on the basis of spectroscopic analyses; the absolute configuration was confirmed by X-ray analysis. PMID:26950110

  5. Volatile diterpene emission from dominant conifers in Japan

    NASA Astrophysics Data System (ADS)

    Matsunaga, S. N.; Chatani, S.; Nakatsuka, S.; Kusumoto, D.; Kubota, K.; Utsumi, Y.; Enoki, T.; Tani, A.; Hiura, T.

    2011-07-01

    Reactive volatile organic compounds (VOCs) are known to affect atmospheric chemistry, especially biogenic VOCs (BVOCs) which have a significant impact on regional air quality due to their large emission rates and high reactivities. Diterpenes (Kaur-16-ene and a diterpene likely to be Hibaene) were detected in all of the 205 enclosure air samples collected over multiple seasons at two different sites from Cryptomeria japonica and Chamaecyparis obtusa trees, the dominant coniferous trees in Japan. The emission rate of Kaur-16-ene, was determined to be from 0.01 to 7.1 μg dwg-1 h-1 (average: 0.61 μg dwg-1 h-1) by branch enclosure measurements and solid phase - liquid extraction techniques. The emission rate was an order of magnitude higher than that of monoterpenes which are known to comprise a major portion of total BVOC emissions. In addition, total emission of Kaur-16-ene at 30 °C was estimated to be comparable to that of total anthropogenic VOC emissions. To our knowledge, this is the first report of volatile diterpene emissions from trees.

  6. Antileishmanial activity of diterpene acids in copaiba oil

    PubMed Central

    dos Santos, Adriana Oliveira; Izumi, Erika; Ueda-Nakamura, Tânia; Dias-Filho, Benedito Prado; da Veiga-Júnior, Valdir Florêncio; Nakamura, Celso Vataru

    2013-01-01

    Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs. PMID:23440116

  7. Structural Characterization of the Degradation Products of a Minor Natural Sweet Diterpene Glycoside Rebaudioside M under Acidic Conditions

    PubMed Central

    Prakash, Indra; Chaturvedula, Venkata Sai Prakash; Markosyan, Avetik

    2014-01-01

    Degradation of rebaudioside M, a minor sweet component of Stevia rebaudiana Bertoni, under conditions that simulated extreme pH and temperature conditions has been studied. Thus, rebaudioside M was treated with 0.1 M phosphoric acid solution (pH 2.0) and 80 °C temperature for 24 h. Experimental results indicated that rebaudioside M under low pH and higher temperature yielded three minor degradation compounds, whose structural characterization was performed on the basis of 1D (1H-, 13C-) & 2D (COSY, HSQC, HMBC) NMR, HRMS, MS/MS spectral data as well as enzymatic and acid hydrolysis studies. PMID:24424316

  8. Cloning of Casbene Synthases from Euphorbiaceae Plants and Implications for Diterpene Biosynthesis in This Family

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A large number of diterpenes have been isolated from Euphorbiaceae plants, many of which are of interest due to toxicity or potential therapeutic activity. Specific Euphorbiaceae diterpenes of medical interest include the latent HIV-1 activator prostratin (and related 12-deoxyphorbol esters), the an...

  9. New adduct of abietane-type diterpene from Salvia leriifolia Benth.

    PubMed

    Hussain, Amjad; Adhikari, Achyut; Iqbal Choudhary, M; Ayatollahi, Syed Abdulmajid; Atta-Ur-Rahman

    2016-07-01

    A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy.

  10. Phenylethanoid and aliphatic alcohol glycosides from Acanthus ilicifolius.

    PubMed

    Wu, Jun; Zhang, Si; Xiao, Qiang; Li, Qingxin; Huang, Jianshe; Long, Lijuan; Huang, Liangmin

    2003-06-01

    A phenylethanoid glycoside (ilicifolioside A) and an aliphatic alcohol glycoside (ilicifolioside B), have been isolated from the aerial parts of Acanthus ilicifolius, together with eight known compounds. Their structures were determined from spectroscopic analyses.

  11. Bioactive phenylpropanoid glycosides from Tabebuia avellanedae.

    PubMed

    Suo, Maorong; Ohta, Tomihisa; Takano, Fumihide; Jin, Shouwen

    2013-06-24

    Three novel phenylpropanoid glycosides 2, 5, 6 were isolated from water extract of Tabebuia avellanedae, together with three known phenylpropanoid glycosides 1, 3, 4. All compounds were identified on the basis of spectroscopic analysis and chemical methods and, for known compounds, by comparison with published data. All isolated compounds showed strong antioxidant activity in the DPPH assay, and compound 5 give the highest antioxidant activity among all compounds, with an IC₅₀ of 0.12 µM. All compounds exhibited moderate inhibitory effect on cytochrome CYP3A4 enzyme.

  12. Five new phenolic glycosides from Hedyotis scandens.

    PubMed

    Wang, Guo-Cai; Li, Tao; Deng, Fang-Ye; Li, Yao-Lan; Ye, Wen-Cai

    2013-03-01

    Five new phenolic glycosides, hedyotosides A-E (1-5), including a new cyanogenic glycoside (1), along with 10 known compounds (6-15) were isolated from the whole plants of Hedyotis scandens. The structures of compounds 1-5 were established by extensive spectroscopic analyses and acid hydrolysis. All the isolated compounds were evaluated for their in vitro antiviral activity against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay. Compounds 6 and 15 showed anti-RSV effects with IC(50) values of 20 and 25 μg/mL, respectively. PMID:23333151

  13. Naphthalene glycosides in Cassia senna and Cassia angustifolia.

    PubMed

    Lemli, J; Toppet, S; Cuveele, J; Janssen, G

    1981-09-01

    From leaves and pods of Cassia senna L. and C. angustifolia Vahl. were isolated the naphthalene glycosides 6-hydroxymusizin glycoside and the new tinnevellin glycoside. The structures were established mainly by spectroscopic methods ( (1)H NMR, (13)C NMR, MS). PMID:17402001

  14. Identification and characterization of component organic and glycosidic acids of crude resin glycoside fraction from Calystegia soldanella.

    PubMed

    Takigawa, Ayako; Setoguchi, Hiroaki; Okawa, Masafumi; Kinjo, Junei; Miyashita, Hiroyuki; Yokomizo, Kazumi; Yoshimitsu, Hitoshi; Nohara, Toshihiro; Ono, Masateru

    2011-01-01

    Alkaline hydrolysis of the crude resin glycoside fraction of the leaves, stems, and roots of Calystegia soldanella ROEM. et SCHULT. (Convolvulaceae) gave four new glycosidic acids, named calysolic acids A, B, C, and D, along with one known glycosidic acid, soldanellic acid B, and three organic acids, 2S-methylbutyric, tiglic, and 2S,3S-nilic acids. The structures of the new glycosidic acids were characterized on the basis of spectroscopic data and chemical evidence.

  15. Anticancer Activity of Sea Cucumber Triterpene Glycosides

    PubMed Central

    Aminin, Dmitry L.; Menchinskaya, Ekaterina S.; Pisliagin, Evgeny A.; Silchenko, Alexandra S.; Avilov, Sergey A.; Kalinin, Vladimir I.

    2015-01-01

    Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata). They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor), Akt (protein kinase B), ERK (extracellular signal-regulated kinases), FAK (focal adhesion kinase), MMP-9 (matrix metalloproteinase-9) and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics. PMID:25756523

  16. New triterpene glycosides from Ziziphi Spinosae Semen.

    PubMed

    Wang, Yu; Ding, Bo; Luo, Dan; Chen, Liu-Yuan; Hou, Yun-Long; Dai, Yi; Yao, Xin-Sheng

    2013-10-01

    Four new dammarane-type triterpene glycosides, named jujubosides I-IV (1-4), were isolated from Ziziphi Spinosae Semen, along with seven known saponins (5-11). The structures of new compounds were established on the basis of extensive spectroscopic analysis. All compounds were evaluated for the effects on neonatal rat cardiomyocyte injury induced by hydrogen peroxide in vitro. PMID:23912064

  17. A new isoflavone glycoside from Pueraria alopecuroides.

    PubMed

    Yang, Junlin; Fan, Qingfei; Zhang, Huanli; Song, Qishi

    2016-01-01

    A new isoflavone glycoside, (-)-tuberosin-3-O-β-D-glucopyranoside (1), along with 10 known compounds 1a-10, was isolated from Pueraria alopecuroides. Their structures were determined on the basis of spectral data including 1D and 2D NMR and HREIMS. These compounds were isolated from this plant for the first time. PMID:26525177

  18. Two new glycosides from Leonurus japonicus.

    PubMed

    Chang, Jin-Ming; Shen, Chien-Chang; Huang, Yu-Ling; Shieh, Bor-Jinn; Chen, Chien-Chih

    2010-09-01

    Two new glycosides, 1,6-di-O-syringoyl-β-D-glucopyranose (1) and quercetin 3-O-[(3-O-syringoyl-α-L-rhamnopyranosyl)-(1→6)-β-D-glucopyranoside] (2), along with seven known compounds were isolated from the MeOH extract of Leonurus japonicus. The structures of these compounds were elucidated by spectral analysis.

  19. Twisting of glycosidic bonds by hydrolases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Patterns of scissile bond twisting have been found in crystal structures of glycoside hydrolases (GHs) that are complexed with substrates and inhibitors. To estimate the increased potential energy in the substrates that results from this twisting, we have plotted torsion angles for the scissile bond...

  20. New xanthone glycosides from Securidaca inappendiculata.

    PubMed

    Yang, Xue-Dong; An, Ning; Xu, Li-Zhen; Yang, Shi-Lin

    2002-06-01

    Three new xanthone glycosides, securixanside A (1), securixanside B (2), and securixanside C (3) were isolated from the stems of Securidaca inappendiculata. These compounds were characterized by spectrometric and chemical methods, including FABMS and one- and two-dimensional NMR experiments. PMID:12067160

  1. A new sterol glycoside from Securidaca inappendiculata.

    PubMed

    Zhang, Li-Jie; Yang, Xue-Dong; Xu, Li-Zhen; Zou, Zhong-Mei; Yang, Shi-Lin

    2005-08-01

    From the roots of Securidaca inappendiculata, one new sterol glycoside securisteroside (1) has been isolated, along with two known sterols, spinasterol (2) and 3-O-beta-D-glucopyranosyl-spinasterol (3). The new sterol was characterized by chemical and spectrometric methods, including EIMS, FABMS and one- and two-dimensional NMR experiments. PMID:16087640

  2. Immunosuppressive auronol glycosides from Artocarpus tonkinensis.

    PubMed

    Thuy, T T; Kamperdick, C; Ninh, P T; Lien, T P; Thao, T T P; Sung, T V

    2004-04-01

    Activity-guided fractionation of the n-butanol extract from the leaves of Artocarpus tonkinensis led to the isolation of the auronol glycosides maesopsin 4-O-glucoside (1), as well as the new alphitonin-4-O-glucoside (2). These structures were identified on the basis of MS and NMR spectroscopic data. The lymphocyte stimulation test showed both compounds having immunosuppressive activity.

  3. A new phenylethanoid glycoside from Clerodendrum inerme.

    PubMed

    Nan, Haihan; Wu, Jun; Zhang, Si

    2005-10-01

    A new phenylethanoid glycoside, 2-(3-methoxy-4-hydroxylphenyl) ethyl-O-2",3"-diacetyl-alpha-L-rhamnopyranosyl-(1-->3)-4-O-(E)-feruloyl-beta-D-glucopyranoside, was isolated from the aerial parts of Clerodendrum inerme (L.) Gaertn, together with monomelittoside, melittoside, inerminoside A1, verbascoside, isoverbascoside, campneoside I. Their structures were determined by spectroscopic methods.

  4. Enzymatic Processing of Bioactive Glycosides from Natural Sources

    NASA Astrophysics Data System (ADS)

    Weignerová, Lenka; Křen, Vladimír

    A number of biologically active natural products are glycosides. Often, the glycosidic residue is crucial for their activity. In other cases, glycosylation only improves their pharmacokinetic parameters. Enzymatic modification of these glycosides - both extension of the glycoside moiety and its selective trimming - is advantageous due to their selectivity and mildness of the reaction conditions in the presence of reactive and sensitive complex aglycones. Enzymatic reactions enable the resulting products to be used as "natural products", e.g., in nutraceuticals. This chapter concentrates on naturally occurring glycosides used in medicine but also in the food and flavor industry (e.g., sweeteners). Both "classical" and modern methods will be discussed.

  5. Triterpene glycosides of sea cucumbers (Holothuroidea, Echinodermata) as taxonomic markers.

    PubMed

    Kalinin, Vladimir I; Avilov, Sergey A; Silchenko, Alexandra S; Stonik, Valentin A

    2015-01-01

    Triterpene glycosides are characteristic metabolites of sea cucumbers (Holothurioidea, Echinodermata). The majority of the glycosides belong to the holostane type {lanostane derivatives with an 18(20)-lactone}. Carbohydrate chains of these glycosides contain xylose, glucose, quinovose, 3-O-methylglucose, and, rarely, 3-O-methylxylose, 3-O-methylglucuronic acid, 3-O-methylquinovose, and 6-O-acetyl-glucose. The glycosides are specific for genera, groups of genera and even for species. The advantages and problems in the use of triterpene glycosides as taxonomic markers in the systematics of sea cucumbers are discussed.

  6. Advance on the Flavonoid C-glycosides and Health Benefits.

    PubMed

    Xiao, Jianbo; Capanoglu, Esra; Jassbi, Amir Reza; Miron, Anca

    2016-07-29

    The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

  7. Discovery of a Novel Diterpene in Brown Propolis from the State of Parana, Brazil.

    PubMed

    Tazawa, Shigemi; Arai, Yasuko; Hotta, Sho; Mitsui, Taichi; Nozaki, Hiroshi; Ichihara, Kenji

    2016-02-01

    Propolis is a resinous substance collected by honeybees from certain plant sources. The components of propolis depend on the vegetation of the area in which apiculture is practiced. In Brazil, there are several types of propolis including 'green,' 'red' and 'brown'. Brazilian brown propolis from the state of Parana characteristically includes diterpenes, and we discovered a novel clerodane diterpene, rel-(5S,6S,8R,9R,10S,18R,19S)-18,19-epoxy-2-oxocleroda-3,12(E),14- triene-6,18,19-triol 18,19-diacetate 6-benzoate (3) and five known diterpenes (1, 2, 4, 5 and 6). The chemical structure of the novel diterpene 3 was determined using 1D- and 2D-NMR spectroscopic analyses. Furthermore, the activities of the isolated diterpenes on growth inhibition of several human cancer cell lines (LNCaP, MCF-7, DLD-1 and A549) were evaluated in vitro; diterpene 3 exhibited a potent inhibition of cell growth, and its activity was approximately 15 times higher than that of the other diterpenes. PMID:27032202

  8. Discovery of a Novel Diterpene in Brown Propolis from the State of Parana, Brazil.

    PubMed

    Tazawa, Shigemi; Arai, Yasuko; Hotta, Sho; Mitsui, Taichi; Nozaki, Hiroshi; Ichihara, Kenji

    2016-02-01

    Propolis is a resinous substance collected by honeybees from certain plant sources. The components of propolis depend on the vegetation of the area in which apiculture is practiced. In Brazil, there are several types of propolis including 'green,' 'red' and 'brown'. Brazilian brown propolis from the state of Parana characteristically includes diterpenes, and we discovered a novel clerodane diterpene, rel-(5S,6S,8R,9R,10S,18R,19S)-18,19-epoxy-2-oxocleroda-3,12(E),14- triene-6,18,19-triol 18,19-diacetate 6-benzoate (3) and five known diterpenes (1, 2, 4, 5 and 6). The chemical structure of the novel diterpene 3 was determined using 1D- and 2D-NMR spectroscopic analyses. Furthermore, the activities of the isolated diterpenes on growth inhibition of several human cancer cell lines (LNCaP, MCF-7, DLD-1 and A549) were evaluated in vitro; diterpene 3 exhibited a potent inhibition of cell growth, and its activity was approximately 15 times higher than that of the other diterpenes.

  9. A new labdane diterpene from the rhizomes of Alpinia officinarum.

    PubMed

    Zou, Qiong-Yu; Wu, Hai-Feng; Tang, Yu-Lian; Chen, Di-Zhao

    2016-01-01

    A new labdane diterpene, (Z)-12,14-labdadien-15(16)-olide-17-oic acid (1), and a new natural cadinane sesquiterpene, 4-isopropyl-6-methyl-1-naphthalenemethanol (2), were isolated from the ethanolic extract of the rhizomes of Alpinia officinarum, together with three other products, galangin (3), kaempferol (4) and quercetin (5). Their structures were elucidated by using extensive spectroscopic methods. Compounds 1 and 2 showed no remarkable cytotoxic activity against HeLa and HepG2 cancer cell lines with IC50>50 μg mL(- 1).

  10. New diterpenes from a Godavari mangrove, Ceriops decandra.

    PubMed

    Wang, Hui; Li, Min-Yi; Satyanandamurty, Tirumani; Wu, Jun

    2013-05-01

    Eleven new diterpenes, named decandrins A-K (1-11), including nine abietanes (1-9) and two podocarpanes (10-11), were isolated from the barks of an Indian mangrove, Ceriops decandra, collected in the mangrove swamp of Godavari estuary, Andhra Pradesh, together with four known abietanes. The structures of these compounds were established on the basis of spectroscopic data (new compounds) or comparison with data in the literature (known compounds). This is the first report of abietane and podocarpane diterpenoids from C. decandra.

  11. Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.

    PubMed

    Andersen-Ranberg, Johan; Kongstad, Kenneth Thermann; Nielsen, Morten Thrane; Jensen, Niels Bjerg; Pateraki, Irini; Bach, Søren Spanner; Hamberger, Britta; Zerbe, Philipp; Staerk, Dan; Bohlmann, Jörg; Møller, Birger Lindberg; Hamberger, Björn

    2016-02-01

    Plant-derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are "new-to-nature". Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae.

  12. Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis

    PubMed Central

    Andersen‐Ranberg, Johan; Kongstad, Kenneth Thermann; Nielsen, Morten Thrane; Jensen, Niels Bjerg; Pateraki, Irini; Bach, Søren Spanner; Hamberger, Britta; Zerbe, Philipp; Staerk, Dan; Bohlmann, Jörg; Møller, Birger Lindberg

    2016-01-01

    Abstract Plant‐derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are “new‐to‐nature”. Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae. PMID:26749264

  13. Phytophthora austrocedri Elicitates Changes in Diterpene Profile of Austrocedrus chilensis.

    PubMed

    Olate, Verónica Rachel; Vélez, María Laura; Greslebin, Alina; Schmeda-Hirschmann, Guillermo

    2015-08-18

    The populations of the Andean Cupressaceae Austrocedrus chilensis have been severely affected by a disease caused by the phytopathogenic fungus Phytophthora austrocedri. A study was undertaken to disclose changes in the resin composition of P. austrocedri-infected individuals, including naturally infected and artificially inoculated trees, compared with healthy A. chilensis trees. GC-MS and (1)H-NMR studies showed a clear differentiation among healthy and infected resins, with the diterpene isopimara-8(9),15-dien-19-ol as a relevant constituent in resins from infected trees. The effect of resin fractions from P. austrocedri infected trees on the pathogen was assessed by measuring the mycelial growth in agar plates. The most active fractions from resin obtained from infected trees inhibited fungal growth by nearly 50% at 1 mg/dish (35.37 µg/cm(2)). The main constituent in the active fractions were 18-hydroxymanool and the aldehyde torulosal. Both compounds are oxidation products of manool and can be a chemical response of the tree to the pathogen or be formed from the pathogen as a biotransformation product of manool by microbial oxidation. While the diterpene profiles from A. chilensis tree resins can easily differentiate healthy and P. austrocedri infected individuals, the possible conversion of manool to the antifungal derivatives 4 and 6 by the microorganism remains to be established.

  14. Phytophthora austrocedri Elicitates Changes in Diterpene Profile of Austrocedrus chilensis.

    PubMed

    Olate, Verónica Rachel; Vélez, María Laura; Greslebin, Alina; Schmeda-Hirschmann, Guillermo

    2015-01-01

    The populations of the Andean Cupressaceae Austrocedrus chilensis have been severely affected by a disease caused by the phytopathogenic fungus Phytophthora austrocedri. A study was undertaken to disclose changes in the resin composition of P. austrocedri-infected individuals, including naturally infected and artificially inoculated trees, compared with healthy A. chilensis trees. GC-MS and (1)H-NMR studies showed a clear differentiation among healthy and infected resins, with the diterpene isopimara-8(9),15-dien-19-ol as a relevant constituent in resins from infected trees. The effect of resin fractions from P. austrocedri infected trees on the pathogen was assessed by measuring the mycelial growth in agar plates. The most active fractions from resin obtained from infected trees inhibited fungal growth by nearly 50% at 1 mg/dish (35.37 µg/cm(2)). The main constituent in the active fractions were 18-hydroxymanool and the aldehyde torulosal. Both compounds are oxidation products of manool and can be a chemical response of the tree to the pathogen or be formed from the pathogen as a biotransformation product of manool by microbial oxidation. While the diterpene profiles from A. chilensis tree resins can easily differentiate healthy and P. austrocedri infected individuals, the possible conversion of manool to the antifungal derivatives 4 and 6 by the microorganism remains to be established. PMID:26295220

  15. Energy maps for glycosidic linkage conformations.

    PubMed

    French, Alfred D

    2015-01-01

    Glycosidic linkage conformations are the main factors in determining the shapes of disaccharide, oligosaccharide, and polysaccharide molecules. The conformations are expressed in terms of the torsion angles about the bonds from each ring of the disaccharide moiety to its glycosidic oxygen atom, and the probability of a given conformation is often expressed in terms of its free or potential energy. The energy surface or map for a disaccharide is a display of the energy plotted against the two torsion angles. Successful mapping allows a particular kind of energy calculation to provide the energy values for each conformation and avoids possible pitfalls. Although different methods are discussed, the main emphasis of this chapter is on the technical production of the maps and their exploitation in further understanding the shape of the molecule in question.

  16. Phenolic glycosides from berries of Pimenta dioica.

    PubMed

    Kikuzaki, Hiroe; Miyajima, Yoshiko; Nakatani, Nobuji

    2008-05-01

    Four new phenolic glycosides, (2-hydroxy-3-methoxy-5-allyl)phenyl beta- d-(6-O-E-sinapoyl)glucopyranoside (1), (1' R,5' R)-5-(5-carboxymethyl-2-oxocyclopentyl)-3 Z-pentenyl beta-D-(6-O-galloyl)glucopyranoside (2), (S)-alpha-terpinyl [alpha-L-(2-O-galloyl)arabinofuranosyl]-(1-->6)-beta-D-glucopyranoside (3), and (R)-alpha-terpinyl [alpha-L-(2-O-galloyl)arabinofuranosyl]-(1-->6)-beta-D-glucopyranoside (4), were isolated from the berries of Pimenta dioica together with eight known flavonoids. The structures of 1-4 were elucidated on the basis of MS and NMR data and enzymatic hydrolysis. All four glycosides showed radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals.

  17. Hepatoprotective phenylethanoid glycosides from Cirsium setosum.

    PubMed

    Ma, Qinge; Guo, Yongming; Luo, Baomin; Liu, Wenmin; Wei, Rongrui; Yang, Chunxia; Ding, Chenghua; Xu, Xuefeng; He, Minghui

    2016-08-01

    Two new phenylethanoid glycosides, namely β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(3-methoxyl-4-hydroxyphenyl)-8-propenoate] (1) and β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(4-hydroxyphenyl)-8-propenoate] (2), together with six phenylethanoid glycosides were isolated from Cirsium setosum. Their structures were elucidated by their spectroscopic data and references. Compounds 2, 4, 5, 7 and 8 (10 μM) exhibited moderate hepatoprotective activities. Compounds (3-8) were obtained from this plant for the first time.

  18. A New Cucurbitane Glycoside from Siraitia grosvenorii.

    PubMed

    Chaturvedula, Venkata Sai Prakash; Meneni, Srinivasa Rao

    2015-09-01

    A systematic phytochemical study of the commercial extract of Luo Han Guo (Siraitia grosvenorii) resulted in the isolation of an additional minor new cucurbitane glycoside, mogroside V Al (1). The structure of the new compound was characterized on the basis of 1D (1H and 13C NMR) and 2D (COSY, HMQC, HMBC and NOESY) NMR and high resolution mass spectral (HRMS) data, as well as hydrolysis studies. PMID:26594748

  19. Alkyl and phenolic glycosides from Saussurea stella.

    PubMed

    Wang, Tian-Min; Wang, Ru-Feng; Chen, Hu-Biao; Shang, Ming-Ying; Cai, Shao-Qing

    2013-07-01

    One alkyl glycoside, saussurostelloside A (1), two phenolic glycosides, saussurostellosides B1 (2) and B2 (3), and 27 known compounds, including eleven flavonoids, seven phenolics, six lignans, one neolignan, one phenethyl glucoside and one fatty acid, were isolated from an ethanol extract of Saussurea stella (Asteraceae). Their structures were elucidated by NMR, MS, UV, and IR spectroscopic analysis. Of the known compounds, (+)-medioresinol-di-O-β-D-glucoside (7), picraquassioside C (10), and diosmetin-3'-O-β-D-glucoside (27) were isolated from the Asteraceae family for the first time, while (+)-pinoresinol-di-O-β-D-glucoside (6), di-O-methylcrenatin (11), protocatechuic acid (14), 1,5-di-O-caffeoylquinic acid (17), formononetin (28), and phenethyl glucoside (29) were isolated from the Saussurea genus for the first time. The anti-inflammatory activities of three new compounds (1-3), five lignans ((-)-arctiin (4), (+)-pinoresinol-4-O-β-D-glucoside (5), (+)-pinoresinol-di-O-β-D-glucoside (6), (+)-medioresinol-di-O-β-D-glucoside (7) and (+)-syringaresinol-4-O-β-D-glucoside (8)), one neolignan (picraquassioside C (10)), and one phenolic glycoside (di-O-methylcrenatin (11)) were evaluated by testing their inhibition of the release of β-glucuronidase from PAF-stimulated neutrophils. Only compound 5 showed moderate inhibition of the release of β-glucuronidase, with an inhibition ratio of 39.1%.

  20. Six new cassane diterpenes from the twigs and leaves of Tara (Caesalpinia spinosa Kuntze).

    PubMed

    He, Dongyang; Li, Yuanping; Tang, Hongbo; Ma, Ruijing; Li, Xiaonian; Wang, Liqin

    2015-09-01

    Six new cassane diterpenes, isoneocaesalpin H (1), caespinosin A (2), caespinosin B (3), a cassane diterpene with unique 6/6/7 carbon rings, and caespinosins C-E (4-6) were isolated from the twigs and leaves of Tara (Caesalpinia spinosa Kuntze). The absolute configuration of isoneocaesalpin H (1) was determined by single-crystal X-ray crystallographic analysis. Compound 3 represents a class of rare natural cassane diterpene bearing unique 6/6/7 carbon rings. Their structures were identified by 1D and 2D NMR spectral data. Cassane diterpenes were firstly reported from Tara. Compounds 1-5 were evaluated for their cytotoxicity on HL-60, SMMC-7721, A-549, MCF-7 and SW-480 human cancer cell lines, but they were inactive.

  1. Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis.

    PubMed

    Jia, Meirong; Potter, Kevin C; Peters, Reuben J

    2016-09-01

    Diterpenes are widely distributed across many biological kingdoms, where they serve a diverse range of physiological functions, and some have significant industrial utility. Their biosynthesis involves class I diterpene synthases (DTSs), whose activity can be preceded by that of class II diterpene cyclases (DTCs). Here, a modular metabolic engineering system was used to examine the promiscuity of DTSs. Strikingly, both a bacterial and plant DTS were found to exhibit extreme promiscuity, reacting with all available precursors with orthogonal activity, producing an olefin or hydroxyl group, respectively. Such DTS promiscuity enables combinatorial biosynthesis, with remarkably high yields for these unoptimized non-native enzymatic combinations (up to 15mg/L). Indeed, it was possible to readily characterize the 13 unknown products. Notably, 16 of the observed diterpenes were previously inaccessible, and these results provide biosynthetic routes that are further expected to enable assembly of more extended pathways to produce additionally elaborated 'non-natural' diterpenoids.

  2. Mycgranol, a new diterpene from the marine sponge Mycale aff. graveleyi.

    PubMed

    Rudi, Amira; Benayahu, Yehuda; Kashman, Yoel

    2005-02-01

    Mycgranol, a new isocopalane diterpene (methyl 1beta-hydroxy-2-oxoisocopalanoate) was isolated from the Kenyan sponge Mycale (Aegogropila) aff. graveleyi. The structure of the compound was elucidated by interpretation of MS, COSY, HMQC, HMBC, and ROESY data. The absolute configuration of mycgranol was determined to be the same as that of the nudibranch isocopalane diterpenes rather than that of the ent-compounds known from sponges of the genus Spongia. PMID:15730263

  3. Structure and Mechanism of the Diterpene Cyclase ent-Copalyl Diphosphate Synthase

    PubMed Central

    Köksal, Mustafa; Hu, Huayou; Coates, Robert M.; Peters, Reuben J.; Christianson, David W.

    2011-01-01

    The structure of ent-copalyl diphosphate synthase (CPS) reveals three α-helical domains (α, β, γ), as also observed in the related diterpene cyclase taxadiene synthase. However, active sites are located at the interface of the βγ domains in CPS but exclusively in the α domain of taxadiene synthase. Modular domain architecture in plant diterpene cyclases enables the evolution of alternative active sites and chemical strategies for catalyzing isoprenoid cyclization reactions. PMID:21602811

  4. Diterpene alkaloids with an aza-ent-kaurane skeleton from Isodon rubescens.

    PubMed

    Liu, Xu; Yang, Jing; Wang, Wei-Guang; Li, Yan; Wu, Ji-Zhou; Pu, Jian-Xin; Sun, Han-Dong

    2015-02-27

    Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B (1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from Isodon rubescens. Their structures and absolute configurations were determined by spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis. These alkaloids differ from known diterpene alkaloids and diterpenoids and are presumably biosynthesized from ent-kaurane diterpenoids. PMID:25590529

  5. The Identification of Perillyl Alcohol Glycosides with Improved Antiproliferative Activity

    PubMed Central

    2015-01-01

    A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of representative POH glycosides. The most active glycoside from this cumulative study (4′-azido-d-glucoside, PG9) represents one of the most cytotoxic POH analogues reported to date. PMID:25121720

  6. Steroidal glycosides from Furcraea foetida and their cytotoxic activity.

    PubMed

    Yokosuka, Akihito; Sano, Tomoe; Hashimoto, Ken; Sakagami, Hiroshi; Mimaki, Yoshihiro

    2009-10-01

    Two new spirostanol glycosides (1, 2) and a new furostanol glycoside (3), together with nine known steroidal glycosides (4-12) were isolated from the leaves of Furcraea foetida (Agavaceae). The structures of the new compounds were determined by spectroscopic analysis and the results of hydrolytic cleavage. The isolated compounds were evaluated for their cytotoxic activities against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, HSC-2 human oral squamous carcinoma cells, and HSC-4 human oral squamous carcinoma cells.

  7. Facile access to new C-glycosides and C-glycoside scaffolds incorporating functionalised aromatic moieties.

    PubMed

    Redpath, Philip; Ness, Kerry A; Rousseau, Joanne; Macdonald, Simon J F; Migaud, Marie E

    2015-01-30

    The tandem ene/intramolecular Sakurai cyclisation (IMSC) reaction has been successfully applied to the synthesis of a range of C-glycosides, with key intermediates offering opportunities for functionalisation of the glycon moiety. To demonstrate the versatility of the approach to access the 2-deoxy-C-glycoside series, we synthesised diastereomerically pure C-glucoside and galactoside derivatives incorporating functionalised aromatic, heteroaromatic and bicyclic aromatic moieties, in addition to the C-homologue of (±)-β-2-deoxy-glucose 6-phosphate. PMID:25486220

  8. Vibrational spectra and DFT calculations of sonderianin diterpene

    NASA Astrophysics Data System (ADS)

    Oliveira, I. M. M.; Santos, H. S.; Sena, D. M.; Cruz, B. G.; Teixeira, A. M. R.; Freire, P. T. C.; Braz-Filho, R.; Sousa, J. W.; Albuquerque, M. R. J. R.; Bandeira, P. N.; Bernardino, A. C. S. S.; Gusmão, G. O. M.; Bento, R. R. F.

    2015-11-01

    In the present study, the natural product sonderianin diterpene (C21H26O4), a diterpenoid isolated from Croton blanchetianus, with potential application in the drug industry, was characterized by nuclear magnetic resonance, infrared and Raman spectroscopy. Vibrational spectra were supported by Density Functional Theory calculations. Infrared and Raman spectra of sonderianin were recorded at ambient temperature in the regions from 400 cm-1 to 3600 cm-1 and from 40 cm-1 to 3500 cm-1, respectively. DFT calculations with the hybrid functional B3LYP and the basis set 6-31 G(d,p) were performed with the purpose of obtaining information on the structural and vibrational properties of this organic compound. A comparison with experimental spectra allowed us to assign all of the normal modes of the crystal. The assignment of the normal modes was carried out by means of potential energy distribution.

  9. Cembranoid diterpenes from the Caribbean sea whip Eunicea knighti.

    PubMed

    Tello, Edisson; Castellanos, Leonardo; Arevalo-Ferro, Catalina; Duque, Carmenza

    2009-09-01

    Three new cembranoid diterpenes, knightol (1), knightol acetate (2), and knightal (3), along with the known asperdiol (4) and asperdiol acetate (5), were isolated as major compounds from the sea whip Eunicea knighti collected from the Colombian Caribbean. The structures and absolute configurations of 1-5 were determined on the basis of spectroscopic analyses and by a combination of chemical and NMR methods, multiple correlations observed in a ROESY experiment, and using the modified Mosher method. Additionally, five semisynthetic compounds, 6-10, obtained during the chemical transformations of the natural compounds are here reported for the first time. All compounds were tested for antimicrobial activity against marine bacteria associated with heavily fouled surfaces and were also screened for antiquorum sensing (QS) activity. Compounds 1, 3, and 8 showed significant antimicrobial activity against bacterial isolates, and 1, 3, 7, and 8 showed excellent anti-QS inhibition activity measured by means of bioluminescence inhibition with biosensor model systems.

  10. Antimalarial and Antiproliferative Cassane Diterpenes of Caesalpinia sappan.

    PubMed

    Ma, Guoxu; Wu, Haifeng; Chen, Deli; Zhu, Nailiang; Zhu, Yindi; Sun, Zhonghao; Li, Pengfei; Yang, Junshan; Yuan, Jingquan; Xu, Xudong

    2015-10-23

    Bioassay-guided fractionation of a methanol extract of the seeds of Caesalpinia sappan led to the isolation of 12 new cassane-type diterpenes, caesalsappanins A-L (1-12). Their structures were elucidated on the basis of NMR and HRESIMS analysis, and the absolute configuration of compound 1 was determined by single-crystal X-ray crystallography. All isolated compounds were tested against a chloroquine-resistant Plasmodium falciparum strain for antiplasmodial activities and against a small panel of human cancer cell lines for antiproliferative activities. Compounds 7 and 8 displayed antimalarial activity against the chloroquine-resistant K1 strain of P. falciparum with IC50 values of 0.78 and 0.52 μM and selectivity indices of 17.6 and 16.4, respectively. Compound 10 showed antiproliferative activity against the KB cancer cell line with an IC50 value of 7.4 μM. PMID:26398312

  11. A new phenylpropanoid glycoside from Cirsium setosum.

    PubMed

    Ke, Rui; Zhu, En-Yuan; Chou, Gui-xin

    2010-07-01

    To study the chemical constituents of Cirsium setosum (Willd.) MB., 70% ethanol extract of the aerial parts was subjected to column chromatography. One new phenylpropanoid glycoside, sinapyl alcohol 9-O-(E)-p-coumaroyl-4-O-beta-D-glucopyanoside (1) was isolated, along with three known compounds: lycoperodine-1 (2), apigenin-7-O-(6"-(E)-p-coumaroyl)-beta-D-galactopyranoside (3) and quercetin (4). The structures were elucidated on the basis of spectral and chemical evidence. Compound 2 was obtained from Cirsium genus for the first time, compounds 3 and 4 were obtained from this plant for the first time.

  12. Two pentasaccharide resin glycosides from Argyreia acuta.

    PubMed

    Yin, Yong-Qin; Pan, Jie-Tao; Yu, Bang-Wei; Cui, Hong-Hua; Yan, You-Shao; Chen, Yan-Fen

    2016-01-01

    Two new compounds of acutacosides 1 and 2, pentasaccharide resin glycosides were isolated from the aerial parts of Argyreia acuta. The core of the two compounds was operculinic acid A, and they were esterfied at the same position, just one substituent group was linked at C-2 of Rha. The absolute configuration of the aglycone in the two compounds was established by Mosher's method, which was (11S)-hydroxyhexadecanoic acid (jalapinolic acid). Their structures were established by a combination of spectroscopic and chemical methods.

  13. Two pentasaccharide resin glycosides from Argyreia acuta.

    PubMed

    Yin, Yong-Qin; Pan, Jie-Tao; Yu, Bang-Wei; Cui, Hong-Hua; Yan, You-Shao; Chen, Yan-Fen

    2016-01-01

    Two new compounds of acutacosides 1 and 2, pentasaccharide resin glycosides were isolated from the aerial parts of Argyreia acuta. The core of the two compounds was operculinic acid A, and they were esterfied at the same position, just one substituent group was linked at C-2 of Rha. The absolute configuration of the aglycone in the two compounds was established by Mosher's method, which was (11S)-hydroxyhexadecanoic acid (jalapinolic acid). Their structures were established by a combination of spectroscopic and chemical methods. PMID:25925631

  14. Chemical diversity of labdane-type bicyclic diterpene biosynthesis in Actinomycetales microorganisms.

    PubMed

    Yamada, Yuuki; Komatsu, Mamoru; Ikeda, Haruo

    2016-07-01

    Five pairs of bacterial type-A and type-B diterpene synthases have been characterized: BAD86798/BAD86797, AHK61133/AHK61132, BAB39207/BAB39206, CldD/CldB and RmnD/RmnB, and are involved in the formation of pimara-9(11),15-diene, terpente-3,13,15-triene and labda-8(17),12(E),14-triene. Mining of bacterial genome data revealed an additional four pairs of type-A and type-B diterpene synthases: Sros_3191/Sros_3192 of Streptosporangium roseum DSM 43021, Sare_1287/Sare_1288 of Salinispora arenicola CNS-205, SCLAV_5671/SCLAV_5672 and SCLAV_p0491/SCLAV_p0490 of Streptomyces clavuligerus ATCC 27064. Since SCLAV_p0491/SCLAV_p0490 is similar to the labdane-type diterpene synthase pairs, CldD/CldB and RmnD/RmnB based on the alignment of the deduced amino acid sequences and phylogenetic analyses of the aligned sequences, these predicted diterpene synthases were characterized by an enzymatic reaction using a pair of recombinant type-A and type-B diterpene synthases prepared in Escherichia coli and the heterologous expression of two genes encoding type-A and type-B diterpene synthases in an engineered Streptomyces host. The generation of labda-8(17),12(E),14-triene (1) by CldB and CldD was reconfirmed by enzymatic synthesis. Furthermore, labda-8(17),13(16),14-triene (2) was generated by SCLAV_p0491 and CldB, and ladba-7,12(E),14-triene (3) by CldD and SCLAV_p0490. SCLAV_p0491 and SCLAV_p0490 catalyzed the generation of the novel diterpene hydrocarbon, labda-7,13(16),14-triene (4).

  15. Triterpene glycosides from the cultures of Phytolacca americana.

    PubMed

    Takahashi, H; Namikawa, Y; Tanaka, M; Fukuyama, Y

    2001-02-01

    A new triterpene glycoside I was isolated together with the five known triterpene glycosides 2-6 from the cultures of Phytolacca americana. The structure of 1 was elucidated by analysis of spectroscopic data and comparison of its NMR data with those of 2-7 and chemical degradation.

  16. Enzymatic synthesis of epothilone A glycosides

    PubMed Central

    2014-01-01

    Epothilones are extremely cytotoxic chemotherapeutic agents with epoxide, thiazole, and ketone groups that share equipotent kinetic similarity with taxol. The in vitro glycosylation catalyzed by uridine diphosphate glucosyltransferase (YjiC) from Bacillus licheniformis generated six novel epothilone A glycoside analouges including epothilone A 7-O-β-D-glucoside, epothilone A 7-O-β-D-galactoside, epothilone A 3,7-O-β-D-digalactoside, epothilone A 7-O-β-D-2-deoxyglucoside, epothilone A 7-O-β-L-rhamnoside, and epothilone A 7-O-β-L-fucoside. Epothilone A 7-O-β-D-glucoside was structurally elucidated by ultra-high performance liquid chromatography-photo diode array (UPLC-PDA) conjugated with high resolution quantitative time-of-flight-electrospray ionization mass spectroscopy (HR-QTOF ESI-MS/MS) supported by one-and two-dimensional nuclear magnetic resonance studies whereas other epothilone A glycosides were characterized by UPLC-PDA and HR-QTOF ESI-MS/MS analyses. The time dependent conversion study of epothilone A to epothilone A 7-O-β-D-glucoside found to be maximum (~26%) between 3 h to 5 h incubation. PMID:24949266

  17. Diterpenes of marine brown algae of the family Dictyotaceae: their possible role as defense compounds and their use in chemotaxonomy.

    PubMed

    Kelecom, A; Teixeira, V L

    1986-12-15

    Marine brown algae of the family Dictyotaceae are protected against predation. Their survival strategy is, at least in part, based on the production of chemical defenses. These compounds are diterpenes that seem to establish a specific predator-prey relationship, and which are found as food-chain markers. The use of Dictyotaceae diterpenes in chemotaxonomy is briefly discussed.

  18. Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation

    PubMed Central

    Cuadrado, I; Fernández-Velasco, M; Boscá, L; de las Heras, B

    2011-01-01

    Several labdane diterpenes exert anti-inflammatory and cytoprotective actions; therefore, we have investigated whether these molecules protect cardiomyocytes in an anoxia/reperfusion (A/R) model, establishing the molecular mechanisms involved in the process. The cardioprotective activity of three diterpenes (T1, T2 and T3) was studied in the H9c2 cell line and in isolated rat cardiomyocyte subjected to A/R injury. In both cases, treatment with diterpenes T1 and T2 protected from A/R-induced apoptosis, as deduced by a decrease in the percentage of apoptotic and caspase-3 active positive cells, a decrease in the Bcl-2/Bax ratio and an increase in the expression of antiapoptotic proteins. Analysis of cell survival signaling pathways showed that diterpenes T1 and T2 added after A/R increased phospho-AKT and phospho-ERK 1/2 levels. These cardioprotective effects were lost when AKT activity was pharmacologically inhibited. Moreover, the labdane-induced cardioprotection involves activation of AMPK, suggesting a role for energy homeostasis in their mechanism of action. Labdane diterpenes (T1 and T2) also exerted cardioprotective effects against A/R-induced injury in isolated cardiomyocytes and the mechanisms involved activation of specific survival signals (PI3K/AKT pathways, ERK1/2 and AMPK) and inhibition of apoptosis. PMID:22071634

  19. Indole-Diterpene Biosynthetic Capability of Epichloë Endophytes as Predicted by ltm Gene Analysis▿

    PubMed Central

    Young, Carolyn A.; Tapper, Brian A.; May, Kimberley; Moon, Christina D.; Schardl, Christopher L.; Scott, Barry

    2009-01-01

    Bioprotective alkaloids produced by Epichloë and closely related asexual Neotyphodium fungal endophytes protect their grass hosts from insect and mammalian herbivory. One class of these compounds, known for antimammalian toxicity, is the indole-diterpenes. The LTM locus of Neotyphodium lolii (Lp19) and Epichloë festuce (Fl1), required for the biosynthesis of the indole-diterpene lolitrem, consists of 10 ltm genes. We have used PCR and Southern analysis to screen a broad taxonomic range of 44 endophyte isolates to determine why indole-diterpenes are present in so few endophyte-grass associations in comparison to that of the other bioprotective alkaloids, which are more widespread among the endophtyes. All 10 ltm genes were present in only three epichloë endophytes. A predominance of the asexual Neotyphodium spp. examined contained 8 of the 10 ltm genes, with only one N. lolii containing the entire LTM locus and the ability to produce lolitrems. Liquid chromatography-tandem mass spectrometry profiles of indole-diterpenes from a subset of endophyte-infected perennial ryegrass showed that endophytes that contained functional genes present in ltm clusters 1 and 2 were capable of producing simple indole-diterpenes such as paspaline, 13-desoxypaxilline, and terpendoles, compounds predicted to be precursors of lolitrem B. Analysis of toxin biosynthesis genes by PCR now enables a diagnostic method to screen endophytes for both beneficial and detrimental alkaloids and can be used as a resource for screening isolates required for forage improvement. PMID:19181837

  20. Effects of tripterygium glycosides on restenosis following endovascular treatment

    PubMed Central

    HAN, BING; GE, CHANG-QING; ZHANG, HONG-GUANG; ZHOU, CHEN-GUANG; JI, GUO-HUI; YANG, ZHENG; ZHANG, LIANG

    2016-01-01

    The mechanism and associated factors of restenosis following intravascular stent implantation remain to be elucidated. The present two-part experimental and clinical study aimed to investigate the effects of tripterygium glycosides on in-stent restenosis subsequent to intra-arterial therapy. Following endovascular stent implantation in rabbit iliac arteries, post-stent outcomes were evaluated in cyclosporine groups, low-dose and high-dose tripterygium glycosides groups and controls. Post-operative angiography indicated that vessel diameters were similar between groups; however, at 28 days after receiving the therapeutic agents, vessels of the cyclosporine and tripterygium glycosides groups were significantly larger than those of the controls. Furthermore, three groups of patients had comparable baseline levels of interleukin (IL)-10, IL-18 and C-reactive protein, and intima-media thickness. However, 1 month after stent implantation, levels of IL-10 and IL-18 were markedly reduced in the high- and low-dose tripterygium glycosides groups compared with controls. At 6 months after surgery, the stent patency rate in patients with bare stents was significantly lower than in patients receiving tripterygium glycosides (P≤0.009). In addition, the ankle-brachial index was also higher than in those without tripterygium glycosides (P<0.001). Results of the experimental and clinical studies suggest that tripterygium glycosides may inhibit and possibly aid in the prevention of in-stent restenosis formation following endovascular treatment of lower-extremity artery disease. PMID:27108914

  1. Determination of phenylethanoid glycosides and iridoid glycosides from therapeutically used Plantago species by CE-MEKC.

    PubMed

    Gonda, Sándor; Nguyen, Nhat Minh; Batta, Gyula; Gyémánt, Gyöngyi; Máthé, Csaba; Vasas, Gábor

    2013-09-01

    CE methods are valuable tools for medicinal plant quality management, screening, and analysis. Therefore, the aim of the current study was to optimize and validate a CE-MEKC method for simultaneous quantification of four chief bioactive metabolites from Plantago species. The two most important secondary metabolite groups were aimed to be separated. Different electrolyte and surfactant types were tested. Surfactant concentration, BGE pH, electrolyte concentration, and buffering capacity were optimized. The final BGE consisted of 15 mM sodium tetraborate, 20 mM TAPS, and 250 mM DOC at pH 8.50. Acceptable precision, good stability, and accuracy were achieved, with high resolution for phenylethanoid glycosides. Analytes were separated within 20 min. The method was shown to be suitable for the quantification of the iridoid glycosides aucubin and catalpol, and the phenylethanoid glycosides acteoside (verbascoside) and plantamajoside from water extracts of different samples. The method was shown to be applicable to leaf extracts of Plantago lanceolata, Plantago major, and Plantago asiatica, the main species with therapeutic applications, and a biotechnological product, plant tissue cultures (calli) of P. lanceolata. Baseline separation of the main constituents from minor peaks was achieved, regardless of the matrix type.

  2. Determination of phenylethanoid glycosides and iridoid glycosides from therapeutically used Plantago species by CE-MEKC.

    PubMed

    Gonda, Sándor; Nguyen, Nhat Minh; Batta, Gyula; Gyémánt, Gyöngyi; Máthé, Csaba; Vasas, Gábor

    2013-09-01

    CE methods are valuable tools for medicinal plant quality management, screening, and analysis. Therefore, the aim of the current study was to optimize and validate a CE-MEKC method for simultaneous quantification of four chief bioactive metabolites from Plantago species. The two most important secondary metabolite groups were aimed to be separated. Different electrolyte and surfactant types were tested. Surfactant concentration, BGE pH, electrolyte concentration, and buffering capacity were optimized. The final BGE consisted of 15 mM sodium tetraborate, 20 mM TAPS, and 250 mM DOC at pH 8.50. Acceptable precision, good stability, and accuracy were achieved, with high resolution for phenylethanoid glycosides. Analytes were separated within 20 min. The method was shown to be suitable for the quantification of the iridoid glycosides aucubin and catalpol, and the phenylethanoid glycosides acteoside (verbascoside) and plantamajoside from water extracts of different samples. The method was shown to be applicable to leaf extracts of Plantago lanceolata, Plantago major, and Plantago asiatica, the main species with therapeutic applications, and a biotechnological product, plant tissue cultures (calli) of P. lanceolata. Baseline separation of the main constituents from minor peaks was achieved, regardless of the matrix type. PMID:23784714

  3. Steviol glycoside safety: are highly purified steviol glycoside sweeteners food allergens?

    PubMed

    Urban, Jonathan D; Carakostas, Michael C; Taylor, Steve L

    2015-01-01

    Steviol glycoside sweeteners are extracted from the plant Stevia rebaudiana (Bertoni), a member of the Asteraceae (Compositae) family. Many plants from this family can induce hypersensitivity reactions via multiple routes of exposure (e.g., ragweed, goldenrod, chrysanthemum, echinacea, chamomile, lettuce, sunflower and chicory). Based on this common taxonomy, some popular media reports and resources have issued food warnings alleging the potential for stevia allergy. To determine if such allergy warnings are warranted on stevia-based sweeteners, a comprehensive literature search was conducted to identify all available data related to allergic responses following the consumption of stevia extracts or highly purified steviol glycosides. Hypersensitivity reactions to stevia in any form are rare. The few cases documented in the peer-reviewed literature were reported prior to the introduction of high-purity products to the market in 2008 when many global regulatory authorities began to affirm the safety of steviol glycosides. Neither stevia manufacturers nor food allergy networks have reported significant numbers of any adverse events related to ingestion of stevia-based sweeteners, and there have been no reports of stevia-related allergy in the literature since 2008. Therefore, there is little substantiated scientific evidence to support warning statements to consumers about allergy to highly purified stevia extracts. PMID:25449199

  4. New steroidal glycosides from Tribulus terrestris L.

    PubMed

    Chen, Gang; Liu, Tao; Lu, Xuan; Wang, Hai-Feng; Hua, Hui-Ming; Pei, Yue-Hu

    2012-01-01

    Two new steroidal glycosides were isolated from Tribulus terrestris L. Their structures were elucidated as 26-O-β-D-glucopyranosyl-5α-furostan-12-one-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-5α-furostan-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.

  5. A new phenolic glycoside from Juglans mandshurica.

    PubMed

    Yao, Dalei; Jin, Mei; Zhang, Changhao; Luo, Jie; Li, Ren; Zheng, Mingshan; Cui, Jiongmo; Li, Gao

    2014-01-01

    A new phenolic glycoside, 6-O-(4'-hydroxy-3',5'-dimethoxybenzoyl)-d-glucopyranose (4), and nine known compounds (1-3 and 5-10) were isolated from Juglans mandshurica Maxim. Compound structures were elucidated by NMR, HR-ESI-MS and acid hydrolysis. Compounds 5 and 6 are reported from this genus for the first time. Among compounds 1-10, only 1 exhibited cytotoxicity against MGC-803, A549, K562, JAR, HeLa, CaSKi and SiHa cell lines (IC50: 2.0, 5.3, 2.3, 6.9, 4.0, 6.6 and 2.7 μM, respectively).

  6. Antiproliferative Diterpenes from a Malleastrum sp. from the Madagascar dry forest.

    PubMed

    Liu, Yixi; Wiedle, C Houston; Brodie, Peggy J; Callmander, Martin W; Rakotondrajaona, R; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

    2015-09-01

    An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (-)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 µM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum.

  7. Identification of a new diterpene biosynthetic gene cluster that produces O-methylkolavelool in Herpetosiphon aurantiacus.

    PubMed

    Nakano, Chiaki; Oshima, Misaki; Kurashima, Nodoka; Hoshino, Tsutomu

    2015-03-23

    Diterpenoids are usually found in plants and fungi, but are rare in bacteria. We have previously reported new diterpenes, named tuberculosinol and isotuberculosinol, which are generated from the Mycobacterium tuberculosis gene products Rv3377c and Rv3378c. No homologous gene was found at that time, but we recently found highly homologous proteins in the Herpetosiphon aurantiacus ATCC 23779 genome. Haur_2145 was a class II diterpene cyclase responsible for the conversion of geranylgeranyl diphosphate into kolavenyl diphosphate. Haur_2146, homologous to Rv3378c, synthesized (+)-kolavelool through the nucleophilic addition of a water molecule to the incipient cation formed after the diphosphate moiety was released. Haur_2147 afforded (+)-O-methylkolavelool from (+)-kolavelool, so this enzyme was an O-methyltransferase. This new diterpene was indeed detected in H. aurantiacus cells. This is the first report of the identification of a (+)-O-methylkolavelool biosynthetic gene cluster.

  8. Additional diterpenes from Physcomitrella patens synthesized by copalyl diphosphate/kaurene synthase (PpCPS/KS).

    PubMed

    Zhan, Xin; Bach, Søren Spanner; Hansen, Nikolaj Lervad; Lunde, Christina; Simonsen, Henrik Toft

    2015-11-01

    The bifunctional diterpene synthase, copalyl diphosphate/kaurene synthase from the moss Physcomitrella patens (PpCPS/KS), catalyses the formation of at least four diterpenes, including ent-beyerene, ent-sandaracopimaradiene, ent-kaur-16-ene, and 16-hydroxy-ent-kaurene. The enzymatic activity has been confirmed through generation of a targeted PpCPS/KS knock-out mutant in P. patens via homologous recombination, through transient expression of PpCPS/KS in Nicotiana benthamiana, and expression of PpCPS/KS in E. coli. GC-MS analysis of the knock-out mutant shows that it lacks the diterpenoids, supporting that all are products of PpCPS/KS as observed in N. benthamiana and E. coli. These results provide additional knowledge of the mechanism of this bifunctional diterpene synthase, and are in line with proposed reaction mechanisms in kaurene biosynthesis.

  9. Diterpenes from a Chinese collection of the brown alga Dictyota plectens.

    PubMed

    Cheng, Shimiao; Zhao, Min; Sun, Zhongmin; Yuan, Weiping; Zhang, Shuangshuang; Xiang, Zheng; Cai, Yuepiao; Dong, Jianyong; Huang, Kexin; Yan, Pengcheng

    2014-12-26

    Twenty-seven diterpenes of six chemical classes, including seven new diterpenes (1, 2, 6, 10, 11, 16, and 19), have been isolated from a collection of the brown alga Dictyota plectens from the South China Sea. The structures of the new diterpenes were elucidated by extensive spectroscopic analysis and by comparison with reported data. In the in vitro assays, 9, 12, 14, 16, and 22 showed inhibitory activity against HIV-1 replication with IC50 values of 16.1-30.5 μM, compounds 5, 13, 24, and 26 exhibited anti-H5N1 activity with inhibition rates of 50%-62% at 30.0 μM, and 12 and 24 also showed potent inhibition against LPS-induced NO production with inhibition rates of 90% and 86%, respectively, at 10.0 μM.

  10. Spectroscopic manifestation of stretching vibrations of glycosidic linkage in polysaccharides

    NASA Astrophysics Data System (ADS)

    Nikonenko, N. A.; Buslov, D. K.; Sushko, N. I.; Zhbankov, R. G.

    2005-10-01

    Manifestation of stretching vibrations of glycosidic linkage in the infrared spectra of polysaccharides (native, microcrystalline, mercerized celluloses, amylose, starches) has been studied using the regularized method of deconvolution. It has been shown that the glycosidic linkage formation in the polysaccharides is characterized by the appearance of new absorption bands in the 1175-1140 cm -1 range as compared to their corresponding monomers. In the 1000-920 cm -1 region differences between the infrared spectra of polysaccharides due to the changes in the glycosidic linkage configuration have been found.

  11. High-level diterpene production by transient expression in Nicotiana benthamiana

    PubMed Central

    2013-01-01

    Background Characterization of plant terpene synthases is typically done by production of recombinant enzymes in Escherichia coli. This is often difficult due to solubility and codon usage issues. Furthermore, plant terpene synthases which are targeted to the plastids, such as diterpene synthases, have to be shortened in a more or less empirical approach to improve expression. We report here an optimized Agrobacterium-mediated transient expression assay in Nicotiana benthamiana for plant diterpene synthase expression and product analysis. Results Agrobacterium-mediated transient expression of plant diterpene synthases in N. benthamiana led to the accumulation of diterpenes within 3 days of infiltration and with a maximum at 5 days. Over 50% of the products were exported onto the leaf surface, thus considerably facilitating the analysis by reducing the complexity of the extracts. The robustness of the method was tested by expressing three different plant enzymes, cembratrien-ol synthase from Nicotiana sylvestris, casbene synthase from Ricinus communis and levopimaradiene synthase from Gingko biloba. Furthermore, co-expression of a 1-deoxy-D-xylulose-5-phosphate synthase from tomato and a geranylgeranyl diphosphate synthase from tobacco led to a 3.5-fold increase in the amount of cembratrien-ol produced, with maximum yields reaching 2500 ng/cm2. Conclusion With this optimized method for diterpene synthase expression and product analysis, a single infiltrated leaf of N. benthamiana would be sufficient to produce quantities required for the structure elucidation of unknown diterpenes. The method will also be of general use for gene function discovery, pathway reconstitution and metabolic engineering of diterpenoid biosynthesis in plants. PMID:24330621

  12. Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides.

    PubMed

    Dai, Li-Ping; Li, Chun; Yang, Han-Ze; Lu, Yan-Qing; Yu, Hong-Yan; Gao, Hui-Min; Wang, Zhi-Min

    2015-09-22

    Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1); 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2); and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3); together with six known diterpenes henryin (4); kamebanin (5); reniformin C (6); kamebacetal A (7); kamebacetal B (8); and oridonin (9). The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09-8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31-2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity.

  13. Carnosol: A Phenolic Diterpene With Cancer Chemopreventive Potential

    PubMed Central

    Chun, Kyung-Soo; Kundu, Juthika; Chae, In Gyeong; Kundu, Joydeb Kumar

    2014-01-01

    Cancer is an unbeaten health challenge for the humankind. After striving for decades to find a cancer cure, attention has now been shifted to reduce the morbidity and mortality from cancer by halting the course of tumor development. Numerous bioactive phytochemicals, especially those present in edible and non-edible plant species, have been reported to reduce the risk of many cancers. Multiple lines of evidence suggest that carnosol, a phenolic diterpene present in rosemary (Rosmarinus officinalis L.), holds the promise of preventing certain types of cancer. A remarkable progress has been made in delineating the biochemical mechanisms underlying the chemopreventive effects of carnosol. Results from in vitro cell culture studies as well as animal model experiments have revealed that carnosol inhibits experimentally induced carcinogenesis and exhibits potent anti-oxidative, anti-inflammatory, antiproliferative and apoptosis inducing properties. Moreover, carnosol enhances the sensitivity of chemoresistant cancer cells to chemotherapeutic agents. The purpose of this review is to shed light on the detailed mechanistic aspects of cancer chemoprevention with carnosol. PMID:25337578

  14. Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides.

    PubMed

    Dai, Li-Ping; Li, Chun; Yang, Han-Ze; Lu, Yan-Qing; Yu, Hong-Yan; Gao, Hui-Min; Wang, Zhi-Min

    2015-01-01

    Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1); 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2); and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3); together with six known diterpenes henryin (4); kamebanin (5); reniformin C (6); kamebacetal A (7); kamebacetal B (8); and oridonin (9). The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09-8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31-2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity. PMID:26402664

  15. Palmadorins A--C, diterpene glycerides from the antarctic nudibranch Austrodoris kerguelenensis.

    PubMed

    Diyabalanage, Thushara; Iken, Katrin B; McClintock, James B; Amsler, Charles D; Baker, Bill J

    2010-03-26

    The nudibranch Austrodoris kerguelenensis is distributed widely around the Antarctic coast and continental shelves. Earlier collections from McMurdo Sound and the Weddell Sea shelf have afforded a suite of diterpene glyceride esters, a compound class implicated as a chemical defense in nudibranchs. The present chemical investigation of A. kerguelenensis collected near Palmer Station on the Western Antarctic Peninsula has revealed additional examples, palmadorins A-C (1-3), as the first three members of a new series of clerodane diterpenes. In this paper we describe their isolation, structure elucidation, and stereochemical analysis using a combination of one- and two-dimensional NMR spectroscopy and wet chemical methods. PMID:20121160

  16. [Effects of ginkgo diterpene lactones meglumine injection's activated carbon adsorption technology on officinal components].

    PubMed

    Zhou, En-li; Wang, Ren-jie; Li, Miao; Wang, Wei; Xu, Dian-hong; Hu, Yang; Wang, Zhen-zhong; Bi, Yu-an; Xiao, Wei

    2015-10-01

    With the diversion rate of ginkgolide A, B, K as comprehensive evaluation indexes, the amount of activated carbon, ad- sorption time, mix rate, and adsorption temperature were selected as factors, orthogonal design which based on the evaluation method of information entropy was used to optimize activated carbon adsorption technology of ginkgo diterpene lactones meglumine injection. Opti- mized adsorption conditions were as follows: adsorbed 30 min with 0.2% activated carbon in 25 °C, 40 r ·min⁻¹, validation test re- sult display. The optimum extraction condition was stable and feasible, it will provide a basis for ginkgo diterpene lactone meglumine injection' activated carbon adsorption process.

  17. Hikiokoshins A-I, diterpenes from the leaves of Isodon japonicus.

    PubMed

    Tanaka, Naonobu; Tsuji, Eri; Sakai, Kanae; Gonoi, Tohru; Kobayashi, Jun'ichi

    2014-06-01

    Diterpenes, hikiokoshins A-I, and twelve known diterpenes were isolated from the leaves of Isodon japonicus (Burm. f.) H. Hara (Lamiaceae). The hikiokoshins A-I possess various skeletons such as ternifonane {hikiokoshin A}, ent-6,7:8,15-diseco-6,8-cyclokauran-7,20-olide {hikiokoshin B}, ent-6,7-secokauran-7,20-olide {hikiokoshin C}, and ent-7,20-epoxykaurane {hikiokoshins D-I}. Their structures were elucidated on the basis of spectroscopic analysis. Antimicrobial activities of hikiokoshins A and B were evaluated. PMID:24702849

  18. [Effects of ginkgo diterpene lactones meglumine injection's activated carbon adsorption technology on officinal components].

    PubMed

    Zhou, En-li; Wang, Ren-jie; Li, Miao; Wang, Wei; Xu, Dian-hong; Hu, Yang; Wang, Zhen-zhong; Bi, Yu-an; Xiao, Wei

    2015-10-01

    With the diversion rate of ginkgolide A, B, K as comprehensive evaluation indexes, the amount of activated carbon, ad- sorption time, mix rate, and adsorption temperature were selected as factors, orthogonal design which based on the evaluation method of information entropy was used to optimize activated carbon adsorption technology of ginkgo diterpene lactones meglumine injection. Opti- mized adsorption conditions were as follows: adsorbed 30 min with 0.2% activated carbon in 25 °C, 40 r ·min⁻¹, validation test re- sult display. The optimum extraction condition was stable and feasible, it will provide a basis for ginkgo diterpene lactone meglumine injection' activated carbon adsorption process. PMID:27062815

  19. Pahangensin A and B, two new antibacterial diterpenes from the rhizomes of Alpinia pahangensis Ridley.

    PubMed

    Sivasothy, Yasodha; Ibrahim, Halijah; Paliany, Audra Shaleena; Alias, Siti Aisyah; Awang, Khalijah

    2013-12-01

    The rhizomes of Alpinia pahangensis Ridley yielded a new bis-labdanic diterpene for which the name pahangensin A (1) was proposed along with a new labdane diterpene, pahangensin B (2). Their structures were elucidated by spectroscopic methods including, 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Pahangensin A (1) was found to be an antibacterial agent against Staphylococcus aureus, Bacillus cereus and Bacillus subtilis with MIC values less than 100 μg/mL, respectively. Pahangensin B (2) exhibited antibacterial activity (MIC <100 μg/mL) against B. cereus.

  20. New benzophenone and quercetin galloyl glycosides from Psidium guajava L.

    PubMed

    Matsuzaki, Keiichi; Ishii, Rie; Kobiyama, Kaori; Kitanaka, Susumu

    2010-07-01

    New benzophenone and flavonol galloyl glycosides were isolated from an 80% MeOH extract of Psidium guajava L. (Myrtaceae) together with five known quercetin glycosides. The structures of the novel glycosides were elucidated to be 2,4,6-trihydroxybenzophenone 4-O-(6''-O-galloyl)-beta-D: -glucopyranoside (1, guavinoside A), 2,4,6-trihydroxy-3,5-dimethylbenzophenone 4-O-(6''-O-galloyl)-beta-D: -glucopyranoside (2, guavinoside B), and quercetin 3-O-(5''-O-galloyl)-alpha-L: -arabinofuranoside (3, guavinoside C) by NMR, MS, UV, and IR spectroscopies. Isolated phenolic glycosides showed significant inhibitory activities against histamine release from rat peritoneal mast cells, and nitric oxide production from a murine macrophage-like cell line, RAW 264.7.

  1. Resin glycosides from the aerial parts of Operculina turpethum.

    PubMed

    Ding, Wenbing; Jiang, Zi-Hua; Wu, Ping; Xu, Liangxiong; Wei, Xiaoyi

    2012-09-01

    Three glycosidic acids, turpethic acids A-C, and two intact resin glycosides, turpethosides A and B, all having a common pentasaccharide moiety and 12-hydroxy fatty acid aglycones of different chain lengths, were obtained from the aerial parts of Operculina turpethum. Their structures were elucidated by spectroscopic analyses and chemical correlations. The aglycones were characterized as 12-hydroxypentadecanoic acid in two compounds, 12-hydroxyhexadecanoic acid in two other components, and 12-hydroxyheptadecanoic acid in the fifth compound, which were all confirmed by synthesis. The absolute configurations of these aglycones were all established as S by Mosher's method. These compounds represent the first examples of resin glycosides with a monohydroxylated 12-hydroxy fatty acid as an aglycone, and one compound is the first described resin glycoside having a hydroxylated C(17) fatty acid as its aglycone.

  2. Two new glycosides from the florets of Carthamus tinctorius.

    PubMed

    Jiang, Jian-Shuang; Chen, Zhong; Yang, Ya-Nan; Feng, Zi-Ming; Zhang, Pei-Cheng

    2013-01-01

    Two new glycoside compounds, named saffloquinoside C (1) and (-)-4-hydroxybenzoic acid-4-O-[6'-O-(2″-methylbutyryl)-β-D-glucopyranoside] (2), were isolated from the florets of Carthamus tinctorius. Their structures were elucidated by detailed spectroscopic means including UV, IR, HR-ESI-MS, 1D and 2D NMR, and CD data. Compound 1 was a rare quinochalcone glycoside with six five-membered dioxaspirocycle.

  3. Phenolic glycosides from sugar maple (Acer saccharum) bark.

    PubMed

    Yuan, Tao; Wan, Chunpeng; González-Sarrías, Antonio; Kandhi, Vamsikrishna; Cech, Nadja B; Seeram, Navindra P

    2011-11-28

    Four new phenolic glycosides, saccharumosides A-D (1-4), along with eight known phenolic glycosides, were isolated from the bark of sugar maple (Acer saccharum). The structures of 1-4 were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for cytotoxicity effects against human colon tumorigenic (HCT-116 and Caco-2) and nontumorigenic (CCD-18Co) cell lines. PMID:22032697

  4. Phenolic glycosides from sugar maple (Acer saccharum) bark.

    PubMed

    Yuan, Tao; Wan, Chunpeng; González-Sarrías, Antonio; Kandhi, Vamsikrishna; Cech, Nadja B; Seeram, Navindra P

    2011-11-28

    Four new phenolic glycosides, saccharumosides A-D (1-4), along with eight known phenolic glycosides, were isolated from the bark of sugar maple (Acer saccharum). The structures of 1-4 were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for cytotoxicity effects against human colon tumorigenic (HCT-116 and Caco-2) and nontumorigenic (CCD-18Co) cell lines.

  5. A new acylated flavonol glycoside from Derris triofoliata.

    PubMed

    Xu, Lu-Rong; Wu, Jun; Zhang, Si

    2006-01-01

    A new acylated flavonol glycoside, kaempferol 3-O-[(6''''-feruloyl)-beta-D-glucopyranosyl-(1 --> 3)]-[alpha-L-rhamnopyranosyl-(1 --> 6)]-beta-D-glucopyranoside and two known cyclolignan glycosides, (+)-lyoniresinol-3alpha-O-beta-D-glucopyranoside and ( - )-lyoniresinol-3alpha-O-beta-D-glucopyranoside were isolated from n-BuOH extracts of the aerial parts of Derris triofoliata, their structures were determined from spectroscopic and chemical evidences.

  6. Enzymatic 13C Labeling and Multidimensional NMR Analysis of Miltiradiene Synthesized by Bifunctional Diterpene Cyclase in Selaginella moellendorffii*

    PubMed Central

    Sugai, Yoshinori; Ueno, Yohei; Hayashi, Ken-ichiro; Oogami, Shingo; Toyomasu, Tomonobu; Matsumoto, Sadamu; Natsume, Masahiro; Nozaki, Hiroshi; Kawaide, Hiroshi

    2011-01-01

    Diterpenes show diverse chemical structures and various physiological roles. The diversity of diterpene is primarily established by diterpene cyclases that catalyze a cyclization reaction to form the carbon skeleton of cyclic diterpene. Diterpene cyclases are divided into two types, monofunctional and bifunctional cyclases. Bifunctional diterpene cyclases (BDTCs) are involved in hormone and defense compound biosyntheses in bryophytes and gymnosperms, respectively. The BDTCs catalyze the successive two-step type-B (protonation-initiated cyclization) and type-A (ionization-initiated cyclization) reactions of geranylgeranyl diphosphate (GGDP). We found that the genome of a lycophyte, Selaginella moellendorffii, contains six BDTC genes with the majority being uncharacterized. The cDNA from S. moellendorffii encoding a BDTC-like enzyme, miltiradiene synthase (SmMDS), was cloned. The recombinant SmMDS converted GGDP to a diterpene hydrocarbon product with a molecular mass of 272 Da. Mutation in the type-B active motif of SmMDS abolished the cyclase activity, whereas (+)-copalyl diphosphate, the reaction intermediate from the conversion of GGDP to the hydrocarbon product, rescued the cyclase activity of the mutant to form a diterpene hydrocarbon. Another mutant lacking type-A activity accumulated copalyl diphosphate as the reaction intermediate. When the diterpene hydrocarbon was enzymatically synthesized from [U-13C6]mevalonate, all carbons were labeled with 13C stable isotope (>99%). The fully 13C-labeled product was subjected to 13C-13C COSY NMR spectroscopic analyses. The direct carbon-carbon connectivities observed in the multidimensional NMR spectra demonstrated that the hydrocarbon product by SmMDS is miltiradiene, a putative biosynthetic precursor of tanshinone identified from the Chinese medicinal herb Salvia miltiorrhiza. Hence, SmMDS functions as a bifunctional miltiradiene synthase in S. moellendorffii. In this study, we demonstrate that one-dimensional and

  7. Stability of steviol glycosides in several food matrices.

    PubMed

    Jooken, Etienne; Amery, Ruis; Struyf, Tom; Duquenne, Barbara; Geuns, Jan; Meesschaert, Boudewijn

    2012-10-24

    As steviol glycosides are now allowed as a food additive in the European market, it is important to assess the stability of these steviol glycosides after they have been added to different food matrices. We analyzed and tested the stability of steviol glycosides in semiskimmed milk, soy drink, fermented milk drink, ice cream, full-fat and skimmed set yogurt, dry biscuits, and jam. The fat was removed by centrifugation from the dairy and soy drink samples. Proteins were precipitated by the addition of acetonitrile and also removed by centrifugation. Samples of jam were extracted with water. Dry biscuits were extracted with ethanol. The resulting samples were concentrated with solid-phase extraction and analyzed by high-performance liquid chromatography on a C18 stationary phase and a gradient of acetonitrile/aqueous 25 mM phosphoric acid. The accuracy was checked using a standard addition on some samples. For assessing the stability of the steviol glycosides, samples were stored in conditions relevant to each food matrix and analyzed periodically. The results indicate that steviol glycosides can be analyzed with good precision and accuracy in these food categories. The recovery was between 96 and 103%. The method was also validated by standard addition, which showed excellent agreement with the external calibration curve. No sign of decomposition of steviol glycosides was found in any of the samples.

  8. Decomposition of α-Tocopheryl Glycosides in Rat Tissues

    PubMed Central

    Knaś, Małgorzata; Wałejko, Piotr; Maj, Jadwiga; Hryniewicka, Agnieszka; Witkowski, Stanisław; Borzym-Kluczyk, Małgorzata; Dudzik, Danuta; Zwierz, Krzysztof

    2008-01-01

    Background The aim of our investigation was to estimate the stability of α-tocopheryl O-glycosides in relation to activity of exoglycosidases in selected rat tissues. Material and Methods Acetylated glycosides were obtained in glucosidation of α-tocopherol using the Helferich method. The activity of exoglycosidases was determined by the Zwierz et al. method. Protein concentrations were determined by the biuret method. The concentration of released α-tocopherol was determined with the HPLC method. Results The comparison of the amount of released α-tocopherol with the amount of released p-nitrophenol shows that glycoside bound in 2a–5a derivatives of α-tocopherol undergoes hydrolysis significantly harder than in appropriate 2b–5b p-nitrophenyl derivatives. Conclusion The results indicate that tocopheryl O-glycosides are more resistant to enzymatic hydrolysis than appropriate p-nitrophenol O-glycosides 2a–5a. Among examined tocopheryl O-glycosides, galactoside 4 is the only compound that caused the significant increase in tocopherol concentration, as compared to its endogenic content. PMID:19696909

  9. Labdane-Type Diterpene and Two Flavones from Salvia Sharifii Rech. f. and Esfan. and their Biological Activities

    PubMed Central

    Farjam, Mohammad Hossein; Rustaiyan, Abdolhossein; Ezzatzadeh, Elham; Jassbi, Amir Reza

    2013-01-01

    Two flavones, ladanein and 6-hydroxy-5,7,4′-trimethoxyflavone and one labdane-type diterpene, ent-13-epi-manoyloxide, were isolated from an ethyl acetate-methanol extract of the aerial parts of Salvia sharifii. The compounds were purified using several chromatographic methods. Structural elucidation of the compounds was performed using their 1H and 13C-NMR data, EI mass and UV spectral data. The compounds have been subjected to antimicrobial, antioxidant and cytotoxic activity. The diterpene showed higher cytotoxic activity than the flavones while the later compounds were better antioxidants compared with the isolated diterpene. PMID:24250614

  10. The first structure of a bacterial diterpene cyclase: CotB2.

    PubMed

    Janke, Ronja; Görner, Christian; Hirte, Max; Brück, Thomas; Loll, Bernhard

    2014-06-01

    Sesquiterpenes and diterpenes are a diverse class of secondary metabolites that are predominantly derived from plants and some prokaryotes. The properties of these natural products encompass antitumor, antibiotic and even insecticidal activities. Therefore, they are interesting commercial targets for the chemical and pharmaceutical industries. Owing to their structural complexity, these compounds are more efficiently accessed by metabolic engineering of microbial systems than by chemical synthesis. This work presents the first crystal structure of a bacterial diterpene cyclase, CotB2 from the soil bacterium Streptomyces melanosporofaciens, at 1.64 Å resolution. CotB2 is a diterpene cyclase that catalyzes the cyclization of the linear geranylgeranyl diphosphate to the tricyclic cyclooctat-9-en-7-ol. The subsequent oxidation of cyclooctat-9-en-7-ol by two cytochrome P450 monooxygenases leads to bioactive cyclooctatin. Plasticity residues that decorate the active site of CotB2 have been mutated, resulting in alternative monocyclic, dicyclic and tricyclic compounds that show bioactivity. These new compounds shed new light on diterpene cyclase reaction mechanisms. Furthermore, the product of mutant CotB2(W288G) produced the new antibiotic compound (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, which acts specifically against multidrug-resistant Staphylococcus aureus. This opens a sustainable route for the industrial-scale production of this bioactive compound.

  11. Synthesis of an Advanced Intermediate of the Jatrophane Diterpene Pl-4: A Dibromide Coupling Approach

    PubMed Central

    2013-01-01

    The preparation of an advanced intermediate toward the synthesis of the jatrophane diterpene Pl-4 is described. The key step is a regioselective chelation-controlled lithiation of the (Z)-configured bromide in the corresponding vinyl dibromide precursor. The method outlined within this Article is suitable for the facile access of sterically hindered internal vinyl halides for further coupling reactions. PMID:23895274

  12. A New Cassane-type Diterpene from the Seed of Caesalpinia sappan.

    PubMed

    Nguyen, Hai Xuan; Nguyen, Nhan Trung; Dang, Phu Hoang; Thi, Phuoc Ho; Nguyen, Mai Thanh Thi; Can, Mao Van; Dibwe, Dya Fita; Ueda, Jun-Ya; Matsumoto, Kinzo; Awale, Suresh

    2016-06-01

    Phytochemical investigation of the CH2Cl2 extract of the Vietnamese medicinal plant Caesalpinia sappan Linn resulted in the isolation of a new cassane-type diterpene named tomocin I (1). Its chemical structure was determined by NMR spectroscopic and mass spectrometric analysis.

  13. Amitorines A and B, Nitrogenous Diterpene Metabolites of Theonella swinhoei: Isolation, Structure Elucidation, and Asymmetric Synthesis.

    PubMed

    Ota, Koichiro; Hamamoto, Yukiko; Eda, Wakiko; Tamura, Kenta; Sawada, Akiyoshi; Hoshino, Ayako; Mitome, Hidemichi; Kamaike, Kazuo; Miyaoka, Hiroaki

    2016-04-22

    Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate.

  14. Spiro Fused Diterpene-Indole Alkaloids from a Creek-Bottom-Derived Aspergillus terreus

    PubMed Central

    Cai, Shengxin; Du, Lin; Gerea, Alexandra L.; King, Jarrod B.; You, Jianlan

    2013-01-01

    Four metabolites, teraspiridoles A–D (2–5), formed from the merger of diterpene and modified indole scaffold were obtained from an Aspergillus terreus isolate. The structures and absolute configurations of these natural products were established using NMR, mass spectrometry, Marfey’s method, VCD, and ECD data. Teraspiridole B (3) exhibited weak inhibition of planaria regeneration/survival. PMID:23924243

  15. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity.

    PubMed

    Petiwala, Sakina M; Johnson, Jeremy J

    2015-10-28

    Recently, rosemary extracts standardized to diterpenes (e.g. carnosic acid and carnosol) have been approved by the European Union (EU) and given a GRAS (Generally Recognized as Safe) status in the United States by the Food and Drug Administration (FDA). Incorporation of rosemary into our food system and through dietary selection (e.g. Mediterranean Diet) has increased the likelihood of exposure to diterpenes in rosemary. In consideration of this, a more thorough understanding of rosemary diterpenes is needed to understand its potential for a positive impact on human health. Three agents in particular have received the most attention that includes carnosic acid, carnosol, and rosmanol with promising results of anti-cancer activity. These studies have provided evidence of diterpenes to modulate deregulated signaling pathways in different solid and blood cancers. Rosemary extracts and the phytochemicals therein appear to be well tolerated in different animal models as evidenced by the extensive studies performed for approval by the EU and the FDA as an antioxidant food preservative. This mini-review reports on the pre-clinical studies performed with carnosic acid, carnosol, and rosmanol describing their mechanism of action in different cancers.

  16. Dolabelladienols A-C, new diterpenes isolated from Brazilian brown alga Dictyota pfaffii.

    PubMed

    Pardo-Vargas, Alonso; de Barcelos Oliveira, Ingrid; Stephens, Paulo Roberto Soares; Cirne-Santos, Claudio Cesar; de Palmer Paixão, Izabel Christina Nunes; Ramos, Freddy Alejandro; Jiménez, Carlos; Rodríguez, Jaime; Resende, Jackson Antonio Lamounier Camargos; Teixeira, Valeria Laneuville; Castellanos, Leonardo

    2014-07-23

    The marine brown alga Dictyota pfaffii from Atol das Rocas, in Northeast Brazil is a rich source of dolabellane diterpene, which has the potential to be used in future antiviral drugs by inhibiting reverse transcriptase (RT) of HIV-1. Reexamination of the minor diterpene constituents yielded three new dolabellane diterpenes, (1R*,2E,4R*,7S,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (1), (1R*,2E,4R*,7R*,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (2), (1R*,2E,4R*,8E,10S*,11S,12R*)10,18-diacetoxy-7-hydroxy-2,8-dolabelladiene (3), termed dolabelladienols A-C (1-3) respectively, in addition to the known dolabellane diterpenes (4-6). The elucidation of the compounds 1-3 was assigned by 1D and 2D NMR, MS, optical rotation and molecular modeling, along with the relative configuration of compound 4 and the absolute configuration of 5 by X-ray diffraction. The potent anti-HIV-1 activities displayed by compounds 1 and 2 (IC50 = 2.9 and 4.1 μM), which were more active than even the known dolabelladienetriol 4, and the low cytotoxic activity against MT-2 lymphocyte tumor cells indicated that these compounds are promising anti-HIV-1 agents.

  17. Nepetanal and nepetanoate: a new diterpene aldehyde and a benzene derivative ester from Nepeta juncea.

    PubMed

    Hussain, Javid; Jamila, Nargis; Khan, Farman Ullah; Devkota, Krishna Prasad; Shah, M Raza; Anwar, Saeed

    2009-07-01

    One new tricyclic clerodane type diterpene aldehyde nepetanal (1) and one new benzene derivative nepetanoate (2) have been isolated from a plant Nepeta juncea together with two known compounds oleanolic acid (3) and ursolic acid (4). The structures of the isolated compounds were elucidated by means of modern spectroscopic techniques and comparison with literature data.

  18. Amitorines A and B, Nitrogenous Diterpene Metabolites of Theonella swinhoei: Isolation, Structure Elucidation, and Asymmetric Synthesis.

    PubMed

    Ota, Koichiro; Hamamoto, Yukiko; Eda, Wakiko; Tamura, Kenta; Sawada, Akiyoshi; Hoshino, Ayako; Mitome, Hidemichi; Kamaike, Kazuo; Miyaoka, Hiroaki

    2016-04-22

    Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate. PMID:27007992

  19. Resin Glycosides from the Morning Glory Family

    NASA Astrophysics Data System (ADS)

    Pereda-Miranda, Rogelio; Rosas-Ramírez, Daniel; Castañeda-Gómez, Jhon

    Resin glycosides are part of a very extensive family of secondary metabolites known as glycolipids or lipo-oligosaccharides and are constituents of complex resins (glycoresins) (1) unique to the morning glory family, Convolvulaceae (2). These active principles are responsible for the drastic purgative action of all the important Convolvulaceous species used in traditional medicine throughout the world since ancient times. Several commercial purgative crude drugs can be prepared from the roots of different species of Mexican morning glories. Their incorporation as therapeutic agents in Europe is an outstanding example of the assimilation of botanical drugs from the Americas as substitutes for traditional Old World remedies (3). Even though phytochemical investigations on the constituents of these drugs were initiated during the second half of the nineteenth century, the structure of their active ingredients still remains poorly known for some examples of these purgative roots. During the last two decades, the higher resolution capabilities of modern analytical isolation techniques used in conjunction with powerful spectroscopic methods have facilitated the elucidation of the active principles of these relevant herbal products.

  20. Crispene A, B, C and D, Four New Clerodane Type Furanoid Diterpenes from Tinospora crispa (L.)

    PubMed Central

    Hossen, Farhad; Ahasan, Rubaida; Haque, Mohammad Rashedul; Begum, Bilkis; Hasan, Choudhury Mahmood

    2016-01-01

    Background: Tinospora crispa (L.) is used to alleviate the symptoms of diabetes mellitus in folk medicine. It is also used for hypertension and to treat malaria, remedy for diarrhea, and as vermifuge. Materials and Methods: Stems of T. crispa were collected, sun dried for several days followed by oven dried for 24 h at a considerably low temperature and then ground into coarse powder. The powdered stems were soaked in methanol at room temperature for 14 days with occasional shaking. The extract was collected by filtration, and the solvent was evaporated under reduced pressure in a rotary evaporator to obtain a solid residue which was then subjected to fractionation using the modified Kupchan partitioning method into n-hexane, CCl4, CHCl3 and aqueous soluble fractions. The n-hexane soluble fraction was chromatographed over sephadex (LH-20) and the column was eluted with n-hexane: CH2Cl2:MeOH (2:5:1) followed by CH2Cl2:MeOH (9:1) and MeOH (100%) in order to increase the polarities. The column fractions were then concentrated and subjected to thin layer chromatography screening and the fractions with a satisfactory resolution of compounds were rechromatographed over silica gel to isolate the pure compounds. Results: Four new furanoid diterpenes of clerodane types, Crispene A, B, C, and D (1–4), including one known furanoid diterpene glucoside, borapetoside E (5), were isolated from the stems of T. crispa. The structures of these compounds were elucidated by means of extensive spectroscopic analysis and by comparison of their spectral data with closely related compounds. Conclusion: We have reported four new furanoid diterpenes of clerodane types, including one known furanoid diterpene glucoside. This is the first report of any clerodane diterpene having olefinic bond between C-6 and C-7. SUMMARY Crispene A, B, C, and D, four new furanoid diterpenes of clerodane types from Tinospora crispaCrispene C, an unusual furanoid diterpene with olifinic bond between C-6 and C

  1. Glycosidic inhibitors of melanogenesis from leaves of Passiflora edulis.

    PubMed

    Zhang, Jie; Koike, Ryosuke; Yamamoto, Ayako; Ukiya, Motohiko; Fukatsu, Makoto; Banno, Norihiro; Miura, Motofumi; Motohashi, Shigeyasu; Tokuda, Harukuni; Akihisa, Toshihiro

    2013-10-01

    A new flavonoid glycoside, chrysin 6-C-β-rutinoside (chrysin α-L-rhamnopyranosyl-(1→6)-C-β-glucopyranoside; 2), and two new triterpene glycosides, (31R)-31-O-methylpassiflorine (7) and (31S)-31-O-methylpassiflorine (8), along with 14 known glycosides, including three flavonoid glycosides, 1, 3, and 4, six triterpene glycosides, 5, 6, and 9-12, three cyano glycosides, 13-15, and two other glycosides, 16 and 17, were isolated from a MeOH extract of the leaves of Passiflora edulis (passion flower; Passifloraceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluation of compounds 1-17 against the melanogenesis in the B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, isoorientin (1), 2, and (6S,9R)-roseoside (17), exhibited inhibitory effects with 37.3-47.2% reduction of melanin content with no, or almost no, toxicity to the cells (90.8-100.2% cell viability) at 100 μM. Western blot analysis showed that compound 2 reduced the protein levels of MITF, TRP-1, and tyrosinase, in a concentration-dependent manner while exerted almost no influence on the level of TRP-2, suggesting that this compound inhibits melanogenesis on the α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of TRP-1 and tyrosinase. In addition, compounds 1-17 were evaluated for their inhibitory effects against the EpsteinBarr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. PMID:24130028

  2. A single residue change leads to a hydroxylated product from the class II diterpene cyclization catalyzed by abietadiene synthase

    PubMed Central

    Criswell, Jared; Potter, Kevin; Shephard, Freya; Beale, Michael H.; Peters, Reuben J.

    2012-01-01

    Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate. While this reaction typically is terminated via methyl deprotonation to yield copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead. Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a copalyl diphosphate intermediate. Here it is shown that substitution of aspartate for a conserved histidine in the class II active site of abietadiene synthase leads to selective production of 8α-hydroxy-CPP instead, demonstrating striking plasticity. PMID:23167845

  3. Base substitution mutations in uridinediphosphate-dependent glycosyltransferase 76G1 gene of Stevia rebaudiana causes the low levels of rebaudioside A: mutations in UGT76G1, a key gene of steviol glycosides synthesis.

    PubMed

    Yang, Yong-Heng; Huang, Su-Zhen; Han, Yu-Lin; Yuan, Hai-Yan; Gu, Chun-Sun; Zhao, Yan-Hai

    2014-07-01

    Steviol glycosides, extracted from the leaves of Stevia rebaudiana (Bert) Bertoni, are calorie-free sugar substitute of natural origin with intensely sweet (Boileau et al., 2012). Stevioside and rebaudioside A are the two main kinds of the diterpenic glycosides. We analyzed the concentration of stevioside and rebaudioside A in Stevia leaves of about 500 samples (hybrid progenies) and discovered a mutation plant "Z05" with very low levels of rebaudioside A. Because UGT76G1, a uridinediphosphate-dependent glycosyltransferases, is responsible for the conversion from stevioside to rebaudioside A (Richman et al., 2005), so mutation identification was done by sequencing the candidate gene, UGT76G1. In this study molecular analysis of two strains revealed a heterozygotic nonsense mutation of c.389T > G (p.L121X) in UGT76G1. Meanwhile, we found some amino acid substitutions significant change the protein structure. And the difference of enzyme activity between two strains proved the lack of functionality of UGT76G1 of the mutation "Z05". So the nonsense mutation and amino acid substitution mutation resulted in the low levels of rebaudioside A.

  4. New approaches on the analyses of thermolabile coffee diterpenes by gas chromatography and its relationship with cup quality.

    PubMed

    Novaes, Fábio Junior Moreira; Oigman, Silvia Siag; de Souza, Rodrigo Octavio Mendonça Alves; Rezende, Claudia Moraes; de Aquino Neto, Francisco Radler

    2015-07-01

    A new gas chromatography method using pulsed split injector (PS-GC) was validated to quantify thermolabile diterpenes cafestol, kahweol and isokahweol in methanolysed Arabica coffee oils. Linearity was 0.99 from 8 to 69mgmL(-1), recovery ranged from 99% to 101% and precision of less than 4% was obtained. Besides, Soxhlet extraction time was evaluated and Tukey׳s test indicated that the mass of diterpenes obtained in 4h is equivalent to a 16h period, which represents a space-time yield four times higher. The microwave assisted methanolysis proved to be efficient to quantitatively convert the natural diterpene esters in their respective alcohols and fatty acid methyl esters, accompanied by PS-GC. Also, the intact diterpene esters were analyzed by GC for the first time by the comparison between cold on-column (COC) and PS injection techniques. In all these stages, the molecular integrity of the thermolabile furokaurane diterpenes was maintained. The methanolysed oils from 13 samples of green Brazilian Arabica coffees were analyzed by PS-GC and the diterpenes composition varied from 8 to 12% w/w in oil and 0.7-1% in coffee beans. The ratio between cafestol and kahweol was successfully used to predict the quality of coffee even before the roasting and brewing processes.

  5. New approaches on the analyses of thermolabile coffee diterpenes by gas chromatography and its relationship with cup quality.

    PubMed

    Novaes, Fábio Junior Moreira; Oigman, Silvia Siag; de Souza, Rodrigo Octavio Mendonça Alves; Rezende, Claudia Moraes; de Aquino Neto, Francisco Radler

    2015-07-01

    A new gas chromatography method using pulsed split injector (PS-GC) was validated to quantify thermolabile diterpenes cafestol, kahweol and isokahweol in methanolysed Arabica coffee oils. Linearity was 0.99 from 8 to 69mgmL(-1), recovery ranged from 99% to 101% and precision of less than 4% was obtained. Besides, Soxhlet extraction time was evaluated and Tukey׳s test indicated that the mass of diterpenes obtained in 4h is equivalent to a 16h period, which represents a space-time yield four times higher. The microwave assisted methanolysis proved to be efficient to quantitatively convert the natural diterpene esters in their respective alcohols and fatty acid methyl esters, accompanied by PS-GC. Also, the intact diterpene esters were analyzed by GC for the first time by the comparison between cold on-column (COC) and PS injection techniques. In all these stages, the molecular integrity of the thermolabile furokaurane diterpenes was maintained. The methanolysed oils from 13 samples of green Brazilian Arabica coffees were analyzed by PS-GC and the diterpenes composition varied from 8 to 12% w/w in oil and 0.7-1% in coffee beans. The ratio between cafestol and kahweol was successfully used to predict the quality of coffee even before the roasting and brewing processes. PMID:25882422

  6. Complexation of alkyl glycosides with α-cyclodextrin can have drastically different effects on their conversion by glycoside hydrolases.

    PubMed

    Rather, Mohd Younis; Nordberg Karlsson, Eva; Adlercreutz, Patrick

    2015-04-20

    Substrates present in aggregated forms, such as micelles, are often poorly converted by enzymes. Alkyl glycosides constitute typical examples and the critical micelle concentration (CMC) decreases with increasing length of the alkyl group. In this study, possibilities to hydrolyse alkyl glycosides by glycoside hydrolases were explored, and α-cyclodextrin was used as an agent to form inclusion complexes with the alkyl glycosides, thereby preventing micelle formation. The cyclodextrin complexes were accepted as substrates by the enzymes to variable extent. The β-glucosidases originating from Thermotoga neapolitana (Tn Bgl3B) and from almond were not at all able to hydrolyse alkyl β-glucosides in the presence of 100mM α-cyclodextrin. However, Aspergillus niger amyloglucosidase readily accepted the complexes as substrates. In reactions involving decyl and dodecyl maltosides, the presence of 100mM α-cyclodextrin caused an increase in reaction rate in most cases, especially at high substrate concentrations. Surprisingly, the amyloglucosidase-catalyzed hydrolysis of octyl-β-maltoside to glucose and β-octylglucoside was faster in the presence of α-cyclodextrin than without, even at substrate concentrations below CMC. A possible explanation of the observed rate enhancement is that binding sites on the carbohydrate binding domain of amyloglucosidase, known to bind cyclodextrins, help to guide the alkyl glycoside-cyclodextrin complex to the active site, and thereby promote its conversion.

  7. Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

    NASA Astrophysics Data System (ADS)

    Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H.

    2016-09-01

    Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides.

  8. [Hypoglycemic and hypolipidemic effects of quercetin and its glycosides].

    PubMed

    Yan, Shu-xia; Li, Xian; Sun, Chong-de; Chen, Kun-song

    2015-12-01

    Quercetin and its glycosides are important flavonols in traditional herbal drugs and plant-derived food, and they have diverse hiological activities such as antioxidant, anticarcinogenic, anti-inflammatory, hypoglycemic and hypolipidemic activities. Numerous studies have demonstrated that quercetin and its glycosides were effective in the prevention and treatment of non-infectious chronic disease such as diabetes, obesity, and hyperlipidemia. They can regulate glucose and lipid metaholism through different mechanisms. They can decrease blood glucose via protecting pancreatic/p cells or/and improving insulin sensitivity. Also, they have lipid-lowering effects, which may be the result of regulation of lipid catabolism or/and anabolism. Their distributions, as well as the hypoglycemic and hypolipidemic effects are reviewed in this paper. In addition, further bioactivities as well as their dose-activity relationship, structure-activity relationship, bioavailability, and future clinical application of quercetin and its glycosides are discussed and proposed. PMID:27141664

  9. Temperature dependent vibrational modes of glycosidic bond in disaccharide sugars.

    PubMed

    Seo, Jeong-Ah; Kwon, Hyun-Joung; Kim, Hyung Kook; Hwang, Yoon-Hwae

    2008-03-17

    We studied the temperature dependent vibrational modes of the glycosidic bond in trehalose, sucrose, and maltose at wavenumbers ranging from 1000 to 1200 cm(-1). We found that the slope of temperature dependent Raman shifts of the glycosidic bond in trehalose and sucrose changed at temperatures around 120 degrees C, indicating a bond length or a bond angle (dihedral and torsional angles) change. However, we did not observe any slope change in maltose because the melting temperature of maltose is very close to 120 degrees C. We also found, at temperatures below 120 degrees C, that Raman shifts of the vibrational modes of the glycosidic bond in trehalose showed the strongest temperature dependence among the three disaccharides.

  10. 2-methyl-L-erythritol glycosides from Gardenia jasminoides.

    PubMed

    Yang, Liguo; Peng, Kaifeng; Zhao, Shizhe; Zhao, Feng; Chen, Lixia; Qiu, Feng

    2013-09-01

    Two new glycosides, 2-methyl-L-erythritol-4-O-(6-O-trans-sinapoyl)-β-D-glucopyranoside (1) and 2-methyl-L-erythritol-1-O-(6-O-trans-sinapoyl)-β-D-glucopyranoside (2), along with two known triterpenoids (3-4), four quinic acid derivatives (5-8) and one flavonoid (9) were isolated from the fruit of Gardenia jasminoides. Their structures were elucidated through MS and 2D NMR experiments (HMQC and HMBC). Inhibitory effects of the isolated compounds on nitric oxide production in lipopolysaccharide-activated macrophages were evaluated. Though 2-methyl-D-erythritol and its glycosides have been reported in a few references, this is the first report about 2-methyl-L-erythritol glycosides. Based on this finding, we propose that 2-methyl-L-erythritol might be a new intermediate in the non-mevalonate biosynthesis of terpenoids.

  11. Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

    PubMed Central

    Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H

    2016-01-01

    Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides. PMID:27580973

  12. Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages.

    PubMed

    Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H

    2016-01-01

    Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides. PMID:27580973

  13. Studies on the flavone glycosides from Fructus Kochiae.

    PubMed

    Xu, Yun-Hui; Huang, Hao; Zhang, Nian; Kong, De-Yun; Hua, Mo-Li

    2014-01-01

    A series of flavone glycosides were isolated from Fructus Kochiae for the first time, including two new flavone glycosides. The structures were established by interpretation of their spectroscopic data. Two new flavone glycosides are quercetin 3-O-β-d-apiofuranosyl-(1 → 2)-β-d-galactopyranosyl-7-O-β-d-glucopyranoside (1) and quercetin 3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-galactopyranosyl-7-O-β-d-sophoroside (2). The others are quercetin 7-O-β-d-glucopyranoside (3), quercetin 3-O-β-d-apiofuranosyl-(1 → 2)-β-d-galactopyranoside (4), quercetin 3-O-β-d-galactopyranosyl-7-O-β-d-glucopyranoside (5), and quercetin 7-O-β-d-sophoroside (6). PMID:23919635

  14. Sesquiterpene glycosides from the roots of Codonopsis pilosula

    PubMed Central

    Jiang, Yueping; Liu, Yufeng; Guo, Qinglan; Xu, Chengbo; Zhu, Chenggen; Shi, Jiangong

    2015-01-01

    Three new sesquiterpene glycosides, named codonopsesquilosides A−C (1−3), were isolated from an aqueous extract of the dried roots of Codonopsis pilosula. Their structures including absolute configurations were determined by spectroscopic and chemical methods. These glycosides are categorized as C15 carotenoid (1), gymnomitrane (2), and eudesmane (3) types of sesquiterpenoids, respectively. Compound 1 is the first diglycoside of C15 carotenoids to be reported. Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants. The absolute configurations were supported by comparison of the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra of 1−3, their aglycones, and model compounds based on quantum-mechanical time-dependent density functional theory. The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids, as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed. PMID:26904398

  15. Cytotoxic sulfated triterpene glycosides from the sea cucumber Pseudocolochirus violaceus.

    PubMed

    Zhang, Shu-Yu; Yi, Yang-Hua; Tang, Hai-Feng

    2006-07-01

    Bioassay-guided fractionation of the active BuOH extract of the sea cucumber Pseudocolochirus violaceus resulted in the isolation of three new sulfated triterpene glycosides, i.e., violaceusides I, II, and III (1-3, resp.), as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Their structures were elucidated by spectroscopic methods including 2D-NMR and MS experiments, as well as chemical evidence. Compounds 1-3 exhibit the same structural features, i.e., the presence of a 16-oxo group in the holostane-type triterpene aglycone with the C(7)=C(8) bond, but differ in the side chains and the tetrasaccharide moieties. Compound 1 possesses one sulfate group, while 2 and 3 are disulfated glycosides. All the glycosides showed significant in vitro cytotoxicities against human gastric cancer MKN-45 and human colon cancer HCT-116 cells. PMID:17193313

  16. Bioactive triterpene glycosides from the sea cucumber Holothuria fuscocinerea.

    PubMed

    Zhang, Shu-Yu; Yi, Yang-Hua; Tang, Hai-Feng

    2006-10-01

    Bioassay-guided fractionation of the active n-BuOH extract of the sea cucumber Holothuria fuscocinerea resulted in the isolation of three new triterpene glycosides, fuscocinerosides A (1), B (2), and C (3), along with two known glycosides, pervicoside C (4) and holothurin A (5), as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Compounds 1-5 possess the same tetrasaccharide moiety, 3-O-methyl-beta-D-glucopyranosyl-(1-->3)-beta-D- glucopyranosyl-(1-->4)-beta-D-quinovopyranosyl-(1-->2)-4-O-sodiumsulfato-beta-D-xylopyranosyl, linked to C-3 of holostane triterpene aglycones that differ in their side chains and 17-substituents. Their structures were elucidated by extensive spectral studies as well as chemical evidence. All the glycosides showed in vitro cytotoxicity against two human tumor cell lines. PMID:17067169

  17. Ecdysteroid glycosides: identification, chromatographic properties, and biological significance.

    PubMed

    Maria, Annick; Girault, Jean-Pierre; Saatov, Ziyadilla; Harmatha, Juraj; Dinan, Laurence; Lafont, René

    2005-03-01

    Ecdysteroid glycosides are found in both animals and plants. The chromatographic behavior of these molecules is characteristic, as they appear much more polar than their corresponding free aglycones when analyzed by normal-phase high-performance liquid chromatography (HPLC), whereas the presence of glycosidic moieties has a very limited (if any) impact on polarity when using reversed-phase HPLC. Biological activity is greatly reduced because the presence of this bulky substituent probably impairs the interaction with ecdysteroid receptor(s). 2-Deoxy-20-hydroxyecdysone 22-O-beta-D-glucopyranoside, which has been isolated from the dried aerial parts of Silene nutans (Caryophyllaceae), is used as a model compound to describe the rationale of ecdysteroid glycoside purification and identification.

  18. Nickel-catalyzed proton-deuterium exchange (HDX) procedures for glycosidic linkage analysis of complex carbohydrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of non-carbohydrate substituents. The glycosidic linkage positions are often de...

  19. Iridoid glycosides from Harpagophytum procumbens D.C. (devil's claw).

    PubMed

    Qi, Jin; Chen, Ji-Jun; Cheng, Zhi-Hong; Zhou, Jia-Hong; Yu, Bo-Yang; Qiu, Samuel X

    2006-07-01

    Iridoid glycosides, harprocumbide A (6''-O-alpha-D-galactopyranosylharpagoside, 1) and harprocumbide B (6''-O-(cis-p-coumaroyl)-procumbide, 2) were isolated from the tubers of Harpagophytum prucumbens D.C., along with nine known iridoid glycosides 6-O-alpha-D-galactopyranosylharpagoside (3), and harpagoside (4), harpagide (5), 8-cinnamoylmyoporoside (6), 8-O-feruloylhapagide (7), procumbide (8), 6''-O-(p-coumaroyl)-procumbide (9), 8-O-(p-coumaroyl)-harpagide (10) and 8-O-(cis-p-coumaroyl)-harpagide (11). Compound 10 showed marginal inhibition activity against macrophages respiratory burst. PMID:16857222

  20. A glycoside of Nicotina tabacum affects mouse dopaminergic behavior.

    PubMed

    Masuda, Y; Ohnuma, S; Kawagoe, M; Sugiyama, T

    2003-01-01

    Climbing in the forced swimming test is considered a dopaminergic-specific behavior. A substance of Nicotina tabacum affecting dopamine neuronal activity was investigated using the mouse behavioral system. The substance was found to be a glycoside with the peripheral sugar chain structures Fuc alpha 1-2Gal, Gal beta 1-4GlcNAc and GalNAc alpha 1-3GalNAc and with basic polymannoses. The glycoside dose-dependently increased behavior via D2 neuronal activity, but not D1 activity. This suggests that smoking can affect human brain function not only via the nicotinic cholinergic neuron, but also via the D2 neuron.

  1. Synthesis and Photochromic Properties of Configurationally Varied Azobenzene Glycosides

    PubMed Central

    Chandrasekaran, Vijayanand; Johannes, Eugen; Kobarg, Hauke; Sönnichsen, Frank D; Lindhorst, Thisbe K

    2014-01-01

    Spatial orientation of carbohydrates is a meaningful parameter in carbohydrate recognition processes. To vary orientation of sugars with temporal and spatial resolution, photosensitive glycoconjugates with favorable photochromic properties appear to be opportune. Here, a series of azobenzene glycosides were synthesized, employing glycoside synthesis and Mills reaction, to allow “switching” of carbohydrate orientation by reversible E/Z isomerization of the azobenzene N=N double bond. Their photochromic properties were tested and effects of azobenzene substitution as well as the effect of anomeric configuration and the orientation of the sugars 2-hydroxy group were evaluated. PMID:25050228

  2. Flavonol Glycosides from the Leaves of Allium macrostemon.

    PubMed

    Nakane, Risa; Iwashina, Tsukasa

    2015-08-01

    Twelve flavonoids were isolated from Allium macrostemon leaves. Five compounds were identified as kaempferol 3,7-di-O-glucoside (1), kaempferol 3,4'-di-O-glucoside (2), quercetin 3-O-glucoside (3), kaempferol 3-0-glucoside (4) and isorhamnetin 3-O-glucoside (5) by UV spectra, LC-MS, acid hydrolysis and HPLC comparisons with authentic standards. Other flavonoids were characterized as kaempferol glycosides (6-8, 10 and 11) and quercetin glycosides (9 and 12). Other compounds, such as steroidal saponins, have been already found from the bulbs of A. macrostemon. However, flavonoids were reported for the first time from the leaves. PMID:26434122

  3. New Sesquiterpene Glycosides from the Leaves of Eriobotrya japonica.

    PubMed

    Zhaoa, Lei; Li, Han; Rena, Bingru; Wub, Hankui; Chen, Jian; Lia, Weilin

    2015-07-01

    One new sesquiterpene glycoside, named nerolidol-3-O-α-L-rhamnopyranosyl-(1 --> 6)-β-D-glucopyranoside (1), along with one novel natural product nerolidol-3-O-α-L-rhamnopyranosyl-(1 --> 2)-[α-L-rhamnopyranosyl-(1 --> 6)]-β-D-glucopyranoside (2) and two known sesquiterpene glycosides (3-4), were isolated from the leaves of Eriobotrya japonica (Thunb.) Lindl.. Their structures were elucidated on the basis of 1D, 2D NMR and HR-MS data. The chemotaxonomic significance of this type of constituents was discussed.

  4. Antioxidative glycosides from the leaves of Ligustrum robustum.

    PubMed

    He, Zhen-Dan; Lau, Kit-Man; But, Paul Pui-Hay; Jiang, Ren-Wang; Dong, Hui; Ma, Shuang-Cheng; Fung, Kwok-Pui; Ye, Wen-Cai; Sun, Han-Dong

    2003-06-01

    Phytochemical investigation of the ethanol extract of the leaves of Ligustrum robustum, monitored by a bioassay involving the hemolysis of red blood cells induced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride, led to the isolation of three new glycosides, ligurobustosides M (1), N (2), and O (3), along with 10 known ones, osmanthuside B (4), osmanthuside B6 (5), acteoside (6), ligupurpuroside A (7), ligupurpuroside B (8), ligurobustoside C (9), ligurobustoside E (10), ligurobustoside I (11), cosmosiin (12), and rhoifolin (13). The structures of the new compounds were elucidated by spectroscopic methods. Seven of the glycosides showed stronger antioxidant effects than the standard, trolox. PMID:12828473

  5. Steroidal glycosides from Reineckia carnea herba and their antitussive activity.

    PubMed

    Han, Na; Chen, Ling Li; Wang, Yao; Xue, Rui; Zou, Li Bo; Liu, Fang; Yin, Jun

    2013-06-01

    Two new steroidal glycosides, 1α,3α-dihydroxy-5β-pregn-16-en-20-one 3-O-α-L-rhamnopyranoside (1) and 1β,3β,27-trihydroxycholest-16-en-22-one 1,3-di-O-α-L-rhamnoside (2), along with seven known steroidal glycosides (3-9), were isolated from Reineckia carnea herba. Their structures were determined by detailed analysis of their 1D- and 2D-NMR and MS spectra. Compound 9 was isolated for the first time from the Reineckia genus. Except for 8, compounds 2, 3, 4, 5, 6, 7, and 9 displayed clear in vitro antitussive activity.

  6. NMR Tube Degradation Method for Sugar Analysis of Glycosides.

    PubMed

    Giner, José-Luis; Feng, Ju; Kiemle, David J

    2016-09-23

    The sugar subunits of natural glycosides can be conveniently determined by acid hydrolysis and (1)H NMR spectroscopy without isolation or derivatization. The chemical shifts, coupling constants, and integral ratios of the anomeric signals allow each monosaccharide to be identified and its molar ratio to other monosaccharides to be quantified. The NMR data for the anomeric signals of 28 monosaccharides and three disaccharides are reported. Application of the method is demonstrated with the flavonoid glycoside naringin (1), the aminoglycoside antibiotics kanamycin (2) and tobramycin (3), and the saponin digitonin (4). PMID:27603739

  7. Chemical and biological properties of quinochalcone C-glycosides from the florets of Carthamus tinctorius.

    PubMed

    Yue, Shijun; Tang, Yuping; Li, Shujiao; Duan, Jin-Ao

    2013-12-10

    Quinochalcone C-glycosides are regarded as characteristic components that have only been isolated from the florets of Carthamus tinctorius. Recently, quinochalcone C-glycosides were found to have multiple pharmacological activities, which has attracted the attention of many researchers to explore these compounds. This review aims to summarize quinochalcone C-glycosides' physicochemical properties, chromatographic behavior, spectroscopic characteristics, as well as their biological activities, which will be helpful for further study and development of quinochalcone C-glycosides.

  8. Analytical methods for monoterpene glycosides in grape and wine. II. Qualitative and quantitative determination of monoterpene glycosides in grape.

    PubMed

    Voirin, S G; Baumes, R L; Sapis, J C; Bayonove, C L

    1992-03-20

    Free and glycosidically bound terpenes of five Vitis vinifera grape cultivars (muscat of Alexandria, muscat of Frontignan, muscat of Hamburg, muscat Ottonel and Gewürztraminer) were investigated. The free and bound fractions were separated by selective retention on Amberlite XAD-2 resin. The glycosidic fractions were analysed by gas chromatography and gas chromatography-mass spectrometry using either enzymic hydrolysis and subsequent analysis of the released aglycones or trimethylsilyl (TMS) and trifluoroacetyl derivatives. The known monoterpenyl, benzyl and 2-phenylethyl beta-D-glucopyranosides, beta-rutinosides, 6-O-alpha-L-arabinofuranosyl-beta-D-glucopyranosides and 6-O-beta-D-apiofuranosyl-beta-D-glucopyranosides were determined. A number of other glycosides were detected and the structures of some of them, mainly apiosylglucosides and glucosides with aglycones in higher oxidation state than linalol, were tentatively identified using the mass spectra of their TMS and TFA derivatives and the results obtained from the analysis of their aglycones. PMID:1577909

  9. Steviol glycosides in purified stevia leaf extract sharing the same metabolic fate.

    PubMed

    Purkayastha, Sidd; Markosyan, Avetik; Prakash, Indra; Bhusari, Sachin; Pugh, George; Lynch, Barry; Roberts, Ashley

    2016-06-01

    The safety of steviol glycosides is based on data available on several individual steviol glycosides and on the terminal absorbed metabolite, steviol. Many more steviol glycosides have been identified, but are not yet included in regulatory assessments. Demonstration that these glycosides share the same metabolic fate would indicate applicability of the same regulatory paradigm. In vitro incubation assays with pooled human fecal homogenates, using rebaudiosides A, B, C, D, E, F and M, as well as steviolbioside and dulcoside A, at two concentrations over 24-48 h, were conducted to assess the metabolic fate of various steviol glycoside classes and to demonstrate that likely all steviol glycosides are metabolized to steviol. The data show that glycosidic side chains containing glucose, rhamnose, xylose, fructose and deoxy-glucose, including combinations of α(1-2), β-1, β(1-2), β(1-3), and β(1-6) linkages, were degraded to steviol mostly within 24 h. Given a common metabolite structure and a shared metabolic fate, safety data available for individual steviol glycosides can be used to support safety of purified steviol glycosides in general. Therefore, steviol glycosides specifications adopted by the regulatory authorities should include all steviol glycosides belonging to the five groups of steviol glycosides and a group acceptable daily intake established. PMID:26924787

  10. Guaiane sesquiterpenes and isopimarane diterpenes from an endophytic fungus Xylaria sp.

    PubMed

    Wu, Shao-Hua; He, Jian; Li, Xiao-Nian; Huang, Rong; Song, Fei; Chen, You-Wei; Miao, Cui-Ping

    2014-09-01

    Nine oxygenated guaiane-type sesquiterpenes and three isopimarane diterpenes were isolated from the culture broth of an endophytic fungus, Xylaria sp. YM 311647, obtained from Azadirachta indica. The structures of these compounds were elucidated by interpretation of spectroscopic data. The absolute configurations of two of these were confirmed by X-ray crystallographic analysis. All of the compounds were tested for their antifungal activities against five pathogenic fungal cells. The results showed that nine sesquiterpenes were moderately active against Candida albicans and Hormodendrum compactum with MIC values ranging from 32 to 256μg/ml, while the diterpenes were more active; One of these exhibited the most potent inhibitory activity against C. albicans and Pyricularia oryzae with MIC values of 16μg/ml.

  11. Bioactive isopimarane diterpenes from the fungus, Epicoccum sp. HS-1, associated with Apostichopus japonicus.

    PubMed

    Xia, Xuekui; Qi, Jun; Liu, Yayue; Jia, Airong; Zhang, Yonggang; Liu, Changheng; Gao, Cuiling; She, Zhigang

    2015-03-02

    One new isopimarane diterpene (1), together with two known compounds, 11-deoxydiaporthein A (2) and iso-pimara-8(14),15-diene (3) were isolated from the culture of Epicoccum sp., which was associated with Apostichopus japonicus. Their structures were determined by the analysis of 1D and 2D NMR, as well as mass spectroscopic data. The absolute configuration of Compound 1 was deduced by a single-crystal X-ray diffraction experiment using CuKα radiation. In the bioactivity assay, both Compounds 1 and 2 exhibited α-glucosidase inhibitory activity with IC50 values of 4.6 ± 0.1 and 11.9 ± 0.4 μM, respectively. This was the first report on isopimarane diterpenes with α-glucosidase inhibitory activity.

  12. Mode of Action of Diterpene and Characterization of Related Metabolites from the Soft Coral, Xenia elongata

    PubMed Central

    Andrianasolo, Eric H.; Haramaty, Liti; White, Eileen; Lutz, Richard; Falkowski, Paul

    2014-01-01

    Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined using the specific apoptosis induction assay based on genetically engineered mammalian cell line D3 deficient in Bak and Bax and derived from a mouse epithelial cell. The diterpenes induce apoptosis in low micromolar concentrations. The results indicate that the previously isolated compound (1) affects cell in a manner similar to that of HSP90 and HDAC inhibitors and in a manner opposite of PI3 kinase/mTOR inhibitors. Compound (3) inhibits selectively HDAC6 in high micromolar concentrations. PMID:24562393

  13. Bacterial Diterpene Synthases: New Opportunities for Mechanistic Enzymology and Engineered Biosynthesis

    PubMed Central

    Smanski, Michael J.; Peterson, Ryan M.; Huang, Sheng-Xiong; Shen, Ben

    2012-01-01

    Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging. Bacteria are emerging as prolific producers of diterpenoid natural products, and bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis. Here we will first survey diterpenoid natural products of bacterial origin and briefly review their biosynthesis with emphasis on diterpene synthases (DTSs) that channel geranylgeranyl diphosphate to various diterpenoid scaffolds. We will then highlight differences of DTSs of bacterial and higher organism origins and discuss the challenges in discovering novel bacterial DTSs. We will conclude by discussing new opportunities for DTS mechanistic enzymology and applications of bacterial DTS in biocatalysis and metabolic pathway engineering. PMID:22445175

  14. Bioactive Isopimarane Diterpenes from the Fungus, Epicoccum sp. HS-1, Associated with Apostichopus japonicus

    PubMed Central

    Xia, Xuekui; Qi, Jun; Liu, Yayue; Jia, Airong; Zhang, Yonggang; Liu, Changheng; Gao, Cuiling; She, Zhigang

    2015-01-01

    One new isopimarane diterpene (1), together with two known compounds, 11-deoxydiaporthein A (2) and iso-pimara-8(14),15-diene (3) were isolated from the culture of Epicoccum sp., which was associated with Apostichopus japonicus. Their structures were determined by the analysis of 1D and 2D NMR, as well as mass spectroscopic data. The absolute configuration of Compound 1 was deduced by a single-crystal X-ray diffraction experiment using CuKα radiation. In the bioactivity assay, both Compounds 1 and 2 exhibited α-glucosidase inhibitory activity with IC50 values of 4.6 ± 0.1 and 11.9 ± 0.4 μM, respectively. This was the first report on isopimarane diterpenes with α-glucosidase inhibitory activity. PMID:25738327

  15. On the biotransformation of ent-trachylobane to ent-kaur-11-ene diterpenes.

    PubMed

    Fraga, Braulio M; Gonzalez-Vallejo, Victoria; Guillermo, Ricardo

    2011-09-23

    The microbiological transformation of trachinodiol (1) by the fungus Mucor plumbeus afforded the corresponding 1α, 2α, 3α, and 17-hydroxy derivatives (2-4 and 6), respectively. 7β,16α,18-Trihydroxy-ent-kaur-11-ene (sicanatriol) (5) was also obtained in this feeding. The biotransformation of 1 to give 5 by this fungus may occur by enzymatic abstraction of a hydrogen atom, allylic to the cyclopropane ring, and subsequent cleavage of this ring. This route is similar to that postulated by us in plants of the genus Sideritis, where ent-trachylobane and ent-kaur-11-ene diterpenes coexist. This study confirms that hydroxylation of diterpenes by M. plumbeus occurs preferably at ring A carbons.

  16. Guaiane sesquiterpenes and isopimarane diterpenes from an endophytic fungus Xylaria sp.

    PubMed

    Wu, Shao-Hua; He, Jian; Li, Xiao-Nian; Huang, Rong; Song, Fei; Chen, You-Wei; Miao, Cui-Ping

    2014-09-01

    Nine oxygenated guaiane-type sesquiterpenes and three isopimarane diterpenes were isolated from the culture broth of an endophytic fungus, Xylaria sp. YM 311647, obtained from Azadirachta indica. The structures of these compounds were elucidated by interpretation of spectroscopic data. The absolute configurations of two of these were confirmed by X-ray crystallographic analysis. All of the compounds were tested for their antifungal activities against five pathogenic fungal cells. The results showed that nine sesquiterpenes were moderately active against Candida albicans and Hormodendrum compactum with MIC values ranging from 32 to 256μg/ml, while the diterpenes were more active; One of these exhibited the most potent inhibitory activity against C. albicans and Pyricularia oryzae with MIC values of 16μg/ml. PMID:24890390

  17. Morinlongosides A-C, Two New Naphthalene Glycoside and a New Iridoid Glycoside from the Roots of Morinda longissima.

    PubMed

    Cuong, Nguyen Manh; Huong, Tran Thu; Son, Ninh The; Cuong, To Dao; Van, Doan Thi; Khanh, Pham Ngoc; Ha, Vu Thi; Tram, Nguyen Cong Thuy; Long, Pham Quoc; Kim, Young Ho

    2016-01-01

    Two new naphthalene glycosides, morinlongosides A and B (1, 2) and a new iridoid glycoside, morinlongoside C (3), together with four known ones, geniposidic acid (4), (3R)-3-O-[β-D-xylopyranosyl-(1→6)-β-D-glucopyranosyl]-l-octen-3-ol (5), lucidin-3-O-β-primeveroside (6), and morindone-6-O-β-gentiobioside (7), were isolated from the roots of Morinda longissima Y. Z. RUAN. The structures of all isolated compounds (1-7) were elucidated on the basis of spectroscopic data (high resolution (HR)-MS, one and two dimensional (1/2D)-NMR). PMID:27477665

  18. Bioactive saponins and glycosides. XXVII. Structures of new cucurbitane-type triterpene glycosides and antiallergic constituents from Citrullus colocynthis.

    PubMed

    Yoshikawa, Masayuki; Morikawa, Toshio; Kobayashi, Hisanori; Nakamura, Akihiko; Matsuhira, Koudai; Nakamura, Seikou; Matsuda, Hisashi

    2007-03-01

    The methanolic extract from the fruit of Citrullus colocynthis showed an inhibitory effect on ear passive cutaneous anaphylaxis reactions as a type I allergic model in mice. From the methanolic extract, two new cucurbitane-type triterpene glycosides, colocynthosides A and B, were isolated together with 17 known constituents. The structures of colocynthosides A and B were elucidated on the basis of chemical and physicochemical evidence. In addition, the principal cucurbitane-type triterpene glycoside, cucurbitacin E 2-O-beta-D-glucopyranoside, and its aglycon, cucurbitacin E, exhibited the antiallergic activity at a dose of 100 and 1.25 mg/kg, p.o., respectively.

  19. Clerodane type diterpene as a novel antifungal agent from Polyalthia longifolia var. pendula.

    PubMed

    Bhattacharya, Asish K; Chand, Hemender R; John, Jyothis; Deshpande, Mukund V

    2015-04-13

    Bioactivity-guided chemical examination of methanolic extract of leaves of Polyalthia longifolia var. pendula led to the isolation of the active constituent, a diterpene 1 which was identified as 16α-hydroxycleroda-3,13(14)Z-dien-15,16-olide on the basis of its spectral data. Among the tested strains, diterpene 1 was found to exhibit antifungal activities having MIC90 values of 50.3, 100.6 and 201.2 μM against Candida albicans NCIM3557, Cryptococcus neoformans NCIM3542 (human pathogens) and Neurospora crassa NCIM870 (saprophyte), respectively. Initial, structure-activity-relationship (SAR) data generated by synthesizing some derivatives revealed that the double bond between C3-C4 and the free hydroxyl group at C16 are crucial for the antifungal activity of the diterpene 1. The mode of action of 1 in C. albicans is due to compromised cell membrane permeability and also probably due to disruption of cell wall structures. The red blood cell haemolysis of all the compounds (1-4) did not show any significant haemolysis and was found to be less than 15% for all the compounds when tested at highest concentration, i.e. 1200 μM. Interestingly, all the tested compounds inhibited Y-H transition in dimorphic C. albicans NCIM3557 at much lower concentration than their MIC90 values. Determination of ROS generation by diterpene 1 using DCFH-DA and DHR123 (dihydrorhodamine) staining of C. albicans NCIM3557 indicated production of intracellular ROS as a mechanism of antifungal activity.

  20. Palladium-catalyzed Transformations of Salvinorin A, a Neoclerodane Diterpene from Salvia divinorum

    PubMed Central

    Riley, Andrew P.; Day, Victor W.; Navarro, Hernán A.

    2013-01-01

    Transformations that selectively modify the furan ring present in a variety of naturals products would be useful in the synthesis of biological probes but remain largely underexplored. The neoclerodane diterpene salvinorin A, isolated from Salvia divinorum, is an example of a furan-containing natural product. Following selective bromination of salvinorin A, Suzuki-Miyaura and Sonogashira couplings were accomplished in moderate to good yields without hydrolyzing the labile C-2 acetate or altering the stereochemistry of the epimerizable centers. PMID:24246026

  1. A new labdane diterpene from Vitex cauliflora Moldenke from the Madagascar rainforest1

    PubMed Central

    Rasamison, Vincent E.; Ranaivo-Harimanana, Leon; Cao, Shugeng; Pan, Ende; Ratovoson, Fidy; Randriantafika, F.; Rakotondrajaona, R.; Rakotonandrasana, Stephan; Andriantsiferana, Rabodo

    2009-01-01

    Fractionation of an antiplasmodial ethanolic extract from the aerial parts of Vitex cauliflora led to the isolation of the new labdane diterpene 1 together with the known triterpene uvaol. The structure of the new compound 1 was established as 3-oxo,15,17,18-triacetoxy-labda-7,13E-diene on the basis of spectroscopic data (1D and 2D NMR, MS). PMID:19635529

  2. Bioactivity of Diterpens from the Ethyl Acetate Extract of Kingiodendron pinnatum Rox. Hams

    PubMed Central

    Javarappa, Komal Kumar; Prasad, Attemode Girijanna Devi; Mahadesh Prasad, AJ; Mane, Chetana

    2016-01-01

    Background: Kingiodendron pinnatum Rox. Hams. is an endangered medicinal plant used in gonorrhoe, catarrhal conditions of genito-urinary and respiratory tracts. The scientific and pharmacological formulation of K. pinnatum has not been established so far though it is being traditionally used by tribes of the region. Objective: P hytochemical screening and identification of the bioactive compounds from the ethyl acetate extract of Kingiodendron pinnatum Rox. Hams. Materials and Methods: Chromatographic separation was carried out by thin layer chromatography and column chromatography. Bio-autography of the column fractioned extract and TLC chromatogram were evaluated in vitro for antibacterial activity. The PTLC, HP TLC were used for crude extract and HPLC, LCMS, FTIR, 1HNMR and 13CNMR were employed for the isolated compound in the ethyl acetate extract of K. pinnatum. Results: Evaluation of solvent system for chromatographic separation revealed that ethyl acetate: petroleum ether in the ratio of 7:2.5 ml was the most appropriate one for the separation of diterpene compounds. The antibacterial bio-autography screening of TLC separated compound showed positive activity with Staphylococcus aureus and negative activity with Escherichia coli. Spectroscopic analysis of the isolated compound from the ethyl acetate extract of K. pinnatum revealed the presence of diterpene compound. Conclusion: It is evident from the present study that the ethyl acetate extract of K. pinnatum is rich in diterpene compounds and having potential antibacterial activity. SUMMARY Novel extraction method for phytochemicls from Kingidendron pinnatum at RTAntibacterial property of diterpens extracted from Kingiodendron pinnatum Rox. Hams aganist S. aureus Abbreviations Used: TLC: Thin Layer Chromatography, PTLC: Preparatory Thin Layer Chromatography, HPTLC: High perormence Thin Layer chromatography, HPLC: High Performance Liquid Chromatography, LC-MS: Liquid chromatography Mass Spectra, FTIR

  3. Cassane diterpenes with oxygen bridge from the seeds of Caesalpinia sappan.

    PubMed

    Xu, Xudong; Yuan, Jingquan; Zhou, Xingyang; Li, Weiping; Zhu, Nailiang; Wu, Haifeng; Li, Pengfei; Sun, Zhonghao; Yang, Junshan; Ma, Guoxu

    2016-07-01

    The seeds of the medicinal plant Caesalpinia sappan yielded fourteen cassane-type diterpenes, including six new rearranged ones named as caesalppans A-F (1-6). Their structures were elucidated by spectroscopic analysis and comparison with literature data. The isolated new compounds 1-6 possess lactone-type cassane diterpenoid skeleton with an oxygen bridge between C-19 and C-20, and were tested cytotoxic activity against four cancer cell lines using the MTT method. PMID:27316975

  4. Bioactivity of Diterpens from the Ethyl Acetate Extract of Kingiodendron pinnatum Rox. Hams

    PubMed Central

    Javarappa, Komal Kumar; Prasad, Attemode Girijanna Devi; Mahadesh Prasad, AJ; Mane, Chetana

    2016-01-01

    Background: Kingiodendron pinnatum Rox. Hams. is an endangered medicinal plant used in gonorrhoe, catarrhal conditions of genito-urinary and respiratory tracts. The scientific and pharmacological formulation of K. pinnatum has not been established so far though it is being traditionally used by tribes of the region. Objective: P hytochemical screening and identification of the bioactive compounds from the ethyl acetate extract of Kingiodendron pinnatum Rox. Hams. Materials and Methods: Chromatographic separation was carried out by thin layer chromatography and column chromatography. Bio-autography of the column fractioned extract and TLC chromatogram were evaluated in vitro for antibacterial activity. The PTLC, HP TLC were used for crude extract and HPLC, LCMS, FTIR, 1HNMR and 13CNMR were employed for the isolated compound in the ethyl acetate extract of K. pinnatum. Results: Evaluation of solvent system for chromatographic separation revealed that ethyl acetate: petroleum ether in the ratio of 7:2.5 ml was the most appropriate one for the separation of diterpene compounds. The antibacterial bio-autography screening of TLC separated compound showed positive activity with Staphylococcus aureus and negative activity with Escherichia coli. Spectroscopic analysis of the isolated compound from the ethyl acetate extract of K. pinnatum revealed the presence of diterpene compound. Conclusion: It is evident from the present study that the ethyl acetate extract of K. pinnatum is rich in diterpene compounds and having potential antibacterial activity. SUMMARY Novel extraction method for phytochemicls from Kingidendron pinnatum at RTAntibacterial property of diterpens extracted from Kingiodendron pinnatum Rox. Hams aganist S. aureus Abbreviations Used: TLC: Thin Layer Chromatography, PTLC: Preparatory Thin Layer Chromatography, HPTLC: High perormence Thin Layer chromatography, HPLC: High Performance Liquid Chromatography, LC-MS: Liquid chromatography Mass Spectra, FTIR

  5. New isopimarane diterpene and new cineole type glucoside from Nepeta prattii.

    PubMed

    Hou, Zhen-Fu; Tu, Yong-Qiang; Li, Yu

    2002-04-01

    Together with sixteen known compounds, a new isopimarane diterpene (prattol) and a new cineole type glucoside were isolated from Nepeta prattii. Their structures were elucidated on the basis of spectral methods as isopimar-15-en-3 beta,8 beta,20-triol, and (1R, 2R, 4S)-1,8-epoxy-p-methan-2-O-beta-D-glucopyranosyl(1-->6)-beta- D-glucopyranoside.

  6. The Oxeatamides: nitrogenous spongian diterpenes from the New Zealand marine sponge Darwinella oxeata.

    PubMed

    Wojnar, Joanna M; Dowle, Katie O; Northcote, Peter T

    2014-10-24

    As part of our ongoing search for novel and bioactive compounds from New Zealand marine organisms, we investigated the extracts of the sponge Darwinella oxeata. NMR-guided fractionation led to the isolation of nine new nitrogenous spongian diterpenes, oxeatamide A (1), iso-oxeatamide A (2), oxeatamides B-G (3-8), and oxeatamide A 23-methyl ester (9), as well as two known compounds, membranolides C and D (10, 11).

  7. Subcellular Compartmentation of the Diterpene Carnosic Acid and Its Derivatives in the Leaves of Rosemary1

    PubMed Central

    Munné-Bosch, Sergi; Alegre, Leonor

    2001-01-01

    The potent antioxidant properties of rosemary (Rosmarinus officinalis) extracts have been attributed to its major diterpene, carnosic acid. Carnosic acid has received considerable attention in food science and biomedicine, but little is known about its function in the plant in vivo. We recently found that highly oxidized diterpenes increase in rosemary plants exposed to drought and high light stress as a result of the antioxidant activity of carnosic acid (S. Munné-Bosch, K. Schwarz, L. Alegre [1999] Plant Physiol 121: 1047–1052). To elucidate the significance of the antioxidant function of carnosic acid in vivo we measured the relative amounts of carnosic acid and its metabolites in different compartments of rosemary leaves. Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products. Carnosic acid scavenges free radicals within the chloroplasts, giving rise to diterpene alcohols, mainly isorosmanol. This oxidation product is O-methylated within the chloroplasts, and the resulting form, 11,12-di-O-methylisorosmanol, is transferred to the plasma membrane. This appears to represent a mechanism of a way out for free radicals from chloroplasts. Carnosic acid also undergoes direct O-methylation within the chloroplasts, and its derived product, 12-O-methylcarnosic acid, accumulates in the plasma membrane. O-methylated diterpenes do not display antioxidant activity, but they may influence the stability of the plasma membrane. This study shows the relevance of the compartmentation of carnosic acid metabolism to the protection of rosemary plants from oxidative stress in vivo. PMID:11161064

  8. Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase.

    PubMed

    Ignea, Codruta; Trikka, Fotini A; Nikolaidis, Alexandros K; Georgantea, Panagiota; Ioannou, Efstathia; Loupassaki, Sofia; Kefalas, Panagiotis; Kanellis, Angelos K; Roussis, Vassilios; Makris, Antonios M; Kampranis, Sotirios C

    2015-01-01

    Terpenes have numerous applications, ranging from pharmaceuticals to fragrances and biofuels. With increasing interest in producing terpenes sustainably and economically, there has been significant progress in recent years in developing methods for their production in microorganisms. In Saccharomyces cerevisiae, production of the 20-carbon diterpenes has so far proven to be significantly less efficient than production of their 15-carbon sesquiterpene counterparts. In this report, we identify the modular structure of geranylgeranyl diphosphate synthesis in yeast to be a major limitation in diterpene yields, and we engineer the yeast farnesyl diphosphate synthase Erg20p to produce geranylgeranyl diphosphate. Using a combination of protein and genetic engineering, we achieve significant improvements in the production of sclareol and several other isoprenoids, including cis-abienol, abietadiene and β-carotene. We also report the development of yeast strains carrying the engineered Erg20p, which support efficient isoprenoid production and can be used as a dedicated chassis for diterpene production or biosynthetic pathway elucidation. The design developed here can be applied to the production of any GGPP-derived isoprenoid and is compatible with other yeast terpene production platforms.

  9. Two new diterpene derivatives from Euphorbia lunulata Bge and their anti-proliferative activities.

    PubMed

    Liu, Chao; Liao, Zhi-xin; Liu, Shi-jun; Qu, Yan-bo; Wang, Heng-shan

    2014-07-01

    A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type diterpenoid (2), together with twelve known compounds including three diterpenes (3-5), five triterpenes (6-10) and four sterides (11-14) were isolated from the ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR-ESI-MS data. The structure of compound 2 was further analyzed by an X-ray crystallographic study. The in vitro anti-proliferative activities against MCF-7 and NCI-H460 cell lines for compounds 1-5 (diterpene) were evaluated. The results showed marked activity for compound 1 against the two cell lines with the IC50 values 19.5 (NCI-H460) and 18.6 (MCF-7) μM, while for cis-platinum (a positive cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) μM. Compounds 2-5 exhibited moderate cytotoxic activities for the two cell lines with the IC50 values ranging from 32.1 to 58.2 μM.

  10. Antiviral Activity of Diterpene Esters on Chikungunya Virus and HIV Replication.

    PubMed

    Nothias-Scaglia, Louis-Félix; Pannecouque, Christophe; Renucci, Franck; Delang, Leen; Neyts, Johan; Roussi, Fanny; Costa, Jean; Leyssen, Pieter; Litaudon, Marc; Paolini, Julien

    2015-06-26

    Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated from various Euphorbiaceae species, of which some have been shown to be potent inhibitors of chikungunya virus (CHIKV) replication. To further explore this type of compound, the antiviral activity of a series of 29 commercially available natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be the most potent inhibitor, with an EC50 value of 6.0 ± 0.9 nM and a selectivity index (SI) of 686, which is in line with the previously reported anti-CHIKV potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13). Most of the other compounds exhibited low to moderate activity, including an ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 ± 0.1 μM and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1-29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4β-hydroxyphorbol analogues 10, 11, 13, 15, 16, and 18) and ingenane-type (27 and 28) diterpene esters were shown to inhibit HIV replication in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV and anti-HIV data sets demonstrated a linear relationship, which supported the hypothesis made that PKC may be an important target in CHIKV replication.

  11. An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi.

    PubMed

    Lozano, E S; Spina, R M; Tonn, C E; Sosa, M A; Cifuente, D A

    2015-12-01

    The Plant Kingdom is an excellent source for obtaining natural compounds with antiprotozoal activity. In the present work, we studied the effect of the diterpene 12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide (HABTO) obtained from the aerial parts of Salvia cuspidata on Trypanosoma cruzi epimastigotes. This compound was found to inhibit parasite growth even at low concentrations (IC50 5 μg/mL) and with low toxicity on mammalian cells. In addition, this diterpene induced an intense vacuolization within the parasites. In order to obtain analogs with greater lipophilicity, chemical modifications on the enol moiety were carried out to obtain the acetyl (AABTO), the sylil (SABTO) and the allyl (ALLABTO) derivatives. We observed that the SABTO was the most effective one on the parasites, and the effect could be attributed to a greater lipophilicity of this compound. Taking into account these data we conclude that the increase of lipophilicity by chemical modifications is an adequate strategy for improving the trypanocidal activity of this kind abietane diterpenes.

  12. Biosynthesis of the labdane diterpene marrubiin in Marrubium vulgare via a non-mevalonate pathway.

    PubMed

    Knöss, W; Reuter, B; Zapp, J

    1997-09-01

    The biosynthesis of the furanic labdane diterpene marrubiin has been studied in plantlets and shoot cultures of Marrubium vulgare (Lamiaceae). The use of [2-14C]acetate, [2-14C]pyruvate, [2-14C]mevalonic acid and [U-14C]glucose incorporation experiments showed that the labelling of sterols in etiolated shoot cultures of M. vulgare was in accordance with their biosynthesis via the acetate-mevalonate pathway. In contrast, the incorporation rates of these precursors into the diterpene marrubiin could not be explained by biosynthesis of this compound via the acetate-mevalonate pathway. Cultivation of etiolated shoot cultures of M. vulgare on medium containing [1-13C]glucose and subsequent 13C-NMR spectroscopy of marrubiin led to the conclusion that the biosynthesis of marrubiin follows a non-mevalonate pathway. All isoprenic units of 13C-labelled marrubiin were enriched in those carbons that correspond to positions 1 and 5 of a putative precursor isopentenyl diphosphate. This labelling pattern from [1-13C]glucose is consistent with an alternative pathway via trioses, which has already been shown to occur in Eubacteria and Gymnospermae. The labdane skeleton is a precursor of many other skeletal types of diterpenes. Therefore it becomes obvious that in connection with the few known examples of a non-mevalonate pathway to isoprenoids the formation of some isoprenoids in plants via a non-mevalonate pathway might be quite common.

  13. ent-Kaurane diterpenes from the stem bark of Annona vepretorum (Annonaceae) and cytotoxic evaluation.

    PubMed

    Dutra, Lívia M; Bomfim, Larissa M; Rocha, Suellen L A; Nepel, Angelita; Soares, Milena B P; Barison, Andersson; Costa, Emmanoel V; Bezerra, Daniel P

    2014-08-01

    This work describes a novel ent-kaurane diterpene, ent-3β-hydroxy-kaur-16-en-19-al along with five known ent-kaurane diterpenes, ent-3β,19-dihydroxy-kaur-16-eno, ent-3β-hydroxy-kaur-16-eno, ent-3β-acetoxy-kaur-16-eno, ent-3β-hydroxy-kaurenoic acid and kaurenoic acid, as well as caryophyllene oxide, humulene epoxide II, β-sitosterol, stigmasterol and campesterol from the stem bark of Annona vepretorum Mart. (Annonaceae). Cytotoxic activities towards tumor B16-F10, HepG2, K562 and HL60 and non-tumor PBMC cell lines were evaluated for ent-kaurane diterpenes. Among them, ent-3β-hydroxy-kaur-16-en-19-al was the most active compound with higher cytotoxic effect over K562 cell line (IC50 of 2.49 μg/mL) and lower over B16-F10 cell line (IC50 of 21.02 μg/mL).

  14. Two new non-glycosidic iridoids from Sambucus ebulus.

    PubMed

    Tomassini, Lamberto; Foddai, Sebastiano; Ventrone, Antonio; Nicoletti, Marcello

    2013-01-01

    Two new 'Valeriana-type' non-glycosidic iridoids were isolated from the aerial parts (leaves and young branches) of Sambucus ebulus L., a perennial herbaceous species widespread in Europe. The structures were elucidated, by spectroscopic means, as 7-O-acetylpatrinoside aglycone (1) and 10-O-acetylpatrinoside aglycone (2).

  15. New glycosides of acetophenone derivatives and phenylpropanoids from Juniperus occidentalis.

    PubMed

    Inatomi, Yuka; Murata, Hiroko; Inada, Akira; Nakanishi, Tsutomu; Lang, Frank A; Murata, Jin; Iinuma, Munekazu

    2013-04-01

    New glycosides of seven acetophenone derivatives (1-7) and two phenylpropanoids (8, 9), named juniperosides III-XI, have been isolated from the MeOH extract of the leaves and stems of Juniperus occidentalis Hook. (Cupressaceae), together with eleven other known compounds. The structures of these compounds have been successfully elucidated using a variety of spectroscopic techniques.

  16. Marruboside, a new phenylethanoid glycoside from Marrubium vulgare L.

    PubMed

    Sahpaz, Sevser; Hennebelle, Thierry; Bailleul, François

    2002-06-01

    A new phenylethanoid glycoside, marruboside, has been isolated from the aerial parts of Marrubium vulgare L. Its structure was established as 3,4-dihydroxy-beta-phenylethoxy-O-[beta-D-apiofuranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)]-[beta-D-apiofuranosyl-(1-->6)]-4-O-caffeoyl-beta-D-glucopyranoside, on the basis of spectroscopic evidence.

  17. Triterpenoid glycosides from the leaves of Meliosma henryi.

    PubMed

    Alabdul Magid, Abdulmagid; Morjani, Hamid; Harakat, Dominique; Madoulet, Claudie; Dumontet, Vincent; Lavaud, Catherine

    2015-01-01

    Seven triterpenoid glycosides, named meliosmosides A-G, were isolated from the leaves of Meliosma henryi Diels (Sabiaceae). Their structures were elucidated by different spectroscopic methods including 1D and 2D NMR experiments as well as HRESIMS analysis. Isolated compounds were evaluated for their cytotoxic activity against KB cell line. PMID:25468712

  18. Glycosidation of Methanol with Ribose: An Interdisciplinary Undergraduate Laboratory Experiment

    ERIC Educational Resources Information Center

    Simon, Erin; Cook, Katie; Pritchard, Meredith R.; Stripe, Wayne; Bruch, Martha; Bendinskas, Kestutis

    2010-01-01

    This exercise provides students hands-on experience with the topics of glycosidation, hemiacetal and acetal formation, proton nuclear magnetic resonance ([superscript 1]H NMR) spectroscopy, and kinetic and thermodynamic product formation. In this laboratory experiment, the methyl acetal of ribose is synthesized, and the kinetic and thermodynamic…

  19. Three new hecogenin glycosides from fermented leaves of Agave americana.

    PubMed

    Jin, Jian-Ming; Liu, Xi-Kui; Yang, Chong-Ren

    2003-06-01

    Eight steroidal compounds, including three new hecogenin glycosides, agamenosides D-F, were isolated from the fermented leaves of Agave americana. The structures of the new steroidal saponins were elucidated by spectroscopic data and chemical methods. The activity of the isolated compounds on deformations of mycelia germinated from conidia of Pyricularia oaryzae P-2b was evaluated.

  20. Ceylonamides A-F, Nitrogenous Spongian Diterpenes That Inhibit RANKL-Induced Osteoclastogenesis, from the Marine Sponge Spongia ceylonensis.

    PubMed

    El-Desoky, Ahmed H; Kato, Hikaru; Angkouw, Esther D; Mangindaan, Remy E P; de Voogd, Nicole J; Tsukamoto, Sachiko

    2016-08-26

    Seven new spongian diterpenes, ceylonamides A-F (1-6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensis along with eight known spongian diterpenes, 8-15. Compounds 1-6 were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50 value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure-activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity. PMID:27526327

  1. 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A, two diterpenes isolated from Euphorbia helioscopia suppress microglia activation.

    PubMed

    Wang, Hao; Liu, Yu; Zhang, Jingling; Xu, Jing; Cui, Chun-Ai; Guo, Yuanqiang; Jin, Da-Qing

    2016-01-26

    Microglia activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors. In the present study, we found that two diterpenes isolated from Euphorbia helioscopia, 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A suppressed NO and PGE2 production by inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. The diterpenes also inhibited the production of ROS and proinflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, the mechanism involved the NF-κB but not Akt and mitogen-activated protein kinase (MAPK) pathway. Moreover, the two diterpenes also attenuate microglia activation-mediated neuronal death. These results suggest that 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A may provide potential therapeutic strategy for various neuroinflammatory diseases.

  2. Analysis of diterpenic compounds by GC-MS/MS: contribution to the identification of main conifer resins.

    PubMed

    Azemard, Clara; Menager, Matthieu; Vieillescazes, Catherine

    2016-09-01

    The three principal types of molecules composing diterpenic resins are the abietanes, pimaranes and labdanes. The study of their fragmentation was performed by gas chromatography coupled to an ion trap mass spectrometer, on standards and resins used in paint varnishes: colophony and sandarac. We found that the general fragmentation pattern was mostly governed by the location of the double bonds on the different cycles and the presence of functional groups, and not by the nature of the C13 group in the case of abietanes and pimaranes. As for the labdanes, the loss of their alkyl chain is very specific. This study develops an analytical strategy using tandem mass spectrometry (MS/MS) experiments to validate the proposed mechanisms of fragmentation and to find the ions of interest for the identification of diterpenic molecules. Graphical Abstract Analysis of diterpenic compounds by GC-MS/MS. PMID:27449645

  3. Unveiling the mode of action of antibacterial labdane diterpenes from Alpinia nigra (Gaertn.) B. L. Burtt seeds.

    PubMed

    Ghosh, Sudipta; Indukuri, Kiran; Bondalapati, Somasekhar; Saikia, Anil K; Rangan, Latha

    2013-08-01

    The labdane diterpene, (E)-labda-8(17), 12-diene-15, 16-dial (compound A) and its epoxide analogue, (E)-8β, 17-Epoxylabd-12-ene-15, 16-dial (compound B) were isolated from the seeds of Alpinia nigra for the first time. The antibacterial activities of both compounds were evaluated against three Gram-positive and four Gram-negative bacteria, and flow cytometric analysis revealed that these compounds caused significant damage to the bacterial cell membranes. Further, field emission scanning electron microscope imaging and cell leakage analysis confirmed that the labdane diterpenes were responsible for bacterial cell membrane damage and disintegration. Our findings provide new insight into the broad-spectrum effects of two natural labdane diterpenes that may be useful in the future development of herbal antibiotic products.

  4. New flav-3-en-3-ol glycosides, kaempferiaosides C and D, and acetophenone glycosides, kaempferiaosides E and F, from the rhizomes of Kaempferia parviflora.

    PubMed

    Chaipech, Saowanee; Morikawa, Toshio; Ninomiya, Kiyofumi; Yoshikawa, Masayuki; Pongpiriyadacha, Yutana; Hayakawa, Takao; Muraoka, Osamu

    2012-07-01

    Two new flav-3-en-3-ol glycosides, kaempferiaosides C (3) and D(4), and two new acetophenone glycosides, kaempferiaosides E (5) and F (6), were isolated from the Thai natural medicine Krachai Dum, the rhizomes of Kaempferia parviflora Wall. ex Baker. Their structures were established mainly on the basis of 1D and 2D NMR spectral data. PMID:22101441

  5. Malonylated flavonol glycosides from the petals of Clitoria ternatea.

    PubMed

    Kazuma, Kohei; Noda, Naonobu; Suzuki, Masahiko

    2003-01-01

    Three flavonol glycosides, kaempferol 3-O-(2"-O-alpha-rhamnosyl-6"-O-malonyl)-beta-glucoside, quercetin 3-O-(2"-O-alpha-rhamnosyl-6"-O-malonyl)-beta-glucoside, and myricetin 3-O-(2",6"-di-O-alpha-rhamnosyl)-beta-glucoside were isolated from the petals of Clitoria ternatea cv. Double Blue, together with eleven known flavonol glycosides. Their structures were identified using UV, MS, and NMR spectroscopy. They were characterized as kaempferol and quercetin 3-(2(G)- rhamnosylrutinoside)s, kaempferol, quercetin, and myricetin 3-neohesperidosides, 3-rutinosides, and 3-glucosides in the same tissue. In addition, the presence of myricetin 3-O-(2"-O-alpha-rhamnosyl-6"-O-malonyl)-beta-glucoside was inferred from LC/MS/MS data for crude petal extracts. The flavonol compounds identified in the petals of C. ternatea differed from those reported in previous studies. PMID:12482461

  6. Lupane-triterpene glycosides from the leaves of Acanthopanax gracilistylus.

    PubMed

    Yook, Chang-Soo; Liu, Xiang-Qian; Chang, Seung-Yeup; Park, Sang-Yong; Nohara, Toshihiro

    2002-10-01

    A novel lupane-triterpene glycoside, called wujiapioside B (1), was isolated from the leaves of Acanthopanax gracilistylus (Araliaceae) together with three known lupane-triterpene glycosides, acankoreoside C (2), acantrifoside A (3) and 3-epibetulinic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (4). Based on spectroscopic data, the chemical structure of 1 was determined as 3alpha,23-dihydroxy-lup-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester. Compounds 2-3 were obtained for the first time from this plant and compound 4 has not been isolated from Acanthopanax genus yet. PMID:12372869

  7. Croton ruizianus: platelet proaggregating activity of two new pregnane glycosides.

    PubMed

    Piacente, S; Belisario, M A; Del Castillo, H; Pizza, C; De Feo, V

    1998-03-01

    The MeOH extract of the aerial parts of Croton ruizianus afforded two new pregnane glycosides 1 and 2, together with the morphinandienone alkaloids flavinantine (3) and O-methylflavinantine (4). Their structures were elucidated by NMR experiments including 1H-1H (1D TOCSY and 2D DQF-COSY) and 1H-13C (HSQC, HMBC) spectroscopy. The proaggregating activity of the MeOH extract and the isolates were evaluated. Although the MeOH extract and pregnane glycosides (at different doses) were found to promote platelet aggregation, flavinantine (3) and O-methylflavinantine (4) showed only slight activity. The ability of the MeOH extract and the four compounds to act synergistically with thrombin was also evaluated. All the tested compounds were successful in augmenting the aggregating effect of thrombin, although to different degrees.

  8. Phenylpropanoid glycosides from the leaves of Paulownia coreana.

    PubMed

    Kim, Jin-Kyu; Si, Chuan-Ling; Bae, Young-Soo

    2008-02-15

    Study on the water soluble fraction from the leaves of Paulownia coreana led to the isolation of verbascoside (1), isoverbascoside (2), campneoside II (3), and a new phenylpropanoid glycoside, (R,S)-7-hydroxy-7-(3,4-dihydroxyphenyl)-ethyl-O-alpha-L-rhamnopyranosyl(1 --> 3)-beta-d-(6-O-caffeoyl)-glucopyranoside (4). The structures of these compounds were established on the basis of spectroscopic evidence. PMID:18266154

  9. A new triterpene glycoside from the roots of Symphytum officinale.

    PubMed

    Ahmad, V U; Noorwala, M; Mohammad, F V; Sener, B

    1993-03-01

    Chemical investigation of the EtOH-soluble portion of Symphytum officinale roots has resulted in the isolation of a new pentacyclic triterpene glycoside of oleanolic acid. Its structure was elucidated by spectroscopic studies, including 2D nmr, and chemical evidences as 3-O-[beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)-alpha-L -arabinopyranosyl]-oleanolic acid [1]. PMID:8482944

  10. Two aurone glycosides from heartwood of Pterocarpus santalinus.

    PubMed

    Kesari, Achyut Narayan; Gupta, Rajesh Kumar; Watal, Geeta

    2004-12-01

    Two new aurone glycosides, 6 hydroxy 5 methyl 3',4',5' trimethoxy aurone 4-O-alpha-L-rhamnopyranoside and 6,4' dihydroxy aurone 4-O-rutinoside have been isolated from the ethanolic extract of the wood of Pterocarpus santalinus. Their structures were determined on the basis of chemical and spectroscopic analysis (UV, IR, EIMS, (1)H and (13)C NMR). PMID:15541741

  11. New phenolic glycosides from the seeds of Cucurbita moschata.

    PubMed

    Li, Fa-Sheng; Dou, De-Qiang; Xu, Liang; Chi, Xiao-Feng; Kang, Ting-Guo; Kuang, Hai-Xue

    2009-07-01

    Two new phenolic glycosides were isolated from the seeds of Cucurbita moschata. Their structures were elucidated as (2-hydroxy)phenylcarbinyl 5-O-benzoyl-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (1) and 4-beta-D-(glucopyranosyl hydroxymethyl)phenyl 5-O-benzoyl-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (2) on the basis of spectroscopic analysis and chemical evidence.

  12. Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking.

    PubMed

    Nivedha, Anita K; Thieker, David F; Makeneni, Spandana; Hu, Huimin; Woods, Robert J

    2016-02-01

    Molecular docking programs are primarily designed to align rigid, drug-like fragments into the binding sites of macromolecules and frequently display poor performance when applied to flexible carbohydrate molecules. A critical source of flexibility within an oligosaccharide is the glycosidic linkages. Recently, Carbohydrate Intrinsic (CHI) energy functions were reported that attempt to quantify the glycosidic torsion angle preferences. In the present work, the CHI-energy functions have been incorporated into the AutoDock Vina (ADV) scoring function, subsequently termed Vina-Carb (VC). Two user-adjustable parameters have been introduced, namely, a CHI- energy weight term (chi_coeff) that affects the magnitude of the CHI-energy penalty and a CHI-cutoff term (chi_cutoff) that negates CHI-energy penalties below a specified value. A data set consisting of 101 protein-carbohydrate complexes and 29 apoprotein structures was used in the development and testing of VC, including antibodies, lectins, and carbohydrate binding modules. Accounting for the intramolecular energies of the glycosidic linkages in the oligosaccharides during docking led VC to produce acceptable structures within the top five ranked poses in 74% of the systems tested, compared to a success rate of 55% for ADV. An enzyme system was employed in order to illustrate the potential application of VC to proteins that may distort glycosidic linkages of carbohydrate ligands upon binding. VC represents a significant step toward accurately predicting the structures of protein-carbohydrate complexes. Furthermore, the described approach is conceptually applicable to any class of ligands that populate well-defined conformational states. PMID:26744922

  13. Two new monoterpenoid glycosides from Mentha spicata L.

    PubMed

    Zheng, Jian; Wu, Li-Jun; Zheng, Lu; Wu, Bin; Song, Ai-Hua

    2003-03-01

    Two new monoterpenoid glycosides, spicatoside A and spicatoside B, were isolated from the whole herbs of Mentha spicata L. which have anti-inflammatory and hemostatic activities. Their structures have been determined on the basis of spectral and chemical analysis. They are (+)-5-[1-(beta-D-glucopyranosyloxymethyl)ethenyl]-2-methyl-2-cyclohexen-1-one (1), and (-)-5-[[2-(beta-D-glucopyranosyloxy)-1-hydroxy-l-methyl]ethyl]-2-methyl-2-cyclohexen-1-one (2).

  14. New Iridoid Glycosides with Antidepressant Activity Isolated from Cyperus rotundus.

    PubMed

    Zhou, Zhong-Liu; Yin, Wen-Qing; Yang, Ya-Mei; He, Chun-Hong; Li, Xiao-Na; Zhou, Cui-Ping; Guo, Hong

    2016-01-01

    Based on bioactive screening results, two new iridoid glycosides, named rotunduside G (1) and rotunduside H (2), were isolated from the rhizomes of Cyperus rotundus, together with four known ones, negundoside (3), nishindaside (4), isooleuropein (5) and neonuezhenide (6). Their structures were elucidated on the basis of spectroscopic methods and from literature values. In mice models of despair, 1 and 2 showed significant antidepressant activity. PMID:26726748

  15. Glycosidic linkage conformation of methyl-α-mannopyranoside

    NASA Astrophysics Data System (ADS)

    Coskuner, Orkid; Bergeron, Denis E.; Rincon, Luis; Hudgens, Jeffrey W.; Gonzalez, Carlos A.

    2008-07-01

    We study the preferred conformation of the glycosidic linkage of methyl-α-mannopyranoside in the gas phase and in aqueous solution. Results obtained utilizing Car-Parrinello molecular dynamics (CPMD) simulations are compared to those obtained from classical molecular dynamics (MD) simulations. We describe classical simulations performed with various water potential functions to study the impact of the chosen water potential on the predicted conformational preference of the glycosidic linkage of the carbohydrate in aqueous solution. In agreement with our recent studies, we find that results obtained with CPMD simulations differ from those obtained from classical simulations. In particular, this study shows that the trans (t) orientation of the glycosidic linkage of methyl-α-mannopyranoside is preferred over its gauche anticlockwise (g-) orientation in aqueous solution. CPMD simulations indicate that this preference is due to intermolecular hydrogen bonding with surrounding water molecules, whereas no such information could be demonstrated by classical MD simulations. This study emphasizes the importance of ab initio MD simulations for studying the structural properties of carbohydrates in aqueous solution.

  16. ent-Pimarane and ent-Kaurane Diterpenes from Aldama discolor (Asteraceae) and Their Antiprotozoal Activity.

    PubMed

    Nogueira, Mauro S; Da Costa, Fernando B; Brun, Reto; Kaiser, Marcel; Schmidt, Thomas J

    2016-01-01

    Aldama discolor (syn.Viguiera discolor) is an endemic Asteraceae from the Brazilian "Cerrado", which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. In this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2), ent-2S,4S-2-19-epoxy-pimara-8(3),15-diene-7β-ol (3) and ent-7-oxo-pimara-8,15-diene-3β-ol (4), were isolated from the dichloromethane extract of A. discolor leaves and identified by means of MS and NMR. The compounds were assayed in vitro against Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, Plasmodium falciparum and also tested for cytotoxicity against mammalian cells (L6 cell line). The ent-kaurane 1 showed significant in vitro activity against both P. falciparum (IC 50 = 3.5 μ M) and L. donovani (IC 50 = 2.5 μ M) and ent-pimarane 2 against P. falciparum (IC 50 = 3.8 μ M). Both compounds returned high selectivity indices (SI >10) in comparison with L6 cells, which makes them interesting candidates for in vivo tests. In addition to the diterpenes, the sesquiterpene lactone budlein A (5), which has been reported to possess a strong anti-T. b. rhodesiense activity, was identified as major compound in the A. discolor extract and explains its high activity against this parasite (100% growth inhibition at 2 μ g/mL). PMID:27649126

  17. A comparative study of two clerodane diterpenes from Baccharis trimera (Less.) DC. on the influx and mobilization of intracellular calcium in rat cardiomyocytes.

    PubMed

    Garcia, Francisca Adilfa de Oliveira; Tanae, Mirtes Midori; Torres, Luce Maria Brandão; Lapa, Antônio José; de Lima-Landman, Maria Teresa Riggio; Souccar, Caden

    2014-01-01

    Baccharis trimera (Less.) D.C. (Asteraceae) is a medicinal species native to South America and used in Brazilian folk medicine to treat gastrointestinal and liver diseases, kidney disorders and diabetes. The aqueous extract (AE) of the aerial parts of this species presented two mainly constituents: the ent-clerodane diterpene (Fig. 1) and the neo-clerodane diterpene (Fig. 2). The objective of this work was to study their activities on the blockade of Ca(2+)-induced contractions in KCL-depolarized rat portal vein preparations, and on the influx and mobilization of cytosolic calcium in rat cardiomyocytes by fluorescence measurements. The results showed that both the neo- and the ent-clerodane diterpenes reduced the maximal contractions induced by CaCl2, in KCl depolarized rat portal vein preparations, without modifying the EC50. The data on the concentration of cytosolic calcium ([Ca(2+)]c) showed that, while the neo-clerodane diterpene stimulates the mobilization of [Ca(2+)]c in rat cardiomyocytes, this effect was not observed with the ent-clerodane diterpene. On the other hand, the influx of calcium was not altered by the neo-clerodane diterpene, but was reduced in the presence of the ent-clerodane diterpene, indicating that this compound induces a blockade of the voltage-dependent calcium channels.

  18. Spongian diterpenes from Australian Nudibranchs: an anatomically guided chemical study of Glossodoris atromarginata.

    PubMed

    Somerville, Michael J; Mollo, Ernesto; Cimino, Guido; Rungprom, Wimolpun; Garson, Mary J

    2006-07-01

    An Australian population of the nudibranch mollusk Glossodoris atromarginata has been found to contain furanoditerpenes of the spongian series. Spongia-13(16),14-dien-3-one (1) and 3alpha-acetoxy-19-hydroxyspongia-13(16),14-dien-2-one [corrected] (2) were isolated for the first time from a natural source, along with a series of known diterpenes (3-7). Anatomical dissection of the animals revealed the relative distribution and chemical variation of secondary metabolites. Structural studies have provided a basis for chemical comparisons between populations from different geographic locations. PMID:16872151

  19. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

    PubMed

    Li, Wan-Fei; Wang, Juan; Zhang, Jing-Jie; Song, Xun; Ku, Chuen-Fai; Zou, Juan; Li, Ji-Xin; Rong, Li-Jun; Pan, Lu-Tai; Zhang, Hong-Jie

    2015-11-24

    Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

  20. General diastereoselective synthetic approach toward isospongian diterpenes. Synthesis of (-)-marginatafuran, (-)-marginatone, and (-)-20-acetoxymarginatone.

    PubMed

    Gris, Antonio; Cabedo, Nuria; Navarro, Ismael; de Alfonso, Ignacio; Agulló, Consuelo; Abad-Somovilla, Antonio

    2012-07-01

    This work describes a synthetic approach to the carbocyclic skeleton of isospongian diterpenes that uses the commercially available monoterpene (S)-carvone as a C-ring synthon, which is incorporated into the tetracyclic isospongian framework via a C→ABC→ABCD ring annulation strategy using intramolecular Diels-Alder and ring-closing metathesis reactions. This approach has been successfully used to prepare both the title natural isospongians and several nonnatural oxygenated analogues. A preliminary evaluation of the inhibitory activity of the small collection of synthesized isospongians on the mammalian mitochondrial respiratory chain revealed that most were able to inhibit the integrated electron transfer chain (NADH oxidase activity) in the micromolar range.

  1. Crispene E, a cis-clerodane diterpene inhibits STAT3 dimerization in breast cancer cells.

    PubMed

    Mantaj, Julia; Rahman, S M Abdur; Bokshi, Bishwajit; Hasan, Choudhury M; Jackson, Paul J M; Parsons, Richard B; Rahman, Khondaker M

    2015-04-01

    Crispene E, a new clerodane-type diterpene, inhibited STAT3 dimerization in a cell-free fluorescent polarisation assay and was found to have significant toxicity against STAT3-dependent MDA-MB 231 breast cancer cell line and selectively inhibited the expression of STAT3 and STAT3 target genes cyclin D1, Fascin and bcl-2. Molecular docking studies suggest the molecule inhibits STAT3 by interacting with its SH2 domain. The compound has been isolated from Tinospora crispa and characterized using standard spectroscopic techniques. PMID:25721973

  2. New Non-Toxic Semi-Synthetic Derivatives from Natural Diterpenes Displaying Anti-Tuberculosis Activity.

    PubMed

    Matos, Priscilla M; Mahoney, Brian; Chan, Yohan; Day, David P; Cabral, Mirela M W; Martins, Carlos H G; Santos, Raquel A; Bastos, Jairo K; Page, Philip C Bulman; Heleno, Vladimir C G

    2015-10-07

    We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds were fully characterized using high resolution mass spectrometry, infrared spectroscopy, ¹H- and (13)C-NMR experiments. We also report the evaluation of the anti-tuberculosis potential for all compounds, which showed some promising results for Micobacterium tuberculosis inhibition. Moreover, the toxicity for each of the most active compounds was also assessed.

  3. Antibacterial Activities of a New Brominated Diterpene from Borneon Laurencia spp

    PubMed Central

    Vairappan, Charles Santhanaraju; Ishii, Takahiro; Lee, Tan Kai; Suzuki, Minoru; Zhaoqi, Zhan

    2010-01-01

    In our continuous interest to study the diversity of halogenated metabolites of Malaysian species of the red algal genus Laurencia, we examined the chemical composition of five populations of unrecorded Laurencia sp. A new brominated diterpene, 10-acetoxyangasiol (1), and four other known metabolites, aplysidiol (2), cupalaurenol (3), 1-methyl-2,3,5-tribromoindole (4), and chamigrane epoxide (5), were isolated and identified. Isolated metabolites exhibited potent antibacterial activities against clinical bacteria, Staphylococcus aureus, Staphylococcus sp., Streptococcus pyogenes, Salmonella sp. and Vibrio cholerae. PMID:20631866

  4. 4α-Acetoxyamijidictyol - A New Antifeeding Dolastane Diterpene from the Brazilian Brown Alga Canistrocarpus cervicornis.

    PubMed

    Miguel Bianco, Éverson; Martins Francisco, Thiago; Basílio Pinheiro, Carlos; Bagueira de Vasconcellos Azeredo, Rodrigo; Laneuville Teixeira, Valéria; Crespo Pereira, Renato

    2015-11-01

    Chemical investigation of the CH2 Cl2 crude extract from the brown alga Canistrocarpus cervicornis (Dictyotaceae) led to isolation of one new (1) and four previously reported dolastane diterpenes (2-5). Their structures were characterized by 1D- and 2D-NMR spectroscopic techniques, including a full single crystal X-ray diffraction analysis for 1, 2, and 4. In addition, the new structure 1 was assayed as chemical defense inhibiting the feeding by the sea urchin Lytechinus variegatus. This study constitutes an additional report broadening the known spectrum of action and defensive roles of secondary metabolites of the C. cervicornis and Dictyotales species.

  5. Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation on cytotoxic activities.

    PubMed

    Luo, Yan; Wang, Ke; Zhang, Meng-han; Zhang, Da-yong; Wu, Yang-chang; Wu, Xiao-ming; Hua, Wei-yi

    2015-06-01

    There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs.

  6. Anti-inflammatory diterpene dimers from the root barks of Aphanamixis grandifolia.

    PubMed

    Zhang, Hong-Jian; Zhang, Yang-Mei; Luo, Jian-Guang; Luo, Jun; Kong, Ling-Yi

    2015-07-21

    A total of 14 new diterpene dimers, aphanamenes C-P ()1-14, with four known homologous compounds were isolated from the root barks of Aphanamixis grandifolia Bl. The structures of these compounds were elucidated by spectroscopic analyses, and their absolute configurations were determined using the CD exciton chirality method. In addition, all the compounds exhibited significant inhibition of lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages, with IC50 values between 7.75 and 38.23 μM.

  7. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi

    PubMed Central

    Li, Wan-Fei; Wang, Juan; Zhang, Jing-Jie; Song, Xun; Ku, Chuen-Fai; Zou, Juan; Li, Ji-Xin; Rong, Li-Jun; Pan, Lu-Tai; Zhang, Hong-Jie

    2015-01-01

    Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2). PMID:26610490

  8. Chlorabietols A-C, Phloroglucinol-Diterpene Adducts from the Chloranthaceae Plant Chloranthus oldhamii.

    PubMed

    Xiong, Juan; Hong, Zhi-Lai; Gao, Li-Xin; Shen, Jie; Liu, Shu-Ting; Yang, Guo-Xun; Li, Jia; Zeng, Huaqiang; Hu, Jin-Feng

    2015-11-01

    Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3), were isolated from the roots of the rare Chloranthaceae plant Chloranthus oldhamii. They represent a new class of compounds, featuring an abietane-type diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3-dihydrofuran ring. Their structures were elucidated by detailed spectroscopic analysis, molecular modeling studies, and electronic circular dichroism calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 μM, respectively.

  9. 4α-Acetoxyamijidictyol - A New Antifeeding Dolastane Diterpene from the Brazilian Brown Alga Canistrocarpus cervicornis.

    PubMed

    Miguel Bianco, Éverson; Martins Francisco, Thiago; Basílio Pinheiro, Carlos; Bagueira de Vasconcellos Azeredo, Rodrigo; Laneuville Teixeira, Valéria; Crespo Pereira, Renato

    2015-11-01

    Chemical investigation of the CH2 Cl2 crude extract from the brown alga Canistrocarpus cervicornis (Dictyotaceae) led to isolation of one new (1) and four previously reported dolastane diterpenes (2-5). Their structures were characterized by 1D- and 2D-NMR spectroscopic techniques, including a full single crystal X-ray diffraction analysis for 1, 2, and 4. In addition, the new structure 1 was assayed as chemical defense inhibiting the feeding by the sea urchin Lytechinus variegatus. This study constitutes an additional report broadening the known spectrum of action and defensive roles of secondary metabolites of the C. cervicornis and Dictyotales species. PMID:26567945

  10. A new bis-labdanic diterpene from the rhizomes of Alpinia pahangensis.

    PubMed

    Sivasothy, Yasodha; Ibrahim, Halijah; Paliany, Audra Shaleena; Alias, Siti Aisyah; Md Nor, Nurur Raudzah; Awang, Khalijah

    2013-12-01

    The rhizomes of Alpinia pahangensis yielded a new bis-labdanic diterpene for which the name pahangensin C (1) was proposed along with twelve known analogues (2-13). The structure of 1 was elucidated via spectroscopic methods including 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 2 and 12 were isolated for the first time from the genus Alpinia. This is the second occurrence of compounds 2 and 12 in the Zingiberaceae family. Selected analogues exhibited moderate to strong inhibitory activity against Staphylococcus aureus and Bacillus cereus.

  11. Chlorabietols A-C, Phloroglucinol-Diterpene Adducts from the Chloranthaceae Plant Chloranthus oldhamii.

    PubMed

    Xiong, Juan; Hong, Zhi-Lai; Gao, Li-Xin; Shen, Jie; Liu, Shu-Ting; Yang, Guo-Xun; Li, Jia; Zeng, Huaqiang; Hu, Jin-Feng

    2015-11-01

    Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3), were isolated from the roots of the rare Chloranthaceae plant Chloranthus oldhamii. They represent a new class of compounds, featuring an abietane-type diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3-dihydrofuran ring. Their structures were elucidated by detailed spectroscopic analysis, molecular modeling studies, and electronic circular dichroism calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 μM, respectively. PMID:26444099

  12. New cembranoid diterpene from the South China Sea soft coral Sarcophyton sp.

    PubMed

    Cao, Fei; Zhou, Jing; Xu, Kai-Xia; Zhang, Meng-Qi; Wang, Chang-Yun

    2013-12-01

    One new oxygenated cembranoid diterpene, named sarcophytol W (1), along with six known analogues (2-7) were isolated from a soft coral Sarcophyton sp. collected from the South China Sea. Their structures were elucidated by spectroscopic analyses and by comparison with previously reported data. The absolute configuration of 1was assigned on the basis of the absolute configuration of the related congener 2, which was determined by application of the modified Mosher's method. All the compounds were evaluated for their antibacterial and antifouling activities.

  13. Isolation and characterization of stelladerol, a new antioxidant naphthalene glycoside, and other antioxidant glycosides from edible daylily (hemerocallis) flowers.

    PubMed

    Cichewicz, Robert H; Nair, Muraleedharan G

    2002-01-01

    Daylily (Hemerocallis spp.) flowers are utilized as an important ingredient in traditional Asian cuisine and are also valued for their reputed medicinal effects. In studies of the bioactive methanol and aqueous methanol extracts of lyophilized Hemerocallis cv. Stella de Oro flowers, kaempferol, quercetin, and isorhamnetin 3-O-glycosides (1-9), phenethyl beta-D-glucopyranoside (10), orcinol beta-D-glucopyranoside (11), phloretin 2'-O-beta-D-glucopyranoside (12), phloretin 2'-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside (13), a new naphthalene glycoside, stelladerol (14), and an amino acid (longitubanine A) (15) have been isolated. All of these compounds were tested for their antioxidant and cyclooxygenase inhibitory activities. Stelladerol was found to possess strong antioxidant properties, inhibiting lipid oxidation by 94.6% +/- 1.4 at 10 microM in an in vitro assay. Several of the flavonol 3-O-glycoside isolates also demonstrated modest antioxidant activities at 10 microM. None of the isolates inhibited cyclooxygenase activity at 100 microM. PMID:11754548

  14. Annotation and comparative analysis of the glycoside hydrolase genes in Brachypodium distachyon

    SciTech Connect

    Tyler, Ludmila; Bragg, Jennifer; Wu, Jiajie; Yang, Xiaohan; Tuskan, Gerald A; Vogel, John

    2010-01-01

    Background Glycoside hydrolases cleave the bond between a carbohydrate and another carbohydrate, a protein, lipid or other moiety. Genes encoding glycoside hydrolases are found in a wide range of organisms, from archea to animals, and are relatively abundant in plant genomes. In plants, these enzymes are involved in diverse processes, including starch metabolism, defense, and cell-wall remodeling. Glycoside hydrolase genes have been previously cataloged for Oryza sativa (rice), the model dicotyledonous plant Arabidopsis thaliana, and the fast-growing tree Populus trichocarpa (poplar). To improve our understanding of glycoside hydrolases in plants generally and in grasses specifically, we annotated the glycoside hydrolase genes in the grasses Brachypodium distachyon (an emerging monocotyledonous model) and Sorghum bicolor (sorghum). We then compared the glycoside hydrolases across species, both at the whole-genome level and at the level of individual glycoside hydrolase families. Results We identified 356 glycoside hydrolase genes in Brachypodium and 404 in sorghum. The corresponding proteins fell into the same 34 families that are represented in rice, Arabidopsis, and poplar, helping to define a glycoside hydrolase family profile which may be common to flowering plants. Examination of individual glycoside hydrolase familes (GH5, GH13, GH18, GH19, GH28, and GH51) revealed both similarities and distinctions between monocots and dicots, as well as between species. Shared evolutionary histories appear to be modified by lineage-specific expansions or deletions. Within families, the Brachypodium and sorghum proteins generally cluster with those from other monocots. Conclusions This work provides the foundation for further comparative and functional analyses of plant glycoside hydrolases. Defining the Brachypodium glycoside hydrolases sets the stage for Brachypodium to be a monocot model for investigations of these enzymes and their diverse roles in planta. Insights

  15. Multidrug resistance-reversal effects of resin glycosides from Dichondra repens.

    PubMed

    Song, Wei-Bin; Wang, Wen-Qiong; Zhang, Shu-Wei; Xuan, Li-Jiang

    2015-02-15

    Investigation of hydrophobic extract of Dichondra repens (Convolvulaceae) led to the isolation of three new resin glycosides dichondrins A-C (1-3), and three known resin glycosides cus-1, cus-2, and cuse 3. All the isolated resin glycosides with an acyclic core were evaluated for their multidrug resistance reversal activities, and the combined use of these compounds at a concentration of 25μM increased the cytotoxicity of vincristine by 1.03-1.78-fold.

  16. New aliphatic alcohol and (Z)-4-coumaric acid glycosides from Acanthus ilicifolius.

    PubMed

    Wu, Jun; Zhang, Si; Huang, Jianshe; Xiao, Qiang; Li, Qingxin; Long, Lijuan; Huang, Liangmin

    2003-10-01

    From the aerial parts of Acanthus ilicifolius, a new aliphatic alcohol glycoside (ilicifolioside C) and two new (Z)-4-coumaric acid glycosides, (Z)-4-coumaric acid 4-O-beta-D-glucopyranoside and (Z)-4-coumaric acid 4-O-beta-D-apiofuranosyl-(1"-->2')-O-beta-D-glucopyranoside were isolated. The structural elucidations were based on the analyses of spectroscopic data. Z-Form 4-coumaric acid glycosides were first isolated from plant.

  17. Three new alkaloids and three new phenolic glycosides from Liparis odorata.

    PubMed

    Jiang, Piao; Liu, Hongdong; Xu, Xianghong; Liu, Bo; Zhang, Dongming; Lai, Xuewen; Zhu, Genghua; Xu, Peng; Li, Bin

    2015-12-01

    Three new alkaloids, liparis alkaloid A (1), B (2), C (3), and three new phenolic glycosides, liparis glycoside H (4), I (5), J (6), together with three known phenolic glycosides (7-9) were isolated from the whole plant of Liparis odorata. Their structures were characterized on the basis of extensive 1D-, 2D-NMR and HR-ESI-MS experiments. In addition, compounds 1-3 revealed hypolipidemic effects in the in vitro bioassays, and the ability to inhibit LPS-induced NO production of these isolated phenolic glycosides (4-9) was also evaluated.

  18. Glycosides from marine sponges (Porifera, Demospongiae): structures, taxonomical distribution, biological activities and biological roles.

    PubMed

    Kalinin, Vladimir I; Ivanchina, Natalia V; Krasokhin, Vladimir B; Makarieva, Tatyana N; Stonik, Valentin A

    2012-08-01

    Literature data about glycosides from sponges (Porifera, Demospongiae) are reviewed. Structural diversity, biological activities, taxonomic distribution and biological functions of these natural products are discussed.

  19. Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities and Biological Roles

    PubMed Central

    Kalinin, Vladimir I.; Ivanchina, Natalia V.; Krasokhin, Vladimir B.; Makarieva, Tatyana N.; Stonik, Valentin A.

    2012-01-01

    Literature data about glycosides from sponges (Porifera, Demospongiae) are reviewed. Structural diversity, biological activities, taxonomic distribution and biological functions of these natural products are discussed. PMID:23015769

  20. Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a Diterpene from Azorella and Laretia Species.

    PubMed

    Muñoz, Marcelo A; San-Martín, Aurelio; Joseph-Nathan, Pedro

    2015-08-01

    The absolute configuration of the diterpenoid 9,12-cyclomulin-13-ol (1), a constituent of Azorella and Laretia species, has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations. The obtained normal diterpene absolute configuration confirms that of azorellanol (2), which was determined by single crystal X-ray diffraction.

  1. Boesenberols, Pimarane Diterpenes with TRAIL-Resistance-Overcoming Activity from Boesenbergia pandurata.

    PubMed

    Karmakar, Utpal K; Ishikawa, Naoki; Arai, Midori A; Ahmed, Firoj; Koyano, Takashi; Kowithayakorn, Thaworn; Ishibashi, Masami

    2016-08-26

    TRAIL is a potent and selective inducer of apoptosis in most cancer cells while sparing normal cells, which makes it an attractive target for the development of new cancer therapies. In a screening program on natural resources with the ability to abrogate TRAIL resistance, the bioassay-guided fractionation of Boesenbergia pandurata rhizomes resulted in the isolation of 17 pimarane diterpenes and a monoterpene. Among these, compounds 1-8, named boesenberols A-H, are new pimarane diterpenes. All compounds exhibited TRAIL-resistance-overcoming activity in TRAIL-resistant AGS cells. Subtoxic doses of the major compound 9 sensitized AGS cells to TRAIL-induced apoptosis by up-regulating apoptosis-inducing proteins, such as DR4, DR5, p53, Fas, CHOP, Bak, and cleaved caspases-3, -8, and -9, and down-regulating the levels of cell survival proteins, such as Bcl-2, c-FLIP, and GSK-3β, in TRAIL-resistant AGS cells. Furthermore, compound 9 did not decrease the viability of noncancerous (HEK293) cells at concentrations up to 30 μM. PMID:27508308

  2. Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity.

    PubMed

    Pardo-Vargas, Alonso; Ramos, Freddy A; Cirne-Santos, Claudio Cesar; Stephens, Paulo Roberto; Paixão, Izabel Christina Palmer; Teixeira, Valeria Laneuville; Castellanos, Leonardo

    2014-09-15

    Research on dolabellane diterpenes of brown algae Dictyota spp. has shown that these diterpenoids have strong anti-HIV-1 activity, but there are not data about antiviral activity of dolabellane diterpenes isolated from octocorals, which are antipodes of those isolated from the brown algae. Dolabellanes 13-keto-1(R),11(S)-dolabella-3(E),7(E),12(18)-triene (1) and β-Araneosene (2) were isolated from the Caribbean octocoral Eunicea laciniata, and both showed low anti-HIV-1 activity and low toxicity. Since it was shown that oxygenated dolabellanes from algae have better anti-HIV-1 activity, in this work some derivatives of the main dolabellane of E. laciniata1 were obtained by epoxidation (3), epoxide opening (4), and allylic oxidation (5). The derivatives showed significant improvement in the anti-HIV-1potency (100-fold), being compounds 3 and 5 the most active ones. Their high antiviral activities, along with their low cytotoxicity, make them promissory antiviral compounds; and it is worth noting that the absolute configuration at the ring junction in the dolabellane skeleton does not seem to be determinant in the antiviral potency of these diterpeneoids. PMID:25176328

  3. Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast.

    PubMed

    Ignea, Codruta; Ioannou, Efstathia; Georgantea, Panagiota; Loupassaki, Sofia; Trikka, Fotini A; Kanellis, Angelos K; Makris, Antonios M; Roussis, Vassilios; Kampranis, Sotirios C

    2015-03-01

    Terpenes are a large class of natural products, many of which are used in cosmetics, pharmaceuticals, or biofuels. However, terpene's industrial application is frequently hindered by limited availability of natural sources or low yields of chemical synthesis. In this report, we developed a modular platform based on standardized and exchangeable parts to reproduce and potentially expand the diversity of terpene structures in Saccharomyces cerevisiae. By combining different module-specific parts, we exploited the substrate promiscuity of class I diterpene synthases to produce an array of labdane-type scaffolds. These were subsequently modified by a scaffold decoration module consisting of a mutant library of a promiscuous cytochrome P450 to afford a range of hydroxylated diterpenes. Further P450 protein engineering yielded dedicated and efficient catalysts for specific products. Terpenes produced include precursors of pharmacologically important compounds, molecules that are difficult to obtain from natural sources, or new natural products. The approach described here provides a platform on which additional gene mining, combinatorial biosynthesis, and protein engineering efforts can be integrated to sustainably explore the terpene chemical space.

  4. Structure and Function of Fusicoccadiene Synthase, a Hexameric Bifunctional Diterpene Synthase.

    PubMed

    Chen, Mengbin; Chou, Wayne K W; Toyomasu, Tomonobu; Cane, David E; Christianson, David W

    2016-04-15

    Fusicoccin A is a diterpene glucoside phytotoxin generated by the fungal pathogen Phomopsis amygdali that causes the plant disease constriction canker, first discovered in New Jersey peach orchards in the 1930s. Fusicoccin A is also an emerging new lead in cancer chemotherapy. The hydrocarbon precursor of fusicoccin A is the tricyclic diterpene fusicoccadiene, which is generated by a bifunctional terpenoid synthase. Here, we report X-ray crystal structures of the individual catalytic domains of fusicoccadiene synthase: the C-terminal domain is a chain elongation enzyme that generates geranylgeranyl diphosphate, and the N-terminal domain catalyzes the cyclization of geranylgeranyl diphosphate to form fusicoccadiene. Crystal structures of each domain complexed with bisphosphonate substrate analogues suggest that three metal ions and three positively charged amino acid side chains trigger substrate ionization in each active site. While in vitro incubations reveal that the cyclase domain can utilize farnesyl diphosphate and geranyl diphosphate as surrogate substrates, these shorter isoprenoid diphosphates are mainly converted into acyclic alcohol or hydrocarbon products. Gel filtration chromatography and analytical ultracentrifugation experiments indicate that full-length fusicoccadiene synthase adopts hexameric quaternary structure, and small-angle X-ray scattering data yield a well-defined molecular envelope illustrating a plausible model for hexamer assembly.

  5. The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer's Disease.

    PubMed

    Habtemariam, Solomon

    2016-01-01

    Rosemary (Rosmarinus officinalis L.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents both in vitro and in vivo. The therapeutic potential of these compounds for Alzheimer's disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (Aβ) formation, polymerisation, and pathologies is discussed. PMID:26941822

  6. Four new bioactive lobane diterpenes of the soft coral Lobophytum pauciflorum from Mindoro, Philippines.

    PubMed

    Edrada, R A; Proksch, P; Wray, V; Witte, L; van Ofwegen, L

    1998-03-01

    The marine soft coral Lobophytum pauciflorum collected from Mindoro Island, Philippines, yielded four new lobane diterpene derivatives: the acetate congeners of epoxylobatrienol and lobatrienediol (2 and 7, respectively), a methoxyl congener of lobatetraene (10), and an oxepin congener of lobatrienetriol (11), and six known derivatives (1, 3-6, and 8). The structures of the new compounds were unambiguously established on the basis of NMR spectroscopic (1H, 13C, COSY, 1H-detected direct, and long-range 13C-1H correlations) and mass spectrometric (EIMS) data. All of the compounds were active against the phytopathogenic fungus Cladosporium cucumerinum. Compound 1 was found to be active against the Gram-positive bacteria Bacillus subtilis and the yeast Saccharomyces cerevisiae. The isolated lobane diterpenes were also active in the brine shrimp lethality test. In the latter bioassay, compounds 8 and 10 were the most active congeners with LC50's of 0.64 and 4.18 micrograms/mL, respectively.

  7. The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer's Disease

    PubMed Central

    Habtemariam, Solomon

    2016-01-01

    Rosemary (Rosmarinus officinalis L.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents both in vitro and in vivo. The therapeutic potential of these compounds for Alzheimer's disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (Aβ) formation, polymerisation, and pathologies is discussed. PMID:26941822

  8. Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity.

    PubMed

    Pardo-Vargas, Alonso; Ramos, Freddy A; Cirne-Santos, Claudio Cesar; Stephens, Paulo Roberto; Paixão, Izabel Christina Palmer; Teixeira, Valeria Laneuville; Castellanos, Leonardo

    2014-09-15

    Research on dolabellane diterpenes of brown algae Dictyota spp. has shown that these diterpenoids have strong anti-HIV-1 activity, but there are not data about antiviral activity of dolabellane diterpenes isolated from octocorals, which are antipodes of those isolated from the brown algae. Dolabellanes 13-keto-1(R),11(S)-dolabella-3(E),7(E),12(18)-triene (1) and β-Araneosene (2) were isolated from the Caribbean octocoral Eunicea laciniata, and both showed low anti-HIV-1 activity and low toxicity. Since it was shown that oxygenated dolabellanes from algae have better anti-HIV-1 activity, in this work some derivatives of the main dolabellane of E. laciniata1 were obtained by epoxidation (3), epoxide opening (4), and allylic oxidation (5). The derivatives showed significant improvement in the anti-HIV-1potency (100-fold), being compounds 3 and 5 the most active ones. Their high antiviral activities, along with their low cytotoxicity, make them promissory antiviral compounds; and it is worth noting that the absolute configuration at the ring junction in the dolabellane skeleton does not seem to be determinant in the antiviral potency of these diterpeneoids.

  9. Flavonol glycosides in the petal of Rosa species as chemotaxonomic markers.

    PubMed

    Sarangowa, Ochir; Kanazawa, Tsutomu; Nishizawa, Makoto; Myoda, Takao; Bai, Changxi; Yamagishi, Takashi

    2014-11-01

    Thirteen flavonol glycosides were isolated from the petals of Rosa species belonging to the section Gallicanae, and their structures were identified from their spectroscopic data. These flavonol glycosides, along with two flavonol glycosides isolated from Rosa rugosa, in the petals of 31 Rosa species belonging to sections Gallicanae, Cinnamomeae, Caninae, and Synstylae were quantitatively analyzed by UPLC. The results indicated that the species belonging to these sections could be classified into four types (Type A, B, C and D) based on the pattern of flavonol glycoside contents, whereas the R. rugosa flavonol glycosides were detected only in section Cinnamomeae. A principal components analysis (PCA) calculated from the 15 flavonol glycosides contained in these samples supported the presence of four types. The distribution of the species in Type D (a group of Cinnamomeae) was shown to reflect close interrelationships, but species in Type B (one group of Gallicanae) could be subdivided into two groups, one of which contained species in section Synstylae. Moreover, the flavonol glycosides were grouped by sugar moieties: a disaccharide composed of two hexoses (S1), a hexose (S2), including a hexose with galloyl group, a pentose (S3), and a disaccharide composed of a hexose and a pentose (S4). The ratios of the amounts of S1-S4 to total flavonol glycoside content indicated that differences among the four sections were more distinctive than the amounts of the 15 flavonol glycosides. The 31 samples were divided into Type B, composed of one type of Gallicanae and Synstylae, Type A+C, composed of another type of Gallicanae and Caninae, and Type D, composed of Cinnamomeae. The R. rugosa flavonol glycosides were shown to be important chemotaxonomic markers for the classification of species in Cinnamomeae, and this method of using flavonol glycosides as chemotaxonomic markers could be useful for the identification of Rosa species belonging to sections Gallicanae, Cinnamomeae

  10. Active Site and Laminarin Binding in Glycoside Hydrolase Family 55*

    PubMed Central

    Bianchetti, Christopher M.; Takasuka, Taichi E.; Deutsch, Sam; Udell, Hannah S.; Yik, Eric J.; Bergeman, Lai F.; Fox, Brian G.

    2015-01-01

    The Carbohydrate Active Enzyme (CAZy) database indicates that glycoside hydrolase family 55 (GH55) contains both endo- and exo-β-1,3-glucanases. The founding structure in the GH55 is PcLam55A from the white rot fungus Phanerochaete chrysosporium (Ishida, T., Fushinobu, S., Kawai, R., Kitaoka, M., Igarashi, K., and Samejima, M. (2009) Crystal structure of glycoside hydrolase family 55 β-1,3-glucanase from the basidiomycete Phanerochaete chrysosporium. J. Biol. Chem. 284, 10100–10109). Here, we present high resolution crystal structures of bacterial SacteLam55A from the highly cellulolytic Streptomyces sp. SirexAA-E with bound substrates and product. These structures, along with mutagenesis and kinetic studies, implicate Glu-502 as the catalytic acid (as proposed earlier for Glu-663 in PcLam55A) and a proton relay network of four residues in activating water as the nucleophile. Further, a set of conserved aromatic residues that define the active site apparently enforce an exo-glucanase reactivity as demonstrated by exhaustive hydrolysis reactions with purified laminarioligosaccharides. Two additional aromatic residues that line the substrate-binding channel show substrate-dependent conformational flexibility that may promote processive reactivity of the bound oligosaccharide in the bacterial enzymes. Gene synthesis carried out on ∼30% of the GH55 family gave 34 active enzymes (19% functional coverage of the nonredundant members of GH55). These active enzymes reacted with only laminarin from a panel of 10 different soluble and insoluble polysaccharides and displayed a broad range of specific activities and optima for pH and temperature. Application of this experimental method provides a new, systematic way to annotate glycoside hydrolase phylogenetic space for functional properties. PMID:25752603

  11. Bioactive Iridoid Glycosides from the Whole Plants of Rehmannia chingii.

    PubMed

    Liu, Yan-Fei; Shi, Guo-Ru; Wang, Xin; Zhang, Chun-Lei; Wang, Yan; Chen, Ruo-Yun; Yu, De-Quan

    2016-02-26

    Nine new iridoid glycosides, rehmachingiiosides A-I (1-9), together with 16 known analogues, were isolated from the whole plants of Rehmannia chingii. The structures of compounds 1-9 were elucidated on the basis of spectroscopic data analysis and from chemical evidence. Furthermore, in two vitro assays, compounds 5 and 10 showed an inhibitory effect on LPS-induced NO production with IC50 values of 2.5 and 7.3 μM, and compounds 4, 6, and 10-12 (when evaluated at 10 μM) exhibited evidence of hepatoprotective effects against APAP-induced HepG2 cell damage.

  12. Phenylpropanoid Glycosides from the Leaves of Ananas comosus.

    PubMed

    Chen, Wen-Hao; Huang, Xiao-Juan; Shu, Huo-Ming; Hui, Yang; Guo, Fei-Yan; Song, Xiao-Ping; Ji, Ming-Hui; Chen, Guang-Ying

    2015-12-01

    Two new phenylpropanoid glycosides, named β-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl β-D-6'-O-acetylglucopyranoside (1) and β-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl α-D-glucopyranoside (2), along with two known analogues (3-4) and four glycerides (5-8), were isolated from the EtOAc extract of the leaves of Ananas comosus. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses, as well as HR-ESI-MS experiments. Compounds 1-4 showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli.

  13. Three New Cytotoxic Polyhydroxysteroidal Glycosides from Starfish Craspidaster hesperus

    PubMed Central

    Kang, Jun-Xia; Kang, Yong-Feng; Han, Hua

    2016-01-01

    Three new polyhydroxysteroidal glycosides, hesperuside A (1), B (2), and C (3), as well as a known novaeguinoside A (4), were isolated from the ethanol extract of starfish Craspidaster hesperus collected from the South China Sea. Their structures were elucidated by extensive spectroscopic methods and chemical evidence. The compounds 1–3 present unprecedented carbohydrate chain 3-O-methyl-β-d-galactopyranose, which differ from each other in the side chains. These compounds exhibited cytotoxicity against human tumor cells BEL-7402, MOLT-4, and A-549 in vitro. PMID:27775561

  14. Two new glycosides from the fruits of Morinda citrifolia L.

    PubMed

    Hu, Ming-Xu; Zhang, Hong-Cai; Wang, Yu; Liu, Shu-Min; Liu, Li

    2012-01-01

    To study the chemical constituents of the fruits of noni (Morinda citrifolia L.), and find novel compounds, an n-butanol extract of the ethanol soluble fraction was subjected to repeated silica gel and ODS column chromatography and HPLC. Two new glycosides were isolated and their structures elucidated by NMR and HRFAB-MS spectrometry as (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-β-D-glucopyranosyl-β-D-glucopyranoside and amyl-1-O-β-D-apio-furanosyl-1,6-O-β-D-glucopyranoside, respectively.

  15. Two new flavonoid glycosides from Semen Ziziphi Spinosae.

    PubMed

    Zhang, Lin; Xu, Zhi-Lin; Wu, Chun-Fu; Yang, Jing-Yu; Kano, Yoshihiro; Yuan, Dan

    2012-01-01

    Two novel flavonoid glycosides, 6"'-dihydrophaseoylspinosin (1) and 6″,6"'-diferuloylspinosin (2), were isolated from the MeOH extract of Semen Ziziphi Spinosae, together with six known flavonoids, isovitexin-2″-O-β-(6-O-E-feruloyl)glucopyranoside (3), spinosin (4), isospinosin (5), 6"'-feruloylspinosin (6), swertisin (7), and isovitexin-2″-O-β-d-glucopyranoside (8). The structures of 1 and 2 were elucidated by spectroscopic methods including UV, IR, ESI-TOF-MS, 1D NMR, and 2D NMR experiments. PMID:22296152

  16. Pentasaccharide resin glycosides from Ipomoea cairica and their cytotoxic activities.

    PubMed

    Yu, Bangwei; Luo, Jianguang; Wang, Junsong; Zhang, Dongming; Yu, Shishan; Kong, Lingyi

    2013-11-01

    Six partially acylated pentasaccharide resin glycosides, cairicosides A-F, were isolated from the aerial parts of Ipomoea cairica. These compounds were characterized as a group of macrolactones of simonic acid A, partially acylated with different organic acids. The lactonization site of 11S-hydroxyhexadecanoic acid (jalapinolic acid) was bound to the second saccharide moiety at C-3 in cairicosides A-E, while at C-2 in cairicoside F. Structures were established by spectroscopic and chemical methods. Compounds cairicosides A-E exhibited moderate cytotoxicity against a small panel of human tumor cell lines with IC50 values in the range of 4.28-14.31μM.

  17. Calysolins I-IV, resin glycosides from Calystegia soldanella.

    PubMed

    Takigawa, Ayako; Muto, Haruka; Kabata, Kiyotaka; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro; Ono, Masateru

    2011-11-28

    Four new resin glycosides having intramolecular cyclic ester structures (jalapins), named calysolins I-IV (1-4), were isolated from the methanol extract of leaves, stems, and roots of Calystegia soldanella , along with one known jalapin (5) derivative. The structures of 1-4 were determined on the basis of spectroscopic data and chemical evidence. They fall into two types, one having a 22-membered ring (1 and 4) and the other with a 27-membered ring (2 and 3). The sugar moieties of 1-4 were partially acylated by some organic acids. Compound 4 is the first example of a hexaglycoside of jalapin.

  18. Flavonoid Glycosides from Arnica montana and Arnica chamissonis.

    PubMed

    Merfort, I; Wendisch, D

    1987-10-01

    Five flavonoid glycosides were identified from flowers of ARNICA MONTANA, four from A. CHAMISSONIS subsp. FOLIOSA var. INCANA. The structures were established on the basis of total acid hydrolysis and spectral data (UV, (1)H-NMR, (13)C-NMR, MS) as hispidulin 7- O-beta-glucoside, isorhamnetin 3- O-beta-glucoside, 3- O-beta- D-glucopyranosides of spinacetin, 6-methoxykaempferol and patuletin and querectin 3- O-(6''- O-acetyl)-beta- D-glucopyranoside. The latter compound can serve as distinctive marker between these two ARNICA species. The (1)H-NMR spectra in CD (3)OD are discussed.

  19. FLAVONOL GLYCOSIDES FROM THE NATIVE AMERICAN PLANT GAURA LONGIFLORA

    PubMed Central

    Xu, Wen-Hui; Jacob, Melissa R.; Agarwal, Ameeta K.; Clark, Alice M.; Liang, Zong-Suo; Li, Xing-Cong

    2013-01-01

    Phytochemical investigation of the native American plant Gaura longiflora led to the isolation of three new and eight known flavonol glycosides. The structures of the new compounds were established primarily by spectroscopic data as quercetin 3-O-(2″-O-α-l-rhamnopyranosyl-6″-O-E-p-coumaroyl)-β-D-glucopyranoside (1), kaempferol 3-O-(2″-O-α-l-rhamnopyranosyl-6″-O-E-p-coumaroyl)-β-d-gluco-pyranoside (2) and quercetin 3-O-(2″-O-α-l-rhamnopyranosyl-6″-O-Z-p-coumaroyl)-β-D-glucopyrano-side (3). PMID:24371369

  20. A novel sulfated holostane glycoside from sea cucumber Holothuria leucospilota.

    PubMed

    Han, Hua; Zhang, Wen; Yi, Yang-Hua; Liu, Bao-Shu; Pan, Min-Xiang; Wang, Xiao-Hua

    2010-07-01

    A new sulfated holostane glycoside, leucospilotaside B (1), together with the two related structurally known compounds holothurin B(2) (2) and holothurin B (3), was isolated from sea cucumber Holothuria leucospilota collected from the South China Sea. The structure of 1 was elucidated by spectral analysis (1H-, 13C-, and 2D-NMR, ESI-MS, and HR-ESI-MS) and chemical methods. The compounds 1-3 possess the same disaccharide moiety, but were different in the side chains of the triterpene aglycone. Compound 1 showed significant cytotoxicities against four human tumor cell lines, HL-60, MOLT-4, A-549, and BEL-7402.

  1. The Primary Diterpene Synthase Products of Picea abies Levopimaradiene/Abietadiene Synthase (PaLAS) Are Epimers of a Thermally Unstable Diterpenol*

    PubMed Central

    Keeling, Christopher I.; Madilao, Lina L.; Zerbe, Philipp; Dullat, Harpreet K.; Bohlmann, Jörg

    2011-01-01

    The levopimaradiene/abietadiene synthase from Norway spruce (Picea abies; PaLAS) has previously been reported to produce a mixture of four diterpene hydrocarbons when incubated with geranylgeranyl diphosphate as the substrate: levopimaradiene, abietadiene, neoabietadiene, and palustradiene. However, variability in the assay products observed by GC-MS of this and orthologous conifer diterpene synthases over the past 15 years suggested that these diterpenes may not be the initial enzyme assay products but are rather the products of dehydration of an unstable alcohol. We have identified epimers of the thermally unstable allylic tertiary alcohol 13-hydroxy-8(14)-abietene as the products of PaLAS. The identification of these compounds, not previously described in conifers, as the initial products of PaLAS has considerable implications for our understanding of the complexity of the biosynthetic pathway of the structurally diverse diterpene resin acids of conifer defense. PMID:21518766

  2. Two new nor-triterpene glycosides from peruvian "Uña de Gato" (Uncaria tomentosa).

    PubMed

    Kitajima, Mariko; Hashimoto, Ken-Ichiro; Yokoya, Masashi; Takayama, Hiromitsu; Sandoval, Manuel; Aimi, Norio

    2003-02-01

    Two new 27-nor-triterpene glycosides, tomentosides A (1) and B (2), were isolated from Peruvian "Uña de Gato" (cat's claw, plant of origin: Uncaria tomentosa), a traditional herbal medicine in Peru. Their structures were determined by spectroscopic analysis and chemical interconversions. This is the first report of naturally occurring pyroquinovic acid glycosides.

  3. Two new nor-triterpene glycosides from peruvian "Uña de Gato" (Uncaria tomentosa).

    PubMed

    Kitajima, Mariko; Hashimoto, Ken-Ichiro; Yokoya, Masashi; Takayama, Hiromitsu; Sandoval, Manuel; Aimi, Norio

    2003-02-01

    Two new 27-nor-triterpene glycosides, tomentosides A (1) and B (2), were isolated from Peruvian "Uña de Gato" (cat's claw, plant of origin: Uncaria tomentosa), a traditional herbal medicine in Peru. Their structures were determined by spectroscopic analysis and chemical interconversions. This is the first report of naturally occurring pyroquinovic acid glycosides. PMID:12608878

  4. Species and ionic influences on the accumulation of digitalis glycosides by isolated perfused hearts

    PubMed Central

    Dutta, S.; Marks, B. H.

    1972-01-01

    1. The ability of isolated perfused guinea-pig (digitalis-sensitive species) and rat (digitalis-resistant species) hearts to accumulate radio-labelled digitalis glycosides was studied in relation to the ionic composition of the perfusion medium. 2. It was observed that in both species much less digoxin was accumulated than was digitoxin or proscillaridin. 3. The accumulation of digoxin was markedly inhibited in a low sodium or in high potassium medium. These effects were similar, but relatively less marked, with digitoxin and proscillaridin. Calcium and magnesium removal had relatively smaller effects on the accumulation of both polar and non-polar glycosides. 4. The low accumulation of all digitaloids by the rat heart in comparison to the guinea-pig heart may be due to the formation of unstable complexes between the cellular membranes in the rat heart and the various digitaloids used in this study. Although digitaloids have a reduced affinity for rat hearts and rat heart membranes in comparison to guinea-pigs, the order of the accumulation of different glycosides in both species is the same, i.e. much less with polar glycosides than with non-polar glycosides. 5. It was concluded that non-polar glycosides such as digitoxin and proscillaridin demonstrate the same ion-dependent accumulation mechanism as do the more polar glycosides such as digoxin and ouabain. In addition, the non-polar glycosides possess high capacity for ion-independent binding presumably due to lipophilic interactions with membranes. PMID:4656603

  5. Bebrycoside, a new steroidal glycoside from the Chinese gorgonian coral Bebryce indica.

    PubMed

    Yang, Jin; Qi, Shu-Hua; Zhang, Si; Xiao, Zhi-Hui; Li, Qing-Xin

    2007-02-01

    A new steroidal glycoside, bebrycoside (1), was isolated from the South China Sea gorgonian coral Bebryce indica. The structure of 1 was established by extensive spectroscopic analysis, including 1D and 2D NMR data. This was the first time that the steroidal glycoside was isolated from the genus of Bebryce.

  6. Complete assignments of 1H and 13C NMR data for 10 phenylethanoid glycosides.

    PubMed

    Wu, Jun; Huang, Jianshe; Xiao, Qiang; Zhang, Si; Xiao, Zhihui; Li, Qingxin; Long, Lijuan; Huang, Liangmin

    2004-07-01

    Ten phenylethanoid glycosides, including two new ones, isolated from the aerial parts of the mangrove plant Acanthus ilicifolius were identified. The first complete assignments of the 1H and 13C NMR chemical shifts for these glycosides were achieved by means of 2D NMR techniques, including 1H-1H COSY, TOCSY, HSQC and HMBC spectra.

  7. Host plant influences on iridoid glycoside sequestration of generalist and specialist caterpillars.

    PubMed

    Lampert, Evan C; Bowers, M Deane

    2010-10-01

    The effect of diet on sequestration of iridoid glycosides was examined in larvae of three lepidopteran species. Larvae were reared upon Plantago major, or P. lanceolata, or switched from one to the other in the penultimate instar. Junonia coenia is a specialist on iridoid glycoside-producing plants, whereas the arctiids, Spilosoma congrua and Estigmene acrea, are both polyphagous and eat iridoid-producing plants. All species sequestered iridoids. The specialist J. coenia sequestered from three to seven times the amounts sequestered by the two generalist species. Junonia coenia iridoid glycoside content depended on diet, and they sequestered from 5 to 15% dry weight iridoid glycosides. Estigmene acrea iridoid glycoside sequestration was relatively low, around 2% dry weight and did not vary with diet. Spilosoma congrua sequestration varied with diet and ranged from approximately 3 to 6% dry weight. PMID:20809144

  8. Merremins A-G, resin glycosides from Merremia hederacea with multidrug resistance reversal activity.

    PubMed

    Wang, Wen-qiong; Song, Wei-bin; Lan, Xiao-jing; Huang, Min; Xuan, Li-jiang

    2014-10-24

    Five new pentasaccharide resin glycosides, named merremins A-E (1-5), two new pentasaccharide resin glycoside methyl esters, named merremins F and G (6, 7), and four known resin glycosides, murucoidin IV, murucoidin V, stoloniferin IV, and murucoidin XVII, were obtained from the aerial parts of Merremia hederacea. This is the first report of resin glycosides obtained from M. hederacea. In addition, the new compounds can be divided into three types: those possessing an 18-membered ring (1-4), compound 5 with a 20-membered ring, and those with an acyclic core (6, 7). Furthermore, the different types of resin glycosides were evaluated for their multidrug resistance reversal activities. Compounds 1, 5, 6, and murucoidin V were noncytotoxic and enhanced the cytotoxicity of vinblastine by 2.3-142.5-fold at 25 μM. Compound 5 and murucoidin V, with 20-membered rings, were more active than compound 1, with an 18-membered ring.

  9. Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L.

    PubMed

    Beck, Sebastian; Stengel, Julia

    2016-10-01

    Ginkgo biloba L. is known to be rich in flavonoids and flavonoid glycosides. However, the distribution within specific plant organs (e.g. within leaves) is not known. By using HPLC-MS and MS/MS we have identified a number of previously known G. biloba flavonoid glycosides and biflavonoids from leaves. Namely, kaempferol, quercetin, isorhamnetin, myricetin, laricitrin/mearnsetin and apigenin glycosides were identified. Furthermore, biflavonoids like ginkgetin/isoginkgetin were also detected. The application of MALDI mass spectrometric imaging, enabled the compilation of concentration profiles of flavonoid glycosides and biflavonoids in G. biloba L. leaves. Both, flavonoid glycosides and biflavonoids show a distinct distribution in leaf thin sections of G. biloba L. PMID:27233155

  10. Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L.

    PubMed

    Beck, Sebastian; Stengel, Julia

    2016-10-01

    Ginkgo biloba L. is known to be rich in flavonoids and flavonoid glycosides. However, the distribution within specific plant organs (e.g. within leaves) is not known. By using HPLC-MS and MS/MS we have identified a number of previously known G. biloba flavonoid glycosides and biflavonoids from leaves. Namely, kaempferol, quercetin, isorhamnetin, myricetin, laricitrin/mearnsetin and apigenin glycosides were identified. Furthermore, biflavonoids like ginkgetin/isoginkgetin were also detected. The application of MALDI mass spectrometric imaging, enabled the compilation of concentration profiles of flavonoid glycosides and biflavonoids in G. biloba L. leaves. Both, flavonoid glycosides and biflavonoids show a distinct distribution in leaf thin sections of G. biloba L.

  11. Quantitation of sweet steviol glycosides by means of a HILIC-MS/MS-SIDA approach.

    PubMed

    Well, Caroline; Frank, Oliver; Hofmann, Thomas

    2013-11-27

    Meeting the rising consumer demand for natural food ingredients, steviol glycosides, the sweet principle of Stevia rebaudiana Bertoni (Bertoni), have recently been approved as food additives in the European Union. As regulatory constraints require sensitive methods to analyze the sweet-tasting steviol glycosides in foods and beverages, a HILIC-MS/MS method was developed enabling the accurate and reliable quantitation of the major steviol glycosides stevioside, rebaudiosides A-F, steviolbioside, rubusoside, and dulcoside A by using the corresponding deuterated 16,17-dihydrosteviol glycosides as suitable internal standards. This quantitation not only enables the analysis of the individual steviol glycosides in foods and beverages but also can support the optimization of breeding and postharvest downstream processing of Stevia plants to produce preferentially sweet and least bitter tasting Stevia extracts.

  12. New Glycosides and Trypanocidal Metabolites from Vangueria edulis

    PubMed Central

    Mohamed, Shaymaa M. M.; Elokely, Khaled M.; Bachkeet, Enaam Y.; Bayoumi, Soad A. L.; Carnevale, Vincenzo; Klein, Michael L.; Cutler, Stephen J.

    2016-01-01

    A new iridoid glucoside, 10-methoxy apodanthoside (1), and a new monoterpene glycoside, (3S,6S)-cis linalool-3,7-oxide O-β-D-glucopyranosyl-(1″→5′)-β-D-xylofuranoside (2), were isolated from V. edulis (Rubiaceae), along with eighteen known compounds (3–20), including monoterpenes, iridoid glycosides, and a lignin, which were encountered for the first time in the genus Vangueria,. The structural elucidation of the isolates was based on the analysis of spectroscopic (1D and 2D NMR) and HR-ESI-MS data. Detailed stereochemical studies of 1 and related iridoid glucosides (compounds 3, 4 and 8) were made by matching the calculated ECD peaks with the experimental ones. All isolates were tested for their antiprotozoal, antifungal, and antiplasmodial activities. Compounds 9, 15 and 16 showed good trypanocidal activities against Trypanosoma brucei brucei with IC50 values of 8.18, 9.02 and 7.80 μg/mL, respectively and IC90 values of >10, >10 and 9.76 μg/mL, respectively. Compound 16 showed a moderate activity against Candida glabrata with an IC50 value of 8.66 μg/mL. Compound 20 showed a weak antiplasmodial activity against chloroquine-sensitive (D6) and resistant (W2) Plasmodium falciparum with IC50 values of 3.29 (SI, >1.4) and 4.53 (SI, >1) μg/mL, respectively. PMID:26749819

  13. Separation of phenylpropanoid glycosides from a Chinese herb by HSCCC.

    PubMed

    Chen, Chen; Zhao, Xiao-Hui; Yue, Hui-Lan; Li, Yu-Lin; Chen, Tao

    2014-01-01

    An effective high-speed counter-current chromatography method was established for the preparative isolation and purification of two phenylpropanoid glycosides from the Tibetan medicinal plant Pedicularis longiflora Rudolph. var. tubiformis (Klotz). Tsoong. With a two-phase solvent system composed of chloroform-n-butanol-methanol-water (4:3:4:5, v/v), 40 mg of an extract of Pedicularis longiflora Rudolph. var. tubiformis (Klotz). Tsoong was separated to yield 20 mg of verbascoside and 18 mg of isoacteoside, with purity values of 97 and 98%, respectively. The chemical structures of these two components were identified by proton and carbon nuclear magnetic resonance. In addition, the antioxidant activity of the two phenylpropanoid glycosides was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH)-high-performance liquid chromatography, and the results showed that the two components exhibited strong antioxidant DPPH radical scavenging activity, with IC50 values of 15.6 and 18.9 µg/mL, respectively.

  14. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    PubMed Central

    Rizzo, Benedetta; Zambonin, Laura; Leoncini, Emanuela; Vieceli Dalla Sega, Francesco; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

    2013-01-01

    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. PMID:24327825

  15. Anti HIV-1 flavonoid glycosides from Ochna integerrima.

    PubMed

    Reutrakul, Vichai; Ningnuek, Niwat; Pohmakotr, Manat; Yoosook, Chalobon; Napaswad, Chanita; Kasisit, Jitra; Santisuk, Thawatchai; Tuchinda, Patoomratana

    2007-06-01

    Bioassay-guided fractionation of the anti-HIV-1 active EtOAc extract from leaves and twigs of Ochna integerrima led to the isolation of five new flavonoid glycosides 1 - 5, five known flavonoids 6 - 10, and two known flavonoid glycosides 11 and 12. Structures were determined based on spectroscopic analyses. 6- gamma, gamma-Dimethylallyldihydrokaempferol 7- O- beta-D-glucoside (1), 6-gamma, gamma-dimethylallylquercetin 7- O- beta- D-glucoside (3), 6-(3-hydroxy-3-methylbutyl)taxifolin 7- O- beta-D-glucoside (4), 6-(3-hydroxy-3-methylbutyl)quercetin 7- O-beta-D-glucoside (5), and 6-gamma, gamma-dimethylallyltaxifolin 7-O-beta-D-glucoside (11) showed anti-HIV-1 activities in the syncytium assay using the (Delta Tat/rev)MC99 virus and the 1A2 cell line system with EC(50) values ranging from 14.0 - 102.4 microg/mL. Furthermore, ochnaflavone 7''-O-methyl ether (7) and 2'', 3''-dihydroochnaflavone 7''-O-methyl ether (8) were very active; they exerted activities in the syncytium assay with EC(50) values of 2.0 and 0.9 microg/mL, respectively, and likewise inhibited HIV-1 reverse transcriptase (RT) with IC(50) values of 2.0 and 2.4 microg/mL, respectively.

  16. A new glycosidic flavonoid from Jwarhar mahakashay (antipyretic) Ayurvedic preparation

    PubMed Central

    Gupta, Mradu; Shaw, B. P.; Mukherjee, A.

    2010-01-01

    The aqueous extract of Jwarhar mahakashay Ayurvedic preparation (from the roots of Hemidesmus indicus R. Br., Rubia cordifolia L., Cissampelos pareira L.; fruits of Terminalia chebula Retz., Emblica officinalis Gaertn., Terminalia bellirica Roxb., Vitis vinifera L., Grewia asiatica L., Salvadora persica L. and granules of Saccharum officinarum L.) has been used as a traditional antipyretic. Experimental studies confirmed its antipyretic–analgesic effect with very low ulcerogenicity and toxicity. Flavonoids, glycosides and tannins were later found to be present in the extract. Detailed chemical investigations were undertaken after hydrolysis of extract using spectroscopic and chromatography methods to determine its active chemical constituent. UV-Visible spectroscopy showed absorbance maxima at 220 and 276 nm, while fourier transform infra-red investigations indicated an end carboxylic O–H structure at 2940 cm−1 suggesting the presence of glycoside-linked flavonoids. Thin layer chromatography and high performance liquid chromatography also confirmed the possibility of at least one major and two minor compounds in this abstract. Detailed examination using gas chromatography-mass spectrometry led to the identification of the principal component as 2-(1-oxopropyl)-benzoic acid, which is quite similar to the active compound found in the standard drug Aspirin (2-acetyl-oxybenzoic acid). PMID:20814525

  17. Cycloartane and oleanane-type glycosides from Astragalus pennatulus.

    PubMed

    Un, Rabia; Horo, Ibrahim; Masullo, Milena; Falco, Antonia; Senol, Serdar G; Piacente, Sonia; Alankuş-Çalıskan, Özgen

    2016-03-01

    Four new cycloartane and one new oleanane-type glycosides were isolated from Astragalus pennatulus along with five known cycloartane-type glycosides. The structures of the new compounds were established as 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-3β,6α,16β-trihydroxy-24-oxo-20(R),25-epoxycycloartane (1), 3-O-[β-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl]-3β,16β,24α-trihydroxy-20(R),25-epoxycycloartane (2), 3-O-[β-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl]-3β,16β,25-trihydroxy-20(R),24(S)-epoxycycloartane (3), 3,25-di-O-β-D-glucopyranosyl-6-O-β-D-xylopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (4), 29-O-α-L-rhamnopyranosyl-abrisapogenol B (5) by 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. The aglycone of compound 1, 3β,6α,16β-trihydroxy-24-oxo-20(R),25-epoxycycloartane, is reported for the first time. The cytotoxic activity of the isolated compounds was evaluated against three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma) and DeFew (human B lymphoma) cells. None of the tested compounds caused a significant reduction of the cell number. PMID:26804373

  18. Recovering glycoside hydrolase genes from active tundra cellulolytic bacteria.

    PubMed

    Pinnell, Lee J; Dunford, Eric; Ronan, Patrick; Hausner, Martina; Neufeld, Josh D

    2014-07-01

    Bacteria responsible for cellulose hydrolysis in situ are poorly understood, largely because of the relatively recent development of cultivation-independent methods for their detection and characterization. This study combined DNA stable-isotope probing (DNA-SIP) and metagenomics for identifying active bacterial communities that assimilated carbon from glucose and cellulose in Arctic tundra microcosms. Following DNA-SIP, bacterial fingerprint analysis of gradient fractions confirmed isotopic enrichment. Sequenced fingerprint bands and clone library analysis of 16S rRNA genes identified active bacterial taxa associated with cellulose-associated labelled DNA, including Bacteroidetes (Sphingobacteriales), Betaproteobacteria (Burkholderiales), Alphaproteobacteria (Caulobacteraceae), and Chloroflexi (Anaerolineaceae). We also compared glycoside hydrolase metagenomic profiles from bulk soil and heavy DNA recovered from DNA-SIP incubations. Active populations consuming [(13)C]glucose and [(13)C]cellulose were distinct, based on ordinations of light and heavy DNA. Metagenomic analysis demonstrated a ∼3-fold increase in the relative abundance of glycoside hydrolases in DNA-SIP libraries over bulk-soil libraries. The data also indicate that multiple displacement amplification introduced bias into the resulting metagenomic analysis. This research identified DNA-SIP incubation conditions for glucose and cellulose that were suitable for Arctic tundra soil and confirmed that DNA-SIP enrichment can increase target gene frequencies in metagenomic libraries.

  19. Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities.

    PubMed

    Böttcher, Stephan; Thiem, Joachim

    2015-01-01

    Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zemplén. PMID:26068577

  20. Tissue factor inhibitory sesquiterpene glycoside from Eriobotrya japonica.

    PubMed

    Lee, Ming Hong; Son, Yeon Kyoung; Han, Yong Nam

    2004-06-01

    Tissue factor (TF, tissue thromboplastin) is a membrane bound glycoprotein, which accelerates the blood clotting, activating both the intrinsic and the extrinsic pathways to serve as a cofactor for activated factor VII (VIIa). The TF-factor VIIa complex (TF/VIIa) proteolytically activates factors IX and X, which leads to the generation of thrombin and fibrin clots. In order to isolate TF inhibitors, by means of a bioassay-directed chromatographic separation technique, from the leaves of Eriobotrya japonica Lindley (Rosaceae), a known sesquiterpene glycoside (2) and ferulic acid (3) were isolated as inhibitors that were evaluated using a single-clotting assay method for determining TF activity. Another sesquiterpene glycoside (1) was also isolated but was inactive in the assay system. Compound 3 was yielded by alkaline hydrolysis of compound 2. The structures of compounds 1, 2, and 3 were identified by means of spectral analysis as 3-O-alpha-L-rhamnopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranosyl nerolidol (1), 3-O-alpha-L-rhamnopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-(4-trans-feruloyl)-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranosyl nerolidol (2) and ferulic acid (3), respectively. Compounds 2 and 3 inhibited 50% of the TF activity at concentrations of 2 and 369 microM/TF units, respectively.

  1. Cycloartane and oleanane-type glycosides from Astragalus pennatulus.

    PubMed

    Un, Rabia; Horo, Ibrahim; Masullo, Milena; Falco, Antonia; Senol, Serdar G; Piacente, Sonia; Alankuş-Çalıskan, Özgen

    2016-03-01

    Four new cycloartane and one new oleanane-type glycosides were isolated from Astragalus pennatulus along with five known cycloartane-type glycosides. The structures of the new compounds were established as 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-3β,6α,16β-trihydroxy-24-oxo-20(R),25-epoxycycloartane (1), 3-O-[β-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl]-3β,16β,24α-trihydroxy-20(R),25-epoxycycloartane (2), 3-O-[β-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl]-3β,16β,25-trihydroxy-20(R),24(S)-epoxycycloartane (3), 3,25-di-O-β-D-glucopyranosyl-6-O-β-D-xylopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (4), 29-O-α-L-rhamnopyranosyl-abrisapogenol B (5) by 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. The aglycone of compound 1, 3β,6α,16β-trihydroxy-24-oxo-20(R),25-epoxycycloartane, is reported for the first time. The cytotoxic activity of the isolated compounds was evaluated against three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma) and DeFew (human B lymphoma) cells. None of the tested compounds caused a significant reduction of the cell number.

  2. Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Rasoanaivo, Philippe; Guéritte, Françoise; Litaudon, Marc

    2012-04-27

    In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM). PMID:22439591

  3. Identification of UV-Induced Diterpenes Including a New Diterpene Phytoalexin, Phytocassane F, from Rice Leaves by Complementary GC/MS and LC/MS Approaches.

    PubMed

    Horie, Kiyotaka; Inoue, Yasuno; Sakai, Miki; Yao, Qun; Tanimoto, Yosuke; Koga, Jinichiro; Toshima, Hiroaki; Hasegawa, Morifumi

    2015-04-29

    Rice phytoalexins are regarded as one of the most important weapons against pathogenic microorganisms. We attempted to identify novel phytoalexins and their derivatives using GC/MS and LC/MS analyses. Diterpene derivatives, 9β-pimara-7,15-diene-3β,6β,19-triol, 1, stemar-13-en-2α-ol, 2, and 1α,2α-dihydroxy-ent-12,15-cassadiene-3,11-dione, 3, were isolated from UV-irradiated rice leaves by chromatographic methods. These structures were confirmed by 1D- and 2D-NMR and MS analyses. Interestingly, all three compounds were accumulated following an infection by the rice blast pathogen Magnaporthe oryzae. Compounds 1 and 2 exhibited weak antifungal activity and may be the biosynthetic intermediates of rice phytoalexins momilactones and oryzalexin S, respectively. Compound 3 exhibited relatively high inhibitory activity against the fungal mycelial growth of M. oryzae to the same extent as the known phytoalexin phytocassane A. We conclude that 3 is a member of the cassane-type phytoalexin family and propose the name phytocassane F.

  4. Inhibition of human neutrophil elastase by labdane diterpenes from the fruiting bodies of Ramaria formosa.

    PubMed

    Lee, Ik-Soo; Kim, Kwan-Chul; Yoo, Ick-Dong; Ha, Byung-Jo

    2015-01-01

    Two new labdane diterpenes (1 and 2) were isolated from the fruiting bodies of Ramaria formosa. The structures of these compounds were established by extensive spectroscopic studies and chemical evidence. The inhibitory activity of compounds 1 and 2 against human neutrophil elastase (HNE) was evaluated in vitro. Compounds 1 and 2 inhibited HNE activity moderately. The IC50 values for compounds 1 and 2 were 36.4 ± 1.2 and 40.8 ± 1.5 μM, respectively; the IC50 value for the positive control, EGCG, was 12.5 ± 0.8 μM. In addition, the mechanism by which 2 inhibited HNE was a mixed-type noncompetitive inhibition, with a Ki of 41.5 ± 1.8 μM.

  5. The synthesis and antibacterial activity of pyrazole-fused tricyclic diterpene derivatives.

    PubMed

    Yu, Li-Gang; Ni, Teng-Feng; Gao, Wei; He, Yuan; Wang, Ying-Ying; Cui, Hai-Wei; Yang, Cai-Guang; Qiu, Wen-Wei

    2015-01-27

    The diterpenoid compound 5 was identified as an antibacterial lead in our screening of small synthetic natural product-like (NPL) library. A series of novel diterpene derivatives were synthesized and investigated for their activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Among the compounds tested, 42 and 43 showed highest activity with a MIC of 1 μg/mL against strain Newman, 45 and 52 showed the most potent activity with MIC values of 0.71-3.12 μg/mL against five multidrug-resistant S. aureus. All high-antimicrobial active compounds showed no obvious toxicity to human fibroblast (HAF) cells at the MIC concentration.

  6. Antifungal Diterpene Alkaloids from the Caribbean Sponge Agelas citrina: Unified Configurational Assignments of Agelasidines and Agelasines

    PubMed Central

    Stout, E. Paige; Yu, Lily C.

    2013-01-01

    Three new diterpene alkaloids – the hypotaurocyamines, (−)-agelasidines E and F (5–6), and the adeninium salt, agelasine N (9) – were isolated from the Caribbean sponge Agelas citrina along with six known natural products agelasines B–E (7, 10–12), 2-oxo-agelasine B (8), and (−)-agelasidine C (3). The chemical structures of 5, 6 and 9 were elucidated by analysis of NMR spectra and mass spectrometry. This represents the first report of natural products from the sponge A. citrina. Unified assignment of absolute configurations of the new compounds and known compounds were achieved by chemical correlation, quantitative measurements of molar rotations, and comparative analysis by van’t Hoff’s principle of optical superposition. (−)-Agelasidine C (3) exhibited potent antifungal and modest cytotoxic activity against human chronic lymphocytic leukemia (CLL) cells. PMID:24653665

  7. The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function.

    PubMed

    Pfeffer, Tobias J; Sasse, Florenz; Schmidt, Christoph F; Lakämper, Stefan; Kirschning, Andreas; Scholz, Tim

    2016-04-13

    Tonantzitlolone A, a diterpene isolated from the Mexican plant Stillingia sanguinolenta, shows cytostatic activity. Both the natural product tonantzitlolone A and its synthetic enantiomer induce monoastral spindle formation in cell experiments which indicates inhibitory activity on kinesin-5 mitotic motor molecules. These inhibitory effects on kinesin-5 could be verified in in vitro single-molecule motility assays, where both tonantzitlolones interfered with kinesin-5 binding to its cellular interaction partner microtubules in a concentration-dependent manner, yet with a larger effect of the synthetic enantiomer. In contrast to kinesin-5 inhibition, both tonantzitlolone A enantiomers did not affect conventional kinesin-1 function; hence tonantzitlolones are not unspecific kinesin inhibitors. The observed stronger inhibitory effect of the synthetic enantiomer demonstrates the possibility to enhance the overall moderate anti-proliferative effect of the lead compound tonantzitlolon A by chemical modification.

  8. Extracellular Localization of the Diterpene Sclareol in Clary Sage (Salvia sclarea L., Lamiaceae)

    PubMed Central

    Caissard, Jean-Claude; Olivier, Thomas; Delbecque, Claire; Palle, Sabine; Garry, Pierre-Philippe; Audran, Arthur; Valot, Nadine; Moja, Sandrine; Nicolé, Florence; Magnard, Jean-Louis; Legrand, Sylvain; Baudino, Sylvie; Jullien, Frédéric

    2012-01-01

    Sclareol is a high-value natural product obtained by solid/liquid extraction of clary sage (Salvia sclarea L.) inflorescences. Because processes of excretion and accumulation of this labdane diterpene are unknown, the aim of this work was to gain knowledge on its sites of accumulation in planta. Samples were collected in natura or during different steps of the industrial process of extraction (steam distillation and solid/liquid extraction). Samples were then analysed with a combination of complementary analytical techniques (gas chromatography coupled to a mass spectrometer, polarized light microscopy, environmental scanning electron microscopy, two-photon fluorescence microscopy, second harmonic generation microscopy). According to the literature, it is hypothesized that sclareol is localized in oil pockets of secretory trichomes. This study demonstrates that this is not the case and that sclareol accumulates in a crystalline epicuticular form, mostly on calyces. PMID:23133579

  9. Discovery of Unclustered Fungal Indole Diterpene Biosynthetic Pathways through Combinatorial Pathway Reassembly in Engineered Yeast.

    PubMed

    Tang, Man-Cheng; Lin, Hsiao-Ching; Li, Dehai; Zou, Yi; Li, Jian; Xu, Wei; Cacho, Ralph A; Hillenmeyer, Maureen E; Garg, Neil K; Tang, Yi

    2015-11-01

    The structural diversity and biological activities of fungal indole diterpenes (IDTs) are generated in large part by the IDT cyclases (IDTCs). Identifying different IDTCs from IDT biosynthetic pathways is therefore important toward understanding how these enzymes introduce chemical diversity from a common linear precursor. However, IDTCs involved in the cyclization of the well-known aflavinine subgroup of IDTs have not been discovered. Here, using Saccharomyces cerevisiae as a heterologous host and a phylogenetically guided enzyme mining approach, we combinatorially assembled IDT biosynthetic pathways using IDTCs homologues identified from different fungal hosts. We identified the genetically standalone IDTCs involved in the cyclization of aflavinine and anominine and produced new IDTs not previously isolated. The cyclization mechanisms of the new IDTCs were proposed based on the yeast reconstitution results. Our studies demonstrate heterologous pathway assembly is a useful tool in the reconstitution of unclustered biosynthetic pathways.

  10. Analgesic potential of marrubiin derivatives, a bioactive diterpene present in Marrubium vulgare (Lamiaceae).

    PubMed

    Meyre-Silva, C; Yunes, R A; Schlemper, V; Campos-Buzzi, F; Cechinel-Filho, V

    2005-04-01

    Marrubiin, a furane labdane diterpene, is the main analgesic compound present in Marrubium vulgare, a medicinal plant used in Brazil and other countries to treat several ailments. Considering its important pharmacological action, as well as its high yield, some structural modifications were performed in order to obtain more active compounds. Success was obtained in reducing the lactonic function, in the formation of marrubiinic acid and two esterified derivatives, which exhibited significant analgesic effect against the writhing test in mice. Marrubiinic acid showed better activity and excellent yield, and its analgesic effect was confirmed in other experimental models of pain in mice, suggesting its possible use as a model to obtain new and potent analgesic agents.

  11. New C₂₀-gibberellin diterpene from the leaves of Schefflera sessiliflora De P. V.

    PubMed

    Nguyen, Tan Phat; Tran, Thi Thao Vy; Mai, Dinh Tri; Le, Tien Dung; Phan, Nhat Minh; Bui, Trong Dat

    2015-01-01

    From the leaves of Schefflera sessiliflora De P. V., one new C20-gibberellin diterpene 2β,12β-dihydroxygibberellin (12β-hydroxy-GA110 or 2β-hydroxy-GA112) (1), together with three known compounds, trans-tiliroside (2), kaempferol 3-O-β-D-glucuronopyranoside (3), 5-p-trans-coumaroylquinic acid (4), was isolated for the first time from the genus Schefflera by various chromatography methods. Their structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and comparison with previous reported data. The α-glucosidase inhibitory activity of all compounds was measured. The isolates (2, 3) showed better α-glucosidase inhibitory activity (IC50 = 134.60, 147.10 μM, respectively) than the standard drug acarbose (IC50 = 214.50 μM).

  12. Fuscoside E: a strong anti-inflammatory diterpene from Caribbean octocoral Eunicea fusca.

    PubMed

    Reina, Eduardo; Puentes, Carlos; Rojas, Juan; García, Josué; Ramos, Freddy A; Castellanos, Leonardo; Aragón, Marcela; Ospina, Luis F

    2011-10-01

    The screen of 10 soft coral extracts collected from the Colombian Caribbean Sea in the TPA-induced ear edema model allowed us to identify Eunicea fusca extract among others as an interesting source of active compounds. The new diterpene, fuscoside E (1), along with the known fuscoside B (2), fuscol (3), (+)-germacrene D (4) and a mixture of six sterols (5-10), were isolated from this soft coral. Their structures were elucidated by 1D and 2D NMR spectroscopy techniques. Fuscoside E (1) absolute stereochemistry was determined by chiroptical methods. Fuscoside E (1) and B (2) showed strong anti-inflammatory in the above mentioned bioassay. Additionally, fuscoside E (1) and the sterol mixture (5-10) presented antifouling activity against bacterial strains involved in surface colonization. PMID:21865038

  13. Fuscoside E: a strong anti-inflammatory diterpene from Caribbean octocoral Eunicea fusca.

    PubMed

    Reina, Eduardo; Puentes, Carlos; Rojas, Juan; García, Josué; Ramos, Freddy A; Castellanos, Leonardo; Aragón, Marcela; Ospina, Luis F

    2011-10-01

    The screen of 10 soft coral extracts collected from the Colombian Caribbean Sea in the TPA-induced ear edema model allowed us to identify Eunicea fusca extract among others as an interesting source of active compounds. The new diterpene, fuscoside E (1), along with the known fuscoside B (2), fuscol (3), (+)-germacrene D (4) and a mixture of six sterols (5-10), were isolated from this soft coral. Their structures were elucidated by 1D and 2D NMR spectroscopy techniques. Fuscoside E (1) absolute stereochemistry was determined by chiroptical methods. Fuscoside E (1) and B (2) showed strong anti-inflammatory in the above mentioned bioassay. Additionally, fuscoside E (1) and the sterol mixture (5-10) presented antifouling activity against bacterial strains involved in surface colonization.

  14. Antiangiogenic properties of cafestol, a coffee diterpene, in human umbilical vein endothelial cells

    SciTech Connect

    Wang, Shuaiyu; Yoon, Yeo Cho; Sung, Mi-Jeong; Hur, Haeng-Jeon; Park, Jae-Ho

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Cafestol inhibits tube formation and migration of VEGF-stimulated HUVEC. Black-Right-Pointing-Pointer Cafestol inhibits phosphorylation of FAK and Akt. Black-Right-Pointing-Pointer Cafestol decreases NO production. -- Abstract: As angiogenesis plays important roles in tumor growth and metastasis, searching for antiangiogenic compounds is a promising tactic for treating cancers. Cafestol, a diterpene found mainly in unfiltered coffee, provides benefit through varied biological activity, including antitumorigenic, antioxidative, and anti-inflammatory effects. This study aimed to investigate the effects of cafestol on angiogenesis and to uncover the associated mechanism. We show that cafestol inhibits angiogenesis of human umbilical vascular endothelial cells. This inhibition affects the following specific steps of the angiogenic process: proliferation, migration, and tube formation. The inhibitory effects of cafestol are accompanied by decreasing phosphorylation of FAK and Akt and by a decrease in nitric oxide production. Overall, cafestol inhibits angiogenesis by affecting the angiogenic signaling pathway.

  15. In vitro antimicrobial activity of plant-derived diterpenes against bovine mastitis bacteria.

    PubMed

    Fonseca, Ariana P; Estrela, Fernanda T; Moraes, Thaís S; Carneiro, Luiza J; Bastos, Jairo K; dos Santos, Raquel A; Ambrósio, Sérgio R; Martins, Carlos H G; Veneziani, Rodrigo C S

    2013-01-01

    We evaluated the antibacterial activity of three diterpenes isolated from natural sources against a panel of microorganisms responsible for bovine mastitis. ent-Copalic acid (CA) was the most active metabolite, with promising MIC values (from 1.56 to 6.25 µg mL-1) against Staphylococcus aureus (ATCC and clinical isolate), Staphylococcus epidermidis, Streptococcus agalactiae, and Streptococcus dysgalactiae. We conducted time-kill assays of CA against S. aureus, a commensal organism considered to be a ubiquitous etiological agent of bovine mastitis in dairy farms worldwide. In the first 12 h, CA only inhibited the growth of the inoculums (bacteriostatic effect), but its bactericidal effect was clearly noted thereafter (between 12 and 24 h). In conclusion, CA should be considered for the control of several Gram-positive bacteria related to bovine mastitis. PMID:23884123

  16. Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare.

    PubMed

    Zerbe, Philipp; Chiang, Angela; Dullat, Harpreet; O'Neil-Johnson, Mark; Starks, Courtney; Hamberger, Björn; Bohlmann, Jörg

    2014-09-01

    Marrubium vulgare (Lamiaceae) is a medicinal plant whose major bioactive compounds, marrubiin and other labdane-related furanoid diterpenoids, have potential applications as anti-diabetics, analgesics or vasorelaxants. Metabolite and transcriptome profiling of M. vulgare leaves identified five different candidate diterpene synthases (diTPSs) of the TPS-c and TPS-e/f clades. We describe the in vitro and in vivo functional characterization of the M. vulgare diTPS family. In addition to MvEKS ent-kaurene synthase of general metabolism, we identified three diTPSs of specialized metabolism: MvCPS3 (+)-copalyl diphosphate synthase, and the functional diTPS pair MvCPS1 and MvELS. In a sequential reaction, MvCPS1 and MvELS produce a unique oxygenated diterpene scaffold 9,13-epoxy-labd-14-ene en route to marrubiin and an array of related compounds. In contrast with previously known diTPSs that introduce a hydroxyl group at carbon C-8 of the labdane backbone, the MvCPS1-catalyzed reaction proceeds via oxygenation of an intermediate carbocation at C-9, yielding the bicyclic peregrinol diphosphate. MvELS belongs to a subgroup of the diTPS TPS-e/f clade with unusual βα-domain architecture. MvELS is active in vitro and in vivo with three different prenyl diphosphate substrates forming the marrubiin precursor 9,13-epoxy-labd-14-ene, as identified by nuclear magnetic resonance (NMR) analysis, manoyl oxide and miltiradiene. MvELS fills a central position in the biosynthetic system that forms the foundation for the diverse repertoire of Marrubium diterpenoids. Co-expression of MvCPS1 and MvELS in engineered E. coli and Nicotiana benthamiana offers opportunities for producing precursors for an array of biologically active diterpenoids.

  17. Characterization and Inhibition of a Class II Diterpene Cyclase from Mycobacterium tuberculosis

    PubMed Central

    Mann, Francis M.; Prisic, Sladjana; Hu, Huayou; Xu, Meimei; Coates, Robert M.; Peters, Reuben J.

    2009-01-01

    Mycobacterium tuberculosis remains a widespread and devastating human pathogen, whose ability to infiltrate macrophage host cells from the human immune system is an active area of investigation. We have recently reported the discovery of a novel diterpene from M. tuberculosis, edaxadiene, whose ability to arrest phagosomal maturation in isolation presumably contributes to this critical process in M. tuberculosis infections. (Mann, F. M., Xu, M., Chen, X., Fulton, D. B., Russell, D. G., and Peters, R. J. (2009) J. Am. Chem. Soc., in press). Here, we present characterization of the class II diterpene cyclase that catalyzes the committed step in edaxadiene biosynthesis, i.e. the previously identified halimadienyl-diphosphate synthase (HPS; EC 5.5.1.16). Intriguingly, our kinetic analysis suggests a potential biochemical regulatory mechanism that triggers edaxadiene production upon phagosomal engulfment. Furthermore, we report characterization of potential HPS inhibitors: specifically, two related transition state analogs (15-aza-14,15-dihydrogeranylgeranyl diphosphate (7a) and 15-aza-14,15-dihydrogeranylgeranyl thiolodiphosphate (7b)) that exhibit very tight binding. Although arguably not suitable for clinical use, these nevertheless provide a basis for pharmaceutical design against this intriguing biosynthetic pathway. Finally, we provide evidence indicating that this pathway exists only in M. tuberculosis and is not functional in the closely related Mycobacterium bovis because of an inactivating frameshift in the HPS-encoding gene. Thus, we hypothesize that the inability to produce edaxadiene may be a contributing factor in the decreased infectivity and/or virulence of M. bovis relative to M. tuberculosis in humans. PMID:19574210

  18. Insights into Diterpene Cyclization from Structure of Bifunctional Abietadiene Synthase from Abies grandis*

    PubMed Central

    Zhou, Ke; Gao, Yang; Hoy, Julie A.; Mann, Francis M.; Honzatko, Richard B.; Peters, Reuben J.

    2012-01-01

    Abietadiene synthase from Abies grandis (AgAS) is a model system for diterpene synthase activity, catalyzing class I (ionization-initiated) and class II (protonation-initiated) cyclization reactions. Reported here is the crystal structure of AgAS at 2.3 Å resolution and molecular dynamics simulations of that structure with and without active site ligands. AgAS has three domains (α, β, and γ). The class I active site is within the C-terminal α domain, and the class II active site is between the N-terminal γ and β domains. The domain organization resembles that of monofunctional diterpene synthases and is consistent with proposed evolutionary origins of terpene synthases. Molecular dynamics simulations were carried out to determine the effect of substrate binding on enzymatic structure. Although such studies of the class I active site do lead to an enclosed substrate-Mg2+ complex similar to that observed in crystal structures of related plant enzymes, it does not enforce a single substrate conformation consistent with the known product stereochemistry. Simulations of the class II active site were more informative, with observation of a well ordered external loop migration. This “loop-in” conformation not only limits solvent access but also greatly increases the number of conformational states accessible to the substrate while destabilizing the nonproductive substrate conformation present in the “loop-out” conformation. Moreover, these conformational changes at the class II active site drive the substrate toward the proposed transition state. Docked substrate complexes were further assessed with regard to the effects of site-directed mutations on class I and II activities. PMID:22219188

  19. Identification and Characterization of a Novel Diterpene Gene Cluster in Aspergillus nidulans

    PubMed Central

    Bromann, Kirsi; Toivari, Mervi; Viljanen, Kaarina; Vuoristo, Anu; Ruohonen, Laura; Nakari-Setälä, Tiina

    2012-01-01

    Fungal secondary metabolites are a rich source of medically useful compounds due to their pharmaceutical and toxic properties. Sequencing of fungal genomes has revealed numerous secondary metabolite gene clusters, yet products of many of these biosynthetic pathways are unknown since the expression of the clustered genes usually remains silent in normal laboratory conditions. Therefore, to discover new metabolites, it is important to find ways to induce the expression of genes in these otherwise silent biosynthetic clusters. We discovered a novel secondary metabolite in Aspergillus nidulans by predicting a biosynthetic gene cluster with genomic mining. A Zn(II)2Cys6–type transcription factor, PbcR, was identified, and its role as a pathway-specific activator for the predicted gene cluster was demonstrated. Overexpression of pbcR upregulated the transcription of seven genes in the identified cluster and led to the production of a diterpene compound, which was characterized with GC/MS as ent-pimara-8(14),15-diene. A change in morphology was also observed in the strains overexpressing pbcR. The activation of a cryptic gene cluster by overexpression of its putative Zn(II)2Cys6–type transcription factor led to discovery of a novel secondary metabolite in Aspergillus nidulans. Quantitative real-time PCR and DNA array analysis allowed us to predict the borders of the biosynthetic gene cluster. Furthermore, we identified a novel fungal pimaradiene cyclase gene as well as genes encoding 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase and a geranylgeranyl pyrophosphate (GGPP) synthase. None of these genes have been previously implicated in the biosynthesis of terpenes in Aspergillus nidulans. These results identify the first Aspergillus nidulans diterpene gene cluster and suggest a biosynthetic pathway for ent-pimara-8(14),15-diene. PMID:22506079

  20. Use of dietary rosemary diterpenes to inhibit rancid volatiles in lamb meat packed under protective atmosphere.

    PubMed

    Ortuño, J; Serrano, R; Bañón, S

    2016-08-01

    The objective of the present study was to determine the inhibitory effect of dietary rosemary diterpenes on the formation of the volatile organic compounds (VOCs) responsible for rancid flavour in raw lamb meat. The lamb diet was supplemented during the fattening stage with two levels (200 and 400 mg/kg feed) of a dietary rosemary extract (DRE) containing carnosic acid and carnosol (1 : 1, w/w). The formation of VOCs (determined by headspace solid-phase microextraction at 40°C and MS) and odour deterioration (assessed by quantitative descriptive analysis) were monitored in meat fillets (longissimus dorsi-lumborum muscle) packed in a 70/30 O2/CO2 protective atmosphere and kept at 2°C for up to 14 days. The raw meat odour deteriorated under pro-oxidizing conditions due to the development of an incipient rancidity caused by the formation of volatiles from lipid oxidation. A total of 46 volatile compounds were determined in lamb headspace: 18 aldehydes, seven alcohols, seven organic acids, six ketones, four furan compounds, two benzene compounds, one ester and one terpenoid. The use of DRE contributed to inhibit VOC formation and rancidity. Heptanal, octanal, nonanal and 2-pentyl-furan were the only VOCs affected (P0.75; P<0.001), although similar values were obtained for the coefficients of a large number of carbonyl, alcohols and furan compounds, among other volatiles, which can be considered molecular markers of rancidity in raw lamb meat. Principal component analysis confirmed that the differences in the VOC profile make it possible to identify whether or not samples have been reinforced with dietary rosemary diterpenes. Thus, VOC profiling can be regarded as a useful tool for assessing the dietary treatments used in sheep to improve the oxidative stability of lamb meat.

  1. Use of dietary rosemary diterpenes to inhibit rancid volatiles in lamb meat packed under protective atmosphere.

    PubMed

    Ortuño, J; Serrano, R; Bañón, S

    2016-08-01

    The objective of the present study was to determine the inhibitory effect of dietary rosemary diterpenes on the formation of the volatile organic compounds (VOCs) responsible for rancid flavour in raw lamb meat. The lamb diet was supplemented during the fattening stage with two levels (200 and 400 mg/kg feed) of a dietary rosemary extract (DRE) containing carnosic acid and carnosol (1 : 1, w/w). The formation of VOCs (determined by headspace solid-phase microextraction at 40°C and MS) and odour deterioration (assessed by quantitative descriptive analysis) were monitored in meat fillets (longissimus dorsi-lumborum muscle) packed in a 70/30 O2/CO2 protective atmosphere and kept at 2°C for up to 14 days. The raw meat odour deteriorated under pro-oxidizing conditions due to the development of an incipient rancidity caused by the formation of volatiles from lipid oxidation. A total of 46 volatile compounds were determined in lamb headspace: 18 aldehydes, seven alcohols, seven organic acids, six ketones, four furan compounds, two benzene compounds, one ester and one terpenoid. The use of DRE contributed to inhibit VOC formation and rancidity. Heptanal, octanal, nonanal and 2-pentyl-furan were the only VOCs affected (P0.75; P<0.001), although similar values were obtained for the coefficients of a large number of carbonyl, alcohols and furan compounds, among other volatiles, which can be considered molecular markers of rancidity in raw lamb meat. Principal component analysis confirmed that the differences in the VOC profile make it possible to identify whether or not samples have been reinforced with dietary rosemary diterpenes. Thus, VOC profiling can be regarded as a useful tool for assessing the dietary treatments used in sheep to improve the oxidative stability of lamb meat. PMID:26940773

  2. Insights into Diterpene Cyclization from Structure of Bifunctional Abietadiene Synthase from Abies grandis

    SciTech Connect

    Zhou, Ke; Gao, Yang; Hoy, Julie A.; Mann, Francis M.; Honzatko, Richard B.; Peters, Reuben J.

    2013-09-24

    Abietadiene synthase from Abies grandis (AgAS) is a model system for diterpene synthase activity, catalyzing class I (ionization-initiated) and class II (protonation-initiated) cyclization reactions. Reported here is the crystal structure of AgAS at 2.3 {angstrom} resolution and molecular dynamics simulations of that structure with and without active site ligands. AgAS has three domains ({alpha}, {beta}, and {gamma}). The class I active site is within the C-terminal {alpha} domain, and the class II active site is between the N-terminal {gamma} and {beta} domains. The domain organization resembles that of monofunctional diterpene synthases and is consistent with proposed evolutionary origins of terpene synthases. Molecular dynamics simulations were carried out to determine the effect of substrate binding on enzymatic structure. Although such studies of the class I active site do lead to an enclosed substrate-Mg{sup 2+} complex similar to that observed in crystal structures of related plant enzymes, it does not enforce a single substrate conformation consistent with the known product stereochemistry. Simulations of the class II active site were more informative, with observation of a well ordered external loop migration. This 'loop-in' conformation not only limits solvent access but also greatly increases the number of conformational states accessible to the substrate while destabilizing the nonproductive substrate conformation present in the 'loop-out' conformation. Moreover, these conformational changes at the class II active site drive the substrate toward the proposed transition state. Docked substrate complexes were further assessed with regard to the effects of site-directed mutations on class I and II activities.

  3. Central nervous system activities of two diterpenes isolated from Aloysia virgata.

    PubMed

    Wasowski, Cristina; Marder, Mariel

    2011-03-15

    Using the guide of a competitive assay for the benzodiazepine binding site in the γ-aminobutyric acid type A receptor (GABA(A)), two active diterpenes were isolated from the aerial parts of Aloysia virgata (Ruíz & Pavón) A.L. Jussieu var. platyphylla (Briquet) Moldenke. These compounds, identified as (16R)-16,17,18-trihydroxyphyllocladan-3-one (1) and (16R)-16,17-dihydroxyphyllocladan-3-one (2) on the basis of spectral data, competitively inhibited the binding of [(3)H]-FNZ to the benzodiazepine binding site with K(i)±S.E.M. values of 56±19 μM and 111±13 μM, respectively. The behavioral actions of these diterpenes, intraperitoneally (i.p.) administered in mice, were examined in the plus-maze, holeboard, locomotor activity and light/dark tests. Compound 1 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the holeboard test (the number of head dips at 0.3 mg/kg and 3 mg/kg, the rears at 1 mg/kg and the time spent head-dipping at 3 mg/kg), in the plus-maze assay (the percentage of open arm entries at 1 mg/kg) and in the light/dark test (the time in light and the number of transitions at 1 mg/kg). Compound 2 augmented the number of rearings in the holeboard apparatus (at 0.3 mg/kg and 1 mg/kg) and the locomotor activity (at 1 mg/kg). These results reveal the presence of neuroactive compounds in Aloysia virgata. PMID:21036579

  4. Identification and characterization of a novel diterpene gene cluster in Aspergillus nidulans.

    PubMed

    Bromann, Kirsi; Toivari, Mervi; Viljanen, Kaarina; Vuoristo, Anu; Ruohonen, Laura; Nakari-Setälä, Tiina

    2012-01-01

    Fungal secondary metabolites are a rich source of medically useful compounds due to their pharmaceutical and toxic properties. Sequencing of fungal genomes has revealed numerous secondary metabolite gene clusters, yet products of many of these biosynthetic pathways are unknown since the expression of the clustered genes usually remains silent in normal laboratory conditions. Therefore, to discover new metabolites, it is important to find ways to induce the expression of genes in these otherwise silent biosynthetic clusters. We discovered a novel secondary metabolite in Aspergillus nidulans by predicting a biosynthetic gene cluster with genomic mining. A Zn(II)(2)Cys(6)-type transcription factor, PbcR, was identified, and its role as a pathway-specific activator for the predicted gene cluster was demonstrated. Overexpression of pbcR upregulated the transcription of seven genes in the identified cluster and led to the production of a diterpene compound, which was characterized with GC/MS as ent-pimara-8(14),15-diene. A change in morphology was also observed in the strains overexpressing pbcR. The activation of a cryptic gene cluster by overexpression of its putative Zn(II)(2)Cys(6)-type transcription factor led to discovery of a novel secondary metabolite in Aspergillus nidulans. Quantitative real-time PCR and DNA array analysis allowed us to predict the borders of the biosynthetic gene cluster. Furthermore, we identified a novel fungal pimaradiene cyclase gene as well as genes encoding 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase and a geranylgeranyl pyrophosphate (GGPP) synthase. None of these genes have been previously implicated in the biosynthesis of terpenes in Aspergillus nidulans. These results identify the first Aspergillus nidulans diterpene gene cluster and suggest a biosynthetic pathway for ent-pimara-8(14),15-diene.

  5. Spatio-temporal variation of the diterpene steviol in Stevia rebaudiana grown under different photoperiods.

    PubMed

    Ceunen, Stijn; Geuns, Jan M C

    2013-05-01

    As part of an ongoing study on the effects of photoperiodism on the metabolism of steviol glycosides (SVglys) in Stevia rebaudiana, the spatio-temporal variations of free steviol (SV) have now been evaluated. For its quantitation, an internal standard method was used, based upon a specific fluorometric detection of SV as its methoxycoumarinyl derivative. The level of free SV in leaves did not exceed 30 μg/g dry wt and was at least 1000-fold smaller than that of its glycosidic conjugates. In other organs, free SV was mainly measured in stem tissue and apices, with relatively large amounts measured in the latter. Similarly to SVglys, the content of free SV was influenced by photoperiod and genotype. In plants grown under long-days (LD) of 16 h, more spatial variations were seen compared to those under short-days (SD) of 8h. In the former, upper leaves contained almost four times more free SV compared to lower ones near the end of vegetative growth. In addition, the correlation between SV and its glycosidic conjugates was more linear under SD. Despite the variability of SV levels, a decrease was noted in all conditions after flower opening, which can be related a decreased transcription of the biosynthetic genes involved.

  6. Quantification of flavonol glycosides in Camellia sinensis by MRM mode of UPLC-QQQ-MS/MS.

    PubMed

    Wu, Yahui; Jiang, Xiaolan; Zhang, Shuxiang; Dai, Xinlong; Liu, Yajun; Tan, Huarong; Gao, Liping; Xia, Tao

    2016-04-01

    Phenolic compounds are major components of tea flavour, in which catechins and flavonol glycosides play important roles in the astringent taste of tea infusion. However, the flavonol glycosides are difficult to quantify because of the large variety, as well as the inefficient seperation on chromatography. In this paper, a total of 15 flavonol glycosides in the tea plant (Camellia sinensis) were identified by the high performance liquid chromatography (HPLC) coupled to a time-of-flight mass spectrometer (TOF-MS), and a quantitative method was established based on multiple reaction monitoring (MRM) mode of ultra-high performance liquid chromatography (UPLC) coupled to a triple quadrupole mass spectrometer (QQQ-MS/MS). It provided the limit of detection and quantification to the order of picogram, which was more sensitive than the HPLC detection of the order of nanogram. The relative standard deviations of the intra- and inter-day variations in retention time and signal intensity (peak area) of six analytes were less than 0.26% and 4%, respectively. The flavonol glycosides of four tea cultivars were relatively quantified using the signal intensity (peak area) of product ion, in which six flavonol glycosides were quantified by the authentic standards. The results showed that the flavonol mono-, di- and tri-glycoside mostly accumulated in young leaves of the four tea cultivars. Notably, the myricetin 3-O-galactoside was the major component among the six flavonol glycosides detected.

  7. An Unusual Chimeric Diterpene Synthase from Emericella variecolor and Its Functional Conversion into a Sesterterpene Synthase by Domain Swapping.

    PubMed

    Qin, Bin; Matsuda, Yudai; Mori, Takahiro; Okada, Masahiro; Quan, Zhiyang; Mitsuhashi, Takaaki; Wakimoto, Toshiyuki; Abe, Ikuro

    2016-01-26

    Di- and sesterterpene synthases produce C20 and C25 isoprenoid scaffolds from geranylgeranyl pyrophosphate (GGPP) and geranylfarnesyl pyrophosphate (GFPP), respectively. By genome mining of the fungus Emericella variecolor, we identified a multitasking chimeric terpene synthase, EvVS, which has terpene cyclase (TC) and prenyltransferase (PT) domains. Heterologous gene expression in Aspergillus oryzae led to the isolation of variediene (1), a novel tricyclic diterpene hydrocarbon. Intriguingly, in vitro reaction with the enzyme afforded the new macrocyclic sesterterpene 2 as a minor product from dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). The TC domain thus produces the diterpene 1 and the sesterterpene 2 from GGPP and GFPP, respectively. Notably, a domain swap of the PT domain of EvVS with that of another chimeric sesterterpene synthase, EvSS, successfully resulted in the production of 2 in vivo as well. Cyclization mechanisms for the production of these two compounds are proposed.

  8. Trichocitrin, a new fusicoccane diterpene from the marine brown alga-endophytic fungus Trichoderma citrinoviride cf-27.

    PubMed

    Liang, Xiao-Rui; Miao, Feng-Ping; Song, Yin-Ping; Guo, Zhan-Yong; Ji, Nai-Yun

    2016-07-01

    One new diterpene, trichocitrin (1), and four known secondary metabolites, nafuredin (2), 5-hydroxy-2,3-dimethyl-7-methoxychromone (3), 24-methylenecycloartanol (4) and citrostadienol (5), were isolated from the culture of marine brown alga-endophytic Trichoderma citrinoviride cf-27. Trichocitrin (1) represents the first Trichoderma-derived and furan-bearing fusicoccane diterpene, and its structure and relative configuration were identified by analysis of 1D/2D NMR and mass spectroscopic data. Compounds 1 and 2 exhibited 8.0- and 9.5-mm inhibition zones, respectively, against Escherichia coli at 20 μg/disc and 54.1 and 36.7% growth inhibition, respectively, of Prorocentrum donghaiense at 80 μg/mL.

  9. Dactyloditerpenol acetate, a new prenylbisabolane-type diterpene from Aplysia dactylomela with significant in vitro anti-neuroinflammatory activity

    PubMed Central

    Jiménez-Romero, Carlos; Mayer, Alejandro M. S.; Rodríguez, Abimael D.

    2014-01-01

    A new regular diterpene possessing an unusual 1,6-anti-3-methylcyclohex-2-en-1-ol ring system, dactyloditerpenol acetate (1), has been extracted from the tropical sea hare Aplysia dactylomela and its stereostructure elucidated by spectroscopic methods. The absolute configuration of 1 was determined as 1S, 6S, 7R, 10S, and 11R by application of Kishi’s method for the assignment of absolute configuration of alcohols. The new diterpene potently inhibited in vitro thromboxane B2 (TXB2) (IC50 0.4 μM) and superoxide anion (O2−) (IC50 1 μM) generation from E. coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity. PMID:24279991

  10. An ellagitannin, n-butyl gallate, two aryltetralin lignans, and an unprecedented diterpene ester from Pelargonium reniforme.

    PubMed

    Latté, Klaus Peter; Kaloga, Maki; Schäfer, Andreas; Kolodziej, Herbert

    2008-02-01

    The structural diversity of the metabolic pool of Pelargonium reniforme was extended by the characterization of the 1C4-glucose based ellagitannin pelargoniin E, gallic acid n-butyl ester, (-)-4,4',9'-trihydroxy-3',5'-dimethoxy-2,7'-cyclolignan 9-O-beta-glucopyranoside and reniformin, a diterpene ester comprised of a diterpene acid with an uncommon -(CH2)(2)- bridging element linked to 2-(4-hydroxyphenyl)ethansulfonic acid. These metabolites were associated with the known (alpha,beta)-3,4-di-O-galloyl-glucopyranoside, 4,6-dihydroxy-2beta-glucopyranosyloxyacetophenone, 1-O-galloylglycerol, 6'-O-galloylsalidroside and (+)-isolariciresinol-9'-O-beta-glucopyranoside. All structures were established on the basis of spectroscopic methods.

  11. Acasiane A and B and farnesirane A and B, diterpene derivatives from the roots of Acacia farnesiana.

    PubMed

    Lin, An-Shen; Lin, Chia-Rong; Du, Ying-Chi; Lübken, Tilo; Chiang, Michael Y; Chen, I-Hsiao; Wu, Chin-Chung; Hwang, Tsong-Long; Chen, Shu-Li; Yen, Ming-Hong; Chang, Fang-Rong; Wu, Yang-Chang

    2009-02-01

    Four new diterpenes, acasiane A ( 1), acasiane B ( 2), farnesirane A ( 3), and farnesirane B ( 4), along with three known diterpenes ( 5 - 7), two triterpenes ( 8 and 9), and eight flavonoids ( 10 - 17) were isolated from the roots of Acacia farnesiana. The structures and relative configurations of these compounds were determined by various spectroscopic and x-ray analyses. All isolated compounds were evaluated for their in vitro cytotoxic activities against six human cancer cell lines (Hep G2, Hep 3B, MDA-MB-231, MCF-7, A549, and Ca9 - 22) with the MTT method. Betulinic acid ( 8) displayed moderate cytotoxicity (1.70 - 5.74 microg/mL) towards five human cancer cell lines and the flavonoids had slight effects. In addition, 8, diosmetin ( 13), and 3',4',5-trihydroxy-7-methoxyflavone ( 15) slightly inhibited superoxide anion generation or elastase release by human neutrophils, indicating moderate anti-inflammatory activities.

  12. Three diterpenes from Leonurus japonicus Houtt protect primary cultured rat cortical cells from glutamate-induced toxicity.

    PubMed

    Moon, Hyung-In

    2010-08-01

    To examine the cytoprotective effects of Leonurus japonicus Houtt, its protection against the glutamate-induced toxicity in primary cortical cultured neurons was tested. In order to clarify the cytoprotective mechanism(s) of this observed effect, isolation was performed to seek and identify active fractions and components. By such fractionation, three known diterpenes--prehispanolone (1), leojaponin (2) and iso-preleoheterin (3)--were isolated from the methanol extracts from the air-dried L. japonicus. Among these three compounds, leojaponin (2) exhibited significant cytoprotective activities against glutamate-induced toxicity, exhibiting cell viability of about 50%, at concentrations ranging from 0.1 microm to 10 microm. Therefore, the cytoprotective effect of L. japonicus might be due to the inhibition of glutamate-induced toxicity by the diterpenes it contains.

  13. Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L.

    PubMed

    Inoue, Toshio; Sugimoto, Yukio; Masuda, Hideki; Kamei, Chiaki

    2002-02-01

    Six flavonoid glycosides, eriocitrin (1), narirutin (2), hesperidin (3), luteolin-7-O-rutinoside (4), isorhoifolin (5), diosmin (6), rosmarinic acid (7) and 5,7-dihydroxycromone-7-O-rutinoside (8), were isolated from the aerial part of Mentha piperita L. Among these compounds, compound 4 showed a potent inhibitory effect on histamine release induced by compound 48/80 and antigen-antibody reaction. This compound was more effective than luteolin and luteolin-7-O-glucoside in inhibiting histamine release from rat peritoneal mast cells. Compound 4 also caused a dose-related inhibition of the antigen-induced nasal response and significant effects were observed at doses of 100 and 300 mg/kg. These results indicate that compound 4 may be clinically useful in alleviating the nasal symptoms of allergic rhinitis. PMID:11853178

  14. Uncommon Glycosidases for the Enzymatic Preparation of Glycosides.

    PubMed

    Trincone, Antonio

    2015-01-01

    Most of the reports in literature dedicated to the use of glycosyl hydrolases for the preparation of glycosides are about gluco- (α- and β-form) and galacto-sidase (β-form), reflecting the high-availability of both anomers of glucosides and of β-galactosides and their wide-ranging applications. Hence, the idea of this review was to analyze the literature focusing on hardly-mentioned natural and engineered glycosyl hydrolases. Their performances in the synthetic mode and natural hydrolytic potential are examined. Both the choice of articles and their discussion are from a biomolecular and a biotechnological perspective of the biocatalytic process, shedding light on new applicative ideas and on the assortment of biomolecular diversity. The hope is to elicit new interest for the development of biocatalysis and to gather attention of biocatalyst practitioners for glycosynthesis. PMID:26404386

  15. Phenylpropanoid Glycosides from the Leaves of Ananas comosus.

    PubMed

    Chen, Wen-Hao; Huang, Xiao-Juan; Shu, Huo-Ming; Hui, Yang; Guo, Fei-Yan; Song, Xiao-Ping; Ji, Ming-Hui; Chen, Guang-Ying

    2015-12-01

    Two new phenylpropanoid glycosides, named β-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl β-D-6'-O-acetylglucopyranoside (1) and β-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl α-D-glucopyranoside (2), along with two known analogues (3-4) and four glycerides (5-8), were isolated from the EtOAc extract of the leaves of Ananas comosus. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses, as well as HR-ESI-MS experiments. Compounds 1-4 showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli. PMID:26882684

  16. A new antibacterial benzophenone glycoside from Psidium guajava (Linn.) leaves.

    PubMed

    Ukwueze, Stanley E; Osadebe, Patience O; Okoye, Festus B C

    2015-01-01

    Bioactivity-guided fractionation of methanol extract from the leaves of Psidium guajava L. (Myrtaceae) yielded a new benzophenone glycoside, Guajaphenone A (2) together with two known compounds, Garcimangosone D (1) and Guaijaverin (3). Their structures were elucidated by analysis of spectroscopic data including 1D and 2D NMR and electrospray ionisation mass spectrometry (ESI-MS). The isolated compounds were screened against standard strains of Gram-positive and Gram-negative bacteria using broth dilution assay method, and the MIC values determined and compared with reference antibiotic ceftriaxone. They were found to have significant antibacterial activities against Escherichia coli and Staphylococcus aureus with all of them showing better activities against S. aureus, but displaying weaker activities, in comparison to ceftriaxone. However, despite reduced effect of these compounds against the organisms, this work opens the perspective to use these molecules as 'leads' for the design of novel and selective drug candidates for some tropical infectious diseases. PMID:25631395

  17. Four new flavonol glycosides from the leaves of Brugmansia suaveolens.

    PubMed

    Geller, Fabiana; Murillo, Renato; Steinhauser, Lisa; Heinzmann, Berta; Albert, Klaus; Merfort, Irmgard; Laufer, Stefan

    2014-01-01

    Four new flavonol glycosides were isolated from the leaves of Brugmansia suaveolens: kaempferol 3-O-β-D-glucopyranosyl-(1'''→2'')-O-α-L-arabinopyranoside (1), kaempferol 3-O-β-D-glucopyranosyl-(1'''→2'')-O-α-L-arabinopyranoside-7-O-į-D-gluco-pyranoside (2), kaempferol 3-O-β-D-[6'''-O-(E-caffeoyl)]-glucopyranosyl-(1'''→2'')-O-α-l-arabinopyranoside-7-O-β-D-glucopyranoside (3), and kaempferol 3-O-β-D-[2'''-O-(E-caffeoyl)]-glucopyranosyl-(1'''→2'')-O-α-l-arabinopyranoside-7-O-β-D-glucopyranoside (4). The structure elucidation was performed by MS, 1D and 2D NMR analyses. PMID:24858103

  18. Flavanone glycosides as acetylcholinesterase inhibitors: computational and experimental evidence.

    PubMed

    Remya, C; Dileep, K V; Tintu, I; Variyar, E J; Sadasivan, C

    2014-01-01

    Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is crucially involved in the regulation of neurotransmission. One of the observable facts in the neurodegenerative disorders like Alzheimer's disease is the decrease in the level of acetylcholine. Available drugs that are used for the treatment of Alzheimer's disease are primarily acetylcholinesterase inhibitors with multiple activities. They maintain the level of acetylcholine in the brain by inhibiting the acetylcholinesterase function. Hence acetylcholinesterase inhibitors can be used as lead compounds for the development of drugs against AD. In the present study, the binding potential of four flavanone glycosides such as naringin, hesperidin, poncirin and sakuranin against acetylcholinesterase was analysed by using the method of molecular modeling and docking. The activity of the top scored compound, naringin was further investigated by enzyme inhibition studies and its inhibitory concentration (IC50) towards acetylcholinesterase was also determined. PMID:25593395

  19. A new triterpene glycoside from the stems of Lagerstroemia indica.

    PubMed

    Woo, Kyeong Wan; Cha, Joon Min; Choi, Sang Un; Lee, Kang Ro

    2016-05-01

    A bioassay-guided fractionation and chemical investigation of the stems of Lagerstroemia indica resulted in the isolation and identification of a new triterpene glycoside, lagerindiside (1), along with nine known triterpenes (2-10). The structure of this new compound was elucidated on the basis of 1D and 2D nuclear magnetic resonance spectroscopic data analysis as well as chemical method. The cytotoxic activities of the isolates (1-10) were evaluated by determining their inhibitory effects on four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) using a sulforhodamine B bioassay. Compounds 3 and 4 showed potent cytotoxicity on the tumor cell lines with IC50 values ranging from 3.38 to 6.29 μM. PMID:27107863

  20. New phenolic glycosides from the seeds of Cucurbita moschata.

    PubMed

    Koike, Kazuo; Li, Wei; Liu, Lijuan; Hata, Emiko; Nikaido, Tamotsu

    2005-02-01

    Five new phenolic glycosides, cucurbitosides A-E (1-5), were isolated from the seeds of Cucurbita moschata. Their structures were elucidated as 2-(4-hydroxy)phenylethanol 4-O-(5-O-benzoyl)-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (1), 2-(4-hydroxyphenyl)ethanol 4-O-[5-O-(4-hydroxy)benzoyl]-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (2), 4-hydroxybenzyl alcohol 4-O-(5-O-benzoyl)-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (3), 4-hydroxybenzyl alcohol 4-O-[5-O-(4-hydroxy)benzoyl]-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (4) and 4-hydroxyphenyl 5-O-benzoyl-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (5) on the basis of spectroscopic analysis and chemical evidence.

  1. New flavonolignan glycosides from the aerial parts of Zizania latifolia.

    PubMed

    Lee, Seung-Su; Baek, Nam-In; Baek, Yoon-Su; Chung, Dae-Kyun; Song, Myoung-Chong; Bang, Myun-Ho

    2015-01-01

    Two new flavonolignan glycosides, tricin-4'-O-(threo-β-guaiacylglyceryl) ether 7''-O-β-D-glucopyranose (4) and tricin-4'-O-(erythro-β-guaiacylglyceryl) ether 7''-O-β-D-glucopyranose (5) were isolated from the roots of Zizania latifolia, together with tricin-7-O-β-D-glucopyranose (1), tricin-4'-O-(threo-β-guaiacylglyceryl) ether 7-O-β-D-glucopyranose (2), and tricin-4'-O-(erythro-β-guaiacylglyceryl) ether 7-O-β-D-glucopyranose (3). Their structures were identified on the basis of spectroscopic techniques, including HR-ESI/MS, 1D-NMR (1H, 13C, DEPT), 2D-NMR (gCOSY, gHSQC, gHMBC), and IR spectroscopy. PMID:25830790

  2. Uncommon Glycosidases for the Enzymatic Preparation of Glycosides

    PubMed Central

    Trincone, Antonio

    2015-01-01

    Most of the reports in literature dedicated to the use of glycosyl hydrolases for the preparation of glycosides are about gluco- (α- and β-form) and galacto-sidase (β-form), reflecting the high-availability of both anomers of glucosides and of β-galactosides and their wide-ranging applications. Hence, the idea of this review was to analyze the literature focusing on hardly-mentioned natural and engineered glycosyl hydrolases. Their performances in the synthetic mode and natural hydrolytic potential are examined. Both the choice of articles and their discussion are from a biomolecular and a biotechnological perspective of the biocatalytic process, shedding light on new applicative ideas and on the assortment of biomolecular diversity. The hope is to elicit new interest for the development of biocatalysis and to gather attention of biocatalyst practitioners for glycosynthesis. PMID:26404386

  3. C21 steroidal glycosides from the roots of Cynanchum paniculatum.

    PubMed

    Zhao, Dan; Feng, Baomin; Chen, Shaofei; Chen, Gang; Li, Zhifeng; Lu, Xiaojie; Sang, Xianan; An, Xiao; Wang, Haifeng; Pei, Yuehu

    2016-09-01

    As a part of our continuing research for bioactive constituents from Cynanchum plants, four new C21 steroidal glycosides, cynapanoside D-G (1-4), together with six known compounds (5-10) were isolated from the roots of Cynanchum paniculatum (Bge.) Kitag. Their structures were elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. Compound 8 exhibited potent inhibitory activities against HL-60, HT-29, PC-3 and MCF-7 cell lines with IC50 values of 8.3, 7.5, 34.3 and 19.4μM, respectively and compounds 1-4 and 9 displayed moderate cytotoxicity against the four cell lines. The in vitro antioxidant activities of compounds 1-4, 8 and 9 were assayed by DPPH radical scavenging activity. Antibacterial and antifungal activities of compounds 1-4, 8 and 9 were also tested. PMID:27380712

  4. Phenolic Glycosides from the Twigs of Salix glandulosa.

    PubMed

    Kim, Chung Sub; Kwon, Oh Wook; Kim, Sun Yeou; Choi, Sang Un; Kim, Jae Yoon; Han, Ji Young; Choi, Soo Im; Choi, Jong Gil; Kim, Ki Hyun; Lee, Kang Ro

    2014-08-22

    As a part of an ongoing search for bioactive constituents from Korean medicinal plants, the phytochemical investigations of the twigs of Salix glandulosa afforded 12 new phenolic glycosides (1-12) and a known analogue (13). The structures of 1-13 were characterized by a combination of NMR methods ((1)H and (13)C NMR, (1)H-(1)H COSY, HMQC, and HMBC), chemical hydrolysis, and GC/MS. The absolute configuration of 13 [(1R,2S)-2-hydroxycyclohexyl-2'-O-trans-p-coumaroyl-β-d-glucopyranoside] was determined for the first time. Compounds 1-3, 6, and 7 exhibited inhibitory effects on nitric oxide production in lipopolysaccharide-activated murine microglial cells (IC50 values in the range 6.6-20.5 μM).

  5. Pentasaccharide resin glycosides from Ipomoea cairica and their cytotoxic activities.

    PubMed

    Yu, Bangwei; Luo, Jianguang; Wang, Junsong; Zhang, Dongming; Yu, Shishan; Kong, Lingyi

    2013-11-01

    Six partially acylated pentasaccharide resin glycosides, cairicosides A-F, were isolated from the aerial parts of Ipomoea cairica. These compounds were characterized as a group of macrolactones of simonic acid A, partially acylated with different organic acids. The lactonization site of 11S-hydroxyhexadecanoic acid (jalapinolic acid) was bound to the second saccharide moiety at C-3 in cairicosides A-E, while at C-2 in cairicoside F. Structures were established by spectroscopic and chemical methods. Compounds cairicosides A-E exhibited moderate cytotoxicity against a small panel of human tumor cell lines with IC50 values in the range of 4.28-14.31μM. PMID:23954073

  6. A new antibacterial benzophenone glycoside from Psidium guajava (Linn.) leaves.

    PubMed

    Ukwueze, Stanley E; Osadebe, Patience O; Okoye, Festus B C

    2015-01-01

    Bioactivity-guided fractionation of methanol extract from the leaves of Psidium guajava L. (Myrtaceae) yielded a new benzophenone glycoside, Guajaphenone A (2) together with two known compounds, Garcimangosone D (1) and Guaijaverin (3). Their structures were elucidated by analysis of spectroscopic data including 1D and 2D NMR and electrospray ionisation mass spectrometry (ESI-MS). The isolated compounds were screened against standard strains of Gram-positive and Gram-negative bacteria using broth dilution assay method, and the MIC values determined and compared with reference antibiotic ceftriaxone. They were found to have significant antibacterial activities against Escherichia coli and Staphylococcus aureus with all of them showing better activities against S. aureus, but displaying weaker activities, in comparison to ceftriaxone. However, despite reduced effect of these compounds against the organisms, this work opens the perspective to use these molecules as 'leads' for the design of novel and selective drug candidates for some tropical infectious diseases.

  7. Agrobacterium Mediated Transient Gene Silencing (AMTS) in Stevia rebaudiana: Insights into Steviol Glycoside Biosynthesis Pathway

    PubMed Central

    Guleria, Praveen; Yadav, Sudesh Kumar

    2013-01-01

    Background Steviol glycoside biosynthesis pathway has emerged as bifurcation from ent-kaurenoic acid, substrate of methyl erythritol phosphate pathway that also leads to gibberellin biosynthesis. However, the genetic regulation of steviol glycoside biosynthesis has not been studied. So, in present study RNA interference (RNAi) based Agrobacterium mediated transient gene silencing (AMTS) approach was followed. SrKA13H and three SrUGTs (SrUGT85C2, SrUGT74G1 and SrUGT76G1) genes encoding ent-kaurenoic acid-13 hydroxylase and three UDP glycosyltransferases of steviol glycoside biosynthesis pathway were silenced in Stevia rebaudiana to understand its molecular mechanism and association with gibberellins. Methodology/Principal Findings RNAi mediated AMTS of SrKA13H and three SrUGTs has significantly reduced the expression of targeted endogenous genes as well as total steviol glycoside accumulation. While gibberellins (GA3) content was significantly enhanced on AMTS of SrUGT85C2 and SrKA13H. Silencing of SrKA13H and SrUGT85C2 was found to block the metabolite flux of steviol glycoside pathway and shifted it towards GA3 biosynthesis. Further, molecular docking of three SrUGT proteins has documented highest affinity of SrUGT76G1 for the substrates of alternate pathways synthesizing steviol glycosides. This could be a plausible reason for maximum reduction in steviol glycoside content on silencing of SrUGT76G1 than other genes. Conclusions SrKA13H and SrUGT85C2 were identified as regulatory genes influencing carbon flux between steviol glycoside and gibberellin biosynthesis. This study has also documented the existence of alternate steviol glycoside biosynthesis route. PMID:24023961

  8. Discovering new natural products directly from crude extracts by HPLC-SPE-NMR: chinane diterpenes in Harpagophytum procumbens.

    PubMed

    Clarkson, Cailean; Staerk, Dan; Hansen, Steen Honoré; Smith, Peter J; Jaroszewski, Jerzy W

    2006-04-01

    HPLC-SPE-NMR experiments with crude extracts of Harpagophytum procumbens allowed the rapid identification of novel, unstable chinane-type tricyclic diterpenes (1 and 2), along with numerous other constituents. Dramatic sensitivity gains achieved with this novel hyphenated technique establish a new paradigm in natural products research: rapid and rigorous structure determination of multiple extract components, including minor components, without preparative-scale isolation. PMID:16643019

  9. Biochemical characterization of the castor bean ent-kaurene synthase(-like) family supports quantum chemical view of diterpene cyclization.

    PubMed

    Jackson, Alana J; Hershey, David M; Chesnut, Taylor; Xu, Meimei; Peters, Reuben J

    2014-07-01

    It has become apparent that plants have extensively diversified their arsenal of labdane-related diterpenoids (LRDs), in part via gene duplication and neo-functionalization of the ancestral ent-kaurene synthase (KS) required for gibberellin metabolism. For example, castor bean (Ricinus communis) was previously shown to produce an interesting set of biosynthetically related diterpenes, specifically ent-sandracopimaradiene, ent-beyerene, and ent-trachylobane, in addition to ent-kaurene, using four separate diterpene synthases, albeit these remain unidentified. Notably, despite mechanistic similarity of the underlying reaction to that catalyzed by KSs, ent-beyerene and ent-trachylobane synthases have not yet been identified. Given our interest in LRD biosynthesis, and the recent availability of the castor bean genome sequence, a synthetic biology approach was applied to biochemically characterize the four KS(-like) enzymes [KS(L)s] found in Ricinus communis [i.e., the RcKS(L)s]. In particular, using bacteria engineered to produce the relevant ent-copalyl diphosphate precursor and synthetic genes based on the predicted RcKS(L)s, although this ultimately required correction of a "splicing" error in one of the predicted genes, highlighting the dependence of such a synthetic biology approach on accurate gene sequences. Nevertheless, it is possible to assign each of the four RcKS(L)s to one of the previously observed diterpene synthase activities, providing access to functionally enzymes. Intriguingly, the product distribution of the RcKS(L)s seems to support the distinct diterpene synthase reaction mechanism proposed by quantum chemical calculations, rather than the classically proposed pathway.

  10. A clerodane diterpene inhibit adipogenesis by cell cycle arrest and ameliorate obesity in C57BL/6 mice.

    PubMed

    Beg, Muheeb; Shankar, Kripa; Varshney, Salil; Rajan, Sujith; Singh, Suriya Pratap; Jagdale, Pankaj; Puri, Anju; Chaudhari, Bhushan P; Sashidhara, Koneni V; Gaikwad, Anil Nilkanth

    2015-01-01

    A clerodane diterpene, 16α-Hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide (compound 1) isolated from Polyalthia longifolia had previously been reported as a new structural class of HMG-CoA reductase inhibitor apart from statins. Statins are known to be anti-adipogenic in nature. The distant structural similarity between compound 1 and lovastatin (polyketide class of compound) prompted us to investigate effects of diterpene compound 1 on adipogenesis and thereby obesity. High content microscopy proved diterpene compound 1 exhibits better anti-adipogenic activity and less toxicity in differentiating adipocytes. Moreover, it reduced expression levels of PPARγ, C/EBPα and GLUT4 during differentiation in a time and concentration dependent manner. Diterpene compound 1 during early differentiation reduced MDI induced-Akt/mTOR phosphorylation and expression of cell cycle proteins, and thereby halted mitotic clonal expansion, the decisive factor in early adipogenesis. Further, its anti-adipogenic activity was validated in murine mesenchymal cell-line C3H10T1/2 and human mesenchymal stem cell models of adipogenic differentiation. When compound 1 was administered along with HFD, for another 8 weeks in 2 month HFD fed overweight mice (with BMI > 30 and impaired glucose tolerance), it attenuated weight gain and epididymal fat accumulation. It improved body glucose tolerance, reduced HFD induced increase in total cholesterol and leptin/adiponectin ratio. All these effects were comparable with standard anti-obesity drug Orlistat with added edge of potently decreasing circulating triglyceride levels comparable with normal chow fed group. Histological analysis shows that compound 1 inhibit adipocyte hypertrophy and decreased steatosis in hepatocytes. Both in vivo and in vitro results demonstrate a potential value of compound 1 as a novel anti-adipogenic and anti-obesity agent.

  11. Darwinolide, a New Diterpene Scaffold That Inhibits Methicillin-Resistant Staphylococcus aureus Biofilm from the Antarctic Sponge Dendrilla membranosa.

    PubMed

    von Salm, Jacqueline L; Witowski, Christopher G; Fleeman, Renee M; McClintock, James B; Amsler, Charles D; Shaw, Lindsey N; Baker, Bill J

    2016-06-01

    A new rearranged spongian diterpene, darwinolide, has been isolated from the Antarctic Dendroceratid sponge Dendrilla membranosa. Characterized on the basis of spectroscopic and crystallographic analysis, the central seven-membered ring is hypothesized to originate from a ring-expansion of a spongian precursor. Darwinolide displays 4-fold selectivity against the biofilm phase of methicillin-resistant Staphylococcus aureus compared to the planktonic phase and may provide a scaffold for the development of therapeutics for this difficult to treat infection.

  12. Darwinolide, a New Diterpene Scaffold That Inhibits Methicillin-Resistant Staphylococcus aureus Biofilm from the Antarctic Sponge Dendrilla membranosa

    PubMed Central

    2016-01-01

    A new rearranged spongian diterpene, darwinolide, has been isolated from the Antarctic Dendroceratid sponge Dendrilla membranosa. Characterized on the basis of spectroscopic and crystallographic analysis, the central seven-membered ring is hypothesized to originate from a ring-expansion of a spongian precursor. Darwinolide displays 4-fold selectivity against the biofilm phase of methicillin-resistant Staphylococcus aureus compared to the planktonic phase and may provide a scaffold for the development of therapeutics for this difficult to treat infection. PMID:27175857

  13. Helikaurolides A-D with a Diterpene-Sesquiterpene Skeleton from Supercritical Fluid Extracts of Helianthus annuus L. var. Arianna.

    PubMed

    Torres, Ascensión; Molinillo, José M G; Varela, Rosa M; Casas, Lourdes; Mantell, Casimiro; Martínez de la Ossa, Enrique J; Macías, Francisco A

    2015-10-01

    Four novel compounds (1-4) with an unprecedented skeleton that combines a sesquiterpene lactone and a kaurane diterpene acid were isolated from Helianthus annuus L. var. Arianna extract, which was obtained under supercritical conditions. The structures of 1-4 were elucidated by NMR and MS analyses. The biosynthetic routes involve sesquiterpene lactones and kauranic acid, both of which were previously isolated from this species.

  14. Biochemical characterization of the castor bean ent-kaurene synthase(-like) family supports quantum chemical view of diterpene cyclization

    PubMed Central

    Jackson, Alana J.; Hershey, David M.; Chesnut, Taylor; Xu, Meimei; Peters, Reuben J.

    2014-01-01

    It has become apparent that plants have extensively diversified their arsenal of labdane-related diterpenoids (LRDs), in part via gene duplication and neo-functionalization of the ancestral ent-kaurene synthase (KS) required for gibberellin metabolism. For example, castor bean (Ricinus communis) was previously shown to produce an interesting set of biosynthetically related diterpenes, specifically ent-sandracopimaradiene, ent-beyerene, and ent-trachylobane, in addition to ent-kaurene, using four separate diterpene synthases, albeit these remain unidentified. Notably, despite mechanistic similarity of the underlying reaction to that catalyzed by KSs, ent-beyerene and ent-trachylobane synthases have not yet been identified. Given our interest in LRD biosynthesis, and the recent availability of the castor bean genome sequence, we applied a synthetic biology approach to biochemically characterize the four KS(-like) enzymes [KS(L)s] found in Ricinus communis [i.e., the RcKS(L)s]. In particular, using bacteria engineered to produce the relevant ent-copalyl diphosphate precursor and synthetic genes based on the predicted RcKS(L)s, although this ultimately required correction of a “splicing” error in one of the predicted genes, highlighting the dependence of such a synthetic biology approach on accurate gene sequences. Nevertheless, we can assign each of the four RcKS(L)s to one of the previously observed diterpene synthase activities, providing access to functionally novel enzymes. Intriguingly, the product distribution of the RcKS(L)s seems to support the distinct diterpene synthase reaction mechanism proposed by quantum chemical calculations, rather than the classically proposed pathway. PMID:24810014

  15. Modularity of Conifer Diterpene Resin Acid Biosynthesis: P450 Enzymes of Different CYP720B Clades Use Alternative Substrates and Converge on the Same Products.

    PubMed

    Geisler, Katrin; Jensen, Niels Berg; Yuen, Macaire M S; Madilao, Lina; Bohlmann, Jörg

    2016-05-01

    Cytochrome P450 enzymes of the CYP720B subfamily play a central role in the biosynthesis of diterpene resin acids (DRAs), which are a major component of the conifer oleoresin defense system. CYP720Bs exist in families of up to a dozen different members in conifer genomes and fall into four different clades (I-IV). Only two CYP720B members, loblolly pine (Pinus taeda) PtCYP720B1 and Sitka spruce (Picea sitchensis) PsCYP720B4, have been characterized previously. Both are multisubstrate and multifunctional clade III enzymes, which catalyze consecutive three-step oxidations in the conversion of diterpene olefins to DRAs. These reactions resemble the sequential diterpene oxidations affording ent-kaurenoic acid from ent-kaurene in gibberellin biosynthesis. Here, we functionally characterized the CYP720B clade I enzymes CYP720B2 and CYP720B12 in three different conifer species, Sitka spruce, lodgepole pine (Pinus contorta), and jack pine (Pinus banksiana), and compared their activities with those of the clade III enzymes CYP720B1 and CYP720B4 of the same species. Unlike the clade III enzymes, clade I enzymes were ultimately found not to be active with diterpene olefins but converted the recently discovered, unstable diterpene synthase product 13-hydroxy-8(14)-abietene. Through alternative routes, CYP720B enzymes of both clades produce some of the same profiles of conifer oleoresin DRAs (abietic acid, neoabietic acid, levopimaric acid, and palustric acid), while clade III enzymes also function in the formation of pimaric acid, isopimaric acid, and sandaracopimaric acid. These results highlight the modularity of the specialized (i.e. secondary) diterpene metabolism, which produces conifer defense metabolites through variable combinations of different diterpene synthase and CYP720B enzymes. PMID:26936895

  16. Modularity of Conifer Diterpene Resin Acid Biosynthesis: P450 Enzymes of Different CYP720B Clades Use Alternative Substrates and Converge on the Same Products.

    PubMed

    Geisler, Katrin; Jensen, Niels Berg; Yuen, Macaire M S; Madilao, Lina; Bohlmann, Jörg

    2016-05-01

    Cytochrome P450 enzymes of the CYP720B subfamily play a central role in the biosynthesis of diterpene resin acids (DRAs), which are a major component of the conifer oleoresin defense system. CYP720Bs exist in families of up to a dozen different members in conifer genomes and fall into four different clades (I-IV). Only two CYP720B members, loblolly pine (Pinus taeda) PtCYP720B1 and Sitka spruce (Picea sitchensis) PsCYP720B4, have been characterized previously. Both are multisubstrate and multifunctional clade III enzymes, which catalyze consecutive three-step oxidations in the conversion of diterpene olefins to DRAs. These reactions resemble the sequential diterpene oxidations affording ent-kaurenoic acid from ent-kaurene in gibberellin biosynthesis. Here, we functionally characterized the CYP720B clade I enzymes CYP720B2 and CYP720B12 in three different conifer species, Sitka spruce, lodgepole pine (Pinus contorta), and jack pine (Pinus banksiana), and compared their activities with those of the clade III enzymes CYP720B1 and CYP720B4 of the same species. Unlike the clade III enzymes, clade I enzymes were ultimately found not to be active with diterpene olefins but converted the recently discovered, unstable diterpene synthase product 13-hydroxy-8(14)-abietene. Through alternative routes, CYP720B enzymes of both clades produce some of the same profiles of conifer oleoresin DRAs (abietic acid, neoabietic acid, levopimaric acid, and palustric acid), while clade III enzymes also function in the formation of pimaric acid, isopimaric acid, and sandaracopimaric acid. These results highlight the modularity of the specialized (i.e. secondary) diterpene metabolism, which produces conifer defense metabolites through variable combinations of different diterpene synthase and CYP720B enzymes.

  17. Modularity of Conifer Diterpene Resin Acid Biosynthesis: P450 Enzymes of Different CYP720B Clades Use Alternative Substrates and Converge on the Same Products1[OPEN

    PubMed Central

    Yuen, Macaire M.S.; Bohlmann, Jörg

    2016-01-01

    Cytochrome P450 enzymes of the CYP720B subfamily play a central role in the biosynthesis of diterpene resin acids (DRAs), which are a major component of the conifer oleoresin defense system. CYP720Bs exist in families of up to a dozen different members in conifer genomes and fall into four different clades (I–IV). Only two CYP720B members, loblolly pine (Pinus taeda) PtCYP720B1 and Sitka spruce (Picea sitchensis) PsCYP720B4, have been characterized previously. Both are multisubstrate and multifunctional clade III enzymes, which catalyze consecutive three-step oxidations in the conversion of diterpene olefins to DRAs. These reactions resemble the sequential diterpene oxidations affording ent-kaurenoic acid from ent-kaurene in gibberellin biosynthesis. Here, we functionally characterized the CYP720B clade I enzymes CYP720B2 and CYP720B12 in three different conifer species, Sitka spruce, lodgepole pine (Pinus contorta), and jack pine (Pinus banksiana), and compared their activities with those of the clade III enzymes CYP720B1 and CYP720B4 of the same species. Unlike the clade III enzymes, clade I enzymes were ultimately found not to be active with diterpene olefins but converted the recently discovered, unstable diterpene synthase product 13-hydroxy-8(14)-abietene. Through alternative routes, CYP720B enzymes of both clades produce some of the same profiles of conifer oleoresin DRAs (abietic acid, neoabietic acid, levopimaric acid, and palustric acid), while clade III enzymes also function in the formation of pimaric acid, isopimaric acid, and sandaracopimaric acid. These results highlight the modularity of the specialized (i.e. secondary) diterpene metabolism, which produces conifer defense metabolites through variable combinations of different diterpene synthase and CYP720B enzymes. PMID:26936895

  18. Steroidal glycosides from the underground parts of Yucca glauca and their cytotoxic activities.

    PubMed

    Yokosuka, Akihito; Suzuki, Tomoka; Tatsuno, Satoru; Mimaki, Yoshihiro

    2014-05-01

    Six steroidal glycosides and 14 known compounds were isolated from the underground parts of Yucca glauca (Agavaceae). Their structures were determined from extensive spectroscopic analysis, including analysis of two-dimensional NMR data, and from chemical transformations. The compounds were also evaluated for cytotoxic activities against HL-60 human leukemia cells and A549 human lung adenocarcinoma cells. Four spirostanol glycosides and three furostanol glycosides exhibited cytotoxic activities against both HL-60 and A549 cells. Two of the compounds induced apoptosis in HL-60 cells.

  19. Two new cytotoxic triterpene glycosides from the sea cucumber Holothuria scabra.

    PubMed

    Han, Hua; Yi, Yanghua; Xu, Qiangzhi; La, Mingping; Zhang, Hongwei

    2009-12-01

    Two new triterpene glycosides, scabraside A (1) and B (2), and a structurally known compound (3), were isolated from the sea cucumber Holothuria scabra (Holothuriidae) collected from the South China Sea. Structure of these compounds was elucidated by spectroscopic and chemical methods. The glycosides 1 and 2 exhibit the same common structural features, i. e., the presence of 12- and 17-hydroxy groups in the holostane-type triterpene aglycone with a 9(11)-ene bond, but are different in the side chains of the triterpene aglycone. The glycosides 1 and 2 had significant in vitro cytotoxicity against four human tumor cell lines in comparison to 10-hydroxycamptothecin.

  20. Rhizovarins A-F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189.

    PubMed

    Gao, Shu-Shan; Li, Xiao-Ming; Williams, Katherine; Proksch, Peter; Ji, Nai-Yun; Wang, Bin-Gui

    2016-08-26

    Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A-F (1-6). Among them, compounds 1-3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines. PMID:27462726

  1. Isolation and antioxidant activity of galloyl flavonol glycosides from the seashore plant, Pemphis acidula.

    PubMed

    Masuda, T; Iritani, K; Yonemori, S; Oyama, Y; Takeda, Y

    2001-06-01

    Four kinds of galloyl flavonol glycosides were found in the leaf extract of Pemphis acidula, a plant growing on the subtropical seashore. Their chemical structures were elucidated to be quercetin or kaempferol 6"-O-galloyl-beta-D-glycosides by using spectroscopic and chemical analyses. One of the flavonols, kaempferol-3-O-(6-O-galloyl-beta-D-galactopyranoside), was newly isolated from natural sources and its structure was completely determined in this investigation. The antioxidant-related activities of the galloyl flavonoids were examined by the DPPH antiradical activity, inhibition of methyl linoleate oxidation, and inhibition of oxidative cell death. These results were compared with those of the corresponding non-galloylated flavonol glycosides and their aglycones. The galloyl flavonoids showed more efficient activity than that of the corresponding flavonol glycosides, but not more than that of the corresponding aglycones in the three assays applied.

  2. Solubility Enhancement of Steviol Glycosides and Characterization of Their Inclusion Complexes with Gamma-Cyclodextrin

    PubMed Central

    Upreti, Mani; Strassburger, Ken; Chen, You L.; Wu, Shaoxiong; Prakash, Indra

    2011-01-01

    Steviol glycosidesrebaudioside (reb) A, C and D have low aqueous solubilities. To improve their aqueous solubilities, inclusion complex of steviol glycosides, reb A, C and D and gamma cyclodextrin were prepared by freeze drying method and further characterized by means of differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. The effect of gamma cyclodextrin on chemical shifts of the steviol glycosides was also studied in proton NMR experiments as well as in solid state 13C CP/MAS NMR experiments. These results indicated that the steviol glycosides were clearly in inclusion complex formation with the gamma cyclodextrin which also results in solubility enhancement of these steviol glycosides. Phase solubility studies showed that amounts of soluble reb A, C and D increased with increasing amounts of gamma cyclodextrin indicating formation of 1:1 stoichiometric and higher order inclusion complexes. PMID:22174615

  3. [Problems in the use of cardiac glycosides in ischemic heart disease].

    PubMed

    Modersohn, D; Urbaszek, W

    1975-08-01

    With the help of instances from literature and own experimental and clinical experiences is described that a schematic digitalisation in ischaemic heart diseases is not worth being advocated scientifically. Heart glycosides are indicated especially then, when a heart insufficiency stands in the foreground. In the acute phase of infarction, without manifest heart insufficiency, however, in individual cases they can deteriorate the myocardial oxygen balance and thus the clinical course. In myocardial infarction with severe heart insufficiency up to the cardiogenic shock all therapeutic possibilities should be utilized; to this belongs also the application of glycosides. As a rule in cardiogenic shock after myocardial infarction glycosides have no sufficient measurable influence on haemodynamics. Heart glycosides together with an individually adapted kinetotherapy are of importance for the metaphylaxis in patients with infarction. PMID:1189495

  4. Analysis of supercooling-facilitating (anti-ice nucleation) activity of flavonol glycosides.

    PubMed

    Kasuga, Jun; Fukushi, Yukiharu; Kuwabara, Chikako; Wang, Donghui; Nishioka, Atsushi; Fujikawa, Emiko; Arakawa, Keita; Fujikawa, Seizo

    2010-04-01

    Deep supercooling xylem parenchyma cells (XPCs) of katsura tree (Cercidiphyllum japonicum) contain four kinds of flavonol glycosides with high supercooling-facilitating (anti-ice nucleation) activities. These flavonol glycosides have very similar structures, but their supercooling-facilitating activities are very different. In this study, we analyzed the supercooling-facilitating activities of 12 kinds of flavonol glycosides in order to determine the chemical structures that might affect supercooling-facilitating activity. All of the flavonol glycosides tested showed supercooling-facilitating activity, although the magnitudes of activity differed among the compounds. It was clear that the combination of the position of attachment of the glycosyl moiety, the kind of attached glycosyl moiety and the structure of aglycone determined the magnitude of anti-ice nucleation activity. However, there is still some ambiguity preventing the exact identification of features that affect the magnitude of supercooling-facilitating activity.

  5. Enzyme-catalyzed synthesis of heptyl-β-glycosides: effect of water coalescence at high temperature.

    PubMed

    Montiel, Carmina; Bustos-Jaimes, Ismael; Bárzana, Eduardo

    2013-09-01

    Alkyl glycosides can be synthesized by glycosidases in organic media with limited amounts of water. These systems, however, limit the solubility of the sugar substrates and decrease reaction yields. Herein we report the enzymatic synthesis of heptyl-β-glycosides in heptanol catalyzed by a hyperthermophilic β-glycosidase at 90°C. Our results indicate that dispersion of water in heptanol changes with time producing coalescence of water at the bottom of the reactor, playing a key role in the reaction yield. Water-soluble substrate, enzyme and products are concentrated in the aqueous phase, according to their partition coefficients, promoting side reactions that inactivate the enzyme. Reaction yield of heptyl-β-glycosides was 35% relative to lactose, at 7% water. The increase in the water phase to 12% diminished the enzyme inactivation and increased the heptyl-β-glycosides yield to 52%. Surface-active compounds, SDS and octyl glucoside, increased water dispersion but were unable to prevent coalescence.

  6. Kaempferol glycosides in the flowers of carnation and their contribution to the creamy white flower color.

    PubMed

    Iwashina, Tsukasa; Yamaguchi, Masa-atsu; Nakayama, Masayoshi; Onozaki, Takashi; Yoshida, Hiroyuki; Kawanobu, Shuji; Onoe, Hiroshi; Okamura, Masachika

    2010-12-01

    Three flavonol glycosides were isolated from the flowers of carnation cultivars 'White Wink' and 'Honey Moon'. They were identified from their UV, MS, 1H and 13C NMR spectra as kaempferol 3-O-neohesperidoside, kaempferol 3-O-sophoroside and kaempferol 3-O-glucosyl-(1 --> 2)-[rhamnosyl-(1 --> 6)-glucoside]. Referring to previous reports, flavonols occurring in carnation flowers are characterized as kaempferol 3-O-glucosides with additional sugars binding at the 2 and/or 6-positions of the glucose. The kaempferol glycoside contents of a nearly pure white flower and some creamy white flower lines were compared. Although the major glycoside was different in each line, the total kaempferol contents of the creamy white lines were from 5.9 to 20.9 times higher than the pure white line. Thus, in carnations, kaempferol glycosides surely contribute to the creamy tone of white flowers. PMID:21299117

  7. Effect of diterpenes isolated of the marine alga Canistrocarpus cervicornis against some toxic effects of the venom of the bothrops jararaca snake.

    PubMed

    Domingos, Thaisa Francielle Souza; Vallim, Magui Aparecida; Cavalcanti, Diana Negrão; Sanchez, Eládio Flores; Teixeira, Valéria Laneuville; Fuly, André Lopes

    2015-01-01

    Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture of two secodolastane diterpenes (linearol/isolinearol), previously isolated from the Brazilian marine brown alga, Canistrocarpus cervicornis, was evaluated against some of the toxic effects induced by B. jararaca venom. The mixture of diterpenes was dissolved in dimethylsulfoxide and incubated with venom for 30 min at room temperature, and then several in vivo (hemorrhage, edema and lethality) and in vitro (hemolysis, plasma clotting and proteolysis) assays were performed. The diterpenes inhibited hemolysis, proteolysis and hemorrhage, but failed to inhibit clotting and edema induced by B. jararaca venom. Moreover, diterpenes partially protected mice from lethality caused by B. jararaca venom. The search for natural inhibitors of B. jararaca venom in C. cervicornis algae is a relevant subject, since seaweeds are a rich and powerful source of active molecules which are as yet but poorly explored. Our results suggest that these diterpenes have the potential to be used against Bothropic envenomation accidents or to improve traditional treatments for snake bites.

  8. Molecular Cloning and Functional Analysis of Gene Clusters for the Biosynthesis of Indole-Diterpenes in Penicillium crustosum and P. janthinellum.

    PubMed

    Nicholson, Matthew J; Eaton, Carla J; Stärkel, Cornelia; Tapper, Brian A; Cox, Murray P; Scott, Barry

    2015-07-23

    The penitremane and janthitremane families of indole-diterpenes are abundant natural products synthesized by Penicillium crustosum and P. janthinellum. Using a combination of PCR, cosmid library screening, and Illumina sequencing we have identified gene clusters encoding enzymes for the synthesis of these compounds. Targeted deletion of penP in P. crustosum abolished the synthesis of penitrems A, B, D, E, and F, and led to accumulation of paspaline, a key intermediate for paxilline biosynthesis in P. paxilli. Similarly, deletion of janP and janD in P. janthinellum abolished the synthesis of prenyl-elaborated indole-diterpenes, and led to accumulation in the latter of 13-desoxypaxilline, a key intermediate for the synthesis of the structurally related aflatremanes synthesized by Aspergillus flavus. This study helps resolve the genetic basis for the complexity of indole-diterpene natural products found within the Penicillium and Aspergillus species. All indole-diterpene gene clusters identified to date have a core set of genes for the synthesis of paspaline and a suite of genes encoding multi-functional cytochrome P450 monooxygenases, FAD dependent monooxygenases, and prenyl transferases that catalyse various regio- and stereo- specific oxidations that give rise to the diversity of indole-diterpene products synthesized by this group of fungi.

  9. Contrasting Patterns of Diterpene Acid Induction by Red Pine and White Spruce to Simulated Bark Beetle Attack, and Interspecific Differences in Sensitivity Among Fungal Associates.

    PubMed

    Mason, Charles J; Klepzig, Kier D; Kopper, Brian J; Kersten, Philip J; Illman, Barbara L; Raffa, Kenneth F

    2015-06-01

    Conifers possess a suite of physiochemical defenses that protect their subcortical tissues from bark beetle - fungal complexes. These defenses include rapid induction of terpenoids and phenolics at the site of attack. Studies of the distribution, induction, and bioactivity of conifer terpenoids have focused heavily on monoterpenes. We assessed induction of diterpene acids in white spruce (Picea glauca) and red pine (Pinus resinosa) to fungal associates of two bark beetles, and the responses of four spruce beetle (Dendroctonus rufipennis)-associated fungi to three diterpene acids. Constitutive phloem contents differed between species, in that red pine had extremely low concentrations of diterpene acids, whereas white spruce had substantial constitutive levels. Induction differed quantitatively. Both red pine and white spruce exhibited marked increases, but red pine underwent greater increases and achieved higher concentrations than white spruce. Induction also differed qualitatively in that red pine showed lower diversity and fewer compositional changes during induction than white spruce. In red pine,fungal inoculation accompanying wounding elicited greater increases than wounding alone, but in white spruce total concentrations were higher following wounding alone. Spruce beetle fungal symbiont growth varied among species and compounds. Some diterpenes elicited both stimulatory and inhibitory effects on fungi, depending on concentration. All four fungi exhibited higher tolerances compared to those associated with pine bark beetles in previous studies. Variation in tolerances to, and potentially metabolism of, diterpene acids by symbionts may reflect differences in constitutive levels between spruce and pine, and partially explain differences in concentrations achieved during induction.

  10. Molecular Cloning and Functional Analysis of Gene Clusters for the Biosynthesis of Indole-Diterpenes in Penicillium crustosum and P. janthinellum

    PubMed Central

    Nicholson, Matthew J.; Eaton, Carla J.; Stärkel, Cornelia; Tapper, Brian A.; Cox, Murray P.; Scott, Barry

    2015-01-01

    The penitremane and janthitremane families of indole-diterpenes are abundant natural products synthesized by Penicillium crustosum and P. janthinellum. Using a combination of PCR, cosmid library screening, and Illumina sequencing we have identified gene clusters encoding enzymes for the synthesis of these compounds. Targeted deletion of penP in P. crustosum abolished the synthesis of penitrems A, B, D, E, and F, and led to accumulation of paspaline, a key intermediate for paxilline biosynthesis in P. paxilli. Similarly, deletion of janP and janD in P. janthinellum abolished the synthesis of prenyl-elaborated indole-diterpenes, and led to accumulation in the latter of 13-desoxypaxilline, a key intermediate for the synthesis of the structurally related aflatremanes synthesized by Aspergillus flavus. This study helps resolve the genetic basis for the complexity of indole-diterpene natural products found within the Penicillium and Aspergillus species. All indole-diterpene gene clusters identified to date have a core set of genes for the synthesis of paspaline and a suite of genes encoding multi-functional cytochrome P450 monooxygenases, FAD dependent monooxygenases, and prenyl transferases that catalyse various regio- and stereo- specific oxidations that give rise to the diversity of indole-diterpene products synthesized by this group of fungi. PMID:26213965

  11. Controlling selectivity and enhancing yield of flavonoid glycosides in recombinant yeast.

    PubMed

    Werner, Sean R; Morgan, John A

    2010-09-01

    Flavonoid glycosides are known for their medicinal properties and potential use as natural sweeteners. In this study, Saccharomyces cerevisiae expressing a flavonoid glucosyltransferase from Dianthus caryophyllus was used as a whole-cell biocatalyst. The yeast system's performance was characterized using the flavanone naringenin as a model substrate for the production of naringenin glycosides. It was found that final naringenin glycoside yields increased in a dose-dependent manner with increasing initial naringenin substrate concentrations. However, naringenin concentrations >0.5 mM did not give further enhancements in glycoside yield. In addition, a method for controlling overall selectivity was discovered where the glucose content in the culture medium could be altered to control the selectivity, making either naringenin-7-O-glucoside (N7O) or naringenin-4'-O-glucoside (N4O) the major products. The highest yields achieved were 87 mg/L of N7O and 82 mg/L of N4O using 40MSGI and 2xMSGI media, respectively. The effects of two intermediates involved in UDP-glucose biosynthesis, uridine 5'-monophosphate (UMP) and orotic acid, on glycoside yields were also determined. Addition of UMP to the culture medium significantly decreased glycoside yield. In contrast, addition of orotic acid to the culture medium significantly enhanced the glycoside yield and shifted the selectivity toward N7O. The highest naringenin glycoside yield achieved using 10 mM orotic acid in the 40MSGI media was 155 mg/L, a 71% conversion of substrate to product.

  12. A new taraxastane-type triterpenoid glycoside from the roots of Clematis uncinata.

    PubMed

    Li, Shuo-Guo; Li, Man-Mei; Zhao, Bing-Xin; Wang, Ying; Ye, Wen-Cai

    2015-01-01

    A new taraxastane-type triterpenoid glycoside, clematiunicinoside I (1), together with four known ones (2-5), was isolated from the roots of Clematis uncinata. The structure of the new compound was elucidated on the basis of spectroscopic analyses and acid hydrolysis. The cytotoxic activities of all the compounds against caski cervical cancer (Caski) cells were evaluated. This is the first report of the presence of taraxastane-type triterpenoid glycoside in the genus Clematis. PMID:26651184

  13. A New Resin Glycoside, Muricatin IX, from the Seeds of Ipomoea muricata.

    PubMed

    Ono, Masateru; Taketomi, Saki; Kakiki, Yuichi; Yasuda, Shin; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro

    2016-01-01

    A new resin glycoside, named muricatin IX (1), was isolated from the seeds of Ipomoea muricata (L.) JACQ. (Convolvulaceae). The structure of 1 was determined on the basis of spectroscopic data as well as chemical evidence. Compound 1 is the first representative of resin glycosides in which an organic acid connects the sugar moiety and the aglycone moiety to form macrocyclic ester ring. PMID:27581646

  14. Gmelinosides A-L, twelve acylated iridoid glycosides from Gmelina arborea.

    PubMed

    Hosny, M; Rosazza, J P

    1998-06-26

    Besides the known iridoids 6-O-alpha-L-rhamnopyranosylcatalpol (1), 6-O-(3"-O-trans-feruloyl)-alpha-L-rhamnopyranosylcatalpol (14), 6-O-(2"-O-acetyl-3", 4"-O-di-trans-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (15) and the known phenylpropanoid glycosides verbascoside (acteoside) and martynoside, 12 new acylated iridoid glycosides named gmelinosides A-L (2-13) have been isolated from the leaves of Gmelina arborea. These compounds were structurally characterized using a variety of spectral methods. PMID:9644056

  15. Synthesis of Double C-Glycoside Analogue of sTn

    PubMed Central

    Ress, Dino K.; Baytas, Sultan N.; Wang, Qun; Muñoz, Eva M.; Tokuzoki, Kazuo; Tomiyama, Hiroshi; Linhardt, Robert J.

    2014-01-01

    A sTn double C-glycoside, sTn analogue 2, was synthesized using samarium chemistry developed in our laboratory. Complications in the oxidation reaction affording aldehyde acceptor were overcome by double protection of amide and the use of a room-temperature ionic liquid as solvent. Studies are underway to conjugate the sTn double C-glycoside hapten 2 to KLH carrier protein for biological evaluation as a vaccine. PMID:16277348

  16. Characterization and Modeling of the Collision Induced Dissociation Patterns of Deprotonated Glycosphingolipids: Cleavage of the Glycosidic Bond

    NASA Astrophysics Data System (ADS)

    Rožman, Marko

    2016-01-01

    Glycosphingolipid fragmentation behavior was investigated by combining results from analysis of a series of negative ion tandem mass spectra and molecular modeling. Fragmentation patterns extracted from 75 tandem mass spectra of mainly acidic glycosphingolipid species (gangliosides) suggest prominent cleavage of the glycosidic bonds with retention of the glycosidic oxygen atom by the species formed from the reducing end (B and Y ion formation). Dominant product ions arise from dissociation of sialic acids glycosidic bonds whereas product ions resulting from cleavage of other glycosidic bonds are less abundant. Potential energy surfaces and unimolecular reaction rates of several low-energy fragmentation pathways leading to cleavage of glycosidic bonds were estimated in order to explain observed dissociation patterns. Glycosidic bond cleavage in both neutral (unsubstituted glycosyl group) and acidic glycosphingolipids was the outcome of the charge-directed intramolecular nucleophilic substitution (SN2) mechanism. According to the suggested mechanism, the nucleophile in a form of carboxylate or oxyanion attacks the carbon at position one of the sugar ring, simultaneously breaking the glycosidic bond and yielding an epoxide. For gangliosides, unimolecular reaction rates suggest that dominant product ions related to the cleavage of sialic acid glycosidic bonds are formed via direct dissociation channels. On the other hand, low abundant product ions related to the dissociation of other glycosidic bonds are more likely to be the result of sequential dissociation. Although results from this study mainly contribute to the understanding of glycosphingolipid fragmentation chemistry, some mechanistic findings regarding cleavage of the glycosidic bond may be applicable to other glycoconjugates.

  17. Taming the Reactivity of Glycosyl Iodides To Achieve Stereoselective Glycosidation.

    PubMed

    Gervay-Hague, Jacquelyn

    2016-01-19

    that even highly functionalized aglycon acceptors add. Following the coupling event, the TMS ethers are readily removed by methanolysis, and since all of the byproducts are volatile, multiple reactions can be performed in a single reaction vessel without isolation of intermediates. In this fashion, per-O-TMS monosaccharides can be converted to biologically relevant α-linked glycolipids in one pot. The stereochemical outcome of these reactions can also be switched to β-glycoside formation by addition of silver to chelate the iodide, thus favoring SN2 displacement of the α-iodide. While iodides derived from benzyl and silyl ether-protected oligosaccharides are susceptible to interglycosidic bond cleavage when treated with TMSI, the introduction of a single acetate protecting group prevents this unwanted side reaction. Partial acetylation of armed glycosyl iodides also attenuates HI elimination side reactions. Conversely, fully acetylated glycosyl iodides are deactivated and require metal catalysis in order for glycosidation to occur. Recent findings indicate that I2 activation of per-O-acetylated mono-, di-, and trisaccharides promotes glycosidation of cyclic ethers to give β-linked iodoalkyl glycoconjugates in one step. Products of these reactions have been converted into multivalent carbohydrate displays. With these synthetic pathways elucidated, chemical reactivity can be exquisitely controlled by the judicious selection of protecting groups to achieve high stereocontrol in step-economical processes.

  18. Taming the Reactivity of Glycosyl Iodides To Achieve Stereoselective Glycosidation.

    PubMed

    Gervay-Hague, Jacquelyn

    2016-01-19

    that even highly functionalized aglycon acceptors add. Following the coupling event, the TMS ethers are readily removed by methanolysis, and since all of the byproducts are volatile, multiple reactions can be performed in a single reaction vessel without isolation of intermediates. In this fashion, per-O-TMS monosaccharides can be converted to biologically relevant α-linked glycolipids in one pot. The stereochemical outcome of these reactions can also be switched to β-glycoside formation by addition of silver to chelate the iodide, thus favoring SN2 displacement of the α-iodide. While iodides derived from benzyl and silyl ether-protected oligosaccharides are susceptible to interglycosidic bond cleavage when treated with TMSI, the introduction of a single acetate protecting group prevents this unwanted side reaction. Partial acetylation of armed glycosyl iodides also attenuates HI elimination side reactions. Conversely, fully acetylated glycosyl iodides are deactivated and require metal catalysis in order for glycosidation to occur. Recent findings indicate that I2 activation of per-O-acetylated mono-, di-, and trisaccharides promotes glycosidation of cyclic ethers to give β-linked iodoalkyl glycoconjugates in one step. Products of these reactions have been converted into multivalent carbohydrate displays. With these synthetic pathways elucidated, chemical reactivity can be exquisitely controlled by the judicious selection of protecting groups to achieve high stereocontrol in step-economical processes. PMID:26524481

  19. Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora.

    PubMed Central

    Tamura, G; Gold, C; Ferro-Luzzi, A; Ames, B N

    1980-01-01

    Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many natural glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagne quercetin. Red wine, red grape juice, and tea were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed. PMID:6933540

  20. Transition of phenolics and cyanogenic glycosides from apricot and cherry fruit kernels into liqueur.

    PubMed

    Senica, Mateja; Stampar, Franci; Veberic, Robert; Mikulic-Petkovsek, Maja

    2016-07-15

    Popular liqueurs made from apricot/cherry pits were evaluated in terms of their phenolic composition and occurrence of cyanogenic glycosides (CGG). Analyses consisted of detailed phenolic and cyanogenic profiles of cherry and apricot seeds as well as beverages prepared from crushed kernels. Phenolic groups and cyanogenic glycosides were analyzed with the aid of high-performance liquid chromatography (HPLC) and mass spectrophotometry (MS). Lower levels of cyanogenic glycosides and phenolics have been quantified in liqueurs compared to fruit kernels. During fruit pits steeping in the alcohol, the phenolics/cyanogenic glycosides ratio increased and at the end of beverage manufacturing process higher levels of total analyzed phenolics were detected compared to cyanogenic glycosides (apricot liqueur: 38.79 μg CGG per ml and 50.57 μg phenolics per ml; cherry liqueur 16.08 μg CGG per ml and 27.73 μg phenolics per ml). Although higher levels of phenolics are characteristic for liqueurs made from apricot and cherry pits these beverages nevertheless contain considerable amounts of cyanogenic glycosides.

  1. Influence of steviol glycosides on the stability of vitamin C and anthocyanins.

    PubMed

    Woźniak, Łukasz; Marszałek, Krystian; Skąpska, Sylwia

    2014-11-19

    A high level of sweetness and health-promoting properties make steviol glycosides an interesting alternative to sugars or artificial sweeteners. The radical oxygen species scavenging activity of these compounds may influence the stability of labile particles present in food. Model buffer solutions containing steviol glycosides, a selected food antioxidant (vitamin C or anthocyanins), and preservative were analyzed during storage. The addition of steviol glycosides at concentrations of 50, 125, and 200 mg/L increased the stability of both ascorbic and dehydroascorbic acid (degradation rates decreased up to 3.4- and 4.5-fold, respectively); the effect was intensified by higher sweetener concentrations and higher acidity of the solutions. Glycosides used alone did not affect the stability of anthocyanins; however, they enhanced the protective effect of sugars; half-life times increased by ca. 33% in the presence of sucrose (100 g/L) and by ca. 52% when both sucrose (100 g/L) and glycosides (total 200 mg/L) were used. Steviol glycosides concentrations remained stable during experiments. PMID:25376304

  2. Transition of phenolics and cyanogenic glycosides from apricot and cherry fruit kernels into liqueur.

    PubMed

    Senica, Mateja; Stampar, Franci; Veberic, Robert; Mikulic-Petkovsek, Maja

    2016-07-15

    Popular liqueurs made from apricot/cherry pits were evaluated in terms of their phenolic composition and occurrence of cyanogenic glycosides (CGG). Analyses consisted of detailed phenolic and cyanogenic profiles of cherry and apricot seeds as well as beverages prepared from crushed kernels. Phenolic groups and cyanogenic glycosides were analyzed with the aid of high-performance liquid chromatography (HPLC) and mass spectrophotometry (MS). Lower levels of cyanogenic glycosides and phenolics have been quantified in liqueurs compared to fruit kernels. During fruit pits steeping in the alcohol, the phenolics/cyanogenic glycosides ratio increased and at the end of beverage manufacturing process higher levels of total analyzed phenolics were detected compared to cyanogenic glycosides (apricot liqueur: 38.79 μg CGG per ml and 50.57 μg phenolics per ml; cherry liqueur 16.08 μg CGG per ml and 27.73 μg phenolics per ml). Although higher levels of phenolics are characteristic for liqueurs made from apricot and cherry pits these beverages nevertheless contain considerable amounts of cyanogenic glycosides. PMID:26948641

  3. Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora

    SciTech Connect

    Tamura, G.; Gold, C.; Ferro-Luzzi, A.; Ames, B.N.

    1980-08-01

    Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many natural glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagen quercetin. Red wine, red grape juice, and teas were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed.

  4. New Abietane Diterpenes from Euphorbia Pseudocactus Berger (Euphorbiaceae) and Their Antimicrobial Activity

    PubMed Central

    Abdel-Monem, Azza Ramy; Abdelrahman, Enas Hussein

    2016-01-01

    Background: Euphorbia is the largest genus in Euphorbiaceae. Terpenoids were isolated from most species of this genus. Objective: Since no previous study was reported about Euphorbia pseudocactus Berger, we started here a phytochemical investigation on this species to isolate and identify its terpenoid constituents and to estimate the antimicrobial activity of the isolated compounds. Materials and Methods: The n-hexane fraction of the ethanolic extract of E. pseudocactus Berger was chromatographed on silica gel columns, the structures of the isolated compounds (1–5) were identified based on their MS, 1 D, and 2 D NMR spectral data. The antimicrobial activity of the n-hexane fraction and the isolated compounds (1–4) was investigated using diffusion plate method against Gram-positive (Staphylococcus aureus [12600] and Bacillus subtilis [6051]) and Gram-negative (Pseudomonas aeruginosa [10145] and Escherichia coli [11775]) bacteria, yeast (Candida albicans [7102]), and fungi (Aspergillus flavus). Results: Two triterpenes (glut-5-en-3 β-ol [1] and olean-12,15-diene-3 β-ol [2]) and three abietane diterpene (3-hydoxy-19-cyclopropenoyloxy-abietane [3], ent-abieta-9,12,14-triene-12,16-olide [4], and 12,19-dihydroxy-abieta-5-ene [5]) were isolated. Compound 1 exhibited no antibacterial activity against the tested bacteria, compound 2 and n-hexane fraction exhibited weak activity, whereas compounds 3 and 4 showed moderate activity. All samples showed no activity against the tested yeast and fungi. Discussion and Conclusion: Five compounds were isolated for the 1st time from E. pseudocactus Berger, three of them (3–5) are new natural compounds. As the major isolated compound (1) exhibited no antimicrobial activity, the observed activity of the n-hexane fraction is mainly due to its diterpenoid constituents. SUMMARY Two known triterpenes and three new diterpenes were isolated from n-hexane fraction of Euphorbia pseudocactusThe abietane diterpenoids showed higher

  5. A new indole glycoside from the seeds of Raphanus sativus.

    PubMed

    Jin, Hong-Guang; Ko, Hae Ju; Chowdhury, Md Anisuzzaman; Lee, Dong-Sung; Woo, Eun-Rhan

    2016-06-01

    A new indole glycoside, β-D-glucopyranosyl 2-(methylthio)-1H-indole-3-carboxylate, named raphanuside A (1), as well as eight known compounds, β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (2), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-α-D-glucopyranoside (3), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (4), (3,4-O-disinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (5), isorhamnetin 3,4'-di-O-β-D-glucoside (6), isorhamnetin 3-O-β-D-glucoside-7-O-α-L-rhamnoside (7), isorhamnetin 3-O-β-D-glucoside (8) and 3'-O-methyl-(-)-epicatechin 7-O-β-D-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1-3 and 6-9, were isolated from this plant for the first time. The structures of compounds 1-9 were identified using 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-α stimulated MG-63 cells was also examined. PMID:27193305

  6. Structure and cytotoxicity of steroidal glycosides from Allium schoenoprasum.

    PubMed

    Timité, Gaoussou; Mitaine-Offer, Anne-Claire; Miyamoto, Tomofumi; Tanaka, Chiaki; Mirjolet, Jean-François; Duchamp, Olivier; Lacaille-Dubois, Marie-Aleth

    2013-04-01

    A phytochemical analysis of the whole plant of Allium schoenoprasum, has led to the isolation of four spirostane-type glycosides (1-4), and four known steroidal saponins. Their structures were elucidated mainly by 2D NMR spectroscopic analysis and mass spectrometry as (20S,25S)-spirost-5-en-3β,12β,21-triol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (1), (20S,25S)-spirost-5-en-3β,11α,21-triol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (2), laxogenin 3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-glucopyranoside (3), and (25R)-5α-spirostan-3β,11α-diol 3-O-β-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside (4). Four of the isolated compounds were tested for cytotoxic activity against the HCT 116 and HT-29 human colon cancer cell lines. PMID:23357597

  7. Extracellular Glycoside Hydrolase Activities in the Human Oral Cavity

    PubMed Central

    Walker, Lauren C.; Dodds, Michael W. J.; Hanley, A. Bryan

    2015-01-01

    Carbohydrate availability shifts when bacteria attach to a surface and form biofilm. When salivary planktonic bacteria form an oral biofilm, a variety of polysaccharides and glycoproteins are the primary carbon sources; however, simple sugar availabilities are limited due to low diffusion from saliva to biofilm. We hypothesized that bacterial glycoside hydrolase (GH) activities would be higher in a biofilm than in saliva in order to maintain metabolism in a low-sugar, high-glycoprotein environment. Salivary bacteria from 13 healthy individuals were used to grow in vitro biofilm using two separate media, one with sucrose and the other limiting carbon sources to a complex carbohydrate. All six GHs measured were higher in vitro when grown in the medium with complex carbohydrate as the sole carbon source. We then collected saliva and overnight dental plaque samples from the same individuals and measured ex vivo activities for the same six enzymes to determine how oral microbial utilization of glycoconjugates shifts between the planktonic phase in saliva and the biofilm phase in overnight dental plaque. Overall higher GH activities were observed in plaque samples, in agreement with in vitro observation. A similar pattern was observed in GH activity profiles between in vitro and ex vivo data. 16S rRNA gene analysis showed that plaque samples had a higher abundance of microorganisms with larger number of GH gene sequences. These results suggest differences in sugar catabolism between the oral bacteria located in the biofilm and those in saliva. PMID:26048943

  8. Effects of synthetic glycosides on steroid balance in Macaca fascicularis

    SciTech Connect

    Malinow, M.R.; Elliott, W.H.; McLaughlin, P.; Upson, B.

    1987-01-01

    The predominantly beta-anomer of diosgenin glucoside (DG) was synthesized and its effects on cholesterol homeostasis were tested in monkeys. Cynomolgus macaques (Macaca fascicularis) were fed, during two 3-week periods, a semipurified diet with 0.1% cholesterol and a similar ration containing 1% DG, respectively. A Chow diet was given for 5 weeks between the experimental periods. Cholesterol and bile acid balance were analyzed during the last week of each semipurified diet. Diosgenin glucoside reduced cholesterolemia from 292 mg/dl to 172 mg/dl, decreased intestinal absorption of exogenous cholesterol from 62.4% to 26.0%, and increased secretion of endogenous cholesterol from -0.8 to 93.5 mg/day. The fecal excretion of neutral steroids rose from 40.7 to 157.3 mg/day; that of bile acids changed, nonsignificantly, from 23.1 to 16.0 mg/day. The cholesterol balance was -44 mg/day in the control period, and 88 mg/day in the DG-fed animals. No toxic signs were observed. Thus, when long-term studies demonstrate that the glucoside is well tolerated, DG and other synthetic glycosides with similar activities may be of use in the management of hypercholesterolemia and atherosclerosis.

  9. [Determination of 7 flavonol glycosides in Ginkgo biloba reference extract].

    PubMed

    Wang, Jing-hui; Chen, Jing; Wang, Meng-meng; Fu, Xin-tong; Chen, You-gen; Guo, Hong-zhu

    2015-10-01

    Six flavonol glycosides were isolated and calibrated from Ginkgo biloba extract, and then used to calibrate the content in 2 baiches of G. biloba reference extract, so was rutin. RSD values of rutin, kaempferol-3-O-rutinoside, kaempferol-3-O-rhamnoside-2-glu- coside, quercetin-3-O-rhamnop-yranosyl-2-O-(6-O-p-coumaroyl)-glucoside, kaempferol-3-O-rhamnopyranosyl-2-O-(6-O-p-coum-aroyl) - glucoside were around 1.1%-4.6%, nevertheless, RSD values of quercetin-3-O-glucoside and isorhamnetin-3-O-rutinoside were more than 5%. According to the results, the reference extract of G. biloba can be used as the substitute to determine rutin, kaempferol-3-O- rutinoside, kaempferol-3-O-rhamnoside-2-glucoside, quercetin-3-O-rhamnopyranosyl-2-O-(6-O-p-coumaroyl)-glucoside and kaempferol-3-0-rhamnopyranosyl-2-O-(6-O-p-coumaroyl)-glucoside instead of corresponding reference substances. So reference extract in place of single component reference in assay is feasible. PMID:27062820

  10. Polyketide Glycosides from Bionectria ochroleuca Inhibit Candida albicans Biofilm Formation

    PubMed Central

    2015-01-01

    One of the challenges presented by Candida infections is that many of the isolates encountered in the clinic produce biofilms, which can decrease these pathogens’ susceptibilities to standard-of-care antibiotic therapies. Inhibitors of fungal biofilm formation offer a potential solution to counteracting some of the problems associated with Candida infections. A screening campaign utilizing samples from our fungal extract library revealed that a Bionectria ochroleuca isolate cultured on Cheerios breakfast cereal produced metabolites that blocked the in vitro formation of Candida albicans biofilms. A scale-up culture of the fungus was undertaken using mycobags (also known as mushroom bags or spawn bags), which afforded four known [TMC-151s C–F (1–4)] and three new [bionectriols B–D (5–7)] polyketide glycosides. All seven metabolites exhibited potent biofilm inhibition against C. albicans SC5314, as well as exerted synergistic antifungal activities in combination with amphotericin B. In this report, we describe the structure determination of the new metabolites, as well as compare the secondary metabolome profiles of fungi grown in flasks and mycobags. These studies demonstrate that mycobags offer a useful alternative to flask-based cultures for the preparative production of fungal secondary metabolites. PMID:25302529

  11. Antioxidant flavone glycosides from the leaves of Sasa borealis.

    PubMed

    Park, Hae-Suk; Lim, Ju Hee; Kim, Hyun Jung; Choi, Hyun Jin; Lee, Ik-Soo

    2007-02-01

    Sasa borealis (Poaceae) is a perennial medicinal plant which is a major source of bamboo leaves in Korea. The n-BuOH extract of S. borealis leaves exhibited significant antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and a cytoprotective effect against oxidative damage in HepG2 cells. Bioactivity-guided fractionation by column chromatography led to the isolation of two antioxidative flavonoid C-glycoside derivatives, isoorientin (2) and isoorientin 2"-O-alpha-L-rhamnoside (4) along with tricin 7-O-beta-D-glucopyranoside (1) and apigenin 6-C-beta-D-xylopyranosyl-8-C-beta-D-glucopyranoside (3). Their structures were identified on the basis of chemical and spectroscopic methods. The radical scavenging activity and cytoprotective effect against oxidative damage of all the isolated compounds were also evaluated. Isoorientin (2) and isoorientin 2-O-alpha-L-rhamnoside (4) showed potent free radical scavenging activity with IC50 values of 9.5 and 34.5 microM, respectively, and strong cytoprotective effects against t-BOOH-induced oxidative damage in HepG2 cells, at very low concentrations of 1.1 microM isoorientin and 0.8 microM isoorientin 2-O-alpha-L-rhamnoside. This is the first report of the isolation and antioxidant activity of compounds 2 and 4 from S. borealis. PMID:17366736

  12. Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa peregrina.

    PubMed

    Ayyari, Mahdi; Salehi, Peyman; Ebrahimi, Samad Nejad; Zimmermann, Stefanie; Portmann, Lena; Krauth-Siegel, R Luise; Kaiser, Marcel; Brun, Reto; Rezadoost, Hassan; Rezazadeh, Shamsali; Hamburger, Matthias

    2014-01-01

    O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), along with 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of Moringa peregrina. The compounds were tested for in vitro activity against Trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4 with an IC50 of 0.10 µM against T.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity. Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T.b. rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity. Administration of 10 mg/kg body weight/day resulted in a 95% reduction of parasitemia on day 7 postinfection, but did not cure the animals. Because of its high in vitro activity and its ability to irreversibly inhibit trypanothione reductase, an attractive parasite-specific target enzyme, 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure for the development and characterization of novel antitrypanosomal drugs.

  13. Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death.

    PubMed

    Feng, Qian; Leong, Wa Seng; Liu, Liang; Chan, Wai-In

    2016-01-01

    Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34⁺CD38(-) leukemic stem-like cells, but not the more mature CD34⁺CD38⁺ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G₂/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future. PMID:27110755

  14. [Determination of 7 flavonol glycosides in Ginkgo biloba reference extract].

    PubMed

    Wang, Jing-hui; Chen, Jing; Wang, Meng-meng; Fu, Xin-tong; Chen, You-gen; Guo, Hong-zhu

    2015-10-01

    Six flavonol glycosides were isolated and calibrated from Ginkgo biloba extract, and then used to calibrate the content in 2 baiches of G. biloba reference extract, so was rutin. RSD values of rutin, kaempferol-3-O-rutinoside, kaempferol-3-O-rhamnoside-2-glu- coside, quercetin-3-O-rhamnop-yranosyl-2-O-(6-O-p-coumaroyl)-glucoside, kaempferol-3-O-rhamnopyranosyl-2-O-(6-O-p-coum-aroyl) - glucoside were around 1.1%-4.6%, nevertheless, RSD values of quercetin-3-O-glucoside and isorhamnetin-3-O-rutinoside were more than 5%. According to the results, the reference extract of G. biloba can be used as the substitute to determine rutin, kaempferol-3-O- rutinoside, kaempferol-3-O-rhamnoside-2-glucoside, quercetin-3-O-rhamnopyranosyl-2-O-(6-O-p-coumaroyl)-glucoside and kaempferol-3-0-rhamnopyranosyl-2-O-(6-O-p-coumaroyl)-glucoside instead of corresponding reference substances. So reference extract in place of single component reference in assay is feasible.

  15. Extracellular Glycoside Hydrolase Activities in the Human Oral Cavity.

    PubMed

    Inui, Taichi; Walker, Lauren C; Dodds, Michael W J; Hanley, A Bryan

    2015-08-15

    Carbohydrate availability shifts when bacteria attach to a surface and form biofilm. When salivary planktonic bacteria form an oral biofilm, a variety of polysaccharides and glycoproteins are the primary carbon sources; however, simple sugar availabilities are limited due to low diffusion from saliva to biofilm. We hypothesized that bacterial glycoside hydrolase (GH) activities would be higher in a biofilm than in saliva in order to maintain metabolism in a low-sugar, high-glycoprotein environment. Salivary bacteria from 13 healthy individuals were used to grow in vitro biofilm using two separate media, one with sucrose and the other limiting carbon sources to a complex carbohydrate. All six GHs measured were higher in vitro when grown in the medium with complex carbohydrate as the sole carbon source. We then collected saliva and overnight dental plaque samples from the same individuals and measured ex vivo activities for the same six enzymes to determine how oral microbial utilization of glycoconjugates shifts between the planktonic phase in saliva and the biofilm phase in overnight dental plaque. Overall higher GH activities were observed in plaque samples, in agreement with in vitro observation. A similar pattern was observed in GH activity profiles between in vitro and ex vivo data. 16S rRNA gene analysis showed that plaque samples had a higher abundance of microorganisms with larger number of GH gene sequences. These results suggest differences in sugar catabolism between the oral bacteria located in the biofilm and those in saliva.

  16. In vitro and in vivo antitumor effect of trachylobane-360, a diterpene from Xylopia langsdorffiana.

    PubMed

    Pita, João Carlos Lima Rodrigues; Xavier, Aline Lira; de Sousa, Tatyanna Kelvia Gomes; Mangueira, Vivianne Mendes; Tavares, Josean Fechine; de Oliveira Júnior, Robson José; Veras, Robson Cavalcante; Pessoa, Hilzeth de Luna Freire; da Silva, Marcelo Sobral; Morelli, Sandra; Ávila, Veridiana de Melo Rodrigues; da Silva, Teresinha Gonçalves; Diniz, Margareth de Fátima Formiga Melo; Castello-Branco, Marianna Vieira Sobral

    2012-01-01

    Trachylobane-360 (ent-7α-acetoxytrachyloban-18-oic acid) was isolated from Xylopia langsdorffiana. Studies have shown that it has weak cytotoxic activity against tumor and non-tumor cells. This study investigated the in vitro and in vivo antitumor effects of trachylobane-360, as well as its cytotoxicity in mouse erythrocytes. In order to evaluate the in vivo toxicological aspects related to trachylobane-360 administration, hematological, biochemical and histopathological analyses of the treated animals were performed. The compound exhibited a concentration-dependent effect in inducing hemolysis with HC₅₀ of 273.6 µM, and a moderate in vitro concentration-dependent inhibitory effect on the proliferation of sarcoma 180 cells with IC₅₀ values of 150.8 µM and 150.4 µM, evaluated by the trypan blue exclusion test and MTT reduction assay, respectively. The in vivo inhibition rates of sarcoma 180 tumor development were 45.60, 71.99 and 80.06% at doses of 12.5 and 25 mg/kg of trachylobane-360 and 25 mg/kg of 5-FU, respectively. Biochemical parameters were not altered. Leukopenia was observed after 5-FU treatment, but this effect was not seen with trachylobane-360 treatment. The histopathological analysis of liver and kidney showed that both organs were mildly affected by trachylobane-360 treatment. Trachylobane-360 showed no immunosuppressive effect. In conclusion, these data reinforce the anticancer potential of this natural diterpene.

  17. The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

    PubMed

    Lozano, E; Strauss, M; Spina, R; Cifuente, D; Tonn, C; Rivarola, H W; Sosa, M A

    2016-02-01

    The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.

  18. A new myrsinol-type diterpene polyester from Euphorbia dracunculoides Lam.

    PubMed

    Wang, Li; Yang, Jing; Chi, Yu-Qian; Ouyang, Wen-Bin; Zang, Zhen; Huang, Sheng-Xiong; Cao, Pei; Zhao, Yong

    2015-01-01

    A new myrsinol-type diterpene polyester, 14-deoxo-3β-O-propinoyl-2α,5α,7β,15β-tetra-O-acetyl-14α-O-benzoyl-myrsinol (1), and its known analogue, 14-deoxo-3β-O-prorionyl-5α,15β-di-O-acetyl-7β-O-nicotinoyl-myrsinol-14β-acetate (2), together with a monoterpenoid, pubinernoid A (3), two indole alkaloids, neoechinulin A (4) and dihydroxyisoechinulin A (5), two benzene derivatives, siringin (6) and (3-methoxyphenyl) acetic acid (7), were isolated from the 70% acetone extract of the aerial parts of Euphorbia dracunculoides Lam. Their structures were elucidated on the basis of spectroscopic evidence and comparison with literature reports. The absolute configuration of 1 was deduced by comparing experimental and calculated ECD spectra. Among them, compounds 4 and 5 were first obtained from the plant source. In addition, the (13)C NMR data of compound 2 was reported for the first time.

  19. Antioxidant activity and mechanism of the abietane-type diterpene ferruginol.

    PubMed

    Saijo, H; Kofujita, H; Takahashi, K; Ashitani, T

    2015-01-01

    The antioxidant activity of the abietane-type diterpene ferruginol was evaluated by comparison with that of carnosic acid, ( ± )-α-tocopherol and dibutylhydroxytoluene using 2,2-diphenyl-1-picrylhydrazyl, β-carotene bleaching and linoleic acid assays. Ferruginol had the lowest antioxidant activity of this group using the 2,2-diphenyl-1-picrylhydrazyl and β-carotene methods in polar solvent buffer. However, ferruginol exhibited stronger activity than carnosic acid and α-tocopherol for linoleic acid oxidation under non-solvent conditions. Five peaks corresponding to ferruginol derivatives were detected through GC-MS analysis of the reaction between ferruginol and methyl linoleate. The three reaction products were identified as dehydroferruginol, 7β-hydroxyferruginol and sugiol, and the other two peaks were assumed to be 7α-hydroxyferruginol and the quinone methide derivative of ferruginol. The time course of the reaction suggests that the quinone methide was produced early in the reaction and reacted further to produce dehydroferruginol, 7-hydroxyferruginol and sugiol. Thus, we inferred that quinone methide formation was a key step in the antioxidant reaction of ferruginol.

  20. (+)-Dehydroabietic Acid, an Abietane-Type Diterpene, Inhibits Staphylococcus aureus Biofilms in Vitro

    PubMed Central

    Fallarero, Adyary; Skogman, Malena; Kujala, Janni; Rajaratnam, Mohanathas; Moreira, Vânia M.; Yli-Kauhaluoma, Jari; Vuorela, Pia

    2013-01-01

    Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates. PMID:23739682

  1. Advanced Structural Determination of Diterpene Esters Using Molecular Modeling and NMR Spectroscopy.

    PubMed

    Nothias-Scaglia, Louis-Félix; Gallard, Jean-François; Dumontet, Vincent; Roussi, Fanny; Costa, Jean; Iorga, Bogdan I; Paolini, Julien; Litaudon, Marc

    2015-10-23

    Three new jatrophane esters (1-3) were isolated from Euphorbia amygdaloides ssp. semiperfoliata, including an unprecedented macrocyclic jatrophane ester bearing a hemiketal substructure, named jatrohemiketal (3). The chemical structures of compounds 1-3 and their relative configurations were determined by spectroscopic analysis. The absolute configuration of compound 3 was determined unambiguously through an original strategy combining NMR spectroscopy and molecular modeling. Conformational search calculations were performed for the four possible diastereomers 3a-3d differing in their C-6 and C-9 stereocenters, and the lowest energy conformer was used as input structure for geometry optimization. The prediction of NMR parameters ((1)H and (13)C chemical shifts and (1)H-(1)H coupling constants) by density functional theory (DFT) calculations allowed identifying the most plausible diastereomer. Finally, the stereostructure of 3 was solved by comparison of the structural features obtained by molecular modeling for 3a-3d with NMR-derived data (the values of dihedral angles deduced from the vicinal proton-proton coupling constants ((3)JHH) and interproton distances determined by ROESY). The methodology described herein provides an efficient way to solve or confirm structural elucidation of new macrocyclic diterpene esters, in particular when no crystal structure is available.

  2. Intracellular Generation of a Diterpene-Peptide Conjugate that Inhibits 14-3-3-Mediated Interactions.

    PubMed

    Parvatkar, Prakash; Kato, Nobuo; Uesugi, Motonari; Sato, Shin-Ichi; Ohkanda, Junko

    2015-12-23

    Synthetic agents that disrupt intracellular protein-protein interactions (PPIs) are highly desirable for elucidating signaling networks and developing new therapeutics. However, designing cell-penetrating large molecules equipped with the many functional groups necessary for binding to large interfaces remains challenging. Here, we describe a rational strategy for the intracellular oxime ligation-mediated generation of an amphipathic bivalent inhibitor composed of a peptide and diterpene natural product, fusicoccin, which binds 14-3-3 protein with submicromolar affinity. Our results demonstrate that co-treatment of cells with small module molecules, the aldehyde-containing fusicoccin 1 and the aminooxy-containing peptide 2, generates the corresponding conjugate 3 in cells, resulting in significant cytotoxicity. In contrast, chemically synthesized 3 is not cytotoxic, likely due to its inability to penetrate cells. Compound 3, but not 1 or 2, disrupts endogenous 14-3-3/cRaf interactions, suggesting that cell death is caused by inhibition of 14-3-3 activity. These results suggest that intracellular generation of large-sized molecules may serve as a new approach for modulating PPIs.

  3. Induction of Mitochondrial Dysfunction and Oxidative Stress in Leishmania donovani by Orally Active Clerodane Diterpene

    PubMed Central

    Kathuria, Manoj; Bhattacharjee, Arindam; Sashidhara, Koneni V.; Singh, Suriya Pratap

    2014-01-01

    This study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (K-09) in Leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (VL). K-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in L. donovani promastigotes. Mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the cytosol, impairing ATP production. Oxidative stress caused the depletion of reduced glutathione, while pretreatment with antioxidant N-acetyl cysteine (NAC) was able to abrogate oxidative stress. However, NAC failed to restore the mitochondrial membrane potential or intracellular calcium homeostasis after K-09 treatment, suggesting that the generation of oxidative stress is a downstream event relative to the other events. Caspase-3/-7-like protease activity and genomic DNA fragmentation were observed. Electron microscopy studies revealed gross morphological alterations typical of apoptosis, including severe mitochondrial damage, pyknosis of the nucleus, structural disruption of the mitochondrion-kinetoplast complex, flagellar pocket alterations, and the displacement of organelles. Moreover, an increased number of lipid droplets was detected after K-09 treatment, which is suggestive of altered lipid metabolism. Our results indicate that K-09 induces mitochondrial dysfunction and oxidative stress-mediated apoptotic cell death in L. donovani promastigotes, sharing many features with metazoan apoptosis. These mechanistic insights provide a basis for further investigation toward the development of K-09 as a potential drug candidate for VL. PMID:25070112

  4. The coffee diterpene kahweol suppress the inducible nitric oxide synthase expression in macrophages.

    PubMed

    Kim, Ji Young; Jung, Kyung Sik; Lee, Kyung Jin; Na, Han Kwang; Chun, Hyo-Kon; Kho, Yung-Hee; Jeong, Hye Gwang

    2004-09-30

    Excessive nitric oxide production by inducible nitric oxide synthase (iNOS) in stimulated inflammatory cells is thought to be a causative factor of cellular injury in cases of inflammation. In recent studies, it has been shown that kahweol, coffee-specific diterpene, exhibit chemoprotective effects. In this study, we investigated the effects of kahweol on the production of and the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The nitrite production induced by LPS was markedly reduced in a dose-dependent manner. In addition, kahweol suppressed the expression of iNOS protein and iNOS mRNA. Since iNOS transcription has been shown to be under the control of the transcription factor, NF-kappaB, the effects of kahweol on NF-kappaB activation were examined. Transient transfection experiments showed that kahweol inhibited NF-kappaB-dependent transcriptional activity. Moreover, electrophoretic mobility shift assay experiments indicated that kahweol blocked the LPS-induced activation of NF-kappaB. The results of these studies suggest that the suppression of the transcriptional activation of iNOS by kahweol might be mediated through the inhibition of NF-kappaB activation. Taken together, the results of our study provide evidence that kahweol possess an anti-inflammatory potential, which constitutes a previously unrecognized biologic activity, and which may provide new insights into the inflammatory process. PMID:15327829

  5. Phenolic diterpenes from rosemary suppress cAMP responsiveness of gluconeogenic gene promoters.

    PubMed

    Yun, Young Sook; Noda, Sachie; Shigemori, Genta; Kuriyama, Ryunosuke; Takahashi, Shigeru; Umemura, Mariko; Takahashi, Yuji; Inoue, Hideshi

    2013-06-01

    The cAMP/protein kinase A/cAMP response element (CRE)-binding protein pathway is important for various physiological aspects including regulation of gluconeogenic gene expression. Rosemary, a well-known herb, has been reported to decrease blood glucose levels. We found that methanol extracts of rosemary suppressed forskolin (FSK)-stimulated luciferase expression under the control of CRE, as well as the promoters for cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) and glucose-6-phosphatase (G6Pase) catalytic subunit genes in human hepatoma HepG2 cells. Three abietane-type diterpenes and two flavonoids were isolated from the rosemary extracts. Among these, 7-O-methylrosmanol (1) and royleanonic acid (3) effectively suppressed FSK-induced luciferase expression under the control of the CRE, PEPCK-C and G6Pase gene promoters. PEPCK-C and G6Pase, which play a key role in the homeostatic regulation of blood glucose levels, are important for managing type II diabetes mellitus. Therefore, the ability of rosemary and its components to suppress cAMP responsiveness of the PEPCK-C or G6Pase gene may contribute to its antihyperglycemic activity.

  6. Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells.

    PubMed

    de Oliveira, Pollyanna Francielli; Munari, Carla Carolina; Nicolella, Heloiza Diniz; Veneziani, Rodrigo Cassio Sola; Tavares, Denise Crispim

    2016-10-01

    Manool, a diterpene isolated from Salvia officinalis, was evaluated by the XTT colorimetric assay for cytotoxicity and selectivity against different cancer cell lines: B16F10 (murine melanoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), HepG2 (human hepatocellular carcinoma), and MO59J, U343 and U251 (human glioblastoma). A normal cell line (V79, Chinese hamster lung fibroblasts) was used to compare the selectivity of the test substance. Manool exhibited higher cytotoxic activity against HeLa (IC50 = 6.7 ± 1.1 µg/mL) and U343 (IC50 = 6.7 ± 1.2 µg/mL) cells. In addition, in the used experimental protocols, the treatment with manool was significantly more cytotoxic for different tumor cell lines than for the normal cell line V79 (IC50 = 49.3 ± 3.3 µg/mL), and showed high selectivity. These results suggest that manool may be used to treat cancer without affecting normal cells.

  7. Formamido-diterpenes from the South China Sea sponge Acanthella cavernosa.

    PubMed

    Xu, Ying; Lang, Jun-Hui; Jiao, Wei-Hua; Wang, Ru-Ping; Peng, Ying; Song, Shao-Jiang; Zhang, Bao-Hua; Lin, Hou-Wen

    2012-07-01

    Seven new formamido-diterpenes, cavernenes A-D (1-4), kalihinenes E and F (5-6), and kalihipyran C (7), together with five known compounds (8-12), were isolated from the South China Sea sponge Acanthella cavernosa. Structures were established using IR, HRESIMS, 1D and 2D NMR, and single X-ray diffraction techniques. The isolated compounds were assessed for their cytotoxicity against a small panel of human cancer cell lines (HCT-116, A549, HeLa, QGY-7701, and MDA-MB-231) with IC(50) values in the range of 6-18 μM. In addition, compound 9 showed weak antifungal activity against Trichophyton rubrum and Microsporum gypseum with MIC values of 8 and 32 μg/mL, respectively, compound 10 displayed weak antifungal activity against fungi Candida albicans, Cryptococcus neoformans, T. rubrum, and M. gypseum with MIC values of 8, 8, 4, and 8 μg/mL, respectively.

  8. Isolation, structure, and bioactivities of abiesadines A-Y, 25 new diterpenes from Abies georgei Orr.

    PubMed

    Yang, Xian-Wen; Feng, Lin; Li, Su-Mei; Liu, Xiao-Hua; Li, Yong-Li; Wu, Liang; Shen, Yun-Heng; Tian, Jun-Mian; Zhang, Xi; Liu, Xin-Ru; Wang, Ning; Liu, Yonghong; Zhang, Wei-Dong

    2010-01-15

    Twenty-five new (abiesadines A-Y, 1-25) and 29 known (26-54) diterpenes were isolated from the aerial parts of Abies georgei. Abiesadine A (1) is a novel 8,14-seco-abietane, while abiesadine B (2) is a novel 9,10-seco-abietane. The structures of the new compounds were established on the basis of spectroscopic data analysis. Manool (52) showed the strongest effect against LPS-induced NO production in RAW264.7 macrophages with the IC(50) value of 11.0microg/mL. In another anti-inflammatory assay against TNFalpha-triggered NF-kappaB activity, (12R,13R)-8,12-epoxy-14-labden-13-ol (54) exhibited the strongest effect (IC(50)=8.7microg/mL). For antitumor assays, pomiferin A (26) and 8,11,13-abietatriene-7alpha,18-diol (29) both showed the most significant activity against LOVO cells (IC(50)=9.2microg/mL). While 7-oxocallitrisic acid (46) exhibited significant cytotoxicity against QGY-7703 tumor cells (IC(50)=10.2microg/mL).

  9. Tritoniopsins A-D, cladiellane-based diterpenes from the South China Sea nudibranch Tritoniopsis elegans and its prey Cladiella krempfi.

    PubMed

    Ciavatta, Maria Letizia; Manzo, Emiliano; Mollo, Ernesto; Mattia, Carlo Andrea; Tedesco, Consiglia; Irace, Carlo; Guo, Yue-Wei; Li, Xiu-Bao; Cimino, Guido; Gavagnin, Margherita

    2011-09-23

    Four diterpenes, tritoniopsins A-D (1-4), have been isolated from the South China Sea nudibranch Tritoniopsis elegans and its prey, the soft coral Cladiella krempfi. They display an unprecedented pyran ring in the cladiellane framework, thus representing a novel cladiellane-based diterpene family. Their structures have been mainly characterized by NMR and mass spectrometric techniques, whereas the relative configuration of compound 1 was secured by X-ray analysis. Antiproliferative assays on tumor and nontumor cell lines have been carried out for the main metabolite, tritoniopsin B (2). PMID:21861494

  10. Tritoniopsins A-D, cladiellane-based diterpenes from the South China Sea nudibranch Tritoniopsis elegans and its prey Cladiella krempfi.

    PubMed

    Ciavatta, Maria Letizia; Manzo, Emiliano; Mollo, Ernesto; Mattia, Carlo Andrea; Tedesco, Consiglia; Irace, Carlo; Guo, Yue-Wei; Li, Xiu-Bao; Cimino, Guido; Gavagnin, Margherita

    2011-09-23

    Four diterpenes, tritoniopsins A-D (1-4), have been isolated from the South China Sea nudibranch Tritoniopsis elegans and its prey, the soft coral Cladiella krempfi. They display an unprecedented pyran ring in the cladiellane framework, thus representing a novel cladiellane-based diterpene family. Their structures have been mainly characterized by NMR and mass spectrometric techniques, whereas the relative configuration of compound 1 was secured by X-ray analysis. Antiproliferative assays on tumor and nontumor cell lines have been carried out for the main metabolite, tritoniopsin B (2).

  11. Involvement of an ent-copalyl diphosphate synthase in tissue-specific accumulation of specialized diterpenes in Andrographis paniculata.

    PubMed

    Misra, Rajesh Chandra; Garg, Anchal; Roy, Sudeep; Chanotiya, Chandan Singh; Vasudev, Prema G; Ghosh, Sumit

    2015-11-01

    Ent-labdane-related diterpene (ent-LRD) specialized (i.e. secondary) metabolites of the medicinal plant kalmegh (Andrographis paniculata) have long been known for several pharmacological activities. However, our understanding of the ent-LRD biosynthetic pathway has remained largely incomplete. Since ent-LRDs accumulate in leaves, we carried out a comparative transcriptional analysis using leaf and root tissues, and identified 389 differentially expressed transcripts, including 223 transcripts that were preferentially expressed in leaf tissue. Analysis of the transcripts revealed various specialized metabolic pathways, including transcripts of the ent-LRD biosynthetic pathway. Two class II diterpene synthases (ApCPS1 and ApCPS2) along with one (ApCPS1') and two (ApCPS2' and ApCPS2″) transcriptional variants that were the outcomes of alternative splicing of the precursor mRNA and alternative transcriptional termination, respectively, were identified. ApCPS1 and ApCPS2 encode for 832- and 817-amino acids proteins, respectively, and are phylogenetically related to the dicotyledons ent-copalyl diphosphate synthases (ent-CPSs). The spatio-temporal patterns of ent-LRD metabolites accumulation and gene expression suggested a likely role for ApCPS1 in general (i.e. primary) metabolism, perhaps by providing precursor for the biosynthesis of phytohormone gibberellin (GA). However, ApCPS2 is potentially involved in tissue-specific accumulation of ent-LRD specialized metabolites. Bacterially expressed recombinant ApCPS2 catalyzed the conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP), the general precursor of diterpenes to ent-copalyl diphosphate (ent-CPP), the precursor of ent-LRDs. Taken together, these results advance our understanding of the tissue-specific accumulation of specialized ent-LRDs of medicinal importance.

  12. [Study on limit detection of flavones in diterpene ginkgolides meglumine injection materials by LC-MS and HPLC-DAD].

    PubMed

    Bi, Sen; Li, Yan-jing; Huang, Wen-zhe; Kang, Dan-yu; Ding, Gang; Xiao, Wei

    2015-08-01

    Limit test of flavones in diterpene ginkgolides meglumine injection materials by UV-Vis and HPLC-DAD method was studied in this essay. The HPLC-DAD method has lower LOD (about 1% of the UV-Vis), that is, the sensitivity is higher than UV-Vis method. Through the analysis of the kinds of flavonoids ingredients in the samples by LC-MS, the three compounds with highest contents are kaempferol, quercetin and isorhamnetin. Kaempferol, quercetin and isorhamnetin were chosen as reference compounds for HPLC analysis, and the HPLC separation analysis was carried on an Agilent Eclipse plus C18 column (4.6 mm x 250 mm, 5 μm) with methanol and water containing 0.4% phosphoric acid (50: 50) as mobile phase, and the flow rate was 1.0 mL x min(-1). The detection wavelength was set at 360 nm. This method has good specificity, precision and reproducibility. The LODs of quercetin, kaempferide and isorhamnetin were 27.6, 22.3, 29.5 μg x L(-1). The average recovery was 87.9% (RSD 3.3%), 91.7% (RSD 3.1%), 88.3 (RSD 1.3%) for quercetin, kaempferide and isorhamnetin, respectively. Based on the 10 batches of sample results and sensitivity of different HPLC, the content of total flavonoids ingredients of diterpene ginkgolides meglumine injection materials was limited no more than 2 x 10(-5). This method is simple, quick and has good maneuverability, and could be used to the limit test of flavonoids in the diterpene ginkgolides meglumine injection materials.

  13. [Study on limit detection of flavones in diterpene ginkgolides meglumine injection materials by LC-MS and HPLC-DAD].

    PubMed

    Bi, Sen; Li, Yan-jing; Huang, Wen-zhe; Kang, Dan-yu; Ding, Gang; Xiao, Wei

    2015-08-01

    Limit test of flavones in diterpene ginkgolides meglumine injection materials by UV-Vis and HPLC-DAD method was studied in this essay. The HPLC-DAD method has lower LOD (about 1% of the UV-Vis), that is, the sensitivity is higher than UV-Vis method. Through the analysis of the kinds of flavonoids ingredients in the samples by LC-MS, the three compounds with highest contents are kaempferol, quercetin and isorhamnetin. Kaempferol, quercetin and isorhamnetin were chosen as reference compounds for HPLC analysis, and the HPLC separation analysis was carried on an Agilent Eclipse plus C18 column (4.6 mm x 250 mm, 5 μm) with methanol and water containing 0.4% phosphoric acid (50: 50) as mobile phase, and the flow rate was 1.0 mL x min(-1). The detection wavelength was set at 360 nm. This method has good specificity, precision and reproducibility. The LODs of quercetin, kaempferide and isorhamnetin were 27.6, 22.3, 29.5 μg x L(-1). The average recovery was 87.9% (RSD 3.3%), 91.7% (RSD 3.1%), 88.3 (RSD 1.3%) for quercetin, kaempferide and isorhamnetin, respectively. Based on the 10 batches of sample results and sensitivity of different HPLC, the content of total flavonoids ingredients of diterpene ginkgolides meglumine injection materials was limited no more than 2 x 10(-5). This method is simple, quick and has good maneuverability, and could be used to the limit test of flavonoids in the diterpene ginkgolides meglumine injection materials. PMID:26790294

  14. Bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases

    SciTech Connect

    Li L. L.; van der Lelie D.; Taghavi, S.; McCorkle, S. M.; Zhang, Y.-B.; Blewitt, M. G.; Brunecky, R.; Adney, W. S.; Himmel, M. E.; Brumm, P.; Drinkwater, C.; Mead, D. A.; Tringe, S. G.

    2011-08-01

    To efficiently deconstruct recalcitrant plant biomass to fermentable sugars in industrial processes, biocatalysts of higher performance and lower cost are required. The genetic diversity found in the metagenomes of natural microbial biomass decay communities may harbor such enzymes. Our goal was to discover and characterize new glycoside hydrolases (GHases) from microbial biomass decay communities, especially those from unknown or never previously cultivated microorganisms. From the metagenome sequences of an anaerobic microbial community actively decaying poplar biomass, we identified approximately 4,000 GHase homologs. Based on homology to GHase families/activities of interest and the quality of the sequences, candidates were selected for full-length cloning and subsequent expression. As an alternative strategy, a metagenome expression library was constructed and screened for GHase activities. These combined efforts resulted in the cloning of four novel GHases that could be successfully expressed in Escherichia coli. Further characterization showed that two enzymes showed significant activity on p-nitrophenyl-{alpha}-L-arabinofuranoside, one enzyme had significant activity against p-nitrophenyl-{beta}-D-glucopyranoside, and one enzyme showed significant activity against p-nitrophenyl-{beta}-D-xylopyranoside. Enzymes were also tested in the presence of ionic liquids. Metagenomics provides a good resource for mining novel biomass degrading enzymes and for screening of cellulolytic enzyme activities. The four GHases that were cloned may have potential application for deconstruction of biomass pretreated with ionic liquids, as they remain active in the presence of up to 20% ionic liquid (except for 1-ethyl-3-methylimidazolium diethyl phosphate). Alternatively, ionic liquids might be used to immobilize or stabilize these enzymes for minimal solvent processing of biomass.

  15. [Fingerprint and spectrum-effect relationships on Tripterygium glycosides preparation].

    PubMed

    Chi, Jie; Lin, Bing; Liu, Zhi-hong; Yang, Li-na; Liu, Xue-mei; Song, Hong-tao

    2015-04-01

    Tripterygium glycosides preparation which extracted from the traditional Chinese herb Tripterygium wilfordii (TWHY), was widely used to treat the autoimmune diseases. Previous works demonstrated that TWHF had potent anti-inflammatory and immunosuppressive properties. But the different quality and high incident rate of side effects of different manufactures inhibited its clinical application. Since TWHF had been generally known to play a therapeutical effect by synergism of multiple constituents, it was necessary to build the relationship between the HPLC fingerprint and bioactivity so as to ensure the quality safety and efficacy. The HPLC fingerprint showed that description and content of peaks from different manufactures were diverse. Only 11 common peaks were found. In this study, mice spleen cells stimulated by Con A were used to test the proliferation inhibition bioactivity of TWHF preparations, which were incubated with 30, 15, 7.5, 3.75, 1.88 and 0.94 mg x L(-1) TWHF preparations for 48 h. The results showed that mice spleen cells proliferation was inhibited by all TWHF preparations significantly compared with the control group, which suggested the TWHF preparations showed immune suppress activity. The TWHF preparations from 7 manufacture showed different IC50 value, which might belong to different contents which showed in the HPLC fingerprint. Moreover, a relationship between the HPLC fingerprint and the bioactivity were established to identify important constituents by grey relational analysis (GRA). The result showed that all the contents were relative with the IC50, especially No. 5 and 10 peaks, but No. 1 peak, which was proved to be triptolide, had few contribute to the inhibition of mice spleen cells proliferation. The study of relationship between the HPLC fingerprint and the IC50 by GRA could help to investigate mechanism of bioactive and provide an evidence for the quantification of multi-constituents.

  16. Bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases

    PubMed Central

    2011-01-01

    Background To efficiently deconstruct recalcitrant plant biomass to fermentable sugars in industrial processes, biocatalysts of higher performance and lower cost are required. The genetic diversity found in the metagenomes of natural microbial biomass decay communities may harbor such enzymes. Our goal was to discover and characterize new glycoside hydrolases (GHases) from microbial biomass decay communities, especially those from unknown or never previously cultivated microorganisms. Results From the metagenome sequences of an anaerobic microbial community actively decaying poplar biomass, we identified approximately 4,000 GHase homologs. Based on homology to GHase families/activities of interest and the quality of the sequences, candidates were selected for full-length cloning and subsequent expression. As an alternative strategy, a metagenome expression library was constructed and screened for GHase activities. These combined efforts resulted in the cloning of four novel GHases that could be successfully expressed in Escherichia coli. Further characterization showed that two enzymes showed significant activity on p-nitrophenyl-α-L-arabinofuranoside, one enzyme had significant activity against p-nitrophenyl-β-D-glucopyranoside, and one enzyme showed significant activity against p-nitrophenyl-β-D-xylopyranoside. Enzymes were also tested in the presence of ionic liquids. Conclusions Metagenomics provides a good resource for mining novel biomass degrading enzymes and for screening of cellulolytic enzyme activities. The four GHases that were cloned may have potential application for deconstruction of biomass pretreated with ionic liquids, as they remain active in the presence of up to 20% ionic liquid (except for 1-ethyl-3-methylimidazolium diethyl phosphate). Alternatively, ionic liquids might be used to immobilize or stabilize these enzymes for minimal solvent processing of biomass. PMID:21816041

  17. Biochemistry and toxicology of the diterpenoid glycoside atractyloside.

    PubMed

    Obatomi, D K; Bach, P H

    1998-04-01

    Atractyloside (Atr) is a diterpenoid glycoside that occurs naturally in plants (many of which are used in ethnomedicines) found in Europe, Africa, South America, Asia and the far East. It is also present in animal grazing forage. Atr (and its analogues) may be present at levels as high as 600 mg/kg dried plant material. Consumption of the plants containing Atr or carboxyatractyloside (carboxyAtr) has caused fatal renal proximal tubule necrosis and/or centrilobular hepatic necrosis in man and farm animals. Although pure Atr and crude plant extracts disrupt carbohydrate homeostasis and induce similar pathophysiological lesions in the kidney and liver, it is also possible that the toxicity of Atr may be confounded by the presence of other natural constituents in plants. Atr competitively inhibits the adenine nucleoside carrier in isolated mitochondria and thus blocks oxidative phosphorylation. This has been assumed to explain changes in carbohydrate metabolism and the toxic effects in liver and kidney. Although the acute toxicity of Atr is well described, many aspects of Atr toxicity (subchronic and chronic toxicity, reproductive toxicity, mutagenicity and carcinogenicity) have not been investigated and pharmacokinetic and metabolism data are limited. In vitro proximal tubular cells are selectively sensitive to Atr, whereas other renal cell types are quite resistant. There are also differences in the response of liver and renal tissue to Atr. Thus, not all of the clinical, biochemical and morphological changes caused by Atr can simply be explained on the basis of inhibition of mitochondrial phosphorylation. The relevance to a wider human risk is shown by the presence of Atr analogues in dried roasted Coffea arabica beans (17.5 32 mg/kg). There are no data to help identify the risk of low dose chronic exposure in human coffee consumers, nor is there information on the levels of Atr or its analogues in other commonly consumed human foodstuffs. PMID:9651051

  18. Antioxidant and Anti-Inflammatory Phenolic Glycosides from Clematis tashiroi.

    PubMed

    Zhang, Li-Jie; Huang, Hung-Tse; Huang, Shih-Yen; Lin, Zhi-Hu; Shen, Chien-Chang; Tsai, Wei-Jern; Kuo, Yao-Haur

    2015-07-24

    From the 95% EtOH extract of dried aerial parts of Clematis tashiroi, eight new and four known phenolic (caffeic acid, coumaric acid, ferrulic acid) glycosides were isolated and characterized. The structures of the new isolates (clematisides A-H) were elucidated by spectroscopic data interpretation as trans-4-O-(6-O-trans-caffeoyl-β-D- glucopyranosyl)-9-O-β-D-glucopyranosyl caffeic acid (1), trans-4-O-(6-O-trans-feruloyl-β-D-glucopyranosyll)-9-O-β-D-glucopyranosyl caffeic acid (2), trans-4-O-(6-O-trans-p-coumaroyl-β-D-glucopyranosyl)-9-O-β-D-glucopyranosyl caffeic acid (3), trans-4-O-(6-O-trans-caffeoyl-β-D-glucopyranosyl)-9-O-β-D-glucopyranosyl p-coumaric acid (4), trans-3-O-(6-O-trans-caffeoyl-β-D-glucopyranosyl)-9-O-β-D-glucopyranosyl caffeic acid (5), trans-3-O-(6-O-trans-p-coumaroyl-β-D-glucopyranosyl)-9-O-β-D-glucopyranosyl caffeic acid (6), 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-(6-O-trans-caffeoyl)-β-D-glucopyranoside (7), and 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-{6-O-[4-O-(6-O-trans-caffeoyl)-β-D-glucopyranosyl]-trans-caffeoyl}-β-D-glucopyranoside (8), respectively. In a DPPH radical-scavenging test, compounds 1, 7, and 8 showed more potent antioxidant activity than that of the positive control, vitamin E. In addition, compound 7 also showed inhibitory activity in an antinitric oxide release assay. PMID:26143931

  19. Isolation and identification of some steroidal glycosides of Furcraea selloa.

    PubMed

    El-Sayed, M M; Abdel-Hameed, E S; El-Nahas, H A; El-Wakil, E A

    2006-05-01

    The antischistosomal impact of different extracts of the leaves of Furcraea selloa C. Koch (Family Agavaceae) were screened against adult Schistosoma mansoni worms in vitro using well established culture media. The methanol extract of the plant showed the highest activity as S. mansoni worms recorded 100% mortality at 50 microg/ml after 24 h (EC50 = 29.78 and 29.41 microg/ml for female and male worm respectively). Owing to the high potency of the crude butanolic extract (100% mortality at 20 microg/ ml; EC50 = 10.42 and 8.94 microg/ml for female and male worm respectively) obtained from the methanolic extract, it was submitted to chromatographic separation and isolation using silica gel and Sephadex columns as well as preparative thin layer chromatography. Three steroidal glycosides (saponins) (I-III) were isolated and their structures were elucidated using some spectroscopic and chemical methods. The structure of the three compounds was formulated as 6-O-beta-glucopyranosyl-(1-->4)-beta-D-glucopyranoside chlorogenin (I), 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside crestagenin (II) and 3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranoside gloriogenin (III). Only compound III at 5 micro/ml led to 100% mortality of the S. mansoni (EC50 = 2.25 and 1.91 microg/ml for female and male worm respectively) whereas compounds I and II did not show any activity up to 50 microg/ml.

  20. Synthesis of totarane diterpenes: totarol, maytenoquinone, 6-deoxymaytenoquinone and 8,11,13-totaratriene-12,13-diol.

    PubMed

    Tada, Masahiro; Kurabe, Jun; Yasue, Hiroaki; Ikuta, Tomohisa

    2008-03-01

    The syntheses of four totarane diterpenes-totarol, 8,11,13-totaratriene-12,13-diol, 6-deoxymaytenoquinone and maytenoquinone-are described. Totarol was synthesized via cyclization of a modified polyene. 8,11,13-Totaratriene-12,13-diol was prepared from natural totarol by ortho-oxidation with mCBPO (m-chlorobenzoyl peroxide). Maytenoquinone and 6-deoxymaytenoquinone were synthesized from 8,11,13-totaratriene-12,13-diol. 1H-NMR analysis showed that tautomeric isomerization between 6-deoxymaytenoquinone (2-hydroxy-4-quinone methide) and the ortho-quinone was very slow. PMID:18310937

  1. A Synthetic Butenolide Diterpene is now a Natural Product Isolated from Metaporana sericosepala, a Plant from the Madagascar Dry Forest.

    PubMed

    Presley, Christopher C; Rakotondraibe, L Harinantenaina; Brodie, Peggy J; Callmander, Martin W; Randrianaivo, Richard; Rasamison, Vincent E; Rakotobe, Etienne; Kingston, David G I

    2015-09-01

    Antiproliferative bioassay-guided fractionation of the ethanolic extract of the endemic Madagascan plant Metaporana sericosepala led to the first natural product isolation of a butenolide diterpene, which was synthesized during an anti-inflammatory study in 1988. The structure of the compound was elucidated as 3-homofarnesyl-4-hydroxybutenolide (1) by analysis of its spectroscopic data, including 1D- and 2D-NMR data and chemical evidence. The once synthetic compound can now also be considered as a natural product. Compound 1 had modest antiproliferative activity towards the A2780 ovarian cancer cell line,with an IC50 value of 8 µM.

  2. Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Role of the Furan in Affinity for Opioid Receptors

    PubMed Central

    Simpson, Denise S.; Lovell, Kimberly M.; Lozama, Anthony; Han, Nina; Day, Victor W.; Dersch, Christina M.; Rothman, Richard B.; Prisinzano, Thomas E.

    2011-01-01

    Further synthetic modification of the furan ring of salvinorin A (1), the major active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. A computational study has predicted 1 to be a reproductive toxicant in mammals and is suggestive that use of 1 may be associated with adverse effects. We report in this study that piperidine 21 and thiomorpholine 23 have been identified as selective partial agonists at kappa opioid receptors. This indicates that additional structural modifications of 1 may provide ligands with good selectivity for opioid receptors but with reduced potential for toxicity. PMID:19707679

  3. Scopararanes C-G: new oxygenated pimarane diterpenes from the marine sediment-derived fungus Eutypella scoparia FS26.

    PubMed

    Sun, Li; Li, Dongli; Tao, Meihua; Chen, Yuchan; Dan, Feijun; Zhang, Weimin

    2012-03-01

    Five new oxygenated pimarane diterpenes, named scopararanes C-G (1-5) were isolated from the culture of a marine sediment-derived fungus Eutypella scoparia FS26 obtained from the South China Sea. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The absolute configurations of compounds 1-5, were determined by CD spectroscopic analysis and comparison with literature data. All isolated compounds (1-5) were evaluated for their cytotoxic activities against MCF-7, NCI-H460, and SF-268 tumor cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method.

  4. Water-soluble genistin glycoside isoflavones up-regulate antioxidant metallothionein expression and scavenge free radicals.

    PubMed

    Chung, Mi Ja; Kang, Ah-Young; Lee, Kyung Min; Oh, Eunji; Jun, Hee-Jin; Kim, Sang-Yeon; Auh, Joong Hyuck; Moon, Tae-Wha; Lee, Sung-Joon; Park, Kwan-Hwa

    2006-05-31

    Genistin has antioxidant activities; however, its insolubility in water often limits its biological availability in vivo. Using a novel transglycosylation process, the solubility of genistin glycosides was increased 1000 to 10000-fold, but it was not known whether these modified genistin glycosides maintained antioxidant activity. We found that both genistin and its glycosides similarly up-regulated the transcription of several metallothionein (MT) antioxidant genes (MT1A, MT2A, MT1E, and MT1X), as well as the glucose 6-phosphate dehydrogenase (G6PD) gene in HepG2 cells. This gene induction was mediated by the sequestration of zinc in the cytosol, which up-regulated the metal-responsive transcription factor-1 (MTF-1) that induced MT gene expression. Although not as effective as ascorbic acid, genistin glycosides possessed slightly greater reducing power than genistin. We concluded that genistin and genistin glycosides have a direct antioxidant effect and an indirect antioxidant effect, perhaps via induction of MT by activity of MTF-1.

  5. Proteomic Analysis of a Novel Bacillus Jumbo Phage Revealing Glycoside Hydrolase As Structural Component.

    PubMed

    Yuan, Yihui; Gao, Meiying

    2016-01-01

    Tailed phages with genomes of larger than 200 kbp are classified as Jumbo phages and exhibited extremely high uncharted diversity. The genomic annotation of Jumbo phage is often disappointing because most of the predicted proteins, including structural proteins, failed to make good hits to the sequences in the databases. In this study, 23 proteins of a novel Bacillus Jumbo phage, vB_BpuM_BpSp, were identified as phage structural proteins by the structural proteome analysis, including 14 proteins of unknown function, 5 proteins with predicted function as structural proteins, a glycoside hydrolase, a Holliday junction resolvase, a RNA-polymerase β-subunit, and a host-coding portal protein, which might be hijacked from the host strain during phage virion assembly. The glycoside hydrolase (Gp255) was identified as phage virion component and was found to interact with the phage baseplate protein. Gp255 shows specific lytic activity against the phage host strain GR8 and has high temperature tolerance. In situ peptidoglycan-hydrolyzing activities analysis revealed that the expressed Gp255 and phage structural proteome exhibited glycoside hydrolysis activity against the tested GR8 cell extracts. This study identified the first functional individual structural glycoside hydrolase in phage virion. The presence of activated glycoside hydrolase in phage virions might facilitate the injection of the phage genome during infection by forming pores on the bacterial cell wall. PMID:27242758

  6. Catalpol and methylcatalpol: naturally occurring glycosides in Plantago and Buddleia species

    PubMed Central

    Duff, R. B.; Bacon, J. S. D.; Mundie, C. M.; Farmer, V. C.; Russell, J. D.; Forrester, A. R.

    1965-01-01

    1. A glycoside of the aucubin type has been isolated in crystalline form from Plantago and Buddleia species, and has been shown to be identical with catalpol (Lunn, Edward & Edward, 1962). Catalpol has not been found in the free state before, but occurs as its p-hydroxybenzoyl ester, catalposide, in the genus Catalpa. 2. A second glycoside of this type has been obtained in crystalline form from Buddleia, and has been shown to be a mono-O-methyl derivative of catalpol, for which the name `methylcatalpol' is proposed. 3. Both Plantago and Buddleia species are known to contain aucubin. The concentrations of this glycoside and catalpol are comparable in Plantago. In Buddleia methylcatalpol predominates somewhat over catalpol. Yields of the individual glycosides were about 0·1% of the fresh weight of the leaves. 4. Bobbitt, Spiggle, Mahboob, Philipsborn & Schmid (1962) have suggested structures for catalposide and catalpol based on chemical and physical evidence, in particular on n.m.r. spectra. Reappraisal of this evidence and additional measurements have now confirmed these structures and show that the Buddleia glycoside is the 6-O-methyl derivative of catalpol. PMID:14343132

  7. Ent-Kaurane diterpenes from Annona glabra and their cytotoxic activities.

    PubMed

    Anh, Hoang Le Tuan; Hien, Nguyen Thi Thu; Hang, Dan Thi Thuy; Ha, Tran Minh; Nhiem, Nguyen Xuan; Hien, Truong Thi Thu; Thu, Vu Kim; Thao, Do Thi; Van Minh, Chau; Kiem, Phan Van

    2014-12-01

    A new ent-kaurane glycoside, annoglabasin H (1), and three known ent-kauranes, annoglabasin E (2), annoglabasin B (3), and 19-nor-ent-kaurent-4-ol-17-oic acid (4) were isolated from the fruits of Annona glabra. Their structures were determined by the combination of spectroscopic and chemical methods, including 1D- and 2D-NMR spectroscopy, as well as by comparison with the NMR data reported in the literature. The cytotoxic activities of these compounds were evaluated on four human cancer cell lines, LU-1, MCF-7, SK-Mel2, and KB. Compound 1 exhibited significant cytotoxic activity on all tested human cancer cell lines with IC50 values ranging from 3.7 to 4.6 μM.

  8. A Great Barrier Reef Sinularia sp. Yields Two New Cytotoxic Diterpenes

    PubMed Central

    Wright, Anthony D.; Nielson, Jonathan L.; Tapiolas, Dianne M.; Liptrot, Catherine H.; Motti, Cherie A.

    2012-01-01

    The methanol extract of a Sinularia sp., collected from Bowden Reef, Queensland, Australia, yielded ten natural products. These included the new nitrogenous diterpene (4R*,5R*,9S*,10R*,11Z)-4-methoxy-9-((dimethylamino)-methyl)-12,15-epoxy-11(13)-en-decahydronaphthalen-16-ol (1), and the new lobane, (1R*,2R*,4S*,15E)-loba-8,10,13(14),15(16)-tetraen-17,18-diol-17-acetate (2). Also isolated were two known cembranes, sarcophytol-B and (1E,3E,7E)-11,12-epoxycembratrien-15-ol, and six known lobanes, loba-8,10,13(15)-triene-16,17,18-triol, 14,18-epoxyloba-8,10,13(15)-trien-17-ol, lobatrientriol, lobatrienolide, 14,17-epoxyloba-8,10,13(15)-trien-18-ol-18-acetate and (17R)-loba-8,10,13(15)-trien-17,18-diol. Structures of the new compounds were elucidated through interpretation of spectra obtained after extensive NMR and MS investigations and comparison with literature values. The tumour cell growth inhibition potential of 1 and 2 along with loba-8,10,13(15)-triene-16,17,18-triol, 14,17-epoxyloba-8,10,13(15)-trien-18-ol-18-acetate, lobatrienolide, (1E,3E,7E)-11,12-epoxycembratrien-15-ol and sarcophytol-B were assessed against three human tumour cell lines (SF-268, MCF-7 and H460). The lobanes and cembranes tested demonstrated 50% growth inhibition in the range 6.8–18.5 µM, with no selectivity, whilst 1 was less active (GI50 70–175 µM). PMID:23015765

  9. Phytol, a Diterpene Alcohol from Chlorophyll, as a Drug against Neglected Tropical Disease Schistosomiasis Mansoni

    PubMed Central

    de Moraes, Josué; de Oliveira, Rosimeire N.; Costa, Jéssica P.; Junior, Antonio L. G.; de Sousa, Damião P.; Freitas, Rivelilson M.; Allegretti, Silmara M.; Pinto, Pedro L. S.

    2014-01-01

    Background Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug, praziquantel, it is imperative that new effective drugs are developed. Here, we report that phytol, a diterpene alcohol from chlorophyll widely used as a food additive and in medicinal fields, possesses promising antischistosomal properties in vitro and in a mouse model of schistosomiasis mansoni. Methods and findings In vitro, phytol reduced the motor activity of worms, caused their death and confocal laser scanning microscopy analysis showed extensive tegumental alterations in a concentration-dependent manner (50 to 100 µg/mL). Additionally, phytol at sublethal doses (25 µg/mL) reduced the number of Schistosoma mansoni eggs. In vivo, a single dose of phytol (40 mg/kg) administered orally to mice infected with adult S. mansoni resulted in total and female worm burden reductions of 51.2% and 70.3%, respectively. Moreover, phytol reduced the number of eggs in faeces (76.6%) and the frequency of immature eggs (oogram pattern) was significantly reduced. The oogram also showed increases in the proportion of dead eggs. Confocal microcopy studies revealed tegumental damage in adult S. mansoni recovered from mice, especially in female worms. Conclusions The significant reduction in parasite burden by this chlorophyll molecule validates phytol as a promising drug and offers the potential of a new direction for chemotherapy of human schistosomiasis. Phytol is a common food additive and nonmutagenic, with satisfactory safety. Thus, phytol has potential as a safe and cost-effective addition to antischistosomal therapy. PMID:24392173

  10. Anti-Angiogenic and Anti-Inflammatory Properties of Kahweol, a Coffee Diterpene

    PubMed Central

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel A.

    2011-01-01

    Background Epidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules. Methodology/Principal Findings The experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish), the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells. Conclusion/Significance Taken together, our data indicate that, indeed, kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers. PMID:21858104

  11. The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

    PubMed

    Lozano, E; Strauss, M; Spina, R; Cifuente, D; Tonn, C; Rivarola, H W; Sosa, M A

    2016-02-01

    The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs. PMID:26341064

  12. Anti-Protozoal Activities of Cembrane-Type Diterpenes from Vietnamese Soft Corals.

    PubMed

    Thao, Nguyen Phuong; Luyen, Bui Thi Thuy; Brun, Reto; Kaiser, Marcel; Van Kiem, Phan; Van Minh, Chau; Schmidt, Thomas J; Kang, Jong Seong; Kim, Young Ho

    2015-01-01

    Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an in vitro screening for anti-protozoal activity against Trypanosoma brucei rhodesiense (Tbr), T. cruzi (Tc), Leishmania donovani (Ld), and Plasmodium falciparum (Pf). Twelve of the tested compounds displayed significant activity against at least one of the parasites. Specifically, 7S,8S-epoxy-1,3,11-cembratriene-16-oic methyl ester (1), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (2), crassumol D (12), crassumol E (13), and (1S,2E,4S,6E,8S,11S)-2,6,12(20)-cembrantriene-4,8,11-triol (16) from Lobophytum crassum, L. laevigatum, and Sinularia maxima showed the highest level of inhibitory activity against T. b. rhodesiense, with IC50 values of about 1 µM or less. Lobocrasol A (6) and lobocrasol C (8) from L. crassum and L. laevigatum exhibited particularly significant inhibitory effects on L. donovani with IC50 values < 0.2 µM. The best antiplasmodial effect was exerted by laevigatol A (10), with an IC50 value of about 3.0 µM. The cytotoxicity of the active compounds on L6 rat skeletal myoblast cell was also assessed and found to be insignificant in all cases. This is the first report on anti-protozoal activity of these compounds, and points out the potential of the soft corals in discovery of new anti-protozoal lead compounds. PMID:26184133

  13. The hallucinogenic diterpene salvinorin A inhibits leukotriene synthesis in experimental models of inflammation.

    PubMed

    Rossi, Antonietta; Pace, Simona; Tedesco, Federica; Pagano, Ester; Guerra, Germano; Troisi, Fabiana; Werner, Markus; Roviezzo, Fiorentina; Zjawiony, Jordan K; Werz, Oliver; Izzo, Angelo A; Capasso, Raffaele

    2016-04-01

    Leukotrienes (LTs) are lipid mediators derived from arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including asthma, allergic rhinitis and cardiovascular diseases. Salvinorin A (SA), a diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production. Zymosan-induced peritonitis in mice and carrageenan-induced pleurisy in rats were selected as LT-related models to evaluate the effect of SA on inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced LTB4 biosynthesis in isolated PM. In zymosan-induced peritonitis, SA inhibited cell infiltration, myeloperoxidase activity, vascular permeability and LTC4 production in the peritoneal cavity without decreasing the production of prostaglandin E2. In carrageenan-induced pleurisy in rats, a more sophisticated model of acute inflammation related to LTs, SA significantly inhibited LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases.

  14. New insights into the structure-cytotoxicity relationship of spirostan saponins and related glycosides.

    PubMed

    Pérez-Labrada, Karell; Brouard, Ignacio; Estévez, Sara; Marrero, María Teresa; Estévez, Francisco; Bermejo, Jaime; Rivera, Daniel G

    2012-04-15

    A variety of spirostan saponins and related glycosides were synthesized and evaluated for their cytotoxicity against the human myeloid leukemia cell line (HL-60). A linear glycosylation strategy allowed for accessing a variety of functionalization patterns at both the spirostanic and the saccharide moieties, which provides new information regarding the structure-cytotoxicity relationship of this family of steroidal glycosides. Intriguing results were achieved with respect to hecogenyl and 5α-hydroxy-laxogenyl β-chacotriosides, turning out to be the former very cytotoxic and the latter no cytotoxic at all. Importantly, the partially pivaloylated β-d-glucosides of 5α-hydroxy-laxogenin were the most potent cytotoxic compounds among all tested glycosides. This comprises the first report on acylated spirostanyl glucosides displaying significant cytotoxicity, and therefore, it opens up new opportunities toward the development of saponin analogues as anticancer agents. PMID:22405922

  15. Two new quinochalcone C-glycosides from the florets of Carthamus tinctorius.

    PubMed

    Yue, Shijun; Tang, Yuping; Xu, Chengmei; Li, Shujiao; Zhu, Yue; Duan, Jin-Ao

    2014-09-22

    Two new quinochalcone C-glycosides, named hydroxysafflor yellow B (1) and hydroxysafflor yellow C (2), along with two known quinochalcone C-glycosides, safflomin C (3) and saffloquinoside C (4), and one known flavanone, (2R)-4',5-dihydroxyl-6, 7-di-O-β-d-glucopyranosyl flavanone (5), were isolated from the florets of Carthamus tinctorius. Their structures were determined by extensive spectroscopic (UV, IR, HR-ESI-MS, 1D and 2D NMR) analyses. In addition, these quinochalcone C-glycosides together with hydroxysafflor yellow A and anhydrosafflor yellow B were evaluated for their anti-oxidative effects against H2O2-induced cytotoxicity in cultured H9c2 cells. Among them, compound 2 exhibited significant anti-oxidative effects.

  16. Studies on Kochiae Fructus. V. Antipruritic effects of oleanolic acid glycosides and the structure-requirement.

    PubMed

    Matsuda, H; Dai, Y; Ido, Y; Murakami, T; Matsuda, H; Yoshikawa, M; Kubo, M

    1998-11-01

    We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides. PMID:9853421

  17. Organosolv pretreatment of Sitka spruce wood: conversion of hemicelluloses to ethyl glycosides.

    PubMed

    Bouxin, Florent P; David Jackson, S; Jarvis, Michael C

    2014-01-01

    A range of Organosolv pretreatments, using ethanol:water mixtures with dilute sulphuric acid, were applied to Sitka spruce sawdust with the aim of generating useful co-products as well as improving saccharification yield. The most efficient of the pretreatment conditions, resulting in subsequent saccharification yields of up to 86%, converted a large part of the hemicellulose sugars to their ethyl glycosides as identified by GC/MS. These conditions also reduced conversion of pentoses to furfural, the ethyl glycosides being more stable to dehydration than the parent pentoses. Through comparison with the behaviour of model compounds under the same reaction conditions it was shown that the anomeric composition of the products was consistent with a predominant transglycosylation reaction mechanism, rather than hydrolysis followed by glycosylation. The ethyl glycosides have potential as intermediates in the sustainable production of high-value chemicals. PMID:24269088

  18. Partial characterization of a biologically active steroid glycoside isolated from the starfish Marthasterias glacialis

    PubMed Central

    Mackie, A. M.; Turner, A. B.

    1970-01-01

    1. A steroid glycoside (M2), which induces avoidance and other reactions in the mollusc Buccinum undatum, has been isolated from extracts of the starfish Marthasterias glacialis by ion-exchange chromatography. 2. The steroid glycoside was homogeneous by t.l.c. and contained glucose, quinovose, fucose and sulphate in the molar proportions 1:2:1:1, in addition to a water-insoluble aglycone. 3. The aglycone was identified as a cholestane derivative containing an unusual Δ24-23-ketone system, two secondary hydroxyl groups and an olefinic double bond, and had the molecular formula C27H42O3. 4. The rates of release of sugars and sulphate suggested that fucose was at the non-reducing end of the oligosaccharide, with glucose glycosidically linked to the steroid. The sulphate group appeared to be linked to the other hydroxyl group of the steroid. PMID:5419749

  19. Studies on Kochiae Fructus. V. Antipruritic effects of oleanolic acid glycosides and the structure-requirement.

    PubMed

    Matsuda, H; Dai, Y; Ido, Y; Murakami, T; Matsuda, H; Yoshikawa, M; Kubo, M

    1998-11-01

    We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides.

  20. Two New Quinochalcone C-Glycosides from the Florets of Carthamus tinctorius

    PubMed Central

    Yue, Shijun; Tang, Yuping; Xu, Chengmei; Li, Shujiao; Zhu, Yue; Duan, Jin-Ao

    2014-01-01

    Two new quinochalcone C-glycosides, named hydroxysafflor yellow B (1) and hydroxysafflor yellow C (2), along with two known quinochalcone C-glycosides, safflomin C (3) and saffloquinoside C (4), and one known flavanone, (2R)-4',5-dihydroxyl-6,7-di-O-β-d-glucopyranosyl flavanone (5), were isolated from the florets of Carthamus tinctorius. Their structures were determined by extensive spectroscopic (UV, IR, HR-ESI-MS, 1D and 2D NMR) analyses. In addition, these quinochalcone C-glycosides together with hydroxysafflor yellow A and anhydrosafflor yellow B were evaluated for their anti-oxidative effects against H2O2-induced cytotoxicity in cultured H9c2 cells. Among them, compound 2 exhibited significant anti-oxidative effects. PMID:25247575

  1. Two new bioactive triterpene glycosides from the sea cucumber Pseudocolochirus violaceus.

    PubMed

    Zhang, Shu-Yu; Yi, Yang-Hua; Tang, Hai-Feng; Li, Ling; Sun, Peng; Wu, Jun

    2006-01-01

    By activity-guided fractionation, two new triterpene glycosides, violaceusides A (1) and B (2), were isolated from the sea cucumber Pseudocolochirus violaceus as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. By extensive 2D NMR techniques and chemical evidence, the structures of the two new glycosides were established as 16beta-acetoxy-3-O-[3-O-methyl-beta-D-glucopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-beta-D-quinovopyranosyl-(1 --> 2)-4-O-sodiumsulphate-beta-D-xylopyranosyl]-holosta-7,24-diene-3beta-ol (1) and 16beta-acetoxy-3-O-[3-O-methyl-beta-D-glucopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 2)-4-O-sodiumsulphate-beta-D-xylopyranosyl]-holosta-7,24-diene-3beta-ol (2), respectively. The two glycosides also exhibited significant cytotoxicity against HL-60 and BEL-7402 cancer cell lines. PMID:16753775

  2. Molecular docking and inhibition kinetics of α-glucosidase activity by labdane diterpenes isolated from tora seeds (Alpinia nigra B.L. Burtt.).

    PubMed

    Ghosh, Sudipta; Rangan, Latha

    2015-02-01

    Current approach against type 2 diabetes involves α-glucosidase inhibitors like acarbose associated with many side effects. Therefore, as an alternative to the existing drug, many natural products mainly from plant sources have been investigated which inhibit α-glucosidase. Here, we have selected medicinally important Alpinia nigra to explore its α-glucosidase inhibitory activity. Organic extracts of seeds and two purified natural diterpenes I: (E)-labda-8(17), 12-diene-15, 16-dial and II: (E)-8β, 17-epoxylabd-12-ene-15, 16-dial from A. nigra were investigated towards inhibition of α-glucosidase activity. Dose-dependent inhibition pattern were observed for seed extracts and both the compounds. Further, inhibition kinetics studies of the diterpenes indicated a non-competitive type of inhibition against α-glucosidase. Docking studies were carried out which revealed that both the diterpenes interacted within the active site of N-terminal and C-terminal domain of human maltase-glucoamylase enzyme, respectively. This is the first report of α-glucosidase inhibitory activity of these isolated diterpenes and their higher inhibitory potential than any terpenoids studied till date against α-glucosidase.

  3. Quantitative determination of triterpenoid glycosides in Fatsia japonica Decne. & Planch. using high performance liquid chromatography.

    PubMed

    Ye, Xuewei; Yu, Siran; Lian, Xiao-Yuan; Zhang, Zhizhen

    2014-01-01

    Fatsia japonica Decne. & Planch. is a triterpenoid glycoside-rich herb with anti-inflammatory activity for the treatment of rheumatoid arthritis. A method for quantitative analysis of the complex triterpenoid glycosides in this medicinal plant has not been established so far. In this study, a high performance liquid chromatography (HPLC) method was developed for simultaneous qualification of 11 glycosides in F. japonica. The analysis was performed on an ODS-2 Hypersil column (250mm×4.6mm, 5μm) with a binary gradient mobile phase of water and acetonitrile. The established HPLC method was validated in terms of linearity, sensitivity, stability, precision, accuracy, and recovery. Results showed that this method had good linearity with R(2) at 0.99992-0.99999 in the test range of 0.04-9.00μg/μL. The limit of detection (LOD) and limit of quantification (LOQ) for the standard compounds were 0.013-0.020μg/μL and 0.040-0.060μg/μL. The relative standard deviations (RSDs%) of run variations were 0.83-1.40% for intra-day and 0.84-3.59% for inter-day. The analyzed compounds in the samples were stable for at least 36h, and the spike recoveries of the detected glycosides were 99.67-103.11%. The developed HPLC method was successfully applied for the measurements of the contents of 11 triterpenoid glycoside in different parts of F. japonica. Taken together, the HPLC method newly developed in this study could be used for qualitative and quantitative analysis of the bioactive triterpenoid glycosides in F. japonica and its products.

  4. Synthesis of phenylazonaphtol-β-D-O-glycosides, evaluation as substrates for beta-glycosidase activity and molecular studies

    PubMed Central

    2014-01-01

    Background Phenylazonaphtol-β-D-O-glycosides are alternative substrates for the detection of enzymatic activity of β-glycosidases which are involved in various important processes. These azoic compounds are currently exploited as prodrugs for colonic disease due the presence of β-glycosidase activity in the gut flora and therefore allowing the release of the drug at the specific site. Results Phenylazonaphtol-β-D-O-glucoside 3a and galactoside 3b were prepared via diazonium salt conditions under weak acidic conditions which do not compromise the O-glycosidic bond stability, by coupling reaction between 2-naphtol sodium salt with aminoglycosides 1a and 1b. The resulting phenylazonaphtol glycosides 2a and 2b were deprotected affording the phenylazonaphtol glycosides 3a and 3b in quantitative yield. The galactoside glycoside 3b was assayed as substrate for in vitro β-galactosidase enzymatic activity showing strong absorbance after releasing of the azoic chromophore. Also, docking studies were performed to determine the best pose as well as the interactions between the ligand and the residues located at the active site. Conclusions The methodology developed for synthesizing the phenylazonaphtol glycosides described proved to be convenient for generating azoic functionalities in the presence of glycosidic bonds and the glycosides suitable as alternative substrates and potentially useful prodrugs in the treatment of colonic diseases. PMID:24995152

  5. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture

    PubMed Central

    2012-01-01

    Background Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species. Results Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS) enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS) produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP) with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I diTPS (SsSS) then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae). Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants. Conclusions SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol

  6. A Pimarane Diterpene and Cytotoxic Angucyclines from a Marine-Derived Micromonospora sp. in Vietnam's East Sea.

    PubMed

    Mullowney, Michael W; Ó hAinmhire, Eoghainín; Tanouye, Urszula; Burdette, Joanna E; Pham, Van Cuong; Murphy, Brian T

    2015-09-01

    A screening of our actinomycete fraction library against the NCI-60 SKOV3 human tumor cell line led to the isolation of isopimara-2-one-3-ol-8,15-diene (1), lagumycin B (2), dehydrorabelomycin (3), phenanthroviridone (4), and WS-5995 A (5). These secondary metabolites were produced by a Micromonospora sp. isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. Compound 1 is a novel Δ(8,9)-pimarane diterpene, representing one of approximately 20 actinomycete-produced diterpenes reported to date, while compound 2 is an angucycline antibiotic that has yet to receive formal characterization. The structures of 1 and 2 were elucidated by combined NMR and MS analysis and the absolute configuration of 1 was assigned by analysis of NOESY NMR and CD spectroscopic data. Compounds 2-5 exhibited varying degrees of cytotoxicity against a panel of cancerous and non-cancerous cell lines. Overall, this study highlights our collaborative efforts to discover novel biologically active molecules from the large, underexplored, and biodiversity-rich waters of Vietnam's East Sea. PMID:26389922

  7. Indole Diterpene Alkaloids as Novel Inhibitors of the Wnt/β-catenin Pathway in Breast Cancer Cells

    PubMed Central

    Sallam, Asmaa A.; Ayoub, Nehad M.; Foudah, Ahmed I.; Gissendanner, Chris R.; Meyer, Sharon A.; El Sayed, Khalid A.

    2013-01-01

    Penitrems are indole diterpene alkaloids best known for their BK channel inhibition and tremorgenic effects in mammals. In a previous study, penitrems A–F (1–5), their biosynthetic precursors, paspaline (6) and emindole SB (7), and two brominated penitrem analogs 8 and 9 demonstrated promising in vitro antiproliferative, antimigratory, and anti-invasive effects in the MTT (MCF-7 and MDA-MB-231), wound-healing, and Cultrex® BME cell invasion (MDA-MB-231) assays, respectively. The study herein reports the novel ability of penitrem A to suppress total β-catenin levels in MDA-MB-231 mammary cancer cells. Nine new penitrem analogs (10–18) were semisynthetically prepared, in an attempt to identify pharmacophores correlated with BK channel inhibition and tremorgenicity of penitrems and decrease their toxicity. The degree of BK channel inhibition was assessed using the nematode Caenorhabditis elegans, and in vivo tremorgenic EC50 was calculated using CD-1 male mice following an Up-and-Down-Procedure (UDP). Although new analogs were generally less active than parent compound 1, some showed no BK channel inhibition or tremorgenicity and retained the ability of penitrem A (1) to suppress total β-catenin levels in MDA-MB-231 cells. Paspaline (6) and emindole SB (7), both lacking BK channel inhibition and tremorgenicity, represent the simplest indole diterpene skeleton that retains the antiproliferative, antimigratory and total β-catenin suppressing effects shown by the more complex penitrem A (1). PMID:24211635

  8. A Pimarane Diterpene and Cytotoxic Angucyclines from a Marine-Derived Micromonospora sp. in Vietnam's East Sea.

    PubMed

    Mullowney, Michael W; Ó hAinmhire, Eoghainín; Tanouye, Urszula; Burdette, Joanna E; Pham, Van Cuong; Murphy, Brian T

    2015-09-15

    A screening of our actinomycete fraction library against the NCI-60 SKOV3 human tumor cell line led to the isolation of isopimara-2-one-3-ol-8,15-diene (1), lagumycin B (2), dehydrorabelomycin (3), phenanthroviridone (4), and WS-5995 A (5). These secondary metabolites were produced by a Micromonospora sp. isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. Compound 1 is a novel Δ(8,9)-pimarane diterpene, representing one of approximately 20 actinomycete-produced diterpenes reported to date, while compound 2 is an angucycline antibiotic that has yet to receive formal characterization. The structures of 1 and 2 were elucidated by combined NMR and MS analysis and the absolute configuration of 1 was assigned by analysis of NOESY NMR and CD spectroscopic data. Compounds 2-5 exhibited varying degrees of cytotoxicity against a panel of cancerous and non-cancerous cell lines. Overall, this study highlights our collaborative efforts to discover novel biologically active molecules from the large, underexplored, and biodiversity-rich waters of Vietnam's East Sea.

  9. Erythroivorensin: A novel anti-inflammatory diterpene from the root-bark of Erythrophleum ivorense (A Chev.).

    PubMed

    Armah, Francis A; Annan, Kofi; Mensah, Abraham Y; Amponsah, Isaac K; Tocher, Derek A; Habtemariam, Solomon

    2015-09-01

    The stem- and root-bark of Erythrophleum ivorense (A Chev., family, Fabaceae) are routinely employed in the West African traditional medicine to treat inflammation and a variety of other disease conditions. Although the chemistry and pharmacology of cassaine-type diterpene alkaloids isolated from the stem-bark of the plant are fairly established, the root-bark has not yet been investigated. In the present study, the crude aqueous-alcohol extract of the root-bark was demonstrated to display a time- and dose (30-300 mg/kg p.o.)-dependent anti-inflammatory effect in chicks. Comprehensive chromatographic analysis coupled with spectroscopic and X-ray study further allowed the assignment of one of the major anti-inflammatory constituents as a novel cassaine-type diterpene, erythroivorensin. The other major constituents were known anti-inflammatory compounds: a triterpene, betulinic acid and a flavonoid, eriodictyol. The dose (10-100mg/kg p.o.)-dependent anti-inflammatory effects of the three compounds were either comparable or more significant than the positive control, diclofenac.

  10. A Pimarane Diterpene and Cytotoxic Angucyclines from a Marine-Derived Micromonospora sp. in Vietnam’s East Sea

    PubMed Central

    Mullowney, Michael W.; Ó hAinmhire, Eoghainín; Tanouye, Urszula; Burdette, Joanna E.; Pham, Van Cuong; Murphy, Brian T.

    2015-01-01

    A screening of our actinomycete fraction library against the NCI-60 SKOV3 human tumor cell line led to the isolation of isopimara-2-one-3-ol-8,15-diene (1), lagumycin B (2), dehydrorabelomycin (3), phenanthroviridone (4), and WS-5995 A (5). These secondary metabolites were produced by a Micromonospora sp. isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. Compound 1 is a novel Δ8,9-pimarane diterpene, representing one of approximately 20 actinomycete-produced diterpenes reported to date, while compound 2 is an angucycline antibiotic that has yet to receive formal characterization. The structures of 1 and 2 were elucidated by combined NMR and MS analysis and the absolute configuration of 1 was assigned by analysis of NOESY NMR and CD spectroscopic data. Compounds 2–5 exhibited varying degrees of cytotoxicity against a panel of cancerous and non-cancerous cell lines. Overall, this study highlights our collaborative efforts to discover novel biologically active molecules from the large, underexplored, and biodiversity-rich waters of Vietnam’s East Sea. PMID:26389922

  11. A Single Residue Switch for Mg2+-dependent Inhibition Characterizes Plant Class II Diterpene Cyclases from Primary and Secondary Metabolism*

    PubMed Central

    Mann, Francis M.; Prisic, Sladjana; Davenport, Emily K.; Determan, Mara K.; Coates, Robert M.; Peters, Reuben J.

    2010-01-01

    Class II diterpene cyclases mediate the acid-initiated cycloisomerization reaction that serves as the committed step in biosynthesis of the large class of labdane-related diterpenoid natural products, which includes the important gibberellin plant hormones. Intriguingly, these enzymes are differentially susceptible to inhibition by their Mg2+ cofactor, with those involved in gibberellin biosynthesis being more sensitive to such inhibition than those devoted to secondary metabolism, which presumably limits flux toward the potent gibberellin phytohormones. Such inhibition has been suggested to arise from intrasteric Mg2+ binding to the DXDD motif that cooperatively acts as the catalytic acid, whose affinity must then be modulated in some fashion. While further investigating class II diterpene cyclase catalysis, we discovered a conserved basic residue that seems to act as a counter ion to the DXDD motif, enhancing the ability of aspartic acid to carry out the requisite energetically difficult protonation of a carbon-carbon double bond and also affecting inhibitory Mg2+ binding. Notably, this residue is conserved as a histidine in enzymes involved in gibberellin biosynthesis and as an arginine in those dedicated to secondary metabolism. Interchanging the identity of these residues is sufficient to switch the sensitivity of the parent enzyme to inhibition by Mg2+. These striking findings indicate that this is a single residue switch for Mg2+ inhibition, which not only supports the importance of this biochemical regulatory mechanism in limiting gibberellin biosynthesis, but the importance of its release, presumably to enable higher flux, into secondary metabolism. PMID:20430888

  12. Design, synthesis and biological evaluation of tricyclic diterpene derivatives as novel neuroprotective agents against ischemic brain injury.

    PubMed

    Wang, Ying-Ying; Gao, Yuan-Xue; Gao, Wei; Xu, Yuan; Xu, Ya-Zhou; Wang, Yun-Jie; Chang, Sai; Yu, Li-Gang; Zhang, Lu-Yong; Liao, Hong; Yang, Lian-Fang; Pang, Tao; Qiu, Wen-Wei

    2015-10-20

    Lead compound 7 has neuroprotective effects, and it was discovered by screening a small synthetic natural product-like (NPL) library. Based on the lead, a series of tricyclic diterpene derivatives was designed and synthesized, and their neuroprotective effects were further evaluated against glutamate-, oxygen and glucose deprivation (OGD)- and nutrient deprivation-induced neuronal injury using cell-based assays. To our delight, most of these synthetic compounds exhibited increased neuroprotective effects and blood-brain barrier (BBB) permeability without cellular toxicity. The most potent compound, compound 30, showed significantly improved neuroprotection against neuronal injury in primary neurons. Furthermore, compound 30 exhibited remarkable neuroprotection in transient middle cerebral artery occlusion (tMCAO) rats by reducing their infarct sizes and neurological deficit scores. A mechanistic exploration using in vitro and in vivo experiments showed that the neuroprotection of these compounds was at least partly mediated by improving the levels of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein. Therefore, these tricyclic diterpene derivatives could be used as promising leads for the development of a new type of neuroprotective agents against ischemic brain injury.

  13. Direct and comprehensive analysis of ginsenosides and diterpene alkaloids in Shenfu injection by combinatory liquid chromatography-mass spectrometric techniques.

    PubMed

    Yang, Hua; Liu, Lei; Gao, Wen; Liu, Ke; Qi, Lian-Wen; Li, Ping

    2014-04-01

    Shenfu injection (SFI) is a widely used Chinese herbal formulation for cardiac diseases prepared from red ginseng and processed aconite root. Clinical observations and pharmacological effects on SFI have been well investigated. Chemical analysis and quality control studies of this formulation, however, are relatively limited, especially regarding toxic aconite alkaloids. In this work, a high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) method was applied to comprehensive analysis of constituents in SFI. Highly sensitive MS allows direct analysis of injections without additional sample pretreatment required. Using diagnostic ions and fragmentation rules, we identified 23 trace diterpene alkaloids, nineteen ginseng saponins, one panaxytriol, and one 5-hydroxymethylfurfural in SFI. A LC-MS method with selected ion monitoring was then used to quantify 24 major alkaloids and ginsenosides. The method was validated in terms of linearity, accuracy and precision. Especially, the limits of quantification were low to 0.4-18ng/mL for diterpene alkaloids. The total concentrations of saponins and alkaloids were about 676-742μg/mL and 3-7μg/mL in five batches of SFI samples, respectively. Finally, cosine ratio and euclidean distance were introduced to evaluate the batch-to-batch reproducibility of SFI samples, and the results demonstrated high quality consistency. Global identification and quantification of complex constituents based on LC-MS promises wide applications in quality control and batch monitoring for herbal products.

  14. Protective effects of coffee diterpenes against aflatoxin B1-induced genotoxicity: mechanisms in rat and human cells.

    PubMed

    Cavin, C; Mace, K; Offord, E A; Schilter, B

    2001-06-01

    The coffee-specific diterpenes cafestol and kahweol (C + K) have been reported to be anticarcinogenic in several animal models. Proposed mechanisms involve a co-ordinated modulation of several enzymes responsible for carcinogen detoxification, thus preventing reactive agents interacting with critical target sites. To address the human relevance of the chemoprotective effects of C + K against aflatoxin B(1) (AFB1) genotoxicity observed in rat liver, and to compare the mechanisms of protection involved in both species, animal and human hepatic in vitro test systems were applied. In rat primary hepatocytes, C + K reduced the expression of cytochrome P450 CYP 2C11 and CYP 3A2, the key enzymes responsible for AFB1 activation to the genotoxic metabolite aflatoxin B1-8,9 epoxide (AFBO). In addition, these diterpenes induced significantly GST Yc2, the most efficient rat GST subunit involved in AFBO detoxification. These effects of C + K resulted in a marked dose-dependent inhibition of AFB1-DNA binding in this rat in vitro culture system. Their relevance in humans was addressed using liver epithelial cell lines (THLE) stably transfected to express AFB1 metabolising cytochrome P450s. In these cells, C + K also produced a significant inhibition of AFB1-DNA adducts formation linked with an induction of the human glutathione S-transferase GST-mu. Altogether, these results suggest that C + K may have chemoprotective activity against AFB1 genotoxicity in both rats and humans. PMID:11346484

  15. Isolation and anti-inflammatory activity evaluation of triterpenoids and a monoterpenoid glycoside from Harpagophytum procumbens.

    PubMed

    Qi, Jin; Li, Na; Zhou, Jia-Hong; Yu, Bo-Yang; Qiu, Samuel X

    2010-11-01

    A new triterpenoid glycoside, designated harproside (1), and a new iridoid glycoside, named pagide (2), along with six known triterpenoids (3-8), were obtained from the tubers of Harpagophytum procumbens D. C. (devil's claw), and their structures were established through chemical methods and spectroscopic analyses. In an in vitro assay, the six triterpenoids showed anti-inflammatory activity. Compounds 3, 7, and 8 showed significant inhibitory activity against neutrophil respiratory burst stimulated by PMA, while compounds 4, 5, and 6 showed marginal inhibitory activity. PMID:20577946

  16. A steryl glycoside fraction with hemolytic activity from tubers of Momordica cochinchinensis.

    PubMed

    Ng, T B; Li, W W; Yeung, H W

    1986-10-01

    A hemolytic fraction has been obtained from fresh tubers of Momordica cochinchinensis. The fraction was strongly adsorbed on DEAE-Sepharose CL6B. It did not stain with Coomassie brilliant blue in SDS-polyacrylamide gel electrophoresis and it gave no immunoprecipitin arcs in immunoelectrophoresis. The hemolytic activity of the fraction was resistant to heat and proteolytic enzymes. The behavior of the fraction in thin-layer chromatography and its positive reaction in Liebermann-Burchard test indicated that the hemolytic activity of the fraction can be attributed to a steryl glycoside(s). PMID:3821135

  17. Anticomplement activity of cycloartane glycosides from the rhizome of Cimicifuga foetida.

    PubMed

    Qiu, Minghua; Kim, Jung-Hee; Lee, Hyeong-Kyu; Min, Byung-Sun

    2006-11-01

    A tetranor-cycloartane glycoside and two 9,19-cycloartane glycosides were isolated from the EtOAc-soluble fraction of the rhizome of Cimicifuga foetida. The structures of the compounds were determined to be cimilactone A (1), 25-O-acetylcimigenol 3-O-beta-d-xylopyranoside (2) and cimigenol 3-O-alpha-l-arabinopyranoside (3), respectively, using spectroscopic analysis. The three compounds were examined for their anticomplement activity against the classical pathway of the complement system. Compound 1 showed significant anticomplement activity with an IC(50) value of 28.6 microm, whereas compounds 2 and 3 were inactive.

  18. A steryl glycoside fraction with hemolytic activity from tubers of Momordica cochinchinensis.

    PubMed

    Ng, T B; Li, W W; Yeung, H W

    1986-10-01

    A hemolytic fraction has been obtained from fresh tubers of Momordica cochinchinensis. The fraction was strongly adsorbed on DEAE-Sepharose CL6B. It did not stain with Coomassie brilliant blue in SDS-polyacrylamide gel electrophoresis and it gave no immunoprecipitin arcs in immunoelectrophoresis. The hemolytic activity of the fraction was resistant to heat and proteolytic enzymes. The behavior of the fraction in thin-layer chromatography and its positive reaction in Liebermann-Burchard test indicated that the hemolytic activity of the fraction can be attributed to a steryl glycoside(s).

  19. Identification of Novel Phenyl Butenonyl C-Glycosides with Ureidyl and Sulfonamidyl Moieties as Antimalarial Agents

    PubMed Central

    2014-01-01

    A new series of C-linked phenyl butenonyl glycosides bearing ureidyl(thioureidyl) and sulfonamidyl moieties in the phenyl rings were designed, synthesized, and evaluated for their in vitro antimalarial activities against Plasmodium falciparum 3D7 (CQ sensitive) and K1 (CQ resistant) strains. Among all the compounds screened the C-linked phenyl butenonyl glycosides bearing sulfonamidyl moiety (5a) and ureidyl moiety in the phenyl ring (7d and 8c) showed promising antimalarial activities against both 3D7 and K1 strains with IC50 values in micromolar range and low cytotoxicity offering new HITS for further exploration. PMID:25147607

  20. Sixteen novel C-21 steroidal glycosides from the roots of Cynanchum mooreanum.

    PubMed

    Cui, Bo; Wang, Xinhong; Yang, Yifu; Yang, Yang; Shi, Songshan; Guo, Fujiang; Li, Yiming

    2015-12-01

    Fourteen novel 14,15-diseco-18-nor-pregnane-type steroidal glycosides, mooreanoside A-C (1-3) and mooreanoside F-P (6-16) and two new 14,15-diseco-pregnane-type steroidal glycosides, mooreanoside D-E (4-5) were isolated from the roots of Cynanchum mooreanum Hemsl. Their structures were determined on the basis of spectroscopic and chemical analysis. Compounds 1-6, 8-10, 12-14 and 16 were tested for their immunological activities in vitro against Con-A induced proliferation of mice splenocytes.