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Sample records for cyathane diterpenoid natural

  1. Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids in Higher Fungi.

    PubMed

    Tang, Hao-Yu; Yin, Xia; Zhang, Cheng-Chen; Jia, Qian; Gao, Jin-Ming

    2015-01-01

    Cyathane diterpenoids, occurring exclusively in higher basidiomycete (mushrooms), represent a structurally diverse class of natural products based on a characteristic 5-6-7 tricyclic carbon scaffold, including 105 members reported to date. These compounds show a diverse range of biological activities, such as antimicrobial, anti-MRSA, agonistic toward the kappa-opioid receptor, antiinflammatory, anti-proliferative and nerve growth factor (NGF)-like properties. The present review focuses on the structure diversity, structure elucidation and biological studies of these compounds, including mechanisms of actions and structure-activity relationships (SARs). In addition, new progress in chemical synthesis of cyathane diterpenoids is discussed. PMID:25994862

  2. Anti-inflammatory and cytotoxic cyathane diterpenoids from the medicinal fungus Cyathus africanus.

    PubMed

    Han, Junjie; Chen, Yuhui; Bao, Li; Yang, Xiaoli; Liu, Dailin; Li, Shaojie; Zhao, Feng; Liu, Hongwei

    2013-01-01

    Five novel cyathane diterpenes, cyathins D-H (1-5), as well as three known diterpenes, neosarcodonin O (6), cyathatriol (7),and 11-O-acetylcyathatriol (8), were isolated from the solid culture of Cyathus africanus. The structures of the new compounds were elucidated by spectroscopic methods. The absolute configurations of compounds 2 and 8 were determined by single-crystal X-ray crystallographic analysis, whereas the absolute configuration of C-14 in 1 was determined via the circular dichroism data of the [Rh(2)(OCOCF(3))(4)] complex. Compounds 3, 5, 6, 8, and 9 showed potent inhibition against nitric oxide production in lipopolysaccaride-activated macrophages with an IC(50) value of 2.57, 1.45, 12.0, 10.73, and 9.45μM, respectively. Compounds 6 and 8 showed strong cytotoxicity against Hela and K562 cell lines with the IC(50) value less than 10μM. PMID:23075884

  3. Ingenane Diterpenoids.

    PubMed

    Appendino, Giovanni

    2016-01-01

    Despite a more recent isolation and chemical characterization when compared to phorbol, along with its chemical instability, limited distribution in Nature, and scarce availability, ingenol is the only Euphorbia diterpenoid that has undergone successful pharmaceutical development, with ingenol 3-angelate (ingenol mebutate, Picato(®)) entering the pharmaceutical market in 2012 for the treatment of actinic keratosis. The phytochemical, chemical, and biological literature on members of the ingenane class of diterpenoids is reviewed from their first isolation in 1968 through 2015, highlighting unresolved issues both common to phorboids (biogenesis, relationship between molecular targets, and in vivo activity) and specific to ingenol derivatives (two-dimensional representation, in-out stereoisomerism, versatility of binding mode to PKC, and inconsistencies in the structural elucidation of some classes of derivatives). The biogenesis of ingenol is discussed in the light of the Jakupovic proposal of a dissection between the formation of the macrocyclic Euphorbia diterpenoids and the phorboids, and the clinical development of ingenol mebutate is chronicled in the light of its "reverse-pharmacology" focus. PMID:27380406

  4. Laxitextines A and B, Cyathane Xylosides from the Tropical Fungus Laxitextum incrustatum.

    PubMed

    Mudalungu, Cynthia M; Richter, Christian; Wittstein, Kathrin; Abdalla, Muna Ali; Matasyoh, Josphat C; Stadler, Marc; Süssmuth, Roderich D

    2016-04-22

    Bioassay-guided fractionation of the mycelial extract of a basidiomycete culture collected in Kenya led to the isolation of two new cyathane diterpenoids named laxitextines A (1) and B (2). The producer strain was characterized by detailed taxonomic studies based on rDNA using the 5.8S gene region, the internal transcribed spacer 2 (ITS2), and part of the large subunit that identified the fungus as Laxitextum incrustatum. The structures of 1 and 2 were elucidated by NMR spectroscopic and mass spectrometric analyses. Both compounds exhibited moderate activities against Gram-positive bacteria Bacillus subtilis (DSM 10), Staphylococcus aureus (DSM 346), and methicillin-resistant Staph. aureus (DSM 1182). The two compounds also showed variable antiproliferative activities against mouse fibroblast (L929) and selected human cell lines (breast cancer MCF-7, epidermoid carcinoma A431, and umbilical vein endothelial HUVEC). The IC50 values with respect to the MCF-7 cell line for compounds 1 and 2 were 2.3 and 2.0 μM, respectively. PMID:27043217

  5. New cytotoxic diterpenylnaphthohydroquinone derivatives obtained from a natural diterpenoid.

    PubMed

    Miguel Del Corral, José M; Castro, M Angeles; Lucena Rodri Guez, M; Chamorro, Pablo; Cuevas, Carmen; San Feliciano, Arturo

    2007-09-01

    Diterpenylquinone/hydroquinone derivatives were prepared through Diels-Alder cycloaddition between natural myrcecommunic acid or its methyl ester and p-benzoquinone (p-BQ), using BF(3).Et(2)O as catalyst or under microwave (Mw) irradiation. Acetyl, methyl and benzyl derivatives of several diterpenylnaphthohydroquinone were prepared from cycloadducts following two basic synthetic strategies, either protection before aromatisation or viceversa. Some of them were further functionalised at the B-ring of the decaline core. Most of the new compounds were evaluated and some of them resulted cytotoxic against several tumour cell lines with IC(50) values under the microM level. PMID:17583515

  6. A natural diterpenoid kamebacetal A with anti-tumor activity: Theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Tang, Fu-ming; Zhang, Yi-Heng; Chen, Zhong

    2010-06-01

    Kamebacetal A ( 1) is an ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara. This natural product exhibits significant cytotoxicity against human Bel-7402 and HO-8910 tumor cells. The geometrical conformation of 1 has been optimized at the B3LYP/6-311+G(d) level of theory. The results indicated that the calculated geometric parameters are close to the X-ray crystal structure. The theoretical 13C NMR chemical shifts of 1 were also calculated at the GIAO-B3LYP level of theory with different basis sets. The calculated NMR chemical shifts are in closer agreement with the experimental results. A molecular electrostatic potential (MEP) map was used in an attempt to identify key features of the kamebacetal A to account for its anti-tumor activity. MEP investigations reveal that compound 1, which shows anti-tumor activity, possesses electron-rich regions that extend over the hydroxyl and carbonyl groups of compound 1. The data generated in this study is valuable as it provides an insight into kamebacetal A molecular and structure-activity relationships.

  7. Production of bioactive cyathane diterpenes by a bird's nest fungus Cyathus gansuensis growing on cooked rice.

    PubMed

    Wang, Botao; Han, Junjie; Xu, Wei; Chen, Yuhui; Liu, Hongwei

    2014-01-01

    Cyathane diterpenes are important bioactive substances produced by some edible and medicinal fungi. Seven new cyathane type diterpenes, named as cyathins J-P (1-7), together with two known diterpenes (8 and 9), were isolated from the solid culture of the bird's nest fungus Cyathus gansuensis growing on cooked rice. The structures of the new secondary metabolites were elucidated by NMR experiments. Bioactivity screening indicated that compounds 1, 2, 4, and 8 showed moderate inhibitory activity against NO production in lipopolysaccharide-activated macrophages with an IC50 value of 42, 78, 80, and 16 μM, respectively. The fungus C. gansuensis is a promising source of bioactive secondary metabolites and has application potential in preparing healthy food. PMID:24444922

  8. Diterpenoids from Fagonia mollis.

    PubMed

    Sallam, Amal; Nugroho, Alfarius Eko; Hirasawa, Yusuke; Chin-Piow, Wong; Kaneda, Toshio; Shirota, Osamu; Gedara, Sahar R; Morita, Hiroshi

    2014-09-01

    A new acyclic diterpenoid (1) and a new erythroxan diterpenoid (2), together with 4 erythroxan diterpenoids and 3 triterpenoids, have been isolated from the aerial parts of Fagonia mollis. Their structures were elucidated on the basis of 1D and 2D NMR data. The cytotoxic activity of the isolated compounds was investigated against HL-60 cancer cells. PMID:25918782

  9. New clerodane diterpenoids from Croton crassifolius.

    PubMed

    Qiu, Maosong; Cao, Di; Gao, Youheng; Li, Shuhua; Zhu, Jinping; Yang, Bao; Zhou, Lian; Zhou, Yuan; Jin, Jing; Zhao, Zhongxiang

    2016-01-01

    Two new clerodane diterpenoids (1-2), one new clerodane diterpenoid alkaloid (3), as well as thirteen known compounds were isolated from Croton crassifolius. The structures of new compounds were established by a combination of spectroscopic methods, including HRMS, (1)H NMR, (13)C NMR, (1)H (1)H COSY, HSQC, HMBC, NOESY and X-ray crystallographic analysis. Compound 3 is firstly reported as the clerodane-type diterpenoid alkaloid in natural products. All of the compounds were evaluated for in vitro cytotoxic activities against CT26.WT cell using the MTT method. PMID:26611371

  10. Analysis of cyathane-type diterpenoids from Cyathus striatus and Hericium erinaceus by high-resolution MALDI MS imaging.

    PubMed

    Bhandari, Dhaka Ram; Shen, Tian; Römpp, Andreas; Zorn, Holger; Spengler, Bernhard

    2014-01-01

    Fungal secondary metabolites in both fruiting bodies and pellets from submerged cultures of basidiomycetes were analyzed by atmospheric pressure matrix-assisted laser desorption/ionization-mass spectrometry imaging at a lateral resolution of 15 μm, a mass resolution of 140,000 at m/z 200 and a mass accuracy of better than 2 ppm. The striatals A, B, C, and D, and a number of erinacine type metabolites were detected in the basidiomycetes Cyathus striatus and Hericium erinaceus, respectively. The two fungi were selected as model species, as they are well-known for efficient production of terpenoid secondary metabolites with interesting biological activities, e.g., antibacterial, fungicidal, cytotoxic properties, and stimulating effects on nerve growth factor synthesis. The localization of metabolites revealed a mostly homogeneous distribution of the striatals in the pellets of C. striatus, while a concentration gradient, increasing to the center, was observed in the pellets of H. erinaceus. A mostly homogeneous distribution of metabolites was also found in the fruiting body of H. erinaceus. PMID:24287632

  11. Diterpenoids from Leaves of Rubus chingii.

    PubMed

    Shu, Jicheng; Huang, Yingzheng; Cui, Hangqing; Peng, Caiying; Liu, Jianqun; Huang, Huilian

    2016-03-01

    The leaves of Rubus chingii were examined for their phytochemical composition and anti-yeast activity. In the process, seven diterpenoids (compounds 1-7), including a new natural compound (14β, 16-epoxy-7-pimarene-3α, 15β-diol, 1), were isolated and elucidated. Compound 1 exhibited moderate anti-Candida activity. PMID:27169185

  12. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2015-12-19

    Covering January to December 2014. Previous review, Nat. Prod. Rep., 2015, 32, 76-87 This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes, labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 200 references. PMID:26514379

  13. Functional identification of rice syn-copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products.

    PubMed

    Xu, Meimei; Hillwig, Matthew L; Prisic, Sladjana; Coates, Robert M; Peters, Reuben J

    2004-08-01

    Rice produces a number of phytoalexins, and at least one allelopathic agent, from syn-copalyl diphosphate (CPP), representing the only known metabolic fate for this compound. Thus, the class II terpene synthase that converts the universal diterpenoid precursor geranylgeranyl diphosphate to syn-CPP catalyzes the committed step in biosynthesis of these natural products. Here the extensive sequence information available for rice was coupled to recombinant expression and functional analysis to identify syn-copalyl diphosphate synthase (OsCPSsyn). In addition, OsCPSsyn mRNA was found to be specifically induced in leaves by conditions that stimulate phytoalexin biosynthesis. Therefore, transcription of OsCPSsyn seems to be an important regulatory point for controlling the production of these defensive compounds. Finally, alignments carried out with OsCPSsyn revealed that class II terpene synthases exhibit a sequence conservation pattern substantially different from that of the prototypical class I enzymes. One particularly notable feature is the specific conservation of the functionally cryptic 'insertional' sequence element in class II terpene synthases, indicating that this region is important for the corresponding cyclization reaction. PMID:15255861

  14. NMR spectroscopicsearch module for Spektraris, an online resource for plant natural product identification – taxane diterpenoids from Taxus × media cell suspension cultures as a case study

    PubMed Central

    Fischedick, Justin T.; Johnson, Sean R.; Ketchum, Raymond E.B.; Croteau, Rodney B.; Lange, B. Markus

    2014-01-01

    Development and testing of Spektraris-NMR an online spectral resource, is reported for the NMR-based structural identification of plant natural products (PNPs). Spektraris-NMRallows users to search with multiple spectra at once and returns a table with alist of hits arranged according to the goodness of fit between query data and database entries. For each hit, a link to a tabulated alignment of 1H-NMR and 13C-NMR spectroscopic peaks (query versus database entry) is provided. Furthermore, full spectroscopic records and experimental meta information about each database entry can be accessed online. To test the utility of Spektraris-NMR for PNP identification, the database was populated with NMR data (total of 466 spectra) for ∼250 taxanes, which are structurally complex diterpenoids (including the anticancer drug taxol) commonly found in the genus Taxus. NMR data generated used was then generated with metabolites purified from Taxus cell suspension cultures to search Spektraris-NMR, and were able to identify eight taxanes with high confidence. A ninth isolated metabolite could be assigned, based on spectral searches, to a taxane skeletal class, but no high confidence hit was produced. Using various spectroscopic methods, this metabolite was characterized as the taxane 2-deacetylbaccatin IV, a novel taxane. These results indicate that Spektraris-NMR is a valuable resource for rapid and reliable identification of known metabolites and has the potential to contribute to de-replication efforts in the search for novel PNPs. PMID:25534952

  15. New diterpenoids from euphorbia teheranica

    PubMed

    Ahmad; Jassbi

    1999-07-01

    Two novel pentacyclic diterpenoid esters of the cyclomyrsinane type (1, 2), and one tetracyclic diterpenoid ester of the myrsinane type (3) were isolated from the aerial parts of the plant Euphorbia teheranica. The structures of the novel compounds were determined by spectral data interpretation. PMID:10425130

  16. The isolation and synthesis of neodolastane diterpenoids.

    PubMed

    Marković, Dean; Kolympadi, Maria; Deguin, Brigitte; Porée, François-Hugues; Turks, Māris

    2015-02-01

    The neodolastane diterpenoids comprise a group of 44 compounds including guanacastepenes, heptemerones, plicatilisins, radianspenes, 2,15-epoxy-5,13-dihydroxyneodolast-3-en-14-one and sphaerostanol. These fungal and marine natural products are characterized by a tricyclic neodolastane skeleton that consists of fused five-, seven- and six-membered rings. Their reported antibiotic activities against antibiotic-resistant bacteria together with strong antifungal and anticancer activities and their novel structures render these compounds interesting synthetic targets. The aim of this account is to summarise the progress in the isolation, characterisation and synthesis of these diterpenoids as well as to review their biogenetic origins and diverse biological activities since their discovery in 2000. PMID:25366359

  17. ent-kaurane diterpenoids from Annona glabra.

    PubMed

    Chen, C Y; Chang, F R; Cho, C P; Wu, Y C

    2000-07-01

    Three new kaurane diterpenoids, annoglabasin C (16alpha-acetoxy-ent-kauran-19-oic acid-17-methyl ester) (1), annoglabasin D (16alpha-acetoxy-ent-kauran-19-al-17-methyl ester) (2), and annoglabasin E (16alpha-hydro-19-ol-ent-kauran-17-oic acid) (3), and a new norkaurane diterpenoid, annoglabasin F (16alpha-acetoxy-19-nor-ent-kauran-4alpha-ol-17-methyl ester) (4), along with 13 known kaurane derivatives were isolated from the stems of Annona glabra. 16alpha-Methoxy-ent-kauran-19-oic acid (5) and 16alpha-hydro-ent-kauran-17,19-dimethyl ester (6) were obtained for the first time as natural products. The structures of compounds 1-6 were characterized by spectral analysis. PMID:10924186

  18. Diterpenoids from Isodon sculponeatus.

    PubMed

    Jiang, Hua-Yi; Wang, Wei-Guang; Zhou, Min; Wu, Hai-Yan; Zhan, Rui; Li, Xiao-Nian; Du, Xue; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2014-03-01

    Phytochemical investigation of the aerial parts of Isodon sculponeatus afforded six new 7,20-epoxy-ent-kauranoids, sculponins U-Z (1-6), and 11 known diterpenoids (7-17). The structures of these new compounds were elucidated primarily by means of extensive spectroscopic analysis, and the absolute configuration of 1 was determined by single crystal X-ray diffraction. Compound 5 exhibited weak cytotoxic activity against HL-60, SMMC-7721, MCF-7, and SW-480 cell lines, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 value of 13.8 μM. PMID:24418655

  19. Diterpenoid tetracyclic hydrocarbons of petroleum

    SciTech Connect

    Vorob'eva, N.S.; Zemskova, Z.K.; Pekh, T.I.; Petrov, A.A.

    1987-08-01

    Diterpenoid hydrocarbons are fairly widespread in various caustobioliths. However, if petroleums contain mainly acyclic diterpenoids (phytane, pristane and norpristane), cyclic diterpaenes such as fichtelite, pimarane, iosene (kaurane) and hibbane are often found in hydrocarbons isolated from coal and shale. Recent advances in the chemistry of diterpenoids isolated from caustobioliths, are described in a separate paper. Much less is known about petroleum polycyclic diterpenoid hydrocarbons, particularly those with four saturated rings. A series of tetracyclic hydrocarbons C/sub 19/H/sub 32/ (molar mass 260), found in a number of light petroleums and gas condensates from the Jura deposits of Central Kara-Kum (Turkmen S.S.R.), are examined here. These hydrocarbons are present in petroleums and condensates from the Davaly, Erden, Ortakak, Southern Beuideshik deposits, they are always identical and occur in the same ratios. The composition of the tretracyclanes isolated from the Ortakak gas condensates (well 17) will be examined in detail.

  20. Two rings in them all: The labdane-related diterpenoids

    PubMed Central

    Peters, Reuben J.

    2013-01-01

    In his original exposition of the biogenetic isoprenoid rule, L. Ruzicka noted the structural identity between the fused A/B rings of triterpenoids/sterols and certain multicyclic diterpenoids as part of the impetus leading to that profound insight. His prescient hypothesis that this chemical structure relationship reflects similarities in the initial cyclization of these diterpenoids with that occurring in triterpenoid biosynthesis has since been verified. However, this chemical structure relationship does not continue to hold true for the additional rings found in many of these di- and tri- terpenoid natural products. This is now appreciated to arise from differences in their subsequent biogenesis, specifically further cyclization and/or rearrangement of these diterpenoids after formation of an initial bicyclic intermediate in a separately catalyzed reaction. The trivial name for the hydrocarbon skeleton of the most commonly found version of the corresponding unique intermediate forms the basis for a unifying “labdane-related” designation. This defines a large super-family of diterpenoids that contains nearly 7,000 already known natural products. Many of these are found in plants, where the requisite biosynthetic machinery for gibberellin phytohormones, particularly the relevant diterpene cyclases, provides a biosynthetic reservoir that appears to have been repeatedly drawn upon to evolve new labdane-related diterpenoids. The potent biological activity of the “ancestral” gibberellins, which has led to the independent evolution of distinct gibberellin biosynthetic pathways in plants, fungi, and bacteria, is further discussed as an archetypical example of the selective pressure driving the observed diversification of the large super-family of labdane-related diterpenoid natural products. PMID:20890488

  1. Characterization of an orphan diterpenoid biosynthetic operon from Salinispora arenicola.

    PubMed

    Xu, Meimei; Hillwig, Matthew L; Lane, Amy L; Tiernan, Mollie S; Moore, Bradley S; Peters, Reuben J

    2014-09-26

    While more commonly associated with plants than microbes, diterpenoid natural products have been reported to have profound effects in marine microbe-microbe interactions. Intriguingly, the genome of the marine bacterium Salinispora arenicola CNS-205 contains a putative diterpenoid biosynthetic operon, terp1. Here recombinant expression studies are reported, indicating that this three-gene operon leads to the production of isopimara-8,15-dien-19-ol (4). Although 4 is not observed in pure cultures of S. arenicola, it is plausible that the terp1 operon is only expressed under certain physiologically relevant conditions such as in the presence of other marine organisms. PMID:25203741

  2. Characterization of an Orphan Diterpenoid Biosynthetic Operon from Salinispora arenicola

    PubMed Central

    2015-01-01

    While more commonly associated with plants than microbes, diterpenoid natural products have been reported to have profound effects in marine microbe–microbe interactions. Intriguingly, the genome of the marine bacterium Salinispora arenicola CNS-205 contains a putative diterpenoid biosynthetic operon, terp1. Here recombinant expression studies are reported, indicating that this three-gene operon leads to the production of isopimara-8,15-dien-19-ol (4). Although 4 is not observed in pure cultures of S. arenicola, it is plausible that the terp1 operon is only expressed under certain physiologically relevant conditions such as in the presence of other marine organisms. PMID:25203741

  3. Crotofolane diterpenoids from Croton caracasanus.

    PubMed

    Chávez, Katiuska; Compagnoneb, Reinaldo S; Riina, Ricarda; Briceño, Alexander; González, Teresa; Squitieri, Emilio; Landaetab, Carlos; Soscrún, Humberto; Suáreza, Alírica I

    2013-12-01

    Four new crotofolane-type diterpenoids, crotocarasin (A-D) (1-4), together with the known crotofolin E, were isolated from a dichloromethane extract of the stems of Croton caracasanus Pittier. The structures of the new compounds were determined by spectroscopic methods, and the structure of 3 was further confirmed by single-crystal X-ray data analyses. PMID:24555271

  4. Ozonolytic transformations of labdane diterpenoids

    NASA Astrophysics Data System (ADS)

    Vlad, Pavel F.; Aryku, A. N.

    1992-07-01

    Information on the products of ozonolysis of labdane and ent-labdane diterpenoids is correlated. The effects of the ozonolysis conditions, the procedure for treating the products and the location of double bonds and other functional groups on the character of the resulting ozonolysis products are considered. The bibliography includes 91 references.

  5. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  6. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  7. Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

    PubMed Central

    2015-01-01

    Summary This review describes strategies for the chemical synthesis of xenicane diterpenoids and structurally related metabolites. Selected members from the four different subclasses of the Xenia diterpenoid family, the xenicins, xeniolides, xeniaphyllanes and xeniaethers, are presented. The synthetic strategies are discussed with an emphasis on the individual key reactions for the construction of the uncommon nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated. PMID:26734099

  8. Biotransformations of diterpenoids and triterpenoids: a review.

    PubMed

    Bhatti, Haq Nawaz; Khera, Rasheed Ahmad

    2014-01-01

    During the past few years, research has focused on the microbial transformation of a huge variety of organic compounds to obtain compounds of therapeutic and/or industrial interest. Microbial transformation is a useful tool for organic chemists looking for new compounds, as a consequence of the variety of reactions for natural products. Terpenoids are a large family of natural products exhibiting a wide range of biological activities such as antibiotics, anti-inflammatory, anti-HIV and anti-tumor effects; hypotensive agents; sweeteners; insecticides; anti-feedants; phytotoxic agents; perfumery intermediates; and plant growth hormones. This article describes the biotransformation products of diterpenoids and triterpenoids in a variety of biological media. Emphasis is placed on reporting the metabolites that may be of special interest as well as the practical aspects of this work in the field of microbial transformations. This review covers the literature from 1991 to 2012. PMID:24266458

  9. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives.

    PubMed

    Timoshenko, Mariya A; Kharitonov, Yurii V; Shakirov, Makhmut M; Bagryanskaya, Irina Yu; Shults, Elvira E

    2016-02-01

    A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products. PMID:27308214

  10. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives†

    PubMed Central

    Timoshenko, Mariya A.; Kharitonov, Yurii V.; Shakirov, Makhmut M.; Bagryanskaya, Irina Yu.

    2015-01-01

    Abstract A selective synthesis of 7‐ or 14‐nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3‐nitroaniline, 3‐(trifluoromethyl)aniline, and 4‐(trifluoromethyl)aniline yield the subsequent 7α‐, 7β‐ and 14αnitrogen‐containing diterpenoids. The reaction with 2‐nitroaniline, 4‐nitro‐2‐chloroaniline, 4‐methoxy‐2‐nitroaniline, phenylsulfamide, or tert‐butyl carbamate proceeds with the formation of 7α‐nitrogen‐substituted diterpenoids as the main products. PMID:27308214

  11. Clerodane diterpenoids from Croton crassifolius.

    PubMed

    Wang, Guo-Cai; Li, Jia-Gui; Li, Guo-Qiang; Xu, Jiao-Jiao; Wu, Xia; Ye, Wen-Cai; Li, Yao-Lan

    2012-12-28

    Seven new clerodane diterpenoids (1-7) were isolated from roots of Croton crassifolius, along with six known compounds. The structures were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 1, 3, 4, and 7 were confirmed by single-crystal X-ray diffraction analyses. Compounds 1-13 were evaluated for in vitro antiviral activity against herpes simplex virus type 1 using the cytopathic effect reduction assay. PMID:23194476

  12. Labdane Diterpenoids from Leonotis leonurus

    PubMed Central

    Wu, Hankui; Li, Jun; Fronczek, Frank R.; Ferreira, Daneel; Burandt, Charles L.; Setola, Vincent; Roth, Bryan L.; Zjawiony, Jordan K.

    2012-01-01

    Three known (leoleorins A-C) and eight new (leoleorins D-J and 16-epi-leoleorin F) labdane diterpenoids, were isolated from leaves of Leonotis leonurus. The absolute configurations of leoleorins A and D were established by X-ray crystallographic analyses. In competitive binding assay all isolated compounds showed inhibition in excess of 50% at various CNS receptors. Leoleorin C showed moderate binding affinity (Ki = 2.9 μM) for the Sigma 1 receptor. PMID:22445074

  13. A Novel Norclerodane Diterpenoid from the Roots of Croton crassifolius.

    PubMed

    Zhang, Zhan-Xin; Li, Hui-Hong; Fan, Gai-Xia; Li, Zheng-Yu; Dong, Le-Le; Li, Hong-Yu; Fei, Dong-Qing

    2015-11-01

    A chemical investigation of Croton crassifolius afforded a novel norclerodane diterpenoid (1) with an unprecedented six-membered oxygen ring between C-1 and C-12, together with three known compounds. The structure of the new compound was elucidated based on spectroscopic (IR, 1D, and 2D NMR) and HR-ESI-MS techniques. This report describes the first example of a natural norclerodane with a 4H-chromene ring system. PMID:26749826

  14. Two New Diterpenoids from Salvia przewarskii.

    PubMed

    Tsukada, Haruka; Kawabe, Hiroshi; Ohtaka, Aya; Saito, Yoshinori; Okamoto, Yasuko; Tori, Motoo; Kagechika, Hiroyuki; Hirota, Hiroshi; Gong, Xun; Kuroda, Chiaki; Ohsaki, Ayumi

    2016-02-01

    One abietane-type and one dinoricetexane-type diterpenoid, salviskin A (1) and salviskin B (2), respectively, together with fourteen known diterpenoids, were isolated from Salvia przewarskii. Structural elucidation of these compounds was performed by spectroscopic methods including 2D NMR. The compounds isolated were evaluated for their cytotoxicity against HeLa and HL-60 cells. PMID:27032190

  15. Asymmetric synthesis and absolute stereochemistry of a labdane-type diterpenoid isolated from the rhizomes of Isodan yuennanensis.

    PubMed

    Deng, Heping; Cao, Wei; Zhang, Zhijiang; Liu, Bo

    2016-07-14

    The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined. PMID:27251032

  16. Grindelane diterpenoids from Stevia subpubescens.

    PubMed

    Román, L U; Cambrón, J I; del Río, R E; Hernández, J D; Cerda-García-Rojas, C M; Joseph-Nathan, P

    2000-02-01

    Four new 9R,13R-epoxylabdane diterpenes (1-4) and a known clerodane derivative, 3,4beta-epoxy-5beta,10beta-cis-17alpha, 20alpha-clerod-13(14)-en-15,16-olide, were isolated from the leaves of Stevia subpubescens. The structures, which correspond to the grindelane class of diterpenoids, were elucidated by NMR data, chemical correlation, and single-crystal X-ray diffraction analysis of monoacetate 5. The absolute configuration of 1-4 is based on the optical activity of ketone 3 as compared with data of closely related substances. PMID:10691714

  17. Diterpenoid derivatives of Kenyan Croton sylvaticus.

    PubMed

    Ndunda, Beth; Langat, Moses K; Midiwo, Jacob O; Omosa, Leonidah K

    2015-04-01

    Kenyan Croton sylvaticus Hochst. ex Krauss gave four clerodane diterpenoids, the new ent-3,13E-clerodadiene-15-formate (1), the known 15-acetoxy-ent-3,13E-clerodadiene (2), ent-3,13E-clerodadien-15-ol (3) and hardwickiic acid (4), two known halimane diterpenoids, penduliflaworosin (5) and crotohalimaneic acid (6) and one labdane diterpenoid, labda-13E-ene-8a,15-diol (7). The compounds, when tested for their anti-microbial activities against Bacillus subtilis, Xanthomonas campestris and Candida albicans, were found to be inactive. PMID:25973474

  18. Syntheses of Denudatine Diterpenoid Alkaloids: Cochlearenine, N-Ethyl-1α-hydroxy-17-veratroyldictyzine, and Paniculamine.

    PubMed

    Kou, Kevin G M; Li, Beryl X; Lee, Jack C; Gallego, Gary M; Lebold, Terry P; DiPasquale, Antonio G; Sarpong, Richmond

    2016-08-31

    The denudatine-type diterpenoid alkaloids cochlearenine, N-ethyl-1α-hydroxy-17-veratroyldictyzine, and paniculamine have been synthesized for the first time (25, 26, and 26 steps from 16, respectively). These syntheses take advantage of a common intermediate (8) that we have previously employed in preparing aconitine-type natural products. The syntheses reported herein complete the realization of a unified strategy for the preparation of C20, C19, and C18 diterpenoid alkaloids. PMID:27525345

  19. Antimicrobial Diterpenoids of Wedelia trilobata (L.) Hitchc.

    PubMed

    Li, Shi-Fei; Ding, Jia-Yin; Li, Ya-Ting; Hao, Xiao-Jiang; Li, Shun-Lin

    2016-01-01

    Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1-7. Their structures and relative configuration were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR experiments. The antimicrobial activities of all isolated diterpenoids were evaluated against a panel of bacteria and fungi. PMID:27070557

  20. Five New Diterpenoids from an Okinawan Soft Coral, Cespitularia sp.

    PubMed Central

    Roy, Prodip K.; Maarisit, Wilmar; Roy, Michael C.; Taira, Junsei; Ueda, Katsuhiro

    2012-01-01

    Five new diterpenoids 1–5 were isolated from an Okinawan soft coral, Cespitularia sp., together with the known diterpenoid, alcyonolide (6). New diterpenoid structures were elucidated by spectroscopic methods and by comparison of their NMR data with those of related compounds. Alcyonolide (6) was cytotoxic against HCT 116 cells (IC50 5.85 μM), while these new diterpenoids 1–5 were much less active (IC50 28.2–91.4 μM). PMID:23201595

  1. Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels.

    PubMed

    Yang, Li-Guo; Zhang, Ying-Jie; Xie, Jia-Ying; Xia, Wei-Jun; Zhang, Hai-Yuan; Tang, Meng-Yun; Mei, Shuang-Xi; Cui, Tao; Wang, Jing-Kun; Zhu, Zhao-Yun

    2016-09-01

    A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum. PMID:27268073

  2. Cytotoxic diterpenoids from Rabdosia lophanthoides var. gerardianus.

    PubMed

    Lin, Chao-Zhan; Zhao, Wei; Feng, Xiu-Li; Liu, Fang-Le; Zhu, Chen-Chen

    2016-03-01

    Two new abietane diterpenoids, Gerardianin B (1) and Gerardianin C (2), one new lignan glycoside, Gerardianin D (3) and one new lupane-type triterpenoid, Gerardianol A (4), together with seven known abietane diterpenoids were isolated from the aerial parts of Rabdosia lophanthoides var. gerardianus. Their structures were determined by 1D and 2D NMR spectroscopic data. The cytotoxic activities of the nine diterpenoids were evaluated on human cancer cell lines. Compounds 6-11 exhibited significant cytotoxic activities against HepG2 cell lines with IC50 from 4.68 to 9.43μM and HCF-8 cell lines with IC50 from 9.12 to 13.53μM. PMID:26608401

  3. Diterpenoid Biopolymers: New Directions for Renewable Materials Engineering

    PubMed Central

    Hillwig, Matthew L.; Mann, Francis M.; Peters, Reuben J.

    2010-01-01

    Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling, non-renewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. PMID:20857504

  4. Diterpenoid biopolymers: new directions for renewable materials engineering.

    PubMed

    Hillwig, Matthew L; Mann, Francis M; Peters, Reuben J

    2011-02-01

    Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid-based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling nonrenewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. PMID:20857504

  5. [A diterpenoid quinone from Periploca forrestii].

    PubMed

    Wang, Yan; Sun, Lei; Qiao, Shanyi

    2010-06-01

    Tanshinone II A, which was known unique to the salvia, was separated and purified by silica gel column chromatography and recrystallisation from an ethyl acetate-soluble portion (the anti-inflammatory active portion) of ethanol extract of Periploca forrestii. The diterpenoid quinone was obtained from the Periploca for the first time. PMID:20815227

  6. Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity.

    PubMed

    He, Luwei; Han, Junjie; Li, Baowei; Huang, Li; Ma, Ke; Chen, Quan; Liu, Xinzhong; Bao, Li; Liu, Hongwei

    2016-03-23

    Diterpenes has been reported to possess multiple bioactivities consisting of anti-microbial and anti-inflammatory properties. This study reveals a new cyathane-type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP-ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells. PMID:26871659

  7. Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound.

    PubMed

    Li, Dahong; Han, Tong; Liao, Jie; Hu, Xu; Xu, Shengtao; Tian, Kangtao; Gu, Xiaoke; Cheng, Keguang; Li, Zhanlin; Hua, Huiming; Xu, Jinyi

    2016-01-01

    Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field. PMID:27563888

  8. Euphorbesulins A-P, Structurally Diverse Diterpenoids from Euphorbia esula.

    PubMed

    Zhou, Bin; Wu, Yan; Dalal, Seema; Cassera, Maria B; Yue, Jian-Min

    2016-08-26

    Aqueous ethanol extracts of powdered twigs of Euphorbia esula afforded 16 new diterpenoids, named euphorbesulins A-P. These euphorbesulins included presegetane (1-3), jatrophane (4-14), paraliane (15), and isopimarane (16) diterpenoids as well as six known analogues. Compounds 1-3 represent a rare type of presegetane diterpenoid. Their structures were determined by analysis of the spectroscopic data, and the absolute configuration of 1 was established by X-ray crystallography. Diterpenoid 7 showed low nanomolar antimalarial activity, while the remaining compounds showed only moderate or no antimalarial activity. PMID:27447736

  9. Bis-spirolabdane Diterpenoids from Leonotis nepetaefolia

    PubMed Central

    Li, Jun; Fronczek, Frank R.; Ferreira, Daneel; Burandt, Charles L.; Setola, Vincent; Roth, Bryan L.; Zjawiony, Jordan K.

    2012-01-01

    Ten new bis-spirolabdane diterpenoids, leonepetaefolins A–E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids (11–18) as well as two known flavonoids apigenin and cirsiliol, were isolated from the leaves of Leonotis nepetaefolia. The structures of the new compounds were determined on the basis of 1D-and 2D-NMR experiments including 1H, 13C, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY. The absolute configuration of an epimeric mixture of 1 and 2 was determined by X-ray crystallographic analysis. The compounds isolated were evaluated for their binding propensity in several CNS G protein-coupled receptor assays in vitro. PMID:22475308

  10. A new kaurane diterpenoid from Isodon inflexus.

    PubMed

    Xu, Guang-Hua; Cai, Xing-Fu; Jin, Xuejun; Lee, Jung Joon

    2016-01-01

    A new 7,20-epoxy kaurane diterpenoid, 15-acetyldemethylkamebacetal A (1) and six known kaurane diterpenoids (2-7) were isolated from the aerial parts of Isodon inflexus in nuclear transcription factor-κB (NF-κB)-dependent reporter gene assay-guided fractionation. Their chemical structures were determined on the basis of extensive spectroscopic analysis (UV, IR, MS, 1D- and 2D-NMR) and comparison with literature data. The isolated compounds were evaluated for their inhibitory effects on TNF-α-induced NF-κB activation, and all compounds exhibited NF-κB inhibitory activities with IC50 values ranging from 1.91 to 20.15 μM. PMID:26461051

  11. New kaurene diterpenoid glycosides from fenugreek seeds.

    PubMed

    Pang, Xu; Kang, Li-Ping; Yu, He-Shui; Zhao, Yang; Xiong, Cheng-Qi; Zhang, Jie; Ma, Bai-Ping

    2013-01-01

    Two new kaurene diterpenoid glycosides, named Graecumoside A (1) and B (2), were isolated from fenugreek seeds, along with three known flavonoid-C-glycosides, isoorientin (3), isovitexin (4) and vitexin (5). By combined analyses of 1D- and 2D-NMR, and MS spectroscopy, the structures of two new compounds were elucidated as 3-O-β- D-glucopyranosyl kaur-5, 16-dien-3β, 6, 13β-trihydroxy-7-oxo-18-oic acid methyl ester and 3-O-β-neohesperidosyl kaur-5, 16-dien-3β, 6, 13β-trihydroxy-7-oxo-18-oic acid methyl ester, respectively. The kaurene diterpenoid glycosides were first isolated and identified from fenugreek seeds. PMID:22950814

  12. Anti-inflammatory diterpenoids from Croton tonkinensis.

    PubMed

    Kuo, Ping-Chung; Yang, Mei-Lin; Hwang, Tsong-Long; Lai, Yuan-Yu; Li, Yue-Chiun; Thang, Tran Dinh; Wu, Tian-Shung

    2013-02-22

    Phytochemical investigation of the methanolic extract of Croton tonkinensis afforded two known kauranes (1, 2), eight new ent-kauranes (3-10), and 16 known ent-kaurane-type diterpenoids (12-27). In addition, 30 known compounds were identified by comparison of their physical and spectroscopic data with reported data. Among the isolated compounds, ent-18-acetoxykaur-16-en-15-one (20) displayed the most significant inhibition of superoxide anion generation and elastase release. PMID:23347584

  13. New 3,4-seco-Grayanane Diterpenoids from the Flowers of Pieris japonica.

    PubMed

    Cao, Lang; Li, Yanping; Li, Hongmei; Liu, Dan; Li, Rongtao

    2016-01-01

    Three new 3,4-seco-grayanane diterpenoids, neopierisoids D-F (2-4), and a new natural one, neopierisoid C (1), were isolated from the flowers of Pieris japonica. Their structures were elucidated on the basis of extensive spectroscopic analysis, including one and two dimensional (1- and 2D)-NMR, as well as high resolution-electron ionization (HR-EI)-MS. PMID:27477663

  14. A Group of ent-Kaurane Diterpenoids Inhibit Hedgehog Signaling and Induce Cilia Elongation

    PubMed Central

    Jiang, Shiyou; Du, Jiacheng; Kong, Qinghua; Li, Chaocui; Li, Yan; Sun, Handong; Pu, Jianxin; Mao, Bingyu

    2015-01-01

    The Hedgehog (Hh) signaling pathway plays important roles in the tumorigenesis of multiple cancers and is a key target for drug discovery. In a screen of natural products extracted from Chinese herbs, we identified eight ent-Kaurane diterpenoids and two triterpene dilactones as novel Hh pathway antagonists. Epistatic analyses suggest that these compounds likely act at the level or downstream of Smoothened (Smo) and upstream of Suppressor of Fused (Sufu). The ent-Kauranoid-treated cells showed elongated cilia, suppressed Smo trafficking to cilia, and mitotic defects, while the triterpene dilactones had no effect on the cilia and ciliary Smo. These ent-Kaurane diterpenoids provide new prototypes of Hh inhibitors, and are valuable probes for deciphering the mechanisms of Smo ciliary transport and ciliogenesis. PMID:26439749

  15. An unusual mulinane diterpenoid from the Chilean plant Azorella trifurcata (Gaertn) Pers.

    PubMed

    Areche, Carlos; Sepulveda, Beatriz; San Martin, Aurelio; Garcia-Beltrán, Olimpo; Simirgiotis, Mario; Cañete, Alvaro

    2014-09-01

    Four new mulinane-type diterpenoids besides the known compounds mulin-11,13-dien-20-oic acid, 13α-hydroxyazorellane, 13β-hydroxyazorellane, mulinolic acid, azorellanol, and mulin-11,13-dien-18-acetoxy-16,20-dioic acid were isolated from the Chilean plant Azorella trifurcata. One of the new metabolites isolated, 7α-acetoxy-9-epi-13β-hydroxymulinane, possesses a new trans-syn-trans arrangement in a tricyclic ring system not previously encountered in nature. Among the mulinane diterpenoids isolated, mulin-11,13-dien-20-oic acid showed the gastroprotective effect on HCl-EtOH-induced gastric lesions in mice (ED50 = 55 mg kg(-1)). Regarding the mode of gastroprotective action for this active compound, its effect was reduced by pre-treatment of the mice with indomethacin and N-ethylmaleimide, suggesting that prostaglandins and sulfhydryl compounds are positively involved in the gastroprotective activity using this model. PMID:25008488

  16. Leonuketal, a Spiroketal Diterpenoid from Leonurus japonicus.

    PubMed

    Xiong, Liang; Zhou, Qin-Mei; Zou, Yike; Chen, Ming-Hua; Guo, Li; Hu, Guan-Ying; Liu, Zhao-Hua; Peng, Cheng

    2015-12-18

    An architecturally complex spiroketal diterpenoid, leonuketal (1), was isolated from the aerial parts of the plant Leonurus japonicus. This compound possessed an unprecedented tetracyclic skeleton that comprised a bridged spiroketal moiety fused with a ketal-γ-lactone unit. The structure and absolute configuration were determined by spectroscopic analyses, a modified Mosher's method, and ECD (electronic circular dichroism) calculations. Leonuketal (1) showed significant vasorelaxant activity against KCl-induced contraction of rat aorta, with the EC50 value of 2.32 μM. PMID:26634796

  17. New Diterpenoids from Soft Coral Sarcophyton ehrenbergi

    PubMed Central

    Wang, Shang-Kwei; Hsieh, Mu-Keng; Duh, Chang-Yih

    2013-01-01

    Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 µg/mL, respectively. PMID:24177676

  18. Two new diterpenoids from Croton crassifolius.

    PubMed

    Hu, Ying; Zhang, Lei; Wen, Xiao-Qiong; Zeng, Xiao-Jun; Rui, Wen; Cen, Ying-Zhou

    2012-01-01

    Two new clerodane-type diterpenoids were isolated from the roots of Croton crassifolius Geisel. The structures of these compounds were elucidated as 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic acid (1) and methyl 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic ester (2) by spectroscopic methods. PMID:22694251

  19. New Cytotoxic Tigliane Diterpenoids from Croton caudatus.

    PubMed

    Chen, Ying-Ying; Yang, Kun-Xian; Yang, Xing-Wei; Khan, Afsar; Liu, Lu; Wang, Bei; Zhao, Yun-Li; Liu, Ya-Ping; Li, Yan; Luo, Xiao-Dong

    2016-05-01

    Three new tigliane-type diterpenoids were isolated from the methanolic extract of the twigs and leaves of Croton caudatus, trivially named crotusins A-C (1-3). The structures of compounds 1-3 were elucidated on the basis of extensive spectral methods. These new compounds were highly oxygenated and heavily substituted. Cytotoxic activity against five human tumor cell lines was assessed for compounds 1-3 of which compound 3 showed significant inhibitory activity with IC50 values ranging from 0.49 to 4.19 µM against these cells, while crotusins A and B exhibited moderate activity. PMID:27002392

  20. Antimicrobial abietane diterpenoids from Plectranthus elegans.

    PubMed

    Dellar, J E; Cole, M D; Waterman, P G

    1996-02-01

    Two novel abietane diterpenoids have been isolated from the aerial material of Plectranthus elegans and identified as 11-hydroxy-12-oxo-7,9(11),13-abietatriene and 7 alpha,11-dihydroxy-12-methoxy-8,11,13-abietatriene. Their structures were determined through rigorous use of spectroscopic methods. Both inhibited spore germination of the fungus Cladosporium cucumerinum, in direct bioautography, at a dose of 1 microgram. The new diterpenes also inhibited the growth of Gram-positive bacteria, in the concentration range 10-40 micrograms ml-1 in broth dilution assay. No effect was observed against Gram-negative bacteria. The ecological implications of these findings are discussed. PMID:8835454

  1. New jatrophane diterpenoid esters from Euphorbia turczaninowii.

    PubMed

    Liu, L G; Tan, R X

    2001-08-01

    Five new (1-5) and one known (6) jatrophane diterpenoid esters were isolated from the ethanol extract of the whole herb of Euphorbia turczaninowii. Their structures were established by extensive spectroscopic methods. The absolute stereochemistry of 3 beta,5 alpha,8 alpha,15 beta-tetraacetoxy-7 beta-benzoyloxyjatropha-6(17),11E-dien-9,14-dione (1) was confirmed by a single-crystal X-ray analysis coupled with the exciton chirality circular dichroism method. Compounds 1-6 were inactive when evaluated both in a mouse ear inflammation assay and for cytotoxicity against the B16 mouse melanoma cell line. PMID:11520228

  2. New macrocyclic diterpenoids from Euphorbia esula.

    PubMed

    Liu, L G; Meng, J C; Wu, S X; Li, X Y; Zhao, X C; Tan, R X

    2002-03-01

    The structures of two new macrocyclic jatrophane diterpenoid esters from the whole herb of Euphorbia esula, were established as 11,14-epoxy-3beta,5alpha,7beta,8alpha,9alpha,15beta-hexaacetoxy-12-oxo-13alphaH-jatropha-6(17)-ene (1) and 1alpha,3beta-diacetoxy-5alpha,7beta-dibenzoyloxy-9,14-dioxo-11beta,12alpha-epoxy-2alpha,8alpha,15beta-trihydroxy-13betaH-jatropha-6(17)-ene (2) by a combination of 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. Bioassay evaluation of all isolates against the human tumor cell lines (B16, KB, SMMC and BGC) indicated that ester 2 was cytotoxic to B16 with the IC50 value being 1.81 microg/ml. In addition, the irritant activity assay indicated that both diterpenoids were inactive (ID(24)50 > 100 microg/ear). PMID:11914962

  3. Nitrogen-Containing Diterpenoids, Sesquiterpenoids, and Nor-Diterpenoids from Cespitularia taeniata

    PubMed Central

    Wang, Shih-Sheng; Cheng, Yuan-Bin; Lin, Yu-Chi; Liaw, Chia-Ching; Chang, Jiun-Yang; Kuo, Yao-Haur; Shen, Ya-Ching

    2015-01-01

    Two new nitrogen-containing verticillene diterpenoids, cespilamides A and B (1 and 2), three new nitrogen-containing sesquiterpenoids, cespilamides C–E (3–5), and five new norverticillene and verticillene diterpenoids, cespitaenins A–E (6–10), were isolated from the Taiwanese soft coral Cespitularia taeniata. Compound 1 possesses an unusual oxazo ring system at C-10 while compound 2 displays an unprecedented C–C bond cleavage between C-10 and C-11 with an N-ethylphenyl group at C-10. Biogenetic pathways of 1 and 2 are proposed. The absolute configuration of 1 was confirmed by Mosher’s method and molecular mechanics calculations (MM2). The cytotoxicities of compounds 1–10 were evaluated against a small panel of human cancer cell lines. PMID:26389921

  4. Bicyclic sesquiterpenoids and diterpenoids in Australian crude oils

    NASA Astrophysics Data System (ADS)

    Paul Philp, R.; Gilbert, Trevor D.; Friedrich, Jane

    1981-07-01

    Bicyclanes previously reported only in heavily biodegraded Texas Gulf Coast crudes have been found to be ubiquitous in Australian crude oils of non-marine origin from four different basins. The compounds are present in oils, thought to be derived from the same or similar sources, that have undergone varying degrees of biodegradation. They are also found to be present in oils of different geological age. In addition a series of tricyclic diterpenoid hydrocarbons was common to four oils from the Gippsland Basin. Four of these compounds had the molecular formula C 20H 34 and mass spectral fragmentation patterns suggested they were mono-unsaturated diterpenoids. The presence of unsaturated diterpenoids in crude oils appears to be a unique observation. It is proposed that the diterpenoids may be the source of the bicyclanes also observed in these oils.

  5. A new cassane diterpenoid from the seeds of Caesalpinia decapetala.

    PubMed

    Wei, Hua; Liu, Xiao-Qian; Zhu, Jing-Jing; Gao, Liang-Liang; Wang, Zhi-Min; Yan, Li-Hua

    2016-04-01

    Phytochemical investigation on the seeds of Caesalpinia decapetala led to the isolation of a new cassane diterpenoid with an unusual O bridge between C-19 and C-20, named phanginin Q (1), together with three known cassane diterpenoids, caesaljapin (2), caesaldekarin A (3), and caesaldekarin B (4). The structure of the new compound was elucidated by spectroscopic methods, including (1)H NMR, (13)C NMR, HSQC, (1)H - (1)H COSY, HMBC, NOESY, and HR-ESI-MS. PMID:26268793

  6. Total synthesis of diterpenoid steenkrotin A.

    PubMed

    Pan, Saiyong; Xuan, Jun; Gao, Beiling; Zhu, An; Ding, Hanfeng

    2015-06-01

    A concise and diastereoselective total synthesis of the diterpenoid (±)-steenkrotin A is described for the first time. The strategy mainly features three key ring formations: 1) a rhodium-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction to build up the tetrahydrofuran subunit; 2) sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations to construct the [5,7] spirobicyclic skeleton; and 3) an intramolecular aldol condensation/vinylogous retro-aldol/aldol sequence to form the final six-membered ring with inversion of the relative configuration at the C7 position. PMID:25891977

  7. Bioactive diterpenoid containing a reversible "spring-loaded" (E,Z)-dieneone Michael acceptor.

    PubMed

    Gupta, Prasoon; Sharma, Upasana; Schulz, Thomas C; Sherrer, Eric S; McLean, Amanda B; Robins, Allan J; West, Lyndon M

    2011-08-01

    Three new briarane diterpenoids, briareolate esters L-N (1-3), have been isolated from a gorgonian Briareum asbestinum. Briareolate esters L (1) and M (2) are the first natural products possessing a 10-membered macrocyclic ring with a (E,Z)-dieneone and exhibit growth inhibition activity against both human embryonic stem cells (BG02) and a pancreatic cancer cell line (BxPC-3). Briareolate ester L (1) was found to contain a "spring-loaded" (E,Z)-dieneone Michael acceptor group that can form a reversible covalent bond to model sulfur-based nucleophiles. PMID:21749084

  8. Eight new diterpenoids and two new nor-diterpenoids from the stems of Croton cascarilloides.

    PubMed

    Kawakami, Susumu; Toyoda, Hiroki; Harinantenaina, Liva; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2013-01-01

    From the stems of Croton cascarilloides, eight new diterpenoids, named crotocascarins A-H (1-8), having a crotofolane skeleton were isolated along with two new nor-diterpenoids (9 and 10), named crotocascarins α and β, derived through rearrangement of the crotofolane skeleton. The structures of these compounds were elucidated by means of extensive one- and two-dimensional NMR spectroscopic analyses. The absolute structures of the diterpene moiety were determined by application of the circular dichroism (CD) rule for the γ-lactone ring. The relative structures of the two crotofolanes (1 and 2) and one rearranged compound (9) were confirmed by X-ray crystallographic analyses. Compounds 1, 2 and 9 possessed 2-methylbutyric acid in their molecules, the absolute configuration of which was found to be 2S by comparison of its HPLC behavior with that of an authentic sample. Therefore, the absolute structures of these crotocascarins (1, 2 and 9) were unambiguously determined. The absolute structures of crotofolanes are reported for the first time in this paper. PMID:23370306

  9. Diterpenoid glycosyl esters from Phlomis younghusbandii and P. medicinalis roots.

    PubMed

    Katagiri, M; Ohtani, K; Kasai, R; Yamasaki, K; Yang, C R; Tanaka, O

    1994-01-01

    From the roots of Phlomis younghusbandii collected in Tibet, new furanolabdane-type diterpenoid glycosides named phlomisosides III and IV were isolated together with a known sweet furanolabdane-type diterpenoid glycoside, phlomisoside I. The structure of the common aglycone of phlomisosides III and IV, which we have named phlomisoic acid, was established as 15,16-epoxy-8,13(16),14-labdatrien-19-oic acid by MS and NMR spectroscopy. Phlomisosides III and IV are tasteless and the structures of these were determined to be the beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranosyl and the alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester of phlomisoic acid by chemical and spectroscopic methods, respectively. The diterpenoid glycoside constituents of the roots of P. medicinalis collected in Tibet were also elucidated, and baiyunoside and phlomisosides II and III were isolated and identified. PMID:7764482

  10. Structure-cardiac activity relationship of C19-diterpenoid alkaloids.

    PubMed

    Jian, Xi-Xian; Tang, Pei; Liu, Xiu-Xiu; Chao, Ruo-Bing; Chen, Qiao-Hong; She, Xue-Ke; Chen, Dong-Lin; Wang, Feng-Peng

    2012-06-01

    Thirty three C19-diterpenoid alkaloids, twenty-two prepared from known C19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an alpha-hydroxyl group at C-15, a hydroxyl group at C-8, an alpha-methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitine-type C19-diterpenoid alkaloids without any ester groups. In addition, an alpha-hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids. PMID:22816290

  11. 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

  12. New Cembrane Diterpenoids from a Hainan Soft Coral Sinularia sp

    PubMed Central

    Yang, Bin; Zhou, Xuefeng; Huang, Hui; Yang, Xian-Wen; Liu, Juan; Lin, Xiuping; Li, Xiubao; Peng, Yan; Liu, Yonghong

    2012-01-01

    Five new cembrane diterpenoids, named sinuflexibilins A–E (1–5), along with nine other known diterpenoids (6–14), have been isolated from the organic extract of a Hainan soft coral Sinularia sp. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison of their spectral data with those of related metabolites. Compound 13, flexibilide, exhibited significant inhibitory activity of NF-κB activation using the cell-based HEK293 NF-κB luciferase reporter gene assay. PMID:23118718

  13. Diterpenoids from Callicarpa kwangtungensis and their NO inhibitory effects.

    PubMed

    Xu, Jing; Li, Shen; Sun, Xiaocong; Ma, Jun; Liu, Feng; Tong, Ling; Lee, Dongho; Ohizumi, Yasushi; Tuerhong, Muhetaer; Guo, Yuanqiang

    2016-09-01

    A phytochemical investigation of the leaves of Callicarpa kwangtungensis led to the isolation of three new diterpenoids (1-3), callipenes A-C, and eleven known analogues (4-14). Their structures were established on the basis of extensive analysis of NMR spectroscopic data, X-ray diffraction data, and experimental and calculated electronic circular dichroism spectra. Compounds 1 and 2 are rare abietane diterpenoids possessing a peroxide bridge. All of the isolates were found to inhibit LPS-induced NO production in BV-2 cells. PMID:27491749

  14. Hepatoprotective diterpenoids from the roots of Salvia grandifolia.

    PubMed

    Kang, Jie; Zhang, Ting; Li, Li; Sun, Hua; Wang, Ding-Ding; Chen, Ruo-Yun

    2016-05-01

    One new diterpenoid, grandifolia G (1), together with a known diterpenoid (6,7,8,8a-tetrahydro-6,6-dimethyl-2-oxonaphtho[1,8-bc]furan-3-yl)-4-methylfuran-3-carboxylic acid (2), was isolated from 70% EtOH extract of root of Salvia grandifolia. Their structures were determined by UV, IR, HRESIMS, NMR spectra. Compounds 1 and 2 (10 μM) exhibited hepatoprotective activities (61 and 55%) against DL-galactosamine-induced cell damage in HL-7702 cells. PMID:27086714

  15. neo-Clerodane diterpenoids from Scutellaria barbata with cytotoxic activities.

    PubMed

    Dai, Sheng-Jun; Tao, Jia-Yi; Liu, Ke; Jiang, Yong-Tao; Shen, Li

    2006-07-01

    Three neo-clerodane diterpenoids, named barbatins A-C (1-3), and the neo-clerodane diterpenoid nicotinyl ester, named scutebarbatine B (4), were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic analyses (UV, IR, HRFAB-MS, 1D NMR and 2D NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, with IC50 values in the range 3.5-8.1 microM. PMID:16769097

  16. Fimbriatols A–J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes

    PubMed Central

    Ding, Gang; Fei, Jiaodong; Wang, Jing; Xie, Yong; Li, Rongtao; Gong, Ningbo; Lv, Yang; Yu, Changyuan; Zou, Zhongmei

    2016-01-01

    Fimbriatols A–J (1–10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 μg/mL. Compounds 7–10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2′ to C-1′′ instead of the common linkage at C-6′ to C-1′′, and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation. PMID:27484744

  17. Fimbriatols A-J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes.

    PubMed

    Ding, Gang; Fei, Jiaodong; Wang, Jing; Xie, Yong; Li, Rongtao; Gong, Ningbo; Lv, Yang; Yu, Changyuan; Zou, Zhongmei

    2016-01-01

    Fimbriatols A-J (1-10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 μg/mL. Compounds 7-10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2' to C-1'' instead of the common linkage at C-6' to C-1'', and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation. PMID:27484744

  18. The simultaneous analysis of proteins, lipids, and diterpenoid resins found in cultural objects.

    PubMed

    Singer, Brian; McGuigan, Ross

    2007-07-01

    We report a GC-MS method for the simultaneous analysis of proteins oil, and diterpenoid resins found in cultural objects. The method was initially designed for protein analysis of protenaceous paints and adhesives and involves acid hydrolysis as the first step. The amino acids in the protein hydrolysates, thus obtained, are treated with propan-l-ol/ hydrogen chloride and then pentafluoropropionic anhydride. The procedure was found also to yield the propyl esters of fatty acids derived from lipids and diterpenoid acids derived from natural resins, and thus allows the choice of a single method for the analysis of artists media which contain either oil s or proteins or mixtures of both proteins and oils or even resins. Thus natural mixtures such as egg yolk and also mixtures made by the artist such as animal glue/seed oil emulsions can be analysed. Coupled with FTIR analysis of paints and the staining of cross sections, to indicate layer structure the method can help to elucidate the paints and adhesives used by artists. PMID:17867529

  19. Maize Kauralexins: inducible diterpenoid phytoalexins protect against fungal pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytoalexins constitute a broad category of pathogen and insect-inducible biochemicals that locally protect plant tissues. In rice, a complex array of inducible diterpenoid phytoalexins constitute an important component of the plants anti-pathogen defenses. In contrast, despite the demonstration of ...

  20. Prenylbicyclogermacrane diterpenoids from the formosan soft coral Nephthea elongata.

    PubMed

    El-Gamal, Ali Ali Hassan; Wang, Shang-Kwei; Duh, Chang-Yih

    2007-06-01

    Seven new prenylbicyclogermacrane diterpenoids, pacificins K--Q (1--7), were isolated from the methylene chloride solubles of the Formosan soft coral Nephthea elongata. Their structures were elucidated by extensive spectroscopic analysis and their cytotoxicity against selected cancer cells was measured in vitro. PMID:17541187

  1. New clerodane diterpenoids from the roots of Polyalthia laui.

    PubMed

    Yu, Zhang-Xin; Fu, Yan-Hui; Chen, Guang-Ying; Song, Xiao-Ping; Han, Chang-Ri; Li, Xiao-Bao; Song, Xin-Ming; Wu, Ai-Zhen; Chen, Shi-Chen

    2016-06-01

    Five new clerodane diterpenoids, polylauiester A (1), (4→2)-abeo-2,13-diformyl-cleroda-2,12E-dien-14-oic acid (2) and polylauiamides B-D (3-5), together with 11 known clerodane diterpenoids (6-16), were isolated from the roots of Polyalthia laui. Among them, polylauiester A (1) represents the first example of a novel norclerodane diterpenoid only containing 17 carbon atoms on the carbon skeleton, and polylauiamide B (3) is an unusual diterpenoid with a p-substituted benzene ring as a substituent. Their structures were elucidated by extensive spectroscopic methods, and the relative configuration of polylauiamide B (3) was further confirmed by the single crystal X-ray diffraction method. Biological evaluation of new compounds against human Hela, MCF-7 and A549 human cancer cell lines showed that all compounds displayed weak cytotoxicities against various human cancer cell lines in the range of IC50 at 25.01-39.31μM. PMID:27058277

  2. Supression of inflammatory responses by labdane-type diterpenoids

    SciTech Connect

    Giron, Natalia; Rodriguez, Benjamin; Lopez-Fontal, Raquel; Bosca, Lisardo; Hortelano, Sonsoles Heras, Beatriz de las

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-{alpha} in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 {mu}M. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor {kappa}B signaling showed that both compounds inhibit the phosphorylation of I{kappa}B{alpha} and I{kappa}B{beta}, preventing their degradation and the nuclear translocation of the NF-{kappa}B p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  3. Two diterpenoids from the roots of gaultheria yunnanensis

    PubMed

    Zhang; Guo; Li; Zheng; Koike; Jia; Nikaido

    1999-02-01

    Two new diterpenoids, gaultheric acid (1) and gaultheronoterpene (2), were isolated from the roots ofGaultheria yunnanensis. Their structures were elucidated as 12-hydroxy-13-acetyl-8,11, 13-podocarpatrien-18-oic acid (1) and 3beta, 12-dihydroxy-13-acetyl-4(18),8,11,13-podocarpatetraene (2) on the basis of spectral analysis. PMID:10075764

  4. Bioactivity-guided isolation of antiproliferative diterpenoids from Euphorbia kansui.

    PubMed

    Wang, Hong-Ying; Wang, Jun-Song; Wei, Dan-Dan; Wang, Xiao-Bing; Luo, Jun; Yang, Ming-Hua; Kong, Ling-Yi

    2012-06-01

    Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol-type diterpenoids (1-4 and 7-12), of which, 5-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (1) is a new compound, and two are jatrophane-type diterpenoids (13-14). Interconversion of two pairs of positional ester isomers (1-4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel-7402, Bel-7402/5FU, BGC-823 and SGC-7901 cell lines. The 12 ingenol-type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane-type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol-type diterpenoids. The structure--activity relationships were investigated by principal component analysis (PCA) of the pIC₅₀ (-logIC₅₀) values of the compounds tested and their calculated molecular descriptors. The pIC₅₀ values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy (E(HOMO)), absolute hardness (η) and positively charged solvent accessible surface areas (P-ASA). As the values of E(HOMO) increase, η and P-ASA decrease, and the antiproliferative effects of these compounds increase. PMID:22095916

  5. Pericolactines A–C, a New Class of Diterpenoid Alkaloids with Unusual Tetracyclic Skeleton

    PubMed Central

    Wu, Yue-Hua; Chen, Guo-Dong; He, Rong-Rong; Wang, Chuan-Xi; Hu, Dan; Wang, Gao-Qian; Guo, Liang-Dong; Yao, Xin-Sheng; Gao, Hao

    2015-01-01

    Fusicoccane diterpenoids usually possess a fused 5-8-5 tricyclic ring system, which are biogenetically generated from geranylgeranyl diphosphate (GGDP). In our report, three novel diterpenoid alkaloids with fusicoccane skeleton, pericolactines A–C (1–3), were isolated from Periconia sp.. Their structures with absolute configurations were determined by spectroscopic analyses and quantum chemical ECD calculation. Pericolactines A–C (1–3) are a new class of diterpenoid alkaloids with an unusual fused 5-5-8-5 tetracyclic ring system, which derive from a geranylgeranyl diphosphate (GGDP) and serine conjugated biosynthesis. They belong to the atypical diterpenoid alkaloids. PMID:26611465

  6. Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol.

    PubMed

    Garifullin, Bulat F; Strobykina, Irina Yu; Sharipova, Radmila R; Kravchenko, Marionella A; Andreeva, Olga V; Bazanova, Olga B; Kataev, Vladimir E

    2016-08-01

    The first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol moieties were synthesized and evaluated for inhibition activity against Mycobacterium tuberculosis H37Rv. PMID:27267064

  7. Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.

    PubMed

    Pham, Minh Quan; Iscache, Anne Laure; Pham, Quoc Long; Gairin, Jean Edouard

    2016-04-01

    Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC. PMID:26713517

  8. Cytotoxic diterpenoids from Jatropha curcas cv. nigroviensrugosus CY Yang Roots.

    PubMed

    Liu, JieQing; Yang, YuanFeng; Xia, JianJun; Li, XuYang; Li, ZhongRong; Zhou, Lin; Qiu, MingHua

    2015-09-01

    An investigation of phytochemicals from the roots of Jatropha curcas cv. nigroviensrugosus resulted in the isolation of twenty diterpenoids, including lathyranlactone, an unusual diterpenoid lactone possessing a 5/13/3 tricyclic skeleton, jatrocurcasenones A-E and jatrophodiones B-E, as well as 10 known analogues. All isolates were evaluated for cytotoxicity against the HL-60, SMMC-772, A-549, MCF-7 and SW480 human tumor cell lines using the MTS viability assay. Four of the known analogues showed cytotoxic activity in these cell lines, with IC50 values ranging from 2.0 to 23.0 μM. Moreover, the assessment of their cytotoxic structure-activity relationships showed the epoxy ring between C-5 and C-6 and the hydroxyl group at C-2 were the key functionalities for cytotoxicity. PMID:26209936

  9. ent-Kaurane diterpenoids from Croton tonkinensis stimulate osteoblast differentiation.

    PubMed

    Dao, Trong-Tuan; Lee, Kwang-Youl; Jeong, Hyung-Min; Nguyen, Phi-Hung; Tran, Tien Lam; Thuong, Phuong-Thien; Nguyen, Bich-Thu; Oh, Won-Keun

    2011-12-27

    Four new ent-kaurane diterpenoids (1-4) were isolated from the leaves of Croton tonkinensis by bioactivity-guided fractionation using an in vitro osteoblast differentiation assay. Their structures were identified as ent-11β-acetoxykaur-16-en-18-ol (1), ent-11α-hydroxy-18-acetoxykaur-16-ene (2), ent-14β-hydroxy-18-acetoxykaur-16-ene (3), and ent-7α-hydroxy-18-acetoxykaur-16-ene (4). Compounds 1-4 significantly increased alkaline phosphatase activity and osteoblastic gene promoter activity. Compounds 1-3 also increased the levels of ALP and collagen type I alpha mRNA in C2C12 cells in a dose-dependent manner. These results suggest that ent-kaurane diterpenoids from C. tonkinensis have a direct stimulatory effect on osteoblast differentiation and may be potential therapeutic molecules against bone diseases such as osteoporosis. PMID:22085418

  10. Macrocyclic Diterpenoids from the Latex of Euphorbia helioscopia.

    PubMed

    Hua, Juan; Liu, Yan-Chun; Jing, Shu-Xi; Luo, Shi-Hong; Li, Sheng-Hong

    2015-12-01

    One new jatrophane diterpenoid, 7α,9β,15β-triacetoxy-3β-benzoyloxy-14β-hydroxyjatropha-5E,11E-diene (3), together with four known macrocyclic diterpenoids, euphoheliosnoid A (1), epieuphoscopin B (2), euphohelioscopin A (4) and euphoscopin C (5), were isolated from the stem latex of Euphorbia helioscopia. Their structures were established by spectroscopic analyses. In the anti-inflammatory assay, euphohelioscopin A (4) exhibited moderate inhibitory activity on the release of cytokine TNF-α (IC50 = 23.7 ± 1.7 μM), IL-6 (IC50 = 46.1 ± 1.1 μM) and chemokine MCP-1 (IC50 = 33.7 ± 3.8 μM) in lipopolysaccharide (LPS) induced RAW 264.7 macrophages without notable cytotoxicity (IC50 > 80 μM). PMID:26882659

  11. The Chemistry of Perfumes Based on Labdane Diterpenoids

    NASA Astrophysics Data System (ADS)

    Vlad, Pavel F.

    1982-07-01

    The advances in the synthesis of C14-C19 perfumes derived from bicyclic labdane diterpenoids and their enantiomers as well as data concerning the sources of the starting materials are presented. The dependence of the odour of the above compounds on their structure and stereochemistry and the questions arising in the manufacture of some of them and their practical applications are considered. The bibliography includes 242 references

  12. Crystal structure of sepaconitine, a C19-diterpenoid alkaloid from the roots of Aconitum sinomontanum Nakai

    PubMed Central

    Shi, Xin-Wei; Lu, Qiang-Qiang; Zhou, Jun-Hui; Cui, Xin-Ai

    2015-01-01

    The title compound [systematic name: [(1α,14α,16β)-20-ethyl-8,9,10-trihy­droxy-1,14,16-tri­meth­oxy­aconitan-4-yl 2-amino­benzoate], C30H42N2O8, a natural C19-diterpenoid alkaloid, possesses an aconitane carbon skeleton with four six-membered rings and two five-membered rings. The fused ring system contains two chair, one boat, one twist-boat and two envelope conformations. Intra­molecular N—H⋯O hydrogen bonds are observed between the amino and carbonyl groups. The mol­ecules are linked together via O—H⋯O hydrogen bonds, forming a three-dimensional framework. PMID:26396791

  13. Epoxide Opening of a 7,17-Seco-7,8-Epoxy-C19-Diterpenoid Alkaloid.

    PubMed

    Ji, Hong; Wang, Feng-Peng; Chen, Qiao-Hong

    2015-12-01

    A new and effective approach toward epoxide opening of a 7,17-seco-7,8-epoxy-C19-diterpenoid alkaloid is herein described. The starting epoxide was prepared from naturally occurring yunnaconitine via a nine-step transformation. Treatment of this epoxide with trifluoroacetic anhydride in dioxane at 110 degrees C followed by reduction with sodium boron hydride generated two epoxide opening compounds 7 and 8. Each of their structures is characteristic of a Δ8,15 bridgehead double bond and a 7β-oxygen-substituted group. PMID:26882668

  14. Semisynthesis of the antiviral abietane diterpenoid jiadifenoic acid C from callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin.

    PubMed

    González, Miguel A; Zaragozá, Ramón J

    2014-09-26

    The semisynthesis of the antiviral abietane diterpenoid (+)-jiadifenoic acid C starting from the available methyl ester of callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin is reported. A protocol for the isolation of methyl callitrisate (methyl 4-epidehydroabietate) in gram quantities from sandarac resin is also described. Allylic C-17 oxygenation was introduced by regioselective dehydrogenation of the isopropyl group of methyl callitrisate with DDQ followed by selenium-catalyzed allylic oxidation. Ester hydrolysis afforded (+)-jiadifenoic acid C in 22% overall yield from methyl callitrisate. This semisynthetic route provides a convenient source of this anti-Coxsackie virus B natural product for further biological studies. PMID:25166492

  15. Clerodane diterpenoids, long chain esters of coumaric acid and other compounds from Baccharis myrsinites.

    PubMed

    Li, C J; Ahmed, A A; Arias, A C; Mabry, T J

    1997-06-01

    A new clerodane diterpenoid and two new long chain esters of trans- and cis-coumaric acid, in addition to known triterpenoids and one known clerodane diterpenoid, have been isolated and characterized from Baccharis myrsinites. The structures were determined by spectroscopic techniques. PMID:9190087

  16. ent-Kaurane-based regio- and stereoselective inverse electron demand hetero-Diels-Alder reactions: synthesis of dihydropyran-fused diterpenoids.

    PubMed

    Ding, Chunyong; Wang, Lili; Chen, Haijun; Wild, Christopher; Ye, Na; Ding, Ye; Wang, Tianzhi; White, Mark A; Shen, Qiang; Zhou, Jia

    2014-11-14

    A mild and concise approach for the construction of a 3,4-dihydro-2H-pyran ring integrated into the A-ring of the natural product oridonin using an optimized inverse electron demand hetero-Diels-Alder (IED HDA) reaction is reported herein. A self-dimerization of the exocyclic enone installed in the A-ring through a homo-HDA reaction was identified to exclusively give a dimeric ent-kaurane diterpenoid with the spirochroman core. Moreover, efficient cross-HDA cycloadditions of this enone with various vinyl ethers or vinyl sulfides, instead of its own homo-HDA dimerization, were achieved in a regio- and stereoselective manner, thus providing access to novel dihydropyran-fused diterpenoids as potential anticancer agents to overcome chemoresistance. PMID:25225052

  17. A new abietane diterpenoid from Salvia xanthocheila Boiss.

    PubMed

    Habibi, Zohreh; Gandomkar, Somayyeh; Yousefi, Maryam; Ghasemi, Sabrieh

    2013-01-01

    From the chloroform extract of aerial part of Salvia xanthocheila Boiss. one new abietane diterpenoid, xantoquinone (5α,6α-dimethoxy-7,11,14-trioxoabieta-8,12-diene) and one known oleanene triterpenoid namely 1β,3β-dihydroxy-12-oleanene were isolated. The structure of the new terpenoid was elucidated by comprehensive spectroscopic analysis including electron ionisation-mass spectra, (1)H NMR, (13)C NMR, distortionless enchancement by polarisation transfer, H,H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation. PMID:22475036

  18. A new ent-kaurane diterpenoid from Ixora amplexicaulis.

    PubMed

    Chen, Lijun; Zhan, Rui; Jiang, Jinhe; Zhang, Yan; Dong, Yi; Chen, Yegao

    2016-01-01

    A new ent-kaurane diterpenoid, 6α,16α-dihyroxy-ent-kaurane (1), was isolated from the stems of Ixora amplexicaulis, together with (24R)-6β-hydroxy-24-ethyl-cholest-4-en-3-one (2), 7β-hydroxysitosterol (3), maslinic acid (4), 3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (5) and protocatechuric acid (6). Their structures were established by extensive spectroscopic analysis, including 2D NMR techniques. Compounds 2-5 were isolated from the genus Ixora for the first time and 6 obtained originally from I. amplexicaulis. PMID:25941744

  19. Cytotoxic ent-kaurane diterpenoids from Isodon nervosus.

    PubMed

    Gao, You-Heng; Wei, Zhi-Xiong; Cheng, Yi; Wang, Teng-Hua; Ni, Lin; Zhou, Xiao-Hong; Zhang, Li-Yuan

    2013-08-01

    Four new ent-kaurane diterpenoids, rabdonervosins G-J (1-4, resp.), were isolated from the leaves and stems of Isodon nervosus. Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR and HR mass spectra. Compound 2 showed potent cytotoxicity against the HepG2 and PC-9/ZD cell lines with IC50 values of 2.36 and 6.07 μM, respectively, and compound 3 exhibited cytotoxicity against the HepG2 and CNE2 cell lines with IC50 values of 8.64 and 9.77 μM, respectively. PMID:23939796

  20. Bioactive ent-kaurane diterpenoids from Isodon rosthornii.

    PubMed

    Zhan, Rui; Li, Xiao-Nian; Du, Xue; Wang, Wei-Guang; Dong, Ke; Su, Jia; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2013-07-26

    Isorosthin A (1), the first 20-nor-enmein-type diterpenoid, and 15 new ent-kauranoids, isorosthins B-P (2-16), along with 22 known analogues were isolated from the aerial parts of Isodon rosthornii. The structures of 1-16 were elucidated by means of spectroscopic analysis. The relative configuration of 2 and the absolute configuration of 3 were determined by single-crystal X-ray diffraction. Cytotoxicity evaluation against five human tumor lines showed inhibitory effects by several of the compounds tested. Furthermore, 12 of the isolates exhibited inhibitory activity against nitric oxide production in LPS-activated RAW264.7 macrophages. PMID:23819871

  1. Four new diterpenoids isolated from the Euphorbia rapulum.

    PubMed

    Liu, Xiao-Xue; Shang, Lei; Huang, Chao; Feng, Xue-Song; Li, Wen; Sha, Yi; Huang, Jian; Wang, Jin-Hui

    2016-09-01

    Four new diterpenoids named 1-epi-9-hydroxydepressin (1), 1-epi-8-hydroxydepressin (2), 2,13,9-trihydroxy-labda-8(17),12(E),14-triene (3) and tagalsin I (4) were isolated from Euphorbia rapulum. The structures of these compounds were elucidated by means of various spectroscopic methods. All the isolated compounds were evaluated for cytotoxic activities against HepG2, MCF-7, and C6 cell lines, and compound 4 showed moderate selective activity against MCF-7 cell line with an IC50 value of 31.8 μM. PMID:27089930

  2. abeo-taxane diterpenoids from the Taiwanese Yew Taxus sumatrana.

    PubMed

    Wang, Shih-Sheng; Abd El-Razek, Mohamed H; Chen, Yi-Cheng; Chien, Ching-Te; Guh, Jih-Hwa; Kuo, Yao-Haur; Shen, Ya-Ching

    2009-12-01

    Chemical investigation of the acetonic extract of the leaves and twigs of Taxus sumatrana (Taxaceae) led to the isolation of four new taxane diterpene esters, taiwantaxins A-D (1-4, resp.). Their structures were determined primarily on the basis of 1D- and 2D-NMR techniques as well as MS. Compound 1 is a rearranged taxane diterpenoid possessing an opened oxetane ring moiety containing C(4), C(5), and C(20). The metabolites 2 and 3 belong to a 5/6/6 taxene system having a rare five-membered gamma-lactone ring comprising C(8), C(9), C(10), and C(19). Compound 4 is an example of a taxane diterpene containing a 6/8/6 ring system with a tetrahydrofuran ring comprising C(2), C(3), C(4), and C(20). The 11(15-->1)abeo-taxane diterpenoids, taiwantaxins A-C (1-3, resp.) are lacking an O-bearing functionality at either C(13) or C(14). Compound 2 showed significant cytotoxic activity against human PC-3 tumor cells. PMID:20020457

  3. Diterpenoids from the twigs and leaves of Croton caudatus var. tomentosus.

    PubMed

    Song, Jin-Tong; Han, Yang; Wang, Xiao-Ling; Shen, Tao; Lou, Hong-Xiang; Wang, Xiao-Ning

    2015-12-01

    One new 9,10-seco-abietane derivative, crotontomentosin A (1), four new abietane-type diterpenoids, crotontomentosins B-E (2-5), one new ent-halimane-type diterpenoid, crotontomentosin F (6), along with five known diterpenoids (7-11) and one known sesquiterpenoid (12) were obtained from the twigs and leaves of Croton caudatus Geisel. var. tomentosus Hook. The structures of the compounds were established on the basis of extensive spectroscopic data. Compounds 1-4 and 11 exhibited moderate to weak inhibitory activity against the proliferation of the Hela, Hep G2, MDA-MB-231, or A549 cell lines selectively. PMID:26475984

  4. An O-to-N intramolecular acyl migration in C₁₉-diterpenoid alkaloids.

    PubMed

    Chen, Qi-Feng; Jian, Xi-Xian; Chen, Qiao-Hong; Wang, Feng-Peng

    2012-01-01

    The O-acyl group at C-1 of two C₁₉-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C₁₉-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C₁₉-diterpenoid alkaloids. PMID:22568819

  5. New Casbane and Cembrane Diterpenoids from an Okinawan Soft Coral, Lobophytum sp.

    PubMed

    Roy, Prodip K; Ashimine, Runa; Miyazato, Haruna; Taira, Junsei; Ueda, Katsuhiro

    2016-01-01

    A new rare casbane-type diterpenoid 1 and two new cembrane diterpenoids 2, 3 were isolated from an Okinawan soft coral, Lobophytum sp., together with four known cembrane diterpenoids 4-7. Their structures were elucidated by extensive analysis of spectroscopic data (1D and 2D NMR, IR, and MS) and a molecular modeling study. The new isolates showed weak anti-bacterial activity, mild cytotoxicity against HCT116 cells, and anti-inflammatory effect in LPS/IFN-γ-stimulated RAW 264.7 macrophage cells. PMID:27223275

  6. Diterpenoid compounds and other lipids in deep-sea sediments and their geochemical significance

    NASA Technical Reports Server (NTRS)

    Simoneit, B. R. T.

    1977-01-01

    Cyclic diterpenoid compounds have been found by various investigators in the geosphere (e.g., fossil resins, coals, soil, shale, and deep-sea sediments). These compounds occur in significant amounts only in higher plants and are therefore potential markers of terrigenous plant lipids. Diterpenoids with the abietane skeleton (mainly dehydroabietic acid) have been identified in the lipids of sediment samples from the northeast Pacific Ocean, Black Sea, and North Atlantic Ocean. The presence of these resin-derived compounds was correlated with the terrigenous clay components and with the presence of pollen. The presence of polycyclic diterpenoids was also correlated with the distribution patterns and inferred sources of other sediment lipid constituents. Potamic transport, followed by turbidite redistribution, is the probable input mechanism of these resin-derived compounds to the deep-sea sediments. These diterpenoids appear to be excellent biological markers of resinous higher plants.

  7. Diterpenoid alkaloids from the Chinese traditional herbal "Fuzi" and their cytotoxic activity.

    PubMed

    Gao, Feng; Li, Yuan-Yuan; Wang, Dan; Huang, Xing; Liu, Qian

    2012-01-01

    Ten diterpenoid alkaloids, including eight aconitine-type C₁₉-diterpenoid alkaloids and two hetisine-type C₂₀-diterpenoid alkaloids, were isolated from the secondary roots of Aconitum carmichaeli Debx., known as "Fuzi" in Chinese traditional herbal medicine. Their structures were established on the basis of their spectroscopic data and comparison with those of the literature. Among these alkaloids, chasmanine, oxonitine and 15-acetylsongoramine were isolated for the first time from this medicinal plant. The cytotoxic activity of the alkaloids were tested against several cell lines by the MTT method in which aconitine, hypaconitine, mesaconitne and oxonitine were found to strongly inhibit the growth of the HePG2 cell line, which showed that the existence and quantity of the ester groups have a significant influence on the cytotoxicity of the diterpenoid alkaloids. PMID:22628040

  8. Characterization of New Ent-kaurane Diterpenoids of Yunnan Arabica Coffee Beans.

    PubMed

    Chu, Rui; Wan, Luo-Sheng; Peng, Xing-Rong; Yu, Mu-Yuan; Zhang, Zhi-Run; Zhou, Lin; Li, Zhong-Rong; Qiu, Ming-Hua

    2016-08-01

    Five new ent-kaurane diterpenoids, named mascaroside III-V (1-3), and 20-nor-cofaryloside I-II (4-5), together with seven known diterpenoids, were isolated from methanol extracts of the green coffee beans of Yunnan Arabica Coffee. Their chemical structures were elucidated by extensive spectroscopic analyses. Meanwhile, cytotoxicity assay against HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines showed that they have not evident inhibition of cytotoxicity. PMID:27165414

  9. Hapmnioides A-C, Rearranged Labdane-Type Diterpenoids from the Chinese Liverwort Haplomitrium mnioides.

    PubMed

    Zhou, Jinchuan; Zhang, Jiaozhen; Li, Ruijuan; Liu, Jun; Fan, Peihong; Li, Yi; Ji, Mei; Dong, Yiwen; Yuan, Huiqing; Lou, Hongxiang

    2016-09-01

    Many exceptional labdane-type diterpenoids have been exclusively found in liverworts, which serve as taxonomic molecules or play important ecological roles in interactions among organisms. Three unprecedented labdane-type diterpenoids hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the Chinese liverwort Haplomitrium mnioides are reported. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction, and their anti-inflammatory activities were also preliminarily tested. PMID:27513610

  10. Production of bioactive diterpenoids in the euphorbiaceae depends on evolutionarily conserved gene clusters.

    PubMed

    King, Andrew J; Brown, Geoffrey D; Gilday, Alison D; Larson, Tony R; Graham, Ian A

    2014-08-01

    The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways. PMID:25172144

  11. Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids.

    PubMed

    Zhang, Zhong-Tang; Jian, Xi-Xian; Ding, Jia-Yu; Deng, Hong-Ying; Chao, Ruo-Bing; Chen, Qiao-Hong; Chen, Dong-Lin; Wang, Feng-Peng

    2015-12-01

    The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom. PMID:26882669

  12. Diterpenoids from the branch and leaf of Abies fargesii.

    PubMed

    Wu, Wen-Ming; Liu, Ye; Chen, Xu; Jin, An; Zhou, Ming; Tian, Tian; Ruan, Han-Li

    2016-04-01

    Five new abietane diterpenoids, named abifadines A-E (1-5), and nine known ones (6-14), together with two known podocarpenes (15 and 16), were isolated from the branch and leaf of Abies fargesii. Their structures including the relative configurations were established on the basis of extensive spectroscopic analyses. The absolute configuration of 1 was determined through single-crystal X-ray diffraction analysis with Cu Kα irradiation. All the isolates were evaluated for their in vitro cytotoxicities. Only compounds 5 and 12 exhibited weak anti-proliferative effects against three cancer cell lines (B16, MCF7, and HepG2) with IC50 values range from 14.8 to 42.8μM. The antimicrobial activities against Staphylococcus aureus, Escherichia coli and Monilia albicans of all compounds were also tested, but none of them showed significant activities. PMID:26969787

  13. Minor ent-abietane diterpenoids from Euphorbia guyoniana.

    PubMed

    Haba, Hamada; Marcourt, Laurence; Benkhaled, Mohammed; Long, Christophe

    2013-11-01

    Three new abietane-type diterpenoids: ent-abieta-8,11,13-trien-16-ol (1), ent-abieta-8,11,13-trien-11,16-diol (2) and 11,12-dihydroxy-7-oxo-ent-abieta-8,11,13-trien-16-oic acid methyl ester (3), in addition to three known triterpenoids: euphol (4), 24,25-epoxycycloartanol (5) and beta-sitosterol O-beta-D-glucoside (6) were isolated from the chloroform extract of the roots of Euphorbia guyoniana. Structures of the isolated compounds were established on the basis of spectroscopic analyses, including 1D and 2D homo and heteronuclear NMR experiments and ESIMS, and comparison with literature data. PMID:24427931

  14. Cytotoxic diterpenoid pseudodimers from the Korean sponge Phorbas gukhulensis.

    PubMed

    Jeon, Ju-eun; Liao, Lijuan; Kim, Heegyu; Sim, Chung J; Oh, Dong-Chan; Oh, Ki-Bong; Shin, Jongheon

    2013-09-27

    Four new cytotoxic diterpenoid pseudodimers (2-5), along with a previously reported one, gukulenin A (1), were isolated from the marine sponge Phorbas gukhulensis collected off the coast of Gagu-do, Korea. These novel compounds, designated gukulenins C-F (2-5), were determined by extensive spectroscopic analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the tropolone-containing side chains in gukulenins C-E (2-4) were found to have diverse modifications involving acetamides or taurine, whereas gukulenin F (5) was formed from 1 by the ring-opening of a cyclic hemiketal. The relative and absolute configurations were assigned by Murata's and modified Snatzke's methods using a HETLOC experiment and a CD measurement of a dimolybdenum complex, respectively. All of these compounds exhibited significant cytotoxicity against the K562 and A549 cell lines. PMID:24025124

  15. Characterization and Biological Evaluation of Diterpenoids from Casearia graveolens.

    PubMed

    Xu, Jing; Ji, Feifei; Sun, Xiaocong; Cao, Xiangrong; Li, Shen; Ohizumi, Yasushi; Guo, Yuanqiang

    2015-11-25

    Biologically active substances that promote the neurite outgrowth of nerve cells against neuron degeneration may be useful for the treatment of Alzheimer's disease. In a continuing search for bioactive compounds from plants, an ethyl acetate-soluble extract of the twigs of Casearia graveolens showed moderate stimulatory activity of neurite outgrowth from PC12 cells. Further investigation to obtain bioactive compounds led to the isolation of 10 new clerodane diterpenoids, graveopenes A-J (1-10). Their structures including absolute configurations were elucidated based on analysis of their NMR spectroscopic data and experimental and calculated ECD spectra. Compounds 3-6 and 8 were shown to stimulate NGF-mediated neurite outgrowth from PC12 cells. PMID:26474353

  16. Two new labdane diterpenoids from the rhizomes of Isodon yuennanensis.

    PubMed

    Huang, Zhen-Yuan; Huang, Bo; Xiao, Chao-Jiang; Dong, Xiang; Jiang, Bei

    2015-01-01

    Two new labdane diterpenoids, s-trans-8(17),12E,14-labdatrien-20-oic acid (1), s-trans-12E,14-labdadien-20,8β-olide (2), along with 10 known compounds, hinokiol (3), ursonic acid (4), 2α,3α-dihydroxyolean-12-en-28-oic acid (5), 2α,3β,23-trihydroxyolean-12-en-28-oic acid (6), ethyl 3-(3,4-dihydroxyphenyl)lactate (7), ethyl rosmarinate (8), (Z,E)-2-(3,4-dihydroxyphenyl)ethenyl caffeic ester (9), tridecanoic acid (10), β-sitosterol (11) and daucosterol (12), were isolated from the 70% acetone extract of the rhizomes of Isodon yuennanensis. Their structures were elucidated based on the analyses of extensive spectroscopic data and physicochemical properties. PMID:25420949

  17. Cytotoxic ent-kaurane diterpenoids from Isodon wikstroemioides.

    PubMed

    Wu, Hai-Yan; Zhan, Rui; Wang, Wei-Guang; Jiang, Hua-Yi; Du, Xue; Li, Xiao-Nian; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2014-04-25

    Phytochemical investigation of EtOAc extracts of the aerial parts of Isodon wikstroemioides afforded 18 new ent-kaurane diterpenoids (wikstroemioidins E-V, 1-18), along with 17 known analogues (19-35). The absolute configurations of 1 and 16 were confirmed by single-crystal X-ray diffraction analysis. The isolates were screened against five human tumor cell lines; compounds 3, 4, 9, 11-13, 23, 25-28, and 33 exhibited significant cytotoxic activity against all five, with IC50 values ranging from 0.4 to 5.1 μM. In addition, 17 of the isolates strongly inhibited nitric oxide production in LPS-activated RAW264.7 macrophages. PMID:24697496

  18. Three Minor Diterpenoids with Three Carbon Skeletons from Euphorbia peplus.

    PubMed

    Wan, Luo-Sheng; Nian, Yin; Ye, Chen-Jun; Shao, Li-Dong; Peng, Xing-Rong; Geng, Chang-An; Zuo, Zhi-Li; Li, Xiao-Nian; Yang, Jian; Zhou, Ming; Qiu, Ming-Hua

    2016-05-01

    Euphorbia peplus has been used in traditional medicine to treat asthma and psoriasis. Three highly modified diterpenoids, namely, pepluacetal (1) and pepluanol A-B (2-3), have been isolated and identified from this plant. Compounds 1-3 exhibit unprecedented 5/4/7/3, 5/6/7/3, and 5/5/8/3 ring systems, respectively. Their structures with absolute configurations were determined by spectroscopic analyses, X-ray crystallography, and electronic circular dichroism calculations. Since Kv1.3 is a validated target for the treatment of autoimmune diseases, such as multiple sclerosis, type-1 diabetes, asthma, and psoriasis, Kv1.3 was studied in terms of its response to the new compounds. All three compounds inhibit Kv1.3, with compound 3 being the most effective with an IC50 value of 9.50 μM. PMID:27075046

  19. Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum.

    PubMed

    Naman, C Benjamin; Gromovsky, Anthony D; Vela, Cory M; Fletcher, Joshua N; Gupta, Gaurav; Varikuti, Sanjay; Zhu, Xiaohua; Zywot, Emilia M; Chai, Heebyung; Werbovetz, Karl A; Satoskar, Abhay R; Kinghorn, A Douglas

    2016-03-25

    Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice and was found to dose-dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 μM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 μM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates. PMID:26905523

  20. Antimicrobial and Antiparasitic Abietane Diterpenoids from the Roots of Clerodendrum eriophyllum

    PubMed Central

    Machumi, Francis; Samoylenko, Volodymyr; Yenesew, Abiy; Derese, Solomon; Midiwo, Jacob O.; Wiggers, Frank T.; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Walker, Larry A.

    2013-01-01

    Chromatographic separation of the roots of a Kenyan medicinal plant, Clerodendrum eriophyllum, led to the isolation of ten abietane diterpenoids (1-10), one of which (1) was isolated for the first time from a natural source. Using spectroscopic data, the structure of 1 was determined to be 12-hydroxy-8,12-abietadiene-3,11,14-trione. Circular dichroism (CD) spectra showed that the stereochemistry of compounds 1, 3, and 6-8 belongs to the normal series of abietane diterpenes, which confirmed the absolute stereochemistry of the isolated compounds. Compounds 2-10 were evaluated for their in vitro antiplasmodial, antileishmanial, antifungal and antibacterial activities. Compounds 3 and 7 exhibited potent antifungal activity (IC50/MIC 0.58/1.25 and 0.96/2.5 µg/mL, respectively) against C. neoformans, whereas 3, 6 and 7 showed strong antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with IC50/MIC values between 1.33–1.75/2.5–5 and 0.96–1.56/2.5 µg/mL, respectively. In addition, compounds 3 and 9 exhibited potent antileishmanial activity (IC50 0.08 and 0.20 µg/mL, respectively) against L. donovani, while 3 and 7 displayed weak antimalarial activity against Plasmodium falciparum, but 9 was inactive. PMID:20614808

  1. New C20-diterpenoid alkaloids from Aconitum vilmorrianum and structural revision of 2-O-acetylorochrine and orochrine.

    PubMed

    Tang, Tian-Xing; Chen, Qi-Feng; Liu, Xiao-Yu; Jian, Xi-Xian; Wang, Feng-Peng

    2016-04-01

    Three new C20-diterpenoid alkaloids vilmorrianines E (1), F (2), and G (3) were isolated from the whole plants of Aconitum vilmorrianum, along with one artifact N-chloromethyl vilmorrianine E hydrochloride (4), as well as two known alkaloids hemsleyaconitines F (5) and G (6). The structures of 1-4 were established by HR-ESI-MS, 1D-, 2D-NMR (HMQC, HMBC, and NOESY), and single-crystal X-ray diffraction analysis. In addition, the structures of naturally occurring 2-O-acetylorochrine (7) and orochrine (8) were revised to be the known alkaloids heterophylloidine (9) and deacetyl heterophylloidine (10), respectively, on the basis of consideration of transannular effect and chemical correlations. PMID:26479584

  2. Structure-analgesic activity relationship studies on the C(18)- and C(19)-diterpenoid alkaloids.

    PubMed

    Wang, Jian-Li; Shen, Xiang-Li; Chen, Qiao-Hong; Qi, Gong; Wang, Wei; Wang, Feng-Peng

    2009-08-01

    For evaluation of C(18)- and C(19)-diterpenoid alkaloids as analgesics, three C(19)-diterpenoid alkaloids were isolated from the roots of Aconitum hemsleyanum var. circinatum and A. transsecutum; and twenty-five semisynthetic C(18)- or C(19)-diterpenoid alkaloids were prepared from lappaconitine, crassicauline A or yunaconitine. In a mice acetic acid-induced abdominal constriction assay, four crassicauline A analogs and three yunaconitine analogs exhibited good analgesic activities with 77.8-94.1% inhibition range in 0.1-10 mg/kg subcutaneous (s.c.) dose range at the point of 20 min after drug administration. Among them, 8-O-deacetyl-8-O-ethylcrassicauline A (ED(50)=0.0972 mg/kg) and 8-O-ethylyunaconitine (ED(50)=0.0591 mg/kg) were the most potent analgesics relative to the reference drugs lappaconitine (ED(50)=3.50 mg/kg) and crassicauline A (ED(50)=0.0480 mg/kg). Analgesic activity data of these C(18)- and C(19)-diterpenoid alkaloids indicate that a tertiary amine in ring A, an acetoxyl or an ethoxyl group at C-8, an aromatic ester at C-14, and the saturation state of the ring D are important structural features necessary to the analgesic activity of the C(19)-diterpenoid alkaloids. PMID:19652403

  3. Cytotoxic Clerodane Diterpenoids from the Leaves of Casearia grewiifolia.

    PubMed

    Nguyen, Ha T T; Truong, Ngan B; Doan, Huong T M; Litaudon, Marc; Retailleau, Pascal; Do, Thao T; Nguyen, Hung V; Chau, Minh V; Pham, Cuong V

    2015-11-25

    Two new clerodane diterpenoids (1 and 2) and the known compound caseanigrescen D (3) were isolated from the leaves of Casearia grewiifolia by bioassay-guided fractionation. Their structures were determined by analyses of MS and 2D NMR data. The absolute configurations of 1 and 3 were established by analysis of X-ray diffraction data. Compounds 1-3 were evaluated for their cytotoxicity against four cancer cell lines, KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). Caseagrewifolin B (2) had inhibitory activity against KB and HepG-2 cell lines with IC50 values of 6.2 to 7.0 μM, respectively. When tested against the normal cells (NIH/3T3), caseagrewifolin B (2) exhibited a significant selective inhibition against cancer cells in comparison with the normal cells. Caseanigrescen D (3) was cytotoxic against four cancer cell lines; however it had no selective inhibition compared with normal cells. PMID:26516994

  4. Bioactive ent-kaurane diterpenoids from Isodon serra.

    PubMed

    Wan, Jun; Liu, Miao; Jiang, Hua-Yi; Yang, Jin; Du, Xue; Li, Xiao-Nian; Wang, Wei-Guang; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2016-10-01

    Nine 7,20-epoxy-ent-kaurane diterpenoids (15-acetylmegathyrin B, serrin E, 14β-hydroxyrabdocoestin A, serrin F, serrin G, 11-epi-rabdocoestin A, serrin H, serrin I, and 15-acetylenanderianin N), along with seven known ones, were isolated from the aerial parts of Isodon serra. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 15-acetylmegathyrin B was determined by signal-crystal X-ray diffraction. All of these compounds were evaluated for their cytotoxic activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480). Serrin F, rabdocoestin B and 1α,11β-dihydroxy-1α,11β-acetonide-7α,20-epoxy-ent-kaur-16-en-15-one showed cytotoxic activities against all cell lines, with IC50 values ranging from 0.7 to 4.6 μM; serrin F also strongly inhibited NO production in LPS-stimulated RAW264.7 cells. Otherwise, 14β-hydroxyrabdocoestin A, serrins H and I, as well as enanderianin N and megathyrin B, also exhibited inhibitory effects towards NO production, while no cytotoxicity against five cell lines was detected. PMID:27298277

  5. Clerodane-type diterpenoids from tuberous roots of Tinospora sagittata (Oliv.) Gagnep.

    PubMed

    Zhang, Geng; Ma, Haoran; Hu, Song; Xu, Hongfeng; Yang, Bo; Yang, Quanwei; Xue, Yongbo; Cheng, Lu; Jiang, Jie; Zhang, Jinwen; Wang, Fuqian; Zhang, Yonghui

    2016-04-01

    Three new clerodane type diterpenoids (2-4), together with one known analogues (1), were isolated from the tuberous roots of Tinospora sagittata (Oliv.) Gagnep. Compound 3 is an unusual clerodane diterpenoid with the carbonyl functionality at C-3, which represents the first example from this diterpenoid compounds class. The structures were established on the basis of spectroscopic data interpretation. The absolute configuration of 1 was determined for the first time by single-crystal X-ray diffraction analysis with CuKα irradiation. These isolates were evaluated for their cytotoxic activities against five human cancer cell lines and inhibitory activities on LPS-induced NO production in RAW264.7 cells. PMID:26924160

  6. Cytotoxic C20 Diterpenoid Alkaloids from the Australian Endemic Rainforest Plant Anopterus macleayanus.

    PubMed

    Levrier, Claire; Sadowski, Martin C; Nelson, Colleen C; Davis, Rohan A

    2015-12-24

    In order to identify new anticancer compounds from nature, a prefractionated library derived from Australian endemic plants was generated and screened against the prostate cancer cell line LNCaP using a metabolic assay. Fractions from the seeds, leaves, and wood of Anopterus macleayanus showed cytotoxic activity and were subsequently investigated using a combination of bioassay-guided fractionation and mass-directed isolation. This led to the identification of four new diterpenoid alkaloids, 6α-acetoxyanopterine (1), 4'-hydroxy-6α-acetoxyanopterine (2), 4'-hydroxyanopterine (3), and 11α-benzoylanopterine (4), along with four known compounds, anopterine (5), 7β-hydroxyanopterine (6), 7β,4'-dihydroxyanopterine (7), and 7β-hydroxy-11α-benzoylanopterine (8); all compounds were purified as their trifluoroacetate salt. The chemical structures of 1-8 were elucidated after analysis of 1D/2D NMR and MS data. Compounds 1-8 were evaluated for cytotoxic activity against a panel of human prostate cancer cells (LNCaP, C4-2B, and DuCaP) and nonmalignant cell lines (BPH-1 and WPMY-1), using a live-cell imaging system and a metabolic assay. All compounds showed potent cytotoxicity with IC50 values of <400 nM; compound 1 was the most active natural product from this series, with an IC50 value of 3.1 nM toward the LNCaP cell line. The live-cell imaging assay on 1-8 showed a concentration- and time-dependent effect on the cell morphology and proliferation of LNCaP cells. PMID:26600001

  7. LC-MS guided isolation of ent-kaurane diterpenoids from Nouelia insignis.

    PubMed

    Sun, Chang-Li; Geng, Chang-An; Chen, Xing-Long; Yang, Tong-Hua; Yin, Xiu-Juan; Huang, Xiao-Yan; Peng, Hua; Chen, Ji-Jun

    2016-06-01

    The preliminary LC-MS investigation on the stems of Nouelia insignis manifested the existence of diterpenoids. As a result, 15 ent-kaurane diterpenoids, including 7 new glycosides (nouelosides A-G, 1-7), were isolated under the direction of LC-MS analysis. The new compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D and 2D NMR data and chemical methods. Compounds 6 and 15 with the exo-methylene cyclopentanone functional group exhibited obvious nitric oxide production inhibitory activity with IC50 values of 3.84±0.20 and 3.19±0.25μM. PMID:27094114

  8. New clerodane diterpenoids from the twigs and leaves of Croton euryphyllus.

    PubMed

    Pan, Zhenghong; Ning, Desheng; Wu, Xingde; Huang, Sisi; Li, Dianpeng; Lv, Shihong

    2015-03-15

    Three new nor-clerodane diterpenoids, crotoeurins A-C (1-3), together with four known ones were isolated from the twigs and leaves of Croton euryphyllus. Among them, crotoeurin A (1) is a new nor-clerodane diterpenoid dimer with a unique cyclobutane ring via a [2+2] cycloaddition. Their structures were elucidated by spectroscopic analyses and the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis. Compounds 1-3 exhibited neurite outgrowth-promoting activity on NGF-mediated PC12 cells at concentration of 10μM. PMID:25690785

  9. Bioactive diterpenoids from Trigonostemon chinensis: Structures, NO inhibitory activities, and interactions with iNOS.

    PubMed

    Xu, Jing; Peng, Maoqin; Sun, Xiaocong; Liu, Xingyu; Tong, Ling; Su, Guochen; Ohizumi, Yasushi; Lee, Dongho; Guo, Yuanqiang

    2016-10-01

    A phytochemical investigation to obtain new NO inhibitors led to the isolation of two new (1 and 2) and four known (3-6) diterpenoids from Trigonostemon chinensis. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configurations of new compounds were established by experimental and calculated ECD spectra. The inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells of these diterpenoids were evaluated, and all of the compounds showed inhibitory effects. The interactions of bioactive compounds with iNOS protein were also studied by molecular docking. PMID:27570243

  10. Characterization of diterpenoids from Caesalpinia decapetala and their anti-TMV activities.

    PubMed

    Xu, Jing; Cao, Xiangrong; Liu, Feng; Ma, Jun; Liu, Xingyu; Tong, Ling; Su, Guochen; Ohizumi, Yasushi; Lee, Dongho; Wang, Lizhong; Guo, Yuanqiang

    2016-09-01

    Caesalpinia decapetala is a versatile medicinal plant belonging to the Fabaceae plant family. In our survey on plant secondary metabolites to obtain bioactive substances for the development of new agricultural anti-TMV agents, the chemical constituents of C. decapetala were investigated. This investigation led to the isolation of three new and ten known diterpenoids. Their structures including absolute configurations were elucidated based on the extensive NMR spectroscopic data analyses and the time-dependent density functional theory calculations. The following biological screenings revealed that most of these diterpenoids possessed anti-TMV activities. PMID:27491755

  11. Phytotoxic cis-clerodane diterpenoids from the Chinese liverwort Scapania stephanii.

    PubMed

    Li, Rui-Juan; Sun, Yi; Sun, Bin; Wang, Xiao-Ning; Liu, Shan-Shan; Zhou, Jin-Chuan; Ye, Jian-Ping; Zhao, Yu; Liu, Lei; Lee, Kuo-Hsiung; Lou, Hong-Xiang

    2014-09-01

    Five cis-clerodane diterpenoids, stephanialides A-E, along with seven known cis-clerodanes, scaparvins A-C, parvitexins B and C, 3-chloro-4-hydroxy-parvitexin A, and scapanialide B, were isolated from the Chinese liverwort Scapania stephanii. Their structures were established unequivocally on the basis of spectroscopic data. The absolute configuration of stephanialide A was determined by analysis of CD data using the octant rule. Phytotoxic activity evaluation showed that this type of diterpenoids can significantly inhibit root elongation of the seeds of Arabidopsis thaliana, Lepidium sativum and Brassica pekinensis. PMID:24947338

  12. Diterpenoids from the Roots of Euphorbia fischeriana with Inhibitory Effects on Nitric Oxide Production.

    PubMed

    Lee, Jin Woo; Lee, Chul; Jin, Qinghao; Jang, Hari; Lee, Dongho; Lee, Ha-Jin; Shin, Jong Won; Han, Sang Bae; Hong, Jin Tae; Kim, Youngsoo; Lee, Mi Kyeong; Hwang, Bang Yeon

    2016-01-22

    Bioactivity-guided isolation of a methanolic extract of Euphorbia fischeriana led to the isolation of four new abietane-type diterpenoids, fischeriolides A-D (1-4), together with 11 known diterpenoids. Their structures were elucidated based on the interpretation of 1D and 2D NMR spectroscopic and HRESIMS data. The absolute configuration of compound 3 was determined by single-crystal X-ray diffraction analysis and electronic circular dichroism methods. Compounds 5-9 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values in the range 4.9-12.6 μM. PMID:26702644

  13. Eutypenoids A–C: Novel Pimarane Diterpenoids from the Arctic Fungus Eutypella sp. D-1

    PubMed Central

    Zhang, Liu-Qiang; Chen, Xiao-Chong; Chen, Zhao-Qiang; Wang, Gui-Min; Zhu, Shi-Guo; Yang, Yi-Fu; Chen, Kai-Xian; Liu, Xiao-Yu; Li, Yi-Ming

    2016-01-01

    Eutypenoids A–C (1–3), pimarane diterpenoid alkaloid and two ring A rearranged pimarane diterpenoids, were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures, including absolute configurations, were authenticated on the basis of the mass spectroscopy (MS), nuclear magnetic resonance (NMR), X-ray crystallography, and electronic circular dichroism (ECD) analysis. The immunosuppressive effects of eutypenoids A–C (1–3) were studied using a ConA-induced splenocyte proliferation model, which suggested that 2 exhibited potent immunosuppressive activities. PMID:26959036

  14. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae

    PubMed Central

    Zi, Jiachen; Peters, Reuben J.

    2013-01-01

    Miltiradiene (1), is the precursor of phenolic diterpenoids such as ferruginol (2), requiring aromatization and hydroxylation. While this has been attributed to a single cytochrome P450 (CYP76AH1), characterization of the rosemary ortholog CYP76AH4 led to the discovery that these CYPs simply hydroxylate the facilely oxidized aromatic intermediate abietatriene (3). PMID:24108414

  15. Polyacetylated labdane-type diterpenoids, ptychantins P-R from Chinese liverwort Ptychanthus striatus.

    PubMed

    Wu, Jing-Yi; Zhang, Jiao-Zhen; Kang, Ya-Qi; Wang, Xiao; Fan, Pei-Hong; Zhou, Jin-Chuan; Lou, Hong-Xiang

    2015-05-01

    Three new polyacetylated labdane diterpenoids ptychantins P-R (1-3) and four known compounds (4-7) were isolated from an EtOH extract of the Chinese liverwort Ptychanthus striatus (Lehm. & Lindenb.) Nees. Their structures were established by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR). PMID:25677361

  16. (+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †.

    PubMed

    La Bella, Angela; Leonelli, Francesca; Migneco, Luisa Maria; Marini Bettolo, Rinaldo

    2016-01-01

    In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned. PMID:27617995

  17. Diterpenoids from aerial parts of Flickingeria fimbriata and their nuclear factor-kappaB inhibitory activities.

    PubMed

    Li, Hang; Zhao, Jing-jun; Chen, Jin-long; Zhu, Long-ping; Wang, Dong-mei; Jiang, Lin; Yang, De-po; Zhao, Zhi-min

    2015-09-01

    Chemical investigation of the aerial parts of Flickingeria fimbriata (Bl.) Hawkes resulted in isolation of sixteen ent-pimarane diterpenoids, including five rare 16-nor-ent-pimarane diterpenoids, two 15,16-dinor-ent-pimarane diterpenoids and one ent-pimarane diterpenoid. Structures were mainly elucidated by extensive spectroscopic analysis, and their absolute configurations were unequivocally determined by the exciton chirality method, the modified Mosher's method, the CD experiments (including Snatzke's method) and chemical transformations, respectively. All the isolated compounds were screened for inhibitory effects on the nuclear factor-kappaB (NF-κB) in lipopolysaccharide (LPS) induced murine macrophage RAW264.7 cells, using a NF-κB-dependent luciferase reporter gene assay. Several of these compounds displayed comparable or even better activities than the positive control pyrrolidinedithiocarbamate (PDTC) (IC50=26.3 μM) with IC50 values in the range of 14.7-29.2 μM and structure-activity relationships are briefly proposed. PMID:26186245

  18. Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production.

    PubMed

    Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi; Wong, Limsoon; Chua, Nam-Hai; Jang, In-Cheol

    2015-12-01

    Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. PMID:26438788

  19. A new mulinane diterpenoid from the cushion shrub Azorella compacta growing in Perú

    PubMed Central

    Salgado, Francisco; Areche, Carlos; Sepúlveda, Beatriz; Simirgiotis, Mario J.; Cáceres, Fátima; Quispe, Cristina; Quispe, Lina; Cano, Teresa

    2014-01-01

    Background: Azorella compacta is a rare yellow-green compact resinous cushion shrub growing from the high Andes of southern Perú to northwestern Argentina, and which is a producer of biologically active and unique diterpenoids. Objective: This study investigated the secondary metabolites present in a Peruvian sample of Azorella compacta and the evaluation of gastroprotective activity of the isolated compounds in a gastric- induced ulcer model in mice. Material and Methods: Six secondary metabolites (diterpenoids 1-6) present in the dichloromethane (DCM) extract of A. compacta growing in Perú were isolated by a combination of Sephadex LH-20 permeation and silica gel chromatography and their chemical structures were elucidated by spectroscopic methods (NMR) and molecular modeling. The gastroprotective activity of the new compound 1 was evaluated on the HCl/EtOH-induced gastric lesion model in mice and compared to the activity showed by the known compounds. Results: A new mulinane diterpene along with five known diterpenoids have been isolated from a Peruvian sample of A. compacta and the gastroprotective results show that compound 1 is less active than the other known mulinane diterpenoids isolated. Conclusions: A. compacta growing in Perú showed the presence of the new mulinane 1, which was poorly active in the HCl/EtOH-induced gastric lesion model in mice. Indeed, the activity was lower than other diterpenoids (2-6) showing an oxygenated function at C-16 or/and C-20, which confirm the role of an oxygenated group (OH or carboxylic acid) for the gastroprotective activity of mulinane compounds. PMID:25298672

  20. Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells.

    PubMed

    Ma, Yong-Cheng; Ke, Yu; Zi, Xiaolin; Zhao, Wen; Shi, Xiao-Jing; Liu, Hong-Min

    2013-07-01

    Isodon rubescens, a Chinese herb, has been used as a folk, botanical medicine in China for inflammatory diseases and cancer treatment for many years. Recently, we isolated a new ent-kaurene diterpenoid, named Jaridonin, from Isodon rubescens. The chemical structure of Jaridonin was verified by infrared (IR), nuclear magnetic resonance (NMR), and mass spectrum (MS) data as well as X-ray spectra. Jaridonin potently reduced viabilities of several esophageal cancer cell lines, including EC109, EC9706 and EC1. Jaridonin treatment resulted in typical apoptotic morphological characteristics, increased the number of annexin V-positive staining cells, as well as caused a G2/M arrest in cell cycle progression. Furthermore, Jaridonin resulted in a significant loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and then activation of Caspase-9 and -3, leading to activation of the mitochondria mediated apoptosis. Furthermore, these effects of Jaridonin were accompanied by marked reactive oxygen species (ROS) production and increased expression of p53, p21(waf1/Cip1) and Bax, whereas two ROS scavengers, N-acetyl-L-cysteine (LNAC) and Vitamin C, significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA damage, expression of p53 and p21(waf1/Cip1) and reduction of cell viabilities. Taken together, our results suggest that a natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new chemotherapeutic strategy for patients with esophageal cancer. PMID:23597192

  1. Atropurpuran – Missing Biosynthetic Link Leading to the Hetidine and Arcutine C20-Diterpenoid Alkaloids or an Oxidative Degradation Product?

    PubMed Central

    Weber, Manuel; Owens, Kyle; Sarpong, Richmond

    2015-01-01

    A possible biosynthetic link between atropurpuran, the hetidine diterpenoid alkaloids and the alkaloid arcutine and congeners is proposed. The feasibility of aspects of this biosynthesis, especially key 1,2-rearrangements, have been examined computationally. PMID:26028789

  2. Production of Bioactive Diterpenoids in the Euphorbiaceae Depends on Evolutionarily Conserved Gene Clusters[C][W][OPEN

    PubMed Central

    King, Andrew J.; Brown, Geoffrey D.; Gilday, Alison D.; Larson, Tony R.; Graham, Ian A.

    2014-01-01

    The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways. PMID:25172144

  3. Cholinesterase-inhibitory diterpenoids and chemical constituents from aerial parts of Caryopteris mongolica.

    PubMed

    Murata, Toshihiro; Selenge, Erdenechimeg; Oikawa, Saki; Ageishi, Keita; Batkhuu, Javzan; Sasaki, Kenroh; Yoshizaki, Fumihiko

    2015-10-01

    A diterpenoid diglucoside (12,19-di-O-β-D-glucopyranosyl-11-hydroxyabieta-8,11,13-triene-19-one), isoscutellarein 7-O-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranoside, isoscutellarein 7-O-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(p-E-coumaroyl)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(E-caffeoyl)]-β-D-glucopyranoside, and 15 known compounds were isolated from aerial parts of the Mongolian medicinal plant Caryopteris mongolica. The cholinesterase-inhibitory activities of the constituents were estimated. The abietane diterpenoids (12-O-demethylcryptojaponol and 6α-hydroxydemethylcryptojaponol) showed potent inhibitory activity against acetylcholinesterase from human erythrocytes and electric eel, and against butyrylcholinesterase from horse serum. PMID:25900047

  4. Diterpenoids from the Chinese liverwort Heteroscyphus tener and their antiproliferative effects.

    PubMed

    Lin, Zhao-Min; Guo, Yan-Xia; Wang, Shu-Qi; Wang, Xiao-Ning; Chang, Wen-Qiang; Zhou, Jin-Chuan; Yuan, Huiqing; Lou, Hongxiang

    2014-06-27

    Four new ent-labdane diterpenoids, heteroscyphins A-D (1-4), and four known diterpenoids (5-8) were isolated from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn. The absolute configuration of compound 1 was defined by single-crystal X-ray diffraction using Cu Kα radiation. Cytotoxicity tests revealed that compounds 3 and 5 exhibited modest activity against seven cancer cell lines. Compound 5 showed inhibitory effects on prostate cancer (PCa) cell proliferation but with less inhibition on non-neoplastic prostate epithelial cells. Compound 5 markedly caused cell growth arrest at the G0/G1 phase and induced cellular apoptosis through ROS-mediated DNA damage in PCa cells. PMID:24940845

  5. Diterpenoids from the roots of Croton crassifolius and their anti-angiogenic activity.

    PubMed

    Wang, Jia-Jian; Chung, Hau Yin; Zhang, Yu-Bo; Li, Guo-Qiang; Li, Yao-Lan; Huang, Wei-Huan; Wang, Guo-Cai

    2016-02-01

    Six diterpenoids [crassifolin J, K, L, M, N and O] along with eleven known ones were isolated from the supercritical fluid extract (SFE) of the roots of Croton crassifolius (Euphorbiaceae). Their structures were elucidated using spectroscopic methods (IR, UV, HRESIMS, 1D and 2D NMR). The structure and stereochemistry of crassifolin J was confirmed by single-crystal X-ray diffraction analysis, and the absolute configurations of crassifolin K-M were determined by CD spectra. Twenty-three diterpenoids from this plant were screened for their anti-angiogenic activity using a wild-type zebrafish in vivo model. Four of the known compounds were active, of which penduliflaworosin possessed the best activity relative to the positive control (SU5416). Further study demonstrated that penduliflaworosin could inhibit vessel formation on Tg(fli1a:EGFP)y1-type zebrafish embryos. PMID:26725185

  6. Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin.

    PubMed

    Phan, Minh Giang; Phan, Tong Son; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2006-04-01

    From the aerial parts of Scoparia dulcis L. (Scrophulariaceae) grown in Vietnam, four scopadulane-type diterpenoids (4-7), of which 7 is new and was given the trivial name scopadulcic acid C, together with nine known compounds were isolated. Their structures were elucidated by spectroscopic analyses. The absolute configurations of 4-7 were ascertained by applying the modified Mosher's method to iso-dulcinol (6). The isolation of the lignans nirtetralin and niranthin for the first time from S. dulcis is also of chemotaxonomic interest. The cytotoxic activity in KB cells, inhibitory effect on LPS/IFNgamma-induced NO production, inhibition of multidrug resistance (MDR), and antibacterial and antifungal activities of the scopadulane-type diterpenoids 4-7 were examined in this study. PMID:16595962

  7. A New Spatane Diterpenoid from the Cultured Soft Coral Sinularia leptoclados

    PubMed Central

    Tsai, Tsung-Chang; Wu, Yu-Jen; Su, Jui-Hsin; Lin, Wei-Tung; Lin, Yun-Sheng

    2013-01-01

    A new spatane diterpenoid, leptoclalin A (1), along with two previously reported known norcembranoid diterpenes (2 and 3), were isolated from a cultured soft coral Sinularia leptoclados. The structures were determined by extensive spectroscopic analyses and by comparison with the spectral data of related known compounds. Metabolite 1 is rarely found in spatane skeletons reported from soft corals. In addition, compound 1 exhibited weak cytotoxicity towards human tumor cell lines T-47 D and K-562. PMID:23306171

  8. Flexibilins A–C, New Cembrane-Type Diterpenoids from the Formosan Soft Coral, Sinularia flexibilis

    PubMed Central

    Hu, Li-Chung; Su, Jui-Hsin; Chiang, Michael Yen-Nan; Lu, Mei-Chin; Hwang, Tsong-Long; Chen, Yung-Husan; Hu, Wan-Ping; Lin, Nai-Cheng; Wang, Wei-Hsien; Fang, Lee-Shing; Kuo, Yueh-Hsiung; Sung, Ping-Jyun

    2013-01-01

    Three new cembrane-type diterpenoids, flexibilins A–C (1–3), along with a known cembrane, (−)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1–4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils. PMID:23752355

  9. Flexibilins A-C, new cembrane-type diterpenoids from the Formosan soft coral, Sinularia flexibilis.

    PubMed

    Hu, Li-Chung; Su, Jui-Hsin; Chiang, Michael Yen-Nan; Lu, Mei-Chin; Hwang, Tsong-Long; Chen, Yung-Husan; Hu, Wan-Ping; Lin, Nai-Cheng; Wang, Wei-Hsien; Fang, Lee-Shing; Kuo, Yueh-Hsiung; Sung, Ping-Jyun

    2013-06-01

    Three new cembrane-type diterpenoids, flexibilins A-C (1-3), along with a known cembrane, (-)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1-4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils. PMID:23752355

  10. Briarenolides K and L, new anti-inflammatory briarane diterpenoids from an octocoral Briareum sp. (Briareidae).

    PubMed

    Su, Yin-Di; Su, Tzu-Rong; Wen, Zhi-Hong; Hwang, Tsong-Long; Fang, Lee-Shing; Chen, Jih-Jung; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2015-02-01

    Two new briarane-type diterpenoids, briarenolides K (1) and L (2), were isolated from an octocoral identified as Briareum sp. The structures of new briaranes 1 and 2 were elucidated by spectroscopic methods. In the in vitro anti-inflammatory effects test, briaranes 1 and 2 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:25689566

  11. Structure elucidation and complete NMR spectral assignments of four new diterpenoids from Smallantus sonchifolius.

    PubMed

    Dou, De-Qiang; Tian, Fang; Qiu, Ying-Kun; Kang, Ting-Guo; Dong, Feng

    2008-08-01

    Four new diterpenoids, named smaditerpenic acid A-D, together with five known compounds, were isolated from the H(2)O extract of the leaves of Smallantus sonchifolius (yacon) cultivated in Liaoning, China and their structures were elucidated on the basis of one- and two-dimensional NMR (including (1)H, (13)C-NMR, (1)H-(1)H COSY, HSQC, TOCSY, HMBC, and ROESY), electrospray ionization mass spectrometry (ESI-MS), and chemical methods. PMID:18470882

  12. Two new eunicellin diterpenoids from the East China Sea gorgonian Muricella sp.

    PubMed

    Zhao, Chuan; Wang, Jia; Jin, De-Jun; Duan, Hong-Quan; Xing, Guo-Sheng; Tang, Sheng-An

    2016-09-01

    A phytochemical investigation on gorgonian Muricella sp. from East China Sea resulted in the isolation of eight eunicellin diterpenoids including two new ones, muricellins A-B (1, 2). Chemical structures of these compounds were elucidated by spectroscopic techniques (1D and 2D NMR and MS) and by comparison with data reported in the literature. Anti-rheumatoid arthritis activities of 1, 3, 4, and 6 have been evaluated. PMID:27004724

  13. ent-Atisane and ent-kaurane diterpenoids from Isodon rosthornii.

    PubMed

    Zhan, Rui; Li, Xiao-Nian; Du, Xue; Wang, Wei-Guang; Dong, Ke; Su, Jia; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2013-07-01

    A new ent-atisanoid (1) and three new ent-kauranoids (2-4) belonging to different types, along with four known compounds were isolated from Isodon rosthornii. Their structures were established by means of extensive spectroscopic analysis. The absolute configuration of 1 was further determined by X-ray diffraction. Compounds 1 and 5 are the first example of atisane-type diterpenoid from this plant. PMID:23660245

  14. Briarenolides U–Y, New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae)

    PubMed Central

    Su, Yin-Di; Wu, Tung-Ying; Wen, Zhi-Hong; Su, Ching-Chyuan; Chen, Yu-Hsin; Chang, Yu-Chia; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2015-01-01

    Five new 13,14-epoxybriarane diterpenoids, briarenolides U–Y (1–5), were isolated from the octocoral Briareum sp. The structures of briaranes 1–5 were elucidated by spectroscopic methods. Briarenolides U–Y (1–5) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:26633428

  15. New 9-Hydroxybriarane Diterpenoids from a Gorgonian Coral Briareum sp. (Briareidae)

    PubMed Central

    Su, Yin-Di; Sung, Chun-Sung; Wen, Zhi-Hong; Chen, Yu-Hsin; Chang, Yu-Chia; Chen, Jih-Jung; Fang, Lee-Shing; Wu, Yang-Chang; Sheu, Jyh-Horng; Sung, Ping-Jyun

    2016-01-01

    Six new 9-hydroxybriarane diterpenoids, briarenolides ZI–ZVI (1–6), were isolated from a gorgonian coral Briareum sp. The structures of briaranes 1–6 were elucidated by spectroscopic methods and by comparison of their spectroscopic data with those of related analogues. Briarenolides ZII (2) and ZVI (6) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. PMID:26761004

  16. Enzymes for synthetic biology of ambroxide-related diterpenoid fragrance compounds.

    PubMed

    Zerbe, Philipp; Bohlmann, Jörg

    2015-01-01

    Ambrox and related ambroxides are highly priced in the fragrance industry, and valued for their delicate odor and fixative properties. Historically, ambrox was obtained from ambergris, a waxy excretion produced by sperm whales, now an endangered species. Synthetic ambroxides have replaced ambergris in perfume manufacture. Plant labdane diterpenoids can serve as starting material for ambroxide synthesis. Among these, the diterpene alcohol sclareol is the major industrial precursor obtained from cultivated clary sage (Salvia sclarea). In plants, a large family of diterpene synthase (diTPS) enzymes controls key reactions in diterpenoid biosynthesis. Advanced metabolite profiling and high-throughput sequencing of fragrant and medicinal plants have accelerated discovery of novel diTPS functions, providing a resource for combinatorial synthetic biology and metabolic engineering approaches. This chapter highlights recent progress on the discovery, characterization, and engineering of plant diTPSs with potential uses in ambroxide production. It features biosynthesis of sclareol, cis-abienol, and diterpene resin acids, as sources of genes and enzymes for diterpenoid bioproducts. PMID:25846965

  17. Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Wu, Yi fang; Wang, Xue liang

    2014-01-01

    We report here theoretical and experimental studies on the molecular structure and vibrational and NMR spectra of both natural enmein type diterpenoids molecule (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total energy, NMR chemical shifts and vibrational wavenumbers of epinodosinol and epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A complete vibrational assignment is provided for the observed IR spectra of studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent agreement with the experimental values. Quantum chemical calculations at the B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies ΔEg). Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules.

  18. Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study.

    PubMed

    Wang, Tao; Wu, Yi fang; Wang, Xue liang

    2014-01-01

    We report here theoretical and experimental studies on the molecular structure and vibrational and NMR spectra of both natural enmein type diterpenoids molecule (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total energy, NMR chemical shifts and vibrational wavenumbers of epinodosinol and epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A complete vibrational assignment is provided for the observed IR spectra of studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent agreement with the experimental values. Quantum chemical calculations at the B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies ΔEg). Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules. PMID:24013676

  19. Large-scale profiling of diterpenoid glycosides from Stevia rebaudiana using ultrahigh performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Shafii, Behnaz; Vismeh, Ramin; Beaudry, Randy; Warner, Ryan; Jones, A Daniel

    2012-07-01

    The plant Stevia rebaudiana accumulates a suite of diterpenoid metabolites that are natural sweeteners finding increased use as sugar substitutes. To guide breeding of stevia plants that accumulate substances with desirable flavor in high yield, rapid and accurate methods are needed to profile these substances in plant populations. This report describes an 8-min ultrahigh performance liquid chromatography-tandem mass spectrometry method for separation and quantification of seven stevia glycosides including steviolbioside; stevioside; rebaudiosides A, B, and C; rubusoside; and dulcoside as well as aglycones steviol and isosteviol. This negative mode electrospray ionization/multiple reaction monitoring method yielded low limits of detection <1 ng/mL for steviol, 6 ng/mL for isosteviol, and <15 ng/mL for all stevia glycosides. Stevioside and Reb A, B, and C were quantified in more than 1,100 extracts from stevia leaves as part of a large-scale profiling exercise. Leaf tissue levels in this population spanned about two orders of magnitude for stevioside (2-125 mg/g dry weight), Reb A (2.5-164 mg/g), Reb B (0.5-50 mg/g), and Reb C (1.5-125 mg/g), but levels of individual metabolites exhibited independent variation. The wide spread of metabolite levels highlights the utility and importance of performing targeted metabolic profiling for large plant populations. PMID:22580424

  20. Studies on C20-Diterpenoid Alkaloids: Synthesis of the Hetidine Framework and Its Application to the Synthesis of Dihydronavirine and the Atisine Skeleton

    PubMed Central

    2015-01-01

    The full details of a synthesis of the hetidine framework of the C20-diterpenoid alkaloids and its conversion to the atisine core structure are reported. The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described. Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6–7–6] framework that was advanced to the hetidine skeleton. Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines. PMID:25004408

  1. neo-Clerodane diterpenoids from Scutellaria barbata mediated inhibition of P-glycoprotein in MCF-7/ADR cells.

    PubMed

    Xue, Gui-Min; Xia, Yuan-Zheng; Wang, Zhi-Min; Li, Ling-Nan; Luo, Jian-Guang; Kong, Ling-Yi

    2016-10-01

    Ten new (1-10) and seventeen known (11-27) neo-clerodane diterpenoids substituted with nicotinoyloxyl were isolated from the plant Scutellaria barbata and their structures were established by extensive spectroscopic analysis. Chemoreversal effects of these neo-clerodane diterpenoids on multidrug resistance were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein. Four compounds (11, 14, 16, and 18) exhibited better chemoreversal abilities than the classical P-gp inhibitor verapamil and the most potent compound 11 reduced IC50 value of adriamycin in MCF-7/ADR cells from 58.8 μM to 1.3 μM. Mechanistic investigations showed that compound 11 reversed multidrug resistance through suppressing the activity of P-gp and restraining the expression of P-glycoprotein. In the present study, the structure-activity relationships of neo-clerodane diterpenoids were also discussed. PMID:27240278

  2. New ent-Clerodane and Abietane Diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & M. G. Gilbert.

    PubMed

    Ndunda, Beth; Langat, Moses K; Mulholland, Dulcie A; Eastman, Harry; Jacob, Melissa R; Khan, Shabana I; Walker, Larry A; Muhammad, Ilias; Kerubo, Leonidah O; Midiwo, Jacob O

    2016-07-01

    The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1-12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD. The isolated compounds were evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed. PMID:27286332

  3. Engineering a Platform for Photosynthetic Pigment, Hormone and Cembrane-Related Diterpenoid Production in Nicotiana tabacum.

    PubMed

    Zhang, Hongying; Niu, Dexin; Wang, Jing; Zhang, Songtao; Yang, Yongxia; Jia, Hongfang; Cui, Hong

    2015-11-01

    Plants synthesize a large number of isoprenoids that are of nutritional, medicinal and industrial importance. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) catalyzes the first committed step for plastidial isoprenoid biosynthesis. Here, we identified two DXR isogenes, designated NtDXR1 and NtDXR2, from tetraploid common tobacco (Nicotiana tabacum L.). Southern blotting and genotyping analysis revealed that two NtDXR genes existed in the tetraploid tobacco genome; NtDXR1 and NtDXR2 were separately derived from N. tomentosiformis and N. sylvestris. Both NtDXRs were localized in chloroplasts. Expression patterns indicated that NtDXR1 and NtDXR2 had similar expression profiles. NtDXR genes were highly expressed in leaves with or without trichomes; expression was relatively reduced in flowers and stems, weak in leaf trichomes and marginal in roots and seeds. Overexpressing NtDXR1 under control of the 35S promoter resulted in longer primary roots and enhancement of various photosynthetic pigments and hormones in leaves. In contrast, there were no significant changes in cembrane-related diterpenoids synthesized in glandular trichomes. To elucidate further the function of DXR in the biosynthesis of diterpenoids, overexpression vectors for NtDXR1 under the control of a trichome-specific CYP promoter were transferred to tobacco plants. CYP:NtDXR1 tobacco exhibited larger glandular cells and increased cembrane-related diterpenoids in leaf glandular trichomes. Moreover, transcripts of eight MEP (2-C-methyl-d-erythritol 4-phosphate) pathway genes were significantly up-regulated in NtDXR1-overexpressing tobacco plants, indicating that overexpression of NtDXR could boost the expression of downstream genes in the MEP pathway. Our results suggested that overexpression of NtDXR1 could increase the levels of photosynthetic pigments, leaf surface exudates and hormones though the MEP pathway. PMID:26363359

  4. 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. PMID:24990389

  5. Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri.

    PubMed

    Allard, Pierre-Marie; Leyssen, Pieter; Martin, Marie-Thérèse; Bourjot, Mélanie; Dumontet, Vincent; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Poullain, Cyril; Guéritte, Françoise; Litaudon, Marc

    2012-12-01

    The chemical study of the bark and the wood of Trigonostemon cherrieri, a rare endemic plant of New Caledonia, led to the isolation of a series of highly oxygenated daphnane diterpenoid orthoesters (DDO) bearing an uncommon chlorinated moiety: trigocherrins A-F and trigocherriolides A-D. Herein, we describe the isolation and structure elucidation of the DDO (trigocherrins B-F and trigocherriolides A-D). We also report the antiviral activity of trigocherrins A, B and F (1, 2 and 6) and trigocherriolides A, B and C (7-9) against various emerging pathogens: chikungunya virus (CHIKV), Sindbis virus (SINV), Semliki forest virus (SFV) and dengue virus (DENV). PMID:22938995

  6. ent-Labdane Diterpenoids from the Aerial Parts of Eupatorium obtusissmum.

    PubMed

    Castillo, Quírico A; Triana, Jorge; Eiroa, José L; Calcul, Laurent; Rivera, Edwin; Wojtas, Lukasz; Padrón, José M; Boberieth, Lise; Keramane, Mehdi; Abel-Santos, Ernesto; Báez, Luis A; Germosén, Evelyn A

    2016-04-22

    Six new ent-labdane diterpenoids, uasdlabdanes A-F (1-6), were isolated from the aerial parts of Eupatorium obtusissmum. The new structures were elucidated through spectroscopic and spectrometric data analyses. The absolute configurations of compounds 1 and 2 were established by X-ray crystallography, and those of 3-6, by comparison of experimental and calculated electronic circular dichroism spectra. The antiproliferative activity of the compounds was studied in a panel of six representative human solid tumor cell lines and showed GI50 values ranging from 19 to >100 μM. PMID:27023255

  7. Highly Rigid Labdane-Type Diterpenoids from a Chinese Liverwort and Light-Driven Structure Diversification.

    PubMed

    Zhou, Jinchuan; Zhang, Jiaozhen; Cheng, Aixia; Xiong, Yuanxin; Liu, Lei; Lou, Hongxiang

    2015-07-17

    Two unprecedented labdane-type diterpenoids haplomintrins A (1) and B (2) with six rings system were isolated from a Chinese liverwort Haplomitrium mnioides. Light-driven reaction of homologous haplomitrenonolides C (6), A (4), and D (3) afforded haplomintrins A-C (1, 2, and 7), respectively, while 4 was converted to more complex congeners haplomintrins D-G (8-11) through intramolecular cyclization. Formation of 1 and 2 from compounds 6 and 4, respectively, helps us to postulate that a photochemical reaction is involved in the biosynthetic pathway. These structure features can be used as molecular markers of H. mnioides, and their allelopathic effects are also preliminarily tested. PMID:26111119

  8. Acylated neo-clerodane type diterpenoids from the aerial parts of Scutellaria coleifolia Levl. (Lamiaceae).

    PubMed

    Kurimoto, Shin-Ichiro; Pu, Jian-Xin; Sun, Han-Dong; Shibata, Hirofumi; Takaishi, Yoshihisa; Kashiwada, Yoshiki

    2016-04-01

    Twenty new neo-clerodane type diterpenoids, scutefolides G1-S (1-20), were isolated from the 70 % aqueous acetone extract of the aerial parts of Scutellaria coleifolia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of 1, 2, 7, 8, 14 and 15 were determined by means of the CD exciton chirality method. Compounds 1, 2, 5, 7, 8, 12, 14, 15, 18 and 19 were evaluated for their cytotoxic activities against four human cancer cell lines, and anti-bacterial activities against methicillin-resistant Staphylococcus aureus. PMID:26825781

  9. New labdane diterpenoids from Croton laui and their anti-inflammatory activities.

    PubMed

    Yang, Li; Zhang, Yu-Bo; Chen, Li-Feng; Chen, Neng-Hua; Wu, Zhong-Nan; Jiang, Si-Qi; Jiang, Lin; Li, Guo-Qiang; Li, Yao-Lan; Wang, Guo-Cai

    2016-10-01

    Nine new labdane diterpenoids (1-9) were isolated from the aerial parts of Croton laui, along with eight known analogues (10-17). Their structures were identified on the basis of the spectral data (IR, UV, HRESIMS, 1D and 2D NMR), and the structure of 8 was confirmed by single crystal X-ray diffraction analyses. In addition, compounds 1, 4, 7, 8, and 14 showed weak anti-inflammatory activities in LPS-stimulated RAW 264.7 cells. PMID:27575472

  10. A new ent-kaurane diterpenoid glycoside from Isodon japonica var. glaucocalyx.

    PubMed

    Xiang, Zhao-Bao; Wang, Guang-Li; Huang, Lan-Zhi; Heng, Lin-Sen; Li, Xiao-Hui

    2013-01-01

    A new ent-kaurane diterpenoid glycoside (1), named glaucocalyxin G, has been isolated from the n-butanol-soluble fraction of the dried whole plants of Isodon japonica var. glaucocalyx along with two known compounds, namely arjunglucoside (2) and kaempferol-3-O-rutinoside (3). The structures of the isolated compounds were assigned on the basis of their (1)H and (13)C NMR spectra including two-dimensional NMR techniques such as HMQC, HMBC, and NOESY experiments and comparison with the literature data. PMID:23614395

  11. Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides.

    PubMed

    Wu, Hai-Yan; Wang, Wei-Guang; Jiang, Hua-Yi; Du, Xue; Li, Xiao-Nian; Pu, Jian-Xin; Sun, Han-Dong

    2014-10-01

    Seven new ent-kaurane diterpenoids, isowikstroemins A-G (1-7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1-4 exhibited significant activity with IC50 values ranging from 0.9 to 7.0 μM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. PMID:25128423

  12. Hispidanins A-D: four new asymmetric dimeric diterpenoids from the rhizomes of Isodon hispida.

    PubMed

    Huang, Bo; Xiao, Chao-Jiang; Huang, Zhen-Yuan; Tian, Xin-Yan; Cheng, Xia; Dong, Xiang; Jiang, Bei

    2014-07-01

    Hispidanins A-D (1-4), four unprecedented asymmetric dimeric diterpenoids, were obtained from the rhizomes of Isodon hispida. Their structures were elucidated by extensive spectroscopic analysis (1D and 2D NMR, MS, UV, IR), as well as single-crystal X-ray diffraction analysis. Hispidanin B showed significant cytotoxicities against tumor cell lines SGC7901, SMMC7721, and K562, with IC50 values of 10.7, 9.8, and 13.7 μM, respectively. PMID:24956015

  13. New flavonol and diterpenoids from the endophytic fungus Aspergillus sp. YXf3.

    PubMed

    Yan, Tong; Guo, Zhi Kai; Jiang, Rong; Wei, Wei; Wang, Ting; Guo, Ye; Song, Yong Chun; Jiao, Rui Hua; Tan, Ren Xiang; Ge, Hui Ming

    2013-03-01

    One new flavonol, chlorflavonin A (1), four new diterpenoids, aspergiloids E-H (3, 5-7), together with eight known compounds (2, 4, 8-13) were isolated from solid fermentation of Aspergillus sp. (strain no. YXf3), an endophytic fungus from Ginkgo biloba. Their structures were determined through detailed spectroscopic analysis combined with comparison of NMR spectra data with reported ones. All of them were screened on cytotoxicity against KB, SGC-7901, SW1116, and A549 cell lines; compounds 4, 9-11 exhibited moderate activities with IC50 values ranging from 6.74 to 46.64 µM. PMID:23457022

  14. Two pimarane diterpenoids from Ephemerantha lonchophylla and their evaluation as modulators of the multidrug resistance phenotype.

    PubMed

    Na, G X; Wang, T S; Yin, L; Pan, Y; Guo, Y L; LeBlanc, G A; Reinecke, M G; Watson, W H; Krawiec, M

    1998-01-01

    Two new pimarane diterpenoids, lonchophylloids A (1) and B (2), were isolated from the stems of Ephemerantha lonchophylla. The structures of 1 and 2 were established predominantly through the application of extensive 1H-and 13C-NMR, 1D- and 2D-homonuclear and heteronuclear correlation NMR experiments, and X-ray diffraction methods. Consistent with structure--activity predictions, both compounds were capable of sensitizing cells that expressed the multidrug resistance phenotype to the toxicity of the anticancer drug doxorubicin. PMID:9461658

  15. Guanacastane-type diterpenoids from the insect-associated fungus Verticillium dahliae.

    PubMed

    Wu, Fa-Biao; Li, Tian-Xiao; Yang, Ming-Hua; Kong, Ling-Yi

    2016-01-01

    Four new guanacastane-type diterpenoids, namely dahlianes A (1), B (2), C (3), and D (4), were isolated from cultures of Verticillium dahliae. Their structures were elucidated on the basis of extensive spectroscopic data analysis. Their absolute configurations were determined by a combination of Mo2(OAc)4-induced electronic circular dichroism experiment and Mosher ester method. In cytotoxicity evaluation against human tumor cell lines, compounds 2 and 3 exhibited significant cytotoxicities against MCF-7 cell lines with IC50 values of 3.35 and 4.72 μM, respectively. PMID:26221875

  16. New biological potential of abietane diterpenoids isolated from Salvia austriaca against microbial virulence factors.

    PubMed

    Sadowska, Beata; Kuźma, Łukasz; Micota, Bartłomiej; Budzyńska, Aleksandra; Wysokińska, Halina; Kłys, Arkadiusz; Więckowska-Szakiel, Marzena; Różalska, Barbara

    2016-09-01

    The increasing importance of multi-resistant strains and microbial biofilms in the development of chronic infections has driven the search for more effective alternative therapy including plant-origin preparations. The present study evaluates the broadly-defined antimicrobial activity of two abietane diterpenoids isolated from Salvia austriaca transformed roots: taxodone and 15-deoxy-fuerstione. The direct biostatic/biocidal effect of these phytocompounds and their influence on Staphylococcus aureus and Candida albicans virulence factors/mechanisms (adhesion, biofilm formation, agglutination in human plasma, survival in the blood, germ tube and mycelium formation) were tested using in vitro assays. Both phytocompounds significantly inhibited microbial adhesion and biofilm formation when used at ½ and ¼ MIC. Additionally, taxodone was able to limit staphylococcal survival in human blood, as well as C. albicans germ tube formation and hyphal growth. The tested diterpenoids express significant anti-biofilm activity against both staphylococci and yeast, and adversely affect their virulence factors/mechanisms, which are relevant in the course of the infection in vivo. Therefore, they demonstrate considerable biomedical potential as complements for classic therapy with antibiotics. PMID:27417191

  17. Diterpenoids from Copaifera reticulata Ducke with larvicidal activity against Aedes aegypti (L.) (Diptera, Culicidae).

    PubMed

    Geris, Regina; Silva, Ionizete Garcia da; Silva, Heloísa Helena Garcia da; Barison, Andersson; Rodrigues-Filho, Edson; Ferreira, Antônio Gilberto

    2008-01-01

    The objective of this study was to evaluate the larvicidal activity of diterpenoids obtained from the oil-resin of Copaifera reticulata against Aedes aegypti larvae, the principal vector of dengue and urban yellow fever. Four diterpenes were obtained from oil-resin extraction with organic solvents and subsequent chromatographic and spectroscopic procedures allowed to isolation and identification of these compounds as 3-beta-acetoxylabdan-8(17)-13-dien-15-oic acid (1), alepterolic acid (2), 3-beta-hidroxylabdan-8(17)-en-15-oic acid (3), and ent-agatic acid (4). Each compound was previously dissolved in dimethylsulphoxide, and distilled water was added to obtain the desired concentrations. Twenty larvae of third instars were placed into plastic beckers, containing the solution test (25 mL), in a five repetitions scheme, and their mortality, indicated by torpor and darkening of the cephalic capsule, was recorded after 48 h. Probit analyses were used to determine lethal concentrations (LC50 and LC90) and their respective 95% confidence intervals. This study showed that only diterpenoids 1 and 2 exhibited larvicidal properties with LC50 of 0.8 ppm and 87.3 ppm, respectively, revealing the former as the most toxic compound against third instars of Ae. aegypti. Therefore, this compound seems to be an interesting source for new metabolite to be exploited. PMID:18383630

  18. Oscyp71Z2 involves diterpenoid phytoalexin biosynthesis that contributes to bacterial blight resistance in rice.

    PubMed

    Li, Wenqi; Shao, Min; Yang, Jie; Zhong, Weigong; Okada, Kazunori; Yamane, Hisakazu; Qian, Guoliang; Liu, Fengquan

    2013-06-01

    Bacterial blight is one of the most destructive rice diseases, which caused by Xoo, and results in yield losses, endangering worldwide food security. Diterpenoid phytoalexins, a type of antimicrobials produced in rice, are critical for resistance to fungal and bacterial pathogens. This article reports the characterization of the cytochrome P450 gene Oscyp71Z2, which belongs to the CYP71Z subfamily. Overexpression of Oscyp71Z2 in rice enhanced resistance to Xoo at the booting stage. The accumulation of phytoalexins was rapidly and strongly induced in Oscyp71Z2-overexpressing plants, and the transcript levels of genes related to the phytoalexin biosynthesis pathway were elevated. The H₂O₂ concentration in Oscyp71Z2-overexpressing plants was reduced in accordance with the increase in ROS-scavenging ability due to the induction of SOD as well as POD and CAT activation. We also showed that suppression of Oscyp71Z2 had no significantly effect on disease resistance to Xoo in rice. These results demonstrated that Oscyp71Z2 plays an important role in bacterial blight resistance by regulating the diterpenoid phytoalexin biosynthesis and H₂O₂ generation. PMID:23602104

  19. Bioactive diterpenoids and flavonoids from the aerial parts of Scoparia dulcis.

    PubMed

    Liu, Qing; Yang, Qi-Ming; Hu, Hai-Jun; Yang, Li; Yang, Ying-Bo; Chou, Gui-Xin; Wang, Zheng-Tao

    2014-07-25

    Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17β-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-β-D-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 μM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 μM. PMID:24955889

  20. Diterpenoids and aromatic compounds from the three New Zealand liverworts Jamesoniella kirkii, Balantiopsis rosea, and Radula species.

    PubMed

    Nagashima, Fumihiro; Kuba, Yoshiyuki; Asakawa, Yoshinori

    2006-06-01

    Three new aromatics were isolated from the New Zealand liverwort Balantiopsis rosea. A new bibenzyl was isolated from an unidentified Radula species, together with known bibenzyls. Jamesoniella kirkii yielded three known ent-isopimarane and two ent-kaurane diterpenoids. Their structures were confirmed by NMR techniques, chemical reaction, and X-ray crystallographic analysis. PMID:16755068

  1. Sesqui- and diterpenoids from three New Zealand liverworts: Bazzania novae-zelandiae, Gackstroemia sp. and Dendromastigophora sp.

    PubMed

    Nagashima, Fumihiro; Kuba, Yoshiaki; Ogata, Atsushi; Asakawa, Yoshinori

    2010-01-01

    Two new sesquiterpenoids, 1 and 2, were isolated from the unidentified liverwort Gackstroemia species, and three known sesquiterpenoids, 3-5, and a known sesqui- (6) and diterpenoid (7) were isolated from Bazzania novae-zelandiae and the unidentified Dendromastigophora species, respectively. Their structures were determined by spectroscopic analysis. PMID:20013475

  2. A new diterpenoid and a new triterpenoid glucosyl ester from the leaves of Callicarpa japonica Thunb. var. luxurians Rehd.

    PubMed

    Ono, Masateru; Chikuba, Tomoyo; Mishima, Kenji; Yamasaki, Toru; Ikeda, Tsuyoshi; Yoshimitsu, Hitoshi; Nohara, Toshihiro

    2009-07-01

    A new abietane-type diterpenoid and a new oleanane-type triterpenoid glucosyl ester were isolated from the leaves of Callicarpa japonica Thunb. var. luxurians Rehd. (Verbenaceae) along with 11 known compounds, comprising seven triterpenoids, two sterols, a flavonoid, and an aliphatic glycoside. Their chemical structures were determined on the basis of spectroscopic data. PMID:19184273

  3. Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway.

    PubMed

    Bueno, Carlos Alberto; Michelini, Flavia Mariana; Pertino, Mariano Walter; Gómez, Catalina Arredondo; Schmeda-Hirschmann, Guillermo; Alché, Laura Edith

    2015-10-01

    The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are an approach that should be considered. In the present study, we identified two jatropholones (2A and 5B) and one carnosic acid derivative (9C) that significantly inhibited multiplication of TK+ and TK- strains of HSV-1 in Vero cells. Compounds 2A, 5B and 9C also prevented HSV-1- and TLRs-induced inflammatory response in cultivated murine macrophages. In macrophages infected with HSV-1, the inhibitory effect of compounds 2A, 5B and 9C on TNF-α and IL-6 production could be associated with the block of ERK pathway, whereas NF-κB pathway was not hampered by any of the compounds. Besides, 2A, 5B and 9C also inhibited ERK pathway and reduced TNF-α production in macrophages stimulated with TLR2, TLR4 or TLR9 agonists and were able to hinder IL-6 secretion after activation with TLR2 or TLR4, but not with TLR9. The immunomodulatory effect of 2A, 5B and 9C in macrophages infected with HSV-1 may be a consequence of the inhibition of ERK pathway activated by TLRs. The availability of compounds with both antiviral and immunomodulatory properties which affect TLR signaling pathways might be a useful strategy to control the progress of virus-induced disease. PMID:25528328

  4. ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe.

    PubMed

    Lin, Zhaomin; Guo, Yanxia; Gao, Yanhui; Wang, Shuqi; Wang, Xiaoning; Xie, Zhiyu; Niu, Huanmin; Chang, Wenqiang; Liu, Lei; Yuan, Huiqing; Lou, Hongxiang

    2015-05-14

    It is generally accepted that the origin of the cytotoxicity of ent-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the α,β-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines. The results revealed that their anticancer activities are caused by ROS formation through Michael modification of the protein thiols and depletion of glutathione unselectively. We also found that N-acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael adducts, not through a well-recognized ROS scavenging pathway as previously reported. In situ intracellular thiol detection helped us visualize the intracellular distribution of the diterpenoids and determine the potency of their cytotoxicity. An alkaline analogue was found to be more selective because of the altered subcellular distribution. PMID:25856683

  5. Jasmonoyl-l-isoleucine is required for the production of a flavonoid phytoalexin but not diterpenoid phytoalexins in ultraviolet-irradiated rice leaves.

    PubMed

    Miyamoto, Koji; Enda, Isami; Okada, Toshiki; Sato, Yumiko; Watanabe, Kohei; Sakazawa, Tomoko; Yumoto, Emi; Shibata, Kyomi; Asahina, Masashi; Iino, Moritoshi; Yokota, Takao; Okada, Kazunori; Yamane, Hisakazu

    2016-10-01

    Rice produces low-molecular-weight antimicrobial compounds known as phytoalexins, in response to not only pathogen attack but also abiotic stresses including ultraviolet (UV) irradiation. Rice phytoalexins are composed of diterpenoids and a flavonoid. Recent studies have indicated that endogenous jasmonyl-l-isoleucine (JA-Ile) is not necessarily required for the production of diterpenoid phytoalexins in blast-infected or CuCl2-treated rice leaves. However, JA-Ile is required for the accumulation of the flavonoid phytoalexin, sakuranetin. Here, we investigated the roles of JA-Ile in UV-induced phytoalexin production. We showed that UV-irradiation induces the biosynthesis of JA-Ile and its precursor jasmonic acid. We also showed that rice jasmonate biosynthesis mutants produced diterpenoid phytoalexins but not sakuranetin in response to UV, indicating that JA-Ile is required for the production of sakuranetin but not diterpenoid phytoalexins in UV-irradiated rice leaves. PMID:27240428

  6. Simultaneous identification and analysis of cassane diterpenoids in Caesalpinia minax Hance by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

    PubMed

    Wu, Shilong; Wu, Zhaohua; Fu, Chaofan; Wu, Caiyue; Yuan, Jiuzhi; Xian, Xiaoyan; Gao, Huiyuan

    2015-12-01

    Cassane diterpenoids were successfully and simultaneously identified in Caesalpinia minax Hance by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A total of 59 peaks were detected, and among them 51 compounds, including 41 furanocassane diterpenoids, 10 furanolactone cassane diterpenoids were simultaneously identified and characterized on the basis of the protonated molecule, retention behavior, and fragments in MS(2) . Ten compounds, including seven novel compounds, were identified or tentatively identified for the first time in C. minax. In a positive ion mode, the fragmentation pathways of cassane diterpenoids were also analyzed for the first time. The relative amounts of the five main diterpenoids (caesalpinin L, caesalpinin F2 , bondcellpin C, caesalpinin E, and ξ-caesalmin) were simultaneously quantified by high-performance liquid chromatography. Results showed that the newly discovered and known components of C. minax can be used to determine the material basis of bioactivity; this method can also be applied to analyze cassane diterpenoids in herbal medicines from the genus Caesalpinia belonging to the family Fabaceae. PMID:26394613

  7. Notolutesins A-J, dolabrane-type diterpenoids from the Chinese liverwort Notoscyphus lutescens.

    PubMed

    Wang, Song; Li, Rui-Juan; Zhu, Rong-Xiu; Hu, Xiao-Yan; Guo, Yan-Xia; Zhou, Jin-Chuan; Lin, Zhao-Min; Zhang, Jiao-Zhen; Wu, Jing-Yi; Kang, Ya-Qi; Morris-Natschke, Susan L; Lee, Kuo-Hsiung; Yuan, Hui-Qing; Lou, Hong-Xiang

    2014-09-26

    Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 μM against the PC3 human prostate cancer cell line. PMID:25226363

  8. ent-Atisane diterpenoids from Euphorbia fischeriana inhibit mammosphere formation in MCF-7 cells.

    PubMed

    Kuang, Xinzhu; Li, Wei; Kanno, Yuichiro; Yamashita, Naoya; Nemoto, Kiyomitsu; Asada, Yoshihisa; Koike, Kazuo

    2016-01-01

    The discovery of new drugs that target cancer stem cells (CSCs) is a critical approach to overcome the major difficulties of the metastasis, chemotherapeutic resistance and recurrence for successful cancer therapy. Chemical investigation of the roots of Euphorbia fischeriana resulted in the isolation of eight ent-atisane diterpenoids (1-8), including two new compounds: 19-O-β-D-glucopyranosyl-ent-atis-16-ene-3,14-dione (7) and 19-O-(6-galloyl)-β-D-glucopyranosyl-ent-atis-16-ene-3,14-dione (8). The structures were elucidated on extensive spectroscopic analyses, as well as chemical transformations. ent-3β-Hydroxyatis-16-ene-2,14-dione (5), 7 and its aglycon, ent-19-hydroxy-atis-16-ene-3,14-dione (7a), showed significant inhibitory activity on mammosphere formation in human breast cancer MCF-7 cells at a final concentration of 10 μM. PMID:26411465

  9. Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L.) Jaeq.

    PubMed Central

    Khurram, Muhammad; Lawton, Linda A.; Edwards, Christine; Iriti, Marcello; Hameed, Abdul; Khan, Murad A.; Khan, Farman A.; ur Rahman, Shafiq

    2015-01-01

    Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16), 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC) = 64–128 µg/mL) against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa. PMID:26343638

  10. Diterpenoids from the Endophytic Fungus Botryosphaeria sp. P483 of the Chinese Herbal Medicine Huperzia serrata.

    PubMed

    Chen, Yan-Mei; Yang, Yin-He; Li, Xiao-Nian; Zou, Cheng; Zhao, Pei-Ji

    2015-01-01

    Two new tetranorlabdane diterpenoids, named botryosphaerins G (1) and H (2), were isolated from the solid fermentation products of Botryosphaeria sp. P483 along with seven known tetranorlabdane diterpenes (3-9). Their structures were elucidated by extensive analysis, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). Their absolute configuration was confirmed by single-crystal X-ray diffraction analyses using the anomalous scattering of Cu Kα radiation. All of the isolated compounds were tested for activity against phytopathogenic fungi and nematodes. Compounds 2 and 3 showed antifungal activity and compound 2 showed weak nematicidal activity. PMID:26393542

  11. Abietane-type diterpenoids from the roots of Caryopteris mongolica and their cholinesterase inhibitory activities.

    PubMed

    Murata, Toshihiro; Ishikawa, Yoshinobu; Saruul, Erdenebileg; Selenge, Erdenechimeg; Sasaki, Kenroh; Umehara, Kaoru; Yoshizaki, Fumihiko; Batkhuu, Javzan

    2016-10-01

    Eleven abietane-type diterpenoids and two known abietanes were isolated from the roots of Caryopteris mongolica, and their structures were characterized. The absolute configurations at C-5 and C-10 were determined from the NMR data, including from the nuclear Overhauser effect and CD spectra, and the absolute configuration of C-16 in the hydroxypropyl group was determined via a modified Mosher's method. Furthermore, the previously unknown absolute configuration of the C-15 of cyrtophyllone B was determined to be in an R-configuration using X-ray crystallography. To estimate the preventive effects of the isolates for neurodegenerative disease development, their inhibitory activities against acetylcholinesterase (AChE) from human erythrocytes and butyrylcholinesterase (BChE) from horse serum were evaluated. PMID:27298275

  12. Jatrophane diterpenoid esters from Euphorbia sororia serving as multidrug resistance reversal agents.

    PubMed

    Lu, Dongli; Liu, Yongqiang; Aisa, Haji Akber

    2014-01-01

    Six (1-6) new jatrophane diterpenoid esters together with four known compounds (7-10) were isolated from the acetone extract of fructus Euphorbia sororia. Their structures were elucidated by the spectral technology, including the 2D NMR experiments (HMQC, HMBC and NOESY). The absolute configuration of compound 1 and compound 7 were first confirmed by X-ray crystallographic analysis. Compounds 1-7 were assayed for their antiproliferative activity in human cancer cell lines: human mammary adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549). All the compounds were inactive for the cell lines. The multidrug-resistance reversal activity was also tested on KBv200 cells and compound 2 displayed strong multidrug resistance reversal activity, outperforming verapamil at 10 μM. PMID:24291755

  13. Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata.

    PubMed

    Shaikh, Rafik U; Dawane, Ashwini A; Pawar, Rajendra P; Gond, Dhananjay S; Meshram, Rohan J; Gacche, Rajesh N

    2016-03-01

    The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition. PMID:26648323

  14. Cespitulones A and B, Cytotoxic Diterpenoids of a New Structure Class from the Soft Coral Cespitularia taeniata

    PubMed Central

    Lin, Yu-Chi; Wang, Shih-Sheng; Chen, Chung-Hsiung; Kuo, Yao-Haur; Shen, Ya-Ching

    2014-01-01

    Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells. PMID:24905485

  15. A Novel Aromatic-Ring-Hydroxylating Dioxygenase from the Diterpenoid-Degrading Bacterium Pseudomonas abietaniphila BKME-9

    PubMed Central

    Martin, Vincent J. J.; Mohn, William W.

    1999-01-01

    Pseudomonas abietaniphila BKME-9 is able to degrade dehydroabietic acid (DhA) via ring hydroxylation by a novel dioxygenase. The ditA1, ditA2, and ditA3 genes, which encode the α and β subunits of the oxygenase and the ferredoxin of the diterpenoid dioxygenase, respectively, were isolated and sequenced. The ferredoxin gene is 9.2 kb upstream of the oxygenase genes and 872 bp upstream of a putative meta ring cleavage dioxygenase gene, ditC. A Tn5 insertion in the α subunit gene, ditA1, resulted in the accumulation by the mutant strain BKME-941 of the pathway intermediate, 7-oxoDhA. Disruption of the ferredoxin gene, ditA3, in wild-type BKME-9 by mutant-allele exchange resulted in a strain (BKME-91) with a phenotype identical to that of the mutant strain BKME-941. Sequence analysis of the putative ferredoxin indicated that it is likely to be a [4Fe-4S]- or [3Fe-4S]-type ferredoxin and not a [2Fe-2S]-type ferredoxin, as found in all previously described ring-hydroxylating dioxygenases. Expression in Escherichia coli of ditA1A2A3, encoding the diterpenoid dioxygenase without its putative reductase component, resulted in a functional enzyme. The diterpenoid dioxygenase attacks 7-oxoDhA, and not DhA, at C-11 and C-12, producing 7-oxo-11,12-dihydroxy-8,13-abietadien acid, which was identified by 1H nuclear magnetic resonance, UV-visible light, and high-resolution mass spectrometry. The organization of the genes encoding the various components of the diterpenoid dioxygenase, the phylogenetic distinctiveness of both the α subunit and the ferredoxin component, and the unusual Fe-S cluster of the ferredoxin all suggest that this enzyme belongs to a new class of aromatic ring-hydroxylating dioxygenases. PMID:10217753

  16. Structure of a novel diterpenoid ester, fritillahupehin from bulbs of Fritillaria hupehensis Hsiao and K.C. Hsia.

    PubMed

    Ruan, Hanli; Zhang, Yonghui; Wu, Jizhou; Deng, Shukai; Sun, Handong; Fujita, Tetsuro

    2002-07-01

    A new diterpenoid ester, fritillahupehin (1) together with three known fatty acids: palmitic acid (2), lignoceric acid (3) and azelaic acid (4) were isolated from the bulbs of Fritillaria hupehensis Hsiao and K.C. Hsia. The structure of fritillahupehin has been established to be ent-kauran-16beta-yl lignocerate by means of spectroscopic and chemical evidence. Compounds 2-4 were isolated from Fritillaria sp. for the first time. PMID:12234570

  17. Euphorikanin A, a Diterpenoid Lactone with a Fused 5/6/7/3 Ring System from Euphorbia kansui.

    PubMed

    Fei, Dong-Qing; Dong, Le-Le; Qi, Feng-Ming; Fan, Gai-Xia; Li, Hui-Hong; Li, Zheng-Yu; Zhang, Zhan-Xin

    2016-06-17

    Euphorikanin A (1), an unprecedented diterpenoid lactone which possesses a novel 5/6/7/3-fused tetracyclic ring skeleton, was isolated from the roots of Euphorbia kansui. The chemical structure and absolute stereochemistry were elucidated on the basis of extensive spectroscopic methods and single-crystal X-ray diffraction analysis. Compound 1 exhibited moderate cytotoxicity against two human tumor cell lines HeLa and NCI-446. A proposed biosynthetic pathway of compound 1 is also described. PMID:27230557

  18. The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica

    PubMed Central

    Edwards, Jennifer; Brown, Martha; Peak, Emily; Bartholomew, Barbara; Nash, Robert J.; Hoffmann, Karl F.

    2015-01-01

    Background Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Methodology/ Principle Findings Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and

  19. Noncariogenic intense natural sweeteners.

    PubMed

    Kinghorn, A D; Kaneda, N; Baek, N I; Kennelly, E J; Soejarto, D D

    1998-09-01

    There is a definite relationship between the dietary consumption of sucrose and the incidence of dental caries. Noncaloric sucrose substitutes for use in the sweetening of foods, beverages, and medicines may be either synthetic compounds or natural products. In the United States, four potently sweet artificial sweeteners are approved, namely, saccharin, aspartame, acesulfame potassium, and sucralose. Highly sweet plant constituents are used in Japan and some other countries, including the diterpene glycoside stevioside and the protein thaumatin. Recent progress in a research project oriented towards the discovery and evaluation of novel potentially noncariogenic sweeteners from plants has focused on substances in the sesquiterpenoid, diterpenoid, triterpenoid, steroidal saponin, and proanthocyanidin structural classes. The feasibility of using Mongolian gerbil electrophysiological and behavioral assays to monitor the sweetness of plant extracts, chromatographic fractions, and pure isolates has been investigated. An in vivo cariogenicity study on the commercially available natural sweeteners stevioside and rebaudioside A has been carried out. PMID:9735874

  20. Scapaundulin C, a novel labdane diterpenoid isolated from Chinese liverwort Scapania undulate, inhibits acetylcholinesterase activity.

    PubMed

    Kang, Ya-Qi; Zhou, Jin-Chuan; Fan, Pei-Hong; Wang, Shu-Qi; Lou, Hong-Xiang

    2015-12-01

    In the present study, scapaundulin C (1), a new labdane diterpenoid, and four related known compounds scapaundulin A (2), 5α, 8α, 9α-trihydroxy-13E-labden-12-one (3), 5α, 8α-dihydroxy-13E-labden-12-one (4), and (13S)-15-hydroxylabd-8 (17)-en-19-oic acid (5), were isolated from the Chinese liverwort Scapania undulate (L.) Dum., using column chromatography. The structures of these compounds were determined on the basis of 1D- and 2D-NMR analyses. The acetylcholinesterase (AchE) inhibitory activity was evaluated using a bioautographic TLC assay and the cytotoxic activity was evaluated by the MTT method. All the compounds were reported for the first time to exhibit moderate AchE inhibitory activity with minimal inhibitory quantities ranging from 250 to 500 ng. All the compounds were tested for their cytotoxicity against five human tumor cell lines, A549, K562, A2780, Hela, and HT29, and compounds 3 and 4 exhibited moderate inhibitory effects on the growth of A2780 cells. PMID:26721712

  1. Triphenylphosphonium Cations of the Diterpenoid Isosteviol: Synthesis and Antimitotic Activity in a Sea Urchin Embryo Model.

    PubMed

    Strobykina, Irina Yu; Belenok, Mayya G; Semenova, Marina N; Semenov, Victor V; Babaev, Vasiliy M; Rizvanov, Ildar Kh; Mironov, Vladimir F; Kataev, Vladimir E

    2015-06-26

    A series of novel triphenylphosphonium (TPP) cations of the diterpenoid isosteviol (1, 16-oxo-ent-beyeran-19-oic acid) have been synthesized and evaluated in an in vivo phenotypic sea urchin embryo assay for antimitotic activity. The TPP moiety was applied as a carrier to provide selective accumulation of a connected compound into mitochondria. When applied to fertilized eggs, the targeted isosteviol TPP conjugates induced mitotic arrest with the formation of aberrant multipolar mitotic spindles, whereas both isosteviol and the methyltriphenylphosphonium cation were inactive. The structure-activity relationship study revealed the essential role of the TPP group for the realization of the isosteviol effect, while the chemical structure and the length of the linker only slightly influenced the antimitotic potency. The results obtained using the sea urchin embryo model suggested that TPP conjugates of isosteviol induced mitotic spindle defects and mitotic arrest presumably by affecting mitochondrial DNA. Since targeting mitochondria is considered as an encouraging strategy for cancer therapy, TPP-isosteviol conjugates may represent promising candidates for further design as anticancer agents. PMID:26042548

  2. Isopimarane diterpenoids from Kaempferia pulchra rhizomes collected in Myanmar and their Vpr inhibitory activity.

    PubMed

    Win, Nwet Nwet; Ito, Takuya; Matsui, Takashi; Aimaiti, Simayijiang; Kodama, Takeshi; Ngwe, Hla; Okamoto, Yasuko; Tanaka, Masami; Asakawa, Yoshinori; Abe, Ikuro; Morita, Hiroyuki

    2016-04-01

    Viral protein R (Vpr), an accessory gene of HIV-1, plays important roles in viral pathogenesis. Screening of Myanmar medicinal plants that are popular as primary treatments for HIV/AIDS and for HIV-related problems revealed the potent anti-Vpr activity of the CHCl3-soluble extract of Kaempferia pulchra rhizomes, in comparison with that of the positive control, damnacanthal. Fractionation of the active CHCl3-soluble extract led to the identification of 30 isopimarane diterpenoids, including kaempulchraols A-W (1-23). All isolates were assayed for anti-Vpr activity against TREx-HeLa-Vpr cells, in which Vpr expression is tightly regulated by tetracycline. Kaempulchraols B (2), D (4), G (7), Q (17), T (20), U (21), and W (23) exhibited potent anti-Vpr activity, at concentrations ranging from 1.56 to 6.25μM. The structure-activity relationships of the active kaempulchraols suggested that the presence of a hydroxy group at C-14 in an isopimara-8(9),15-diene skeleton and the presence of an acetoxy group at C-1 or C-7 in an isopimara-8(14),15-diene skeleton are the critical factors for the inhibitory effects against TREx-HeLa-Vpr cells. PMID:26916438

  3. Bioactive Enmein-Type ent-Kaurane Diterpenoids from Isodon phyllostachys.

    PubMed

    Yang, Jin; Wang, Wei-Guang; Wu, Hai-Yan; Du, Xue; Li, Xiao-Nian; Li, Yan; Pu, Jian-Xin; Sun, Han-Dong

    2016-01-22

    Thirty-two enmein-type ent-kaurane diterpenoids, including 13 new compounds, were isolated from the aerial parts of Isodon phyllostachys. Compounds 1 and 2 are the first examples of 3,20:6,20-diepoxyenmein-type ent-kauranoids, and the structures of these new compounds were established mainly by analyzing NMR and HREIMS data. The absolute configurations of 1 and 8 and the relative configuration of 9 were determined using single-crystal X-ray diffraction. Compounds 11, 15, 20, and 21 were active against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), with IC50 values ranging from 1.2 to 5.0 μM. Compounds 3, 11, 15, 17, 20, 21, 25, and 29 strongly inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values ranging from 0.74 to 4.93 μM. PMID:26757019

  4. Peltate glandular trichomes of Colquhounia seguinii harbor new defensive clerodane diterpenoids.

    PubMed

    Li, Chun-Huan; Liu, Yan; Hua, Juan; Luo, Shi-Hong; Li, Sheng-Hong

    2014-09-01

    Glandular trichomes produce a wide variety of secondary metabolites that are considered as major defensive chemicals against herbivore attack. The morphology and secondary metabolites of the peltate glandular trichomes of a lianoid Labiatae, Colquhounia seguinii Vaniot, were investigated. Three new clerodane diterpenoids, seguiniilactones A-C (1-3), were identified through precise trichome collection with laser microdissection, metabolic analysis with ultra performance liquid chromatography-tandem mass spectrometer, target compound isolation with classical phytochemical techniques, structure elucidation with spectroscopic methods. All compounds showed significant antifeedant activity against a generalist plant-feeding insect Spodoptera exigua. Seguiniilactone A (1) was approximately 17-fold more potent than the commercial neem oil. α-Substituted α,β-unsaturated γ-lactone functionality was found to be crucial for strong antifeedant activity of this class of compounds. Quantitative results indicated that the levels of these compounds in the peltate glandular trichomes and leaves were sufficiently high to deter the feeding by generalist insects. Moderate antifungal activity was observed for seguiniilactone C (3) against six predominant fungal species isolated from the diseased leaves of C. seguinii, while seguiniilactones A and B were generally inactive. These findings suggested that seguiniilactones A-C might be specialized secondary metabolites in peltate glandular trichomes for the plant defense against insect herbivores and pathogens. PMID:25048077

  5. In vivo activity of benzoyl ester clerodane diterpenoid derivatives from Dodonaea polyandra.

    PubMed

    Simpson, Bradley S; Claudie, David J; Gerber, Jacobus P; Pyke, Simon M; Wang, Jiping; McKinnon, Ross A; Semple, Susan J

    2011-04-25

    Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8α-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8α-(benzoyloxy)methyl-2α-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8α-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2α-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses. PMID:21381684

  6. Jatrophane and ingenane-type diterpenoids from Euphorbia kansui inhibit the LPS-induced NO production in RAW 264.7 cells.

    PubMed

    Lee, Jin Woo; Jin, Qinghao; Jang, Hari; Lee, Dongho; Han, Sang Bae; Kim, Youngsoo; Hong, Jin Tae; Lee, Mi Kyeong; Hwang, Bang Yeon

    2016-07-15

    Bioactivity-guided fractionation of the MeOH extract from the roots of Euphorbia kansui resulted in the isolation of two new jatrophane-type diterpenoids, kanesulones A (1) and B (2), together with six known jatrophane-type diterpenoids (3-8) and ten known ingenane-type diterpenoids (9-18). Their chemical structures were elucidated on the basis of spectroscopic data interpretation, especially 1D and 2D NMR such as HMQC, HMBC, COSY and NOESY, and HRESIMS data as well as CD analysis. Compounds 1-8 and 11-18 exhibited the inhibitory effects on LPS-induced nitric oxide production with IC50 values ranging from 0.7 to 46.5μM in RAW 264.7 macrophages. PMID:27246615

  7. Characterization of isoquinoline alkaloids, diterpenoids and steroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittata and Tinospora capillipes) by high-performance liquid chromatography/electrospray ionization with multistage mass spectrometry.

    PubMed

    Zhang, Yufeng; Shi, Qirong; Shi, Peiying; Zhang, Weidong; Cheng, Yiyu

    2006-01-01

    This study sought to determine the primary components (isoquinoline alkaloids, diterpenoids and steroids) in crude extracts of the Chinese herb Jin-Guo-Lan, prepared from the roots of Tinospora sagittata and T. capillipes, by liquid chromatography/electrospray ionization multistage mass spectrometry coupled with diode-array detection (LC-DAD/ESI-MS(n)). After separation on a reversed-phase C(18) column using gradient elution, positive and negative ESI-MS experiments were performed. In positive ion mode, the three types of compounds showed very different characteristic ions: strong [M](+) or [M+H](+) ions were observed for isoquinoline alkaloids; [M+NH(4)](+) and/or [M+H-CO(2)](+) for diterpenoids; [M+H-nH(2)O](+) (n=1-3) for steroids. These adduct ions and/or fragments were used to deduce the mass and categories of known and unknown components in crude extracts, and their structures were further confirmed by ESI-MS(n) in positive ion mode. Moreover, UV absorption peaks obtained from DAD provided useful functional group information to aid the MS(n)-based identification. As a result, 11 compounds were unambiguously identified by comparing with standard compounds and 13 compounds were tentatively identified or deduced according to their MS(n) data. Two of these compounds (13-hydroxycolumbamine and 13-hydroxyjatrorrhizine) were found to be new compounds and another one (13-hydroxypalmatine) was detected for the first time as a natural product. In addition, a [M-*CH(3)-H(2)O](*+) ion in MS(2) of [M](+) after in-source collision-induced dissociation was used to differentiate positional isomers of protoberberine alkaloids, columbamine and jatrorrhizine. Although the roots of T. sagittata and T. capillipes contain almost identical compounds, the content of the compounds in them is dramatically different, suggesting the necessity for further comparison of the bioactivities of the two species. PMID:16817243

  8. CYP701A8: a rice ent-kaurene oxidase paralog diverted to more specialized diterpenoid metabolism.

    PubMed

    Wang, Qiang; Hillwig, Matthew L; Wu, Yisheng; Peters, Reuben J

    2012-03-01

    All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice. PMID:22247270

  9. Scapairrins A-Q, Labdane-Type Diterpenoids from the Chinese Liverwort Scapania irrigua and Their Cytotoxic Activity.

    PubMed

    Zhang, Jiaozhen; Li, Yi; Zhu, Rongxiu; Li, Lin; Wang, Yongjie; Zhou, Jinchuan; Qiao, Yanan; Zhang, Zhenwei; Lou, Hongxiang

    2015-08-28

    Seventeen new labdane-type diterpenoids, scapairrins A-Q (1-17), including six pairs of diastereoisomers, and three known analogues (18-20) were isolated from the Chinese liverwort Scapania irrigua. The structures of 1-17 were determined based on a combination of the analysis of their MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Cytotoxicity testing showed that compounds 7-10 exhibited inhibitory activities against a small panel of human cancer cell lines. PMID:26252628

  10. A novel isopimarane diterpenoid with acetylcholinesterase inhibitory activity from Nepeta sorgerae, an endemic species to the Nemrut Mountain.

    PubMed

    Yilmaz, Anil; Cağlar, Pinar; Dirmenci, Tuncay; Gören, Nezhun; Topçu, Gülaçti

    2012-06-01

    From the dichloromethane extract of Nepeta sorgerae, the isolation and structure elucidation are now reported of a new isopimarane diterpenoid, named sorgerolone, and two known triterpenoids, oleanolic acid and ursolic acid. Antioxidant activity of the extracts and the isolated terpenoids was determined by the DPPH free radical scavenging and lipid peroxidation inhibition (beta-carotene bleaching) methods. Anticholinesterase activity of the extracts and isolates was investigated by Ellman's method against AChE and BChE enzymes. Although the antioxidant activity results were low, the AChE enzyme inhibition of the extracts and terpenoids was very promising. PMID:22816286

  11. Immunomodulatory Effect of Marine Cembrane-Type Diterpenoids on Dendritic Cells

    PubMed Central

    Lin, Ching-Yen; Lu, Mei-Chin; Su, Jui-Hsin; Chu, Ching-Liang; Shiuan, David; Weng, Ching-Feng; Sung, Ping-Jyun; Huang, Kao-Jean

    2013-01-01

    Dendritic cells (DCs) are antigen presenting cells, which can present antigens to T-cells and play an important role in linking innate and adaptive immunity. DC maturation can be induced by many stimuli, including pro-inflammatory cytokines and bacterial products, such as lipopolysaccharides (LPS). Here, we examined the immunomodulatory effects of marine cembrane compounds, (9E,13E)-5-acetoxy-6-hydroxy-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (1), (9E,13E)-5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (2), lobocrassin B (3), (−)14-deoxycrassin (4), cembranolide B (5) and 13-acetoxysarcocrassolide (6) isolated from a soft coral, Lobophytum crassum, on mouse bone marrow-derived dendritic cells (BMDCs). The results revealed that cembrane-type diterpenoids, especially lobocrassin B, effectively inhibited LPS-induced BMDC activation by inhibiting the production of TNF-α. Pre-treatment of BMDCs with Lobocrassin B for 1 h is essential to prohibit the following activation induced by various toll-like receptor (TLR) agonists, such as LPS, zymosan, lipoteichoic acid (LTA) and Pam2CSK4. Inhibition of NF-κB nuclear translocation by lobocrassin B, which is a key transcription factor for cytokine production in TLR signaling, was evident as assayed by high-content image analysis. Lobocrassin B attenuated DC maturation and endocytosis as the expression levels of MHC class II and the co-stimulatory molecules were downregulated, which may affect the function of DCs to initiate the T-cell responses. Thus, lobocrassin B may have the potential in treatment of immune dysregulated diseases in the future. PMID:23609581

  12. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation.

    PubMed

    Thisoda, Piengpen; Rangkadilok, Nuchanart; Pholphana, Nanthanit; Worasuttayangkurn, Luksamee; Ruchirawat, Somsak; Satayavivad, Jutamaad

    2006-12-28

    Andrographis paniculata has been widely used for the prevention and treatment of common cold especially in Asia and Scandinavia. The three active diterpenoids from this plant, including aqueous plant extracts, were investigated for the inhibitory effect on platelet aggregation in vitro. The results indicated that andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3)) significantly inhibited thrombin-induced platelet aggregation in a concentration-(1-100 microM) and time-dependent manner while neoandrographolide (AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the results indicated that the inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two compounds. In addition, standardized aqueous extracts of A. paniculata containing different amounts of AP(3) inhibited thrombin-induced aggregation to different degrees. The extracts significantly decreased platelet aggregation in a concentration-(10-100 microg/ml) and time-dependent manner. However, the extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml) showed less inhibitory activity against thrombin than the extract with lower level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results indicate that the standardized A. paniculata extract may contain other antiplatelet compounds rather than AP(1) and AP(3), which contribute to high antiplatelet activity. Therefore, the consumption of A. paniculata products may help to prevent or treat some cardiovascular disorders i.e. thrombosis; however, it should be used with caution by patients with bleeding disorders. PMID:17081514

  13. Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages.

    PubMed

    Mon, Htwe H; Christo, Susan N; Ndi, Chi P; Jasieniak, Marek; Rickard, Heather; Hayball, John D; Griesser, Hans J; Semple, Susan J

    2015-12-24

    The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management. PMID:26636180

  14. Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells.

    PubMed

    Bao, Han; Zhang, Le-Le; Liu, Qian-Yu; Feng, Lu; Ye, Yang; Lu, Jin-Jian; Lin, Li-Gen

    2016-01-01

    The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC50 values of 9.9 ± 1.6 µM, 12.2 ± 6.5 µM, 5.3 ± 1.9 µM, and 12.3 ± 3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What's more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed. PMID:27322234

  15. Distribution and carbon isotope patterns of diterpenoids and triterpenoids in modern temperate C3 trees and their geochemical significance

    NASA Astrophysics Data System (ADS)

    Diefendorf, Aaron F.; Freeman, Katherine H.; Wing, Scott L.

    2012-05-01

    Tricyclic diterpenoids and pentacyclic triterpenoids are nearly exclusively produced by gymnosperms and angiosperms, respectively. Even though both classes of terpenoids have long been recognized as plant biomarkers, their potential use as phylogenetically specific δ13C proxies remains largely unexplored. Little is known of how terpenoid abundance and carbon isotope composition vary either with plant phylogenetic position, functional group, or during synthesis. Here, we report terpenoid abundances and isotopic data for 44 tree species in 21 families, representing both angiosperms and gymnosperms, and both deciduous and evergreen leaf habits. Di- and triterpenoid abundances are significantly higher in evergreens compared to deciduous species, reflecting differences in growth strategies and increased chemical investment in longer-lived leaves. Carbon isotope abundances of terpenoid lipids are similar to leaf tissues, indicating biosynthetic isotope effects are small for both the MVA (-0.4‰) and MEP (-0.6‰) pathways. Leaf and molecular isotopic patterns for modern plants are consistent with observations of amber, resins and plant biomarkers in ancient sediments. The δ13C values of ancient diterpenoids are higher than triterpenoids by 2-5‰, consistent with observed isotopic differences between gymnosperms and angiosperms leaves, and support the relatively small lipid biosynthetic effects reported here. All other factors being equal, evergreen plants will dominate the abundance of terpenoids contributed to soils, sediments and ancient archives, with similar inputs estimated for angiosperm and gymnosperm trees when scaled by litter flux.

  16. Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer.

    PubMed

    Li, Dahong; Han, Tong; Tian, Kangtao; Tang, Shuang; Xu, Shengtao; Hu, Xu; Wang, Lei; Li, Zhanlin; Hua, Huiming; Xu, Jinyi

    2016-09-01

    Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a-f and 15a-f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50 of 0.86, 1.74, 1.16 and 3.75μM, respectively, and could produce high level (above 25μM) of NO at the time point of 60min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of anticancer agents. PMID:27491707

  17. The diterpenoid ent-16-kauren-19-oic acid acts as an uncoupler of the bacterial respiratory chain.

    PubMed

    Torres-Bustos, Janet; Farías, Leonardo; Urzúa, Alejandro; Mendoza, Leonora; Wilkens, Marcela

    2009-06-01

    ent-16-Kauren-19-oic acid is a bacteriolytic diterpenoid present in the resin of the medicinal plant Pseudognaphalium vira vira. The compound and its methyl ester showed strong activity against gram-positive bacteria, whereas the derivative 3beta-hydroxy-ent-kauren-19-oic acid was inactive against all assayed bacteria at the maximal concentration used (250 microg/mL). The bacteriolytic effect of ent-16-kauren-19-oic acid (5 microg/mL) was confirmed with cultures of Bacillus cereus and Staphylococcus aureus, whereas the methyl derivative (12 microg/mL) showed only a bacteriostatic effect. Both compounds stimulated oxygen consumption and proton conduction of whole cells, as reflected by an abrupt increase in the extracellular pH. These results indicate that ent-16-kauren-19-oic acid acts as a respiratory chain uncoupler, and that this function is strongly affected by minor structural substitutions, suggesting a tight activity-structure relationship. The ultimate effect of the uncoupling mechanism demonstrated by ent-16-kauren-19-oic acid is bacterial lysis. The disruption of the bacterial membrane integrity caused by the diterpenoid compound was determined using SYTOX Green stain and visualized by fluorescence microscopy. PMID:19296427

  18. Different AhR binding sites of diterpenoid ligands from Andrographis paniculata caused differential CYP1A1 induction in primary culture in mouse hepatocytes.

    PubMed

    Chatuphonprasert, Waranya; Remsungnen, Tawun; Nemoto, Nobuo; Jarukamjorn, Kanokwan

    2011-12-01

    Andrographis paniculata has been employed as a folklore remedy. Andrographolide (Andro), 14-deoxy-11,12-didehydroandrographolide (DHA), andrographiside (AS), and neoandrographolide (Neo), are major diterpenoids isolated from this plant. In the present study, influence of the four diterpenoids on CYP1A1 mRNA expression was investigated in primary cultured mouse hepatocytes. Additionally, binding of these compounds to aryl hydrocarbon receptor (AhR) was examined using molecular docking analysis to clarify mechanism of CYP1A1 induction. Andro and DHA induced CYP1A1 expression by itself, and co-treatment with a CYP1A1 inducer (BNF, beta-naphthoflavone) showed a synergistic increase of CYP1A1 expression. Andro demonstrated higher enhancing activity than DHA at every similar concentration. On the other hand, Neo suppressed BNF-induced CYP1A1 expression, but AS did not modify the induction. Results from molecular docking analysis of BNF and four diterpenoids on ligand binding domain of AhR were consistent with levels of CYP1A1 mRNA expressions. Furthermore, difference of binding sites of BNF in the presence of diterpenoids might affect the synergism or inhibition of CYP1A1 expression. These results suggest that use of A. paniculata as a health supplement should be concerned in term of herb-drugs interactions or risk of carcinogenesis, according to its ability to influence CYP1A1 expression. PMID:21963808

  19. Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells.

    PubMed

    Jo, Si-Kyoung; Hong, Ji-Young; Park, Hyen Joo; Lee, Sang Kook

    2012-11-01

    Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the IC50 values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers. PMID:24009843

  20. Biosynthesis of the Diterpenoid Lycosantalonol via Nerylneryl Diphosphate in Solanum lycopersicum

    PubMed Central

    Matsuba, Yuki; Zi, Jiachen; Jones, A. Daniel; Peters, Reuben J.; Pichersky, Eran

    2015-01-01

    We recently reported that three genes involved in the biosynthesis of monoterpenes in trichomes, a cis-prenyltransferase named neryl diphosphate synthase 1 (NDPS1) and two terpene synthases (TPS19 and TPS20), are present in close proximity to each other at the tip of chromosome 8 in the genome of the cultivated tomato (Solanum lycopersicum). This terpene gene “cluster” also contains a second cis-prenyltransferase gene (CPT2), three other TPS genes, including TPS21, and the cytochrome P450-oxidoreductase gene CYP71BN1. CPT2 encodes a neryneryl diphosphate synthase. Co-expression in E. coli of CPT2 and TPS21 led to the formation of the diterpene lycosantalene, and co-expression in E. coli of CPT2, TPS21 and CYP71BN1 led to the formation of lycosantalonol, an oxidation product of lycosantalene. Here we show that maximal expression of all three genes occurs in the petiolule part of the leaf, but little expression of these genes occurs in the trichomes present on the petiolules. While lycosantalene or lycosantalonol cannot be detected in the petiolules of wild-type plants (or anywhere else in the plant), lycosantalene and lycosantalonol are detected in petiolules of transgenic tomato plants expressing CPT2 under the control of the 35S CaMV promoter. These results suggest that lycosantalene and lycosantalonol are produced in the petiolules and perhaps in other tissues of wild-type plants, but that low rate of synthesis, controlled by the rate-limiting enzyme CPT2, results in product levels that are too low for detection under our current methodology. It is also possible that these compounds are further modified in the plant. The involvement of CPT2, TPS21 and CYP71BN1 in a diterpenoid biosynthetic pathway outside the trichomes, together with the involvement of other genes in the cluster in the synthesis of monoterpenes in trichomes, indicates that this cluster is further evolving into “sub-clusters” with unique biochemical, and likely physiological, roles. PMID

  1. Recombination of diterpenoid structure units: synthesis of antitumor amides bearing functionalized bicyclo[3.2.1]octane ring.

    PubMed

    Mao, Zewei; Li, Yan; Chen, Jingbo; Wang, Yuanyuan; Zhang, Hongbin

    2010-07-15

    In this work, 23 new amides (14-36) bearing a representative diterpenoid structure unit, the functionalized bicyclo[3.2.1]octane ring, have been synthesized and its antitumor potential is studied. In vitro studies demonstrate that a number of amides with the bicyclo[3.2.1]oct-3-en-2-one subunit are active against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 tumor cell lines. The hybrid derivative, compound 20, was found to be the most potent compound (IC(50)=1.05 microM against HL-60) and more active than cisplatin (DDP), the positive control. Additionally, compound 20 exhibited broad spectrum in vitro anticancer activity with IC(50) values of 1.1-4.3 microM against the five tested cancer cell lines. PMID:20621726

  2. Cassane-type diterpenoids from Caesalpinia echinata (Leguminosae) and their NF-κB signaling inhibition activities.

    PubMed

    Mitsui, Taichi; Ishihara, Risa; Hayashi, Ken-ichiro; Matsuura, Nobuyasu; Akashi, Haruo; Nozaki, Hiroshi

    2015-08-01

    Fourteen cassane-type diterpenoids, echinalides H-U, were isolated from the stem of Caesalpinia echinata Lam. (Leguminosae). The structures of the echinalides were elucidated by spectroscopic investigation, including 2D NMR spectroscopic analysis. The structures of echinalide H and echinalide T were further confirmed by single-crystal X-ray diffraction. The absolute configurations of echinalides H, I, J and K were determined by CD spectroscopy. Additionally, the absolute configurations of echinalide L and M were determined by chemical conversion from echinalide H. These compounds were evaluated for inhibitory activity against nuclear factor κB (NF-κB). Echinalide M showed the most potent inhibitory activity (47±11% at 5μM) toward NF-κB-responsive gene expression. PMID:25886884

  3. Antimicrobial Activity of neo-Clerodane Diterpenoids isolated from Lamiaceae Species against Pathogenic and Food Spoilage Microorganisms.

    PubMed

    Bozov, Petko; Girova, Tania; Prisadova, Natalia; Hristova, Yana; Gochev, Velizar

    2015-11-01

    Antimicrobial activity of nineteen neo-clerodane diterpenoids, isolated from the acetone extracts of the aerial parts of Scutellaria and Salvia species (Lamiaceae) were tested against thirteen strains belonging to nine different species of pathogenic and food spoilage bacteria Aeromonas hydrophila, Bacillus cereus, Escherichia coli, Listeria monocytogenes, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella abony and Staphylococcus aureus as well as against two yeast strains belonging to species Candida albicans. Seven of the evaluated compounds scutalpin A, scutalpin E, scutalpin F, salviarin, splenolide A, splenolide B and splendidin demonstrated antimicrobial activity against used test microbial strains, the rest of the compounds were inactive within the studied concentration range. Among all of the tested compounds the highest antimicrobial activity was detected for scutalpin A against Staphylococcus aureus (MIC 25 µg/mL). PMID:26749799

  4. Kujigamberol, a new dinorlabdane diterpenoid isolated from 85million years old Kuji amber using a biotechnological assay.

    PubMed

    Kimura, Ken-ichi; Minamikawa, Yuki; Ogasawara, Yukiko; Yoshida, Jun; Saitoh, Kei-ichi; Shinden, Hisao; Ye, Yue Qi; Takahashi, Shunya; Miyakawa, Tokichi; Koshino, Hiroyuki

    2012-07-01

    A new compound, 15,20-dinor-5,7,9-labdatriene-18-ol (1), named kujigamberol, was isolated from amber, fossilized tree resin from the Kuji area in Japan, has been dated as being 85 million years old (late Cretaceous). Kujigamberol was identified using the hypersensitive mutant yeast (zds1∆ erg3∆ pdr1∆ pdr3∆) with respect to Ca(2+)-signal transduction. The structure was elucidated on the basis of spectroscopic analysis including 1D NMR, 2D NMR and HR-EI-MS. It was different from known diterpenoids with a similar activity isolated from Baltic amber (agathic acid 15-monomethyl ester (2), dehydroabietic acid (3) and pimaric acid (4)). Kujigamberol showed glycogen synthase kinase-3β (GSK-3β) inhibition activity involving the growth restored activity against the mutant yeast and was cytotoxic to HL60 cells (IC(50)=19.6 μM). PMID:22507387

  5. Higginsianins A and B, Two Diterpenoid α-Pyrones Produced by Colletotrichum higginsianum, with in Vitro Cytostatic Activity.

    PubMed

    Cimmino, Alessio; Mathieu, Veronique; Masi, Marco; Baroncelli, Riccardo; Boari, Angela; Pescitelli, Gennaro; Ferderin, Marlène; Lisy, Romana; Evidente, Marco; Tuzi, Angela; Zonno, Maria Chiara; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio

    2016-01-22

    Two new diterpenoid α-pyrones, named higginsianins A (1) and B (2), were isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)dodecahydronaphtho[2,1-b]furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)decahydronaphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (1) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (2), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. 1 and 2 were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of 1 and 2 for antiproliferative activity against a panel of six cancer cell lines revealed that the IC50 values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 μM). Finally, three hemisynthetic derivatives of 1 were prepared and evaluated for antiproliferative activity. Two of these possessed IC50 values and differential sensitivity profiles similar to those of 1. PMID:26697898

  6. Exploring the ester-exchange reactions of diester-diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry.

    PubMed

    Wang, Yong; Shi, Lei; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2003-01-01

    The chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester-exchange reactions for aconitine-type diester-diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of mesaconitine and hypaconitine standards with liquorice root. It was found that diester-diterpenoid aconitines were converted into lipo-alkaloids as well as monoester alkaloids by the decoction of aconite. PMID:12569436

  7. A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids.

    PubMed

    King, Andrew J; Brown, Geoffrey D; Gilday, Alison D; Forestier, Edith; Larson, Tony R; Graham, Ian A

    2016-09-01

    The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi-jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon-carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6-hydroxy-5,9-diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant. PMID:27272333

  8. HPLC-UV and HPLC-positive-ESI-MS analysis of the diterpenoid fraction from caper spurge (Euphorbia lathyris) seed oil.

    PubMed

    Bicchi, C; Appendino, G; Cordero, C; Rubiolo, P; Ortelli, D; Veuthey, J L

    2001-01-01

    Caper spurge (Euphorbia lathyris L.) seed oil contains a series of diterpenoids known as Euphorbia factors, or L-factors, L1-L9. They are esters of several polyols (lathyrol, epoxylathyrol, hydroxylathyrol and ingenol) and account for about 3-5% of the oil. The percentage of ingenol-based L-factors is very low, less than 5% of the diterpenoid fraction, but some of them (factors L5 and L6) are responsible for the irritant and co-carcinogenic activities of the oil. This paper reports an HPLC-UV and HPLC-positive-ESI-MS analysis of the diterpenoid fraction of caper spurge seed oil before and after selective hydrolysis of ingenol-based L-factors. Separation of lathyrane polyols and esters, and ingenol and its esters was achieved using a chromatographic system consisting of a C18 stationary phase and acetonitrile: water as mobile phase. A new macrocyclic constituent, the deoxy Euphorbia factor L1, was identified in the oil. PMID:11705332

  9. ent-kaurane diterpenoids from Croton tonkinensis induce apoptosis in colorectal cancer cells through the phosphorylation of JNK mediated by reactive oxygen species and dual-specificity JNK kinase MKK4.

    PubMed

    Thuong, Phuong Thien; Khoi, Nguyen Minh; Ohta, Saho; Shiota, Shinichiro; Kanta, Hironori; Takeuchi, Kenji; Ito, Fumiaki

    2014-01-01

    To search for new chemotherapeutic agents to treat colorectal cancer, we isolated a number of natural ent-kaurane diterpenoids from the plant Croton tonkinensis. Among them, only CeKDs with the 15-oxo-16-ene moiety induced the apoptosis of colorectal cancer cell lines Caco-2 and LS180. The active CeKD induced the activation of ERK and JNK, but the inactive ones induced that of ERK, but not that of JNK. It thus appears that JNK seemed to play an important role in the apoptotic activity of the active compounds. The dualspecificity JNK kinase MKK4 was activated in both colorectal cancer cells treated with the active CeKD, but MKK7 was not activated. Further, the active CeKD, but not the inactive one, enhanced the generation of intracellular reactive oxygen species (ROS) in both cells. CeKD-induced cell apoptosis and ROS generation, as well as JNK activation, were inhibited by the antioxidant N-acetyl-L-cysteine. These findings suggest that ROS stimulated the phosphorylation of JNK mediated by MKK4 and played a critical role in CeKD-induced apoptosis in colorectal cancer cells. PMID:24476312

  10. Structure elucidation of organic compounds from natural sources using 1D and 2D NMR techniques

    NASA Astrophysics Data System (ADS)

    Topcu, Gulacti; Ulubelen, Ayhan

    2007-05-01

    In our continuing studies on Lamiaceae family plants including Salvia, Teucrium, Ajuga, Sideritis, Nepeta and Lavandula growing in Anatolia, many terpenoids, consisting of over 50 distinct triterpenoids and steroids, and over 200 diterpenoids, several sesterterpenoids and sesquiterpenoids along with many flavonoids and other phenolic compounds have been isolated. For Salvia species abietanes, for Teucrium and Ajuga species neo-clerodanes for Sideritis species ent-kaurane diterpenes are characteristic while nepetalactones are specific for Nepeta species. In this review article, only some interesting and different type of skeleton having constituents, namely rearranged, nor- or rare diterpenes, isolated from these species will be presented. For structure elucidation of these natural diterpenoids intensive one- and two-dimensional NMR techniques ( 1H, 13C, APT, DEPT, NOE/NOESY, 1H- 1H COSY, HETCOR, COLOC, HMQC/HSQC, HMBC, SINEPT) were used besides mass and some other spectroscopic methods.

  11. NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins.

    PubMed

    Li, Dahong; Hu, Xu; Han, Tong; Liao, Jie; Xiao, Wei; Xu, Shengtao; Li, Zhanlin; Wang, Zhenzhong; Hua, Huiming; Xu, Jinyi

    2016-01-01

    A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a-i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a-i also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations. PMID:27617998

  12. hERG Channel Inhibitory Daphnane Diterpenoid Orthoesters and Polycephalones A and B with Unprecedented Skeletons from Gnidia polycephala.

    PubMed

    De Mieri, Maria; Du, Kun; Neuburger, Markus; Saxena, Priyanka; Zietsman, Pieter C; Hering, Steffen; van der Westhuizen, Jan H; Hamburger, Matthias

    2015-07-24

    The hERG channel is an important antitarget in safety pharmacology. Several drugs have been withdrawn from the market or received severe usage restrictions because of hERG-related cardiotoxicity. In a screening of medicinal plants for hERG channel inhibition using a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a dichloromethane extract of the roots of Gnidia polycephala reduced the peak tail hERG current by 58.8 ± 13.4% (n = 3) at a concentration of 100 μg/mL. By means of HPLC-based activity profiling daphnane-type diterpenoid orthoesters (DDOs) 1, 4, and 5 were identified as the active compounds [55.4 ± 7.0% (n = 4), 42.5 ± 16.0% (n = 3), and 51.3 ± 9.4% (n = 4), respectively, at 100 μM]. In a detailed phytochemical profiling of the active extract, 16 compounds were isolated and characterized, including two 2-phenylpyranones (15 and 16) with an unprecedented tetrahydro-4H-5,8-epoxypyrano[2,3-d]oxepin-4-one skeleton, two new DDOs (3 and 4), two new guaiane sesquiterpenoids (11 and 12), and 10 known compounds (1, 2, 5-10, 13, and 14). Structure elucidation was achieved by extensive spectroscopic analysis (1D and 2D NMR, HRMS, and electronic circular dichroism), computational methods, and X-ray crystallography. PMID:26091146

  13. Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells

    PubMed Central

    KANG, NING; CAO, SHI-JIE; ZHOU, YAN; HE, HAO; TASHIRO, SHIN-ICHI; ONODERA, SATOSHI; QIU, FENG; IKEJIMA, TAKASHI

    2015-01-01

    Rabdosia rubescens, a commonly used traditional Chinese medicine, has increasingly gained attention for its use as an antitumor herb. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been reported to induce apoptosis in human laryngeal cancer HEp-2 cells by our group. Here, we made unexpected observations that the caspase-9 inhibitor (C9i) enhanced apoptosis in response to selected stimuli, and HEp-2 cells which were made deficient in caspase-9 using siRNA exhibited no resistance to apoptotic signals and actually demonstrated increased apoptotic sensitivity to oridonin. The results were reversed by the transfection of an exogenous caspase-9 expression vector. Caspase-9 reduced sensitivity to apoptotic stimuli through reactive oxygen species (ROS)-suppressing and autophagy-promoting methods. ROS triggered the progression of apoptosis through activation of both the caspase-9-independent mitochondrial pathway and death receptor pathways, and the autophagy had an anti-apoptotic function in oridonin-treated HEp-2 cells. These collective results suggest that oridonin targets caspase-9 to alter ROS production and autophagy situation to promote HEp-2 cell apoptosis. Therefore, oridonin has the potential to be developed as an anticancer agent, and the combination of oridonin with those agents leading to reduction of caspase-9 expression in tumor cells could represent a novel approach to human laryngeal cancer treatment. PMID:26648189

  14. Six new cytotoxic and anti-inflammatory 11, 20-epoxy-ent-kaurane diterpenoids from Isodon wikstroemioides.

    PubMed

    Wu, Hai-Yan; Wang, Wei-Guang; Du, Xue; Yang, Jin; Pu, Jian-Xin; Sun, Han-Dong

    2015-05-01

    The present study was designed to determine the chemical constituents of EtOAc extracts of the aerial parts of Isodon wikstroemioides. Compounds 1-8 were isolated and purified by normal-phase silica gel and reversed-phase C18silica gel column chromatography and HPLC. Their structures were elucidated by extensive spectroscopic methods. Most of them were evaluated for their in vitro cytotoxicity against human cancer HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cells and their inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. Among the eight 11, 20-epoxy-ent-kauranoids isolated, compounds 1-6 (isowikstroemins H-M) were new diterpenoids. Compounds 1, 3, and 7 exhibited significant cytotoxicity with IC50 values ranging from (0.84 ± 0.02) to (4.09 ± 0.34) μmol · L(-1), while compounds 4 and 5 showed selective cytotoxicity. In addition, compounds 1, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. These results provide a basis for future development of these compounds as anti-cancer and anti-inflammatory agents. PMID:25986288

  15. Natural compounds in the synthesis of chiral organophosphorous ligands

    NASA Astrophysics Data System (ADS)

    Tolstikov, Alexander G.; Khlebnikova, Tatiana B.; Tolstikova, Olga V.; Tolstikov, Genrikh A.

    2003-09-01

    Methods for the synthesis of chiral organophosphorus compounds based on natural optically active compounds (hydroxy acids, amino acids and their derivatives, mono- and disaccharides, mono- and diterpenoids, steroids) are discussed. Particular attention is given to the synthesis of bisphosphines and bisphosphinites. These compounds serve as ligands for transition metal complexes, which catalyse asymmetric hydrogenation. Data on the enantioselectivity of hydrogenation of unsaturated precursors of amino acids and unsaturated prochiral acids as well as on information on the enantioselectivity of hydrosilylation of ketones are surveyed.

  16. Simultaneous determination of seven major diterpenoids in Siegesbeckia pubescens Makino by high-performance liquid chromatography coupled with evaporative light scattering detection.

    PubMed

    Huo, Linan; Jiang, Zhen; Li, Huining; Wang, Mingsheng; Ye, Xiaoxia; Ji, Bin; Guo, Xingjie

    2012-10-01

    A novel HPLC method with evaporative light scattering detection was developed for the simultaneous quantification of seven major diterpenoids of two types, including ent-pimarane type: Kirenol, Hythiemoside B, Darutigenol, and ent-kaurane type: ent-16β,17,18-trihydroxy-kauran-19-oic acid, ent-17,18-dihydroxy-kauran-19-oic acid, ent-16β,17-dihydroxy-kauran-19-oic acid, 16α-hydro-ent-kauran-17,19-dioic acid in the aerial parts of Siegesbeckia pubescens Makino, an important traditional Chinese medicinal herb. Chromatographic separation was achieved on a Waters Symmetry Shield(TM) RP18 column (250 mm× 4.6 mm id, 5 μm) with a gradient mobile phase (A: 0.3% v/v aqueous formic acid and B: acetonitrile) at a flow rate of 1.0 mL/min. The drift tube temperature of evaporative light scattering detection was set at 103°C, and nitrogen flow rate was 3.0 L/min. The method was validated for accuracy, precision, LOD, and LOQ. All calibration curves showed a good linear relationship (r > 0.999) in test range. Precision was evaluated by intra- and interday tests that showed RSDs were less than 3.5%. Accuracy validation showed that the recovery was between 96.5 and 102.0% with RSDs below 2.8%. The validated method was successfully applied to determine the contents of seven diterpenoids in the different parts of Siegesbeckia pubescens Makino from two sources and to determine the contents of ent-pimarane, ent-kaurane, and total diterpenoids. PMID:22887919

  17. CYP701A8: A Rice ent-Kaurene Oxidase Paralog Diverted to More Specialized Diterpenoid Metabolism1[W][OA

    PubMed Central

    Wang, Qiang; Hillwig, Matthew L.; Wu, Yisheng; Peters, Reuben J.

    2012-01-01

    All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice. PMID:22247270

  18. Overexpression of the bZIP transcription factor OsbZIP79 suppresses the production of diterpenoid phytoalexin in rice cells.

    PubMed

    Miyamoto, Koji; Nishizawa, Yoko; Minami, Eiichi; Nojiri, Hideaki; Yamane, Hisakazu; Okada, Kazunori

    2015-01-15

    Phytoalexins are antimicrobial specialised metabolites that are produced by plants in response to pathogen attack. Momilactones and phytocassanes are major diterpenoid phytoalexins in rice that are synthesised from geranylgeranyl diphosphate that is derived from the methylerythritol phosphate (MEP) pathway. We have previously reported that rice cells overexpressing the basic leucine zipper (bZIP) transcription factor OsTGAP1 exhibit a hyperaccumulation of momilactones and phytocassanes, with hyperinductive expression of momilactone and phytocassane biosynthetic genes and MEP pathway genes, upon response to a chitin oligosaccharide elicitor. For a better understanding of OsTGAP1-mediated regulation of diterpenoid phytoalexin production, we identified OsTGAP1-interacting proteins using yeast two-hybrid screening. Among the OsTGAP1-interacting protein candidates, a TGA factor OsbZIP79 was investigated to verify its physical interaction with OsTGAP1 and involvement in the regulation of phytoalexin production. An in vitro pull-down assay demonstrated that OsTGAP1 and OsbZIP79 exhibited a heterodimeric as well as a homodimeric interaction. A bimolecular fluorescence complementation analysis also showed the interaction between OsTGAP1 and OsbZIP79 in vivo. Intriguingly, whereas OsbZIP79 transactivation activity was observed in a transient reporter assay, the overexpression of OsbZIP79 resulted in suppression of the elicitor-inducible expression of diterpenoid phytoalexin biosynthetic genes, and thus caused a decrease in the accumulation of phytoalexin in rice cells. These results suggest that OsbZIP79 functions as a negative regulator of phytoalexin production triggered by a chitin oligosaccharide elicitor in rice cells, although it remains open under which conditions OsbZIP79 can work with OsTGAP1. PMID:25462074

  19. New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin "ladano" of Cistus creticus.

    PubMed

    Kalpoutzakis, E; Aligiannis, N; Mitaku, S; Chinou, I; Harvala, C; Skaltsounis, A L

    2001-01-01

    The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes derived from the two major natural compounds 3 and 4 of the resin "ladano" of Cistus creticus is reported. The chloroethyl carbamidic esters 15 and 20 showed the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and pathogenic fungi. PMID:11302213

  20. ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.

    PubMed

    Liu, Zhi-guo; Li, Zhan-lin; Li, Da-Hong; Li, Ning; Bai, Jiao; Zhao, Feng; Meng, Da-li; Hua, Hui-ming

    2016-01-01

    Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88μM, respectively. A primary structure-activity relationship was also discussed. PMID:26615888

  1. Kaurane-type diterpenoids from Chromoleana odorata, their X-ray diffraction studies and potent α-glucosidase inhibition of 16-kauren-19-oic acid.

    PubMed

    Wafo, Pascal; Kamdem, Ramsay S T; Ali, Zulfiqar; Anjum, Shazia; Begum, Afshan; Oluyemisi, Ogbole O; Khan, Shamsun N; Ngadjui, Bonaventure T; Etoa, Xavier F; Choudhary, Muhammed Iqbal

    2011-06-01

    A new diterpenoid, 15-angeloyloxy-16,17-epoxy-19-kauronic acid (1), along with five known metabolites, 16-kauren-19-oic acid (2), 6'-hydroxy-2',3',4,4'-tetramethoxychalcone (3), isosakuranetin (4), acacetin (5), and kaempferide (6) was isolated from the organic extracts of the roots of Chromoleana odorata. Their structures were determined by spectroscopic evidences. The structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction studies. Compound 2 exhibited significant α-glucosidase inhibitory and antibacterial activities against Escherichia coli and Bacillus subtilis. PMID:21316426

  2. Inhibition of the gastric H+,K+ -ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews.

    PubMed

    Schultz, Carla; Bossolani, Myllene P; Torres, Luce M B; Lima-Landman, Maria Teresa R; Lapa, Antonio J; Souccar, Caden

    2007-04-20

    This work assessed the mechanism underlying the antisecretory gastric acid effect of Plectranthus barbatus Andrews (Lamiaceae) and active constituents. Popularly known as "false-boldo", this plant is used in Brazilian folk medicine to treat gastrointestinal and hepatic ailments. The plant aqueous extract (AE) and isolated compounds were assayed in vivo in pylorus-ligated mice, and in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands and gastric H(+),K(+)-ATPase preparations. Injected into the duodenal lumen, the AE of the plant leaves (0.5 and 1.0 g/kg) decreased the volume (62 and 76%) and total acidity (23 and 50%) of gastric acid secretion in pylorus-ligated mice. Bioguided purification of the AE yielded an active fraction (IC(50)=24 microg/ml) that inhibited acid secretion in rabbit gastric glands with a potency 10 to 18 times greater than that of the originating extract, on both the basal and stimulated acid secretion by histamine (His) (1 microM) or bethanechol (100 microM). At the same concentrations the gastric H(+),K(+)-ATPase activity was also inhibited. The active constituent was chemically identified as the abietanoid dienedione plectrinone A which reduced the H(+),K(+)-ATPase activity with IC(50)=171 microM. The results indicate that inhibition of the gastric proton pump by this diterpenoid may account for the antisecretory acid effect and reputed anti ulcer activity of Plectranthus barbatus. PMID:17166678

  3. Bioassay-guided isolation of an anti-ulcer diterpenoid from Croton reflexifolius: role of nitric oxide, prostaglandins and sulfhydryls.

    PubMed

    Reyes-Trejo, Benito; Sánchez-Mendoza, María Elena; Becerra-García, Anabel Ariana; Cedillo-Portugal, Ernestina; Castillo-Henkel, Carlos; Arrieta, Jesús

    2008-07-01

    Croton reflexifolius H. B. K (Euphorbiaceae) is a very common medicinal plant in the Huastecan region of Mexico that, according to local folk medicine, is considered useful in the treatment of gastritis and gastric ulcer. We have aimed to test the validity of this practice by using the experimental model of an ethanol-induced gastric ulcer in male Wistar rats. The results showed that C. reflexifolius had gastroprotector activity, that the hexane extract had the highest protective activity (64.38+/-7.72%), and that polyalthic acid isolated from this extract was the main active gastroprotector agent. Rats treated orally with polyalthic acid showed a gastroprotective effect similar to that elicited by carbenoxolone. As with carbenoxolone, the effect elicited by polyalthic acid was attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mgkg(-1), i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mgkg(-1), s.c.), a blocker of sulfhydryl groups. This suggested that the gastroprotective mechanism of this diterpenoid involved the participation of both NO and endogenous sulfhydryl groups. Contrary to carbenoxolone, the gastroprotective effect of polyalthic acid was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mgkg(-1), s. c.). In conclusion, Croton reflexifolius contains compounds with gastroprotector activity. Polyalthic acid, which was isolated from this plant, was the main compound with gastroprotector activity, having effectiveness similar to that found with the use of carbenoxolone. Whereas NO and sulfhydryl groups were involved in the mechanisms of gastroprotective action of polyalthic acid, prostaglandins were not. PMID:18549681

  4. Enantioselective Total Syntheses of Various Amphilectane and Serrulatane Diterpenoids via Cope Rearrangements.

    PubMed

    Yu, Xuerong; Su, Fan; Liu, Chang; Yuan, Haosen; Zhao, Shan; Zhou, Zhiyao; Quan, Tianfei; Luo, Tuoping

    2016-05-18

    Ampilectane and serrulatane natural products are structurally and stereochemically complex compounds that display various potent pharmacological activities ranging from anti-inflammatory to antituberculosis. A general synthetic route toward this family of natural products has been developed, which accomplished a number of amphilectane and serrulatane natural products. The key step employed a stereoselective Cope rearrangement either promoted by gold catalysis or thermal conditions, while a regioselective gold-catalyzed 6-endo-dig cyclization was optimized to afford a precursor. The preparation of the chiral β-ketoester as a starting material was established via an optimized asymmetric 1,4-addition followed by trapping with Mander's reagent, and this initially installed stereogenic center provided good control in the subsequent introduction of all the other stereocenters. A rarely investigated one-pot conversion of α-pyrone into phenol was also examined to enable the syntheses. DFT calculations explain the high stereoselectivity of the Cope rearrangement of the intermediate that eventually led to amphilectolide and caribenol A. PMID:27115064

  5. Toxicity of Porella chilensis sesqui- and diterpenoids against larvae of the corn pest Spodoptera frugiperda (J.E. Smith) (Lepidotera: Noctuidae).

    PubMed

    Corzo, F L; Gilabert, M; Alcaide, M F; Bardón, A

    2012-10-01

    Porella, the largest genus of the family Porellaceae (Hepaticae) is widespread in the tropical and subtropical regions of South America. Most Porella species are rich sources of sesqui- and diterpenoids, many of which show interesting biological activities. Secondary metabolites produced by plants can interact with insects and act as antifeedants and growth regulators affecting hormone and nervous systems as well as stomach and muscle tissues. A previous chemical investigation of a Patagonian collection of Porella chilensis yielded sesqui- and diterpenoids that were now evaluated for their effects against Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), a serious pest affecting corn crops mainly in the Americas. Four pinguisanes (1-4), three fusicoccanes (5-7), and one aromadendrane (8) from P. chilensis displayed larvicidal activity against S. frugiperda when incorporated to the larval diet at 100 and 200 μg/g of diet with a significant decrease in the larval growing rate. The observed effects were in part produced by severe alterations of the epithelial cells of the midgut as indicated by our histological studies. PMID:23950093

  6. Qualitative and quantitative characterization of phenolic and diterpenoid constituents in Danshen (Salvia miltiorrhiza) by comprehensive two-dimensional liquid chromatography coupled with hybrid linear ion trap Orbitrap mass.

    PubMed

    Cao, Ji-Liang; Wei, Jin-Chao; Hu, Yuan-Jia; He, Cheng-Wei; Chen, Mei-Wan; Wan, Jian-Bo; Li, Peng

    2016-01-01

    Danshen is one of the most frequently used traditional Chinese herbs owing to its remarkable and reliable therapeutic effects. Phenolic acids and diterpenoids have proved to be the bioactive substance groups. In order to fully profile its chemical compositions and explore new potential bioactive compounds, a comprehensive two-dimensional liquid chromatography system coupled to DAD detector and hybrid linear ion trap (LTQ) Orbitrap mass spectrometry (LC × LC-DAD-ESI/HRMS/MS(n)) was set up in this study based on the column combination of Hypersil gold CN (150 mm × 1 mm, 3 μm) and Accucore C18 (50 mm × 4.6 mm, 2.6 μm). Using the optimal segment gradient program, phenolic acids and diterpenoids were separated into two independent groups and a total of 328 peaks were successfully detected on the contour plot of Danshen. By means of the accurate mass and reliable MS(n) data, 102 compounds were identified or tentatively identified and 7 of them were discovered from Danshen for the first time. Moreover, the LC × LC-DAD system was validated for the quantitative analysis of 14 bioactive analytes using the contour plot, exhibiting satisfactory linearity (r ≥ 0.9976) and high precision for both peak locating (≤ 1.07%) and peak volume calculating (0.34%-4.11%). The established method could afford powerful separation capability, reliable identification data and accurate quantitative results, which is very suitable for analysis of complex herbal samples. PMID:26687169

  7. Henryin, an ent-kaurane Diterpenoid, Inhibits Wnt Signaling through Interference with β-Catenin/TCF4 Interaction in Colorectal Cancer Cells

    PubMed Central

    Li, Xingyao; Pu, Jianxin; Jiang, Shiyou; Su, Jia; Kong, Lingmei; Mao, Bingyu; Sun, Handong; Li, Yan

    2013-01-01

    Aberrant Wnt/β-catenin signaling has been strongly associated with the tumorigenesis of human colorectal cancer. Inhibitors of this pathway may then offer therapeutic strategies as well as chemoprevention for this malignant disease. Henryin is an ent-kaurane diterpenoid isolated from Isodonrubescens var. lushanensis, a plant long been used in folk medicine to prevent inflammation and gastrointestinal disease. In the present study, we report that henryin selectively inhibits the proliferation of human colorectal cancer cells with a GI50 value in the nano-molar range. Microarray analysis and reporter assays showed that henryin worked as a novel antagonist of Wnt signaling pathway. Henryin reduced the expression of Cyclin D1 and C-myc, and induced G1/S phase arrest in HCT116 cells. Concurrently, henryin did not affect the cytosol-nuclear distribution of soluble β-catenin, but impaired the association of β-catenin/TCF4 transcriptional complex likely through directly blocking the binding of β-catenin to TCF4. We also then analyzed the structure-activity relationship among the ent-kaurane type diterpenoids. Our data suggests that henryin, as a novel inhibitor of Wnt signaling, could be a potential candidate for further preclinical evaluation for colon cancer treatment, and as such warrants further exploration. PMID:23844215

  8. Extraction of three bioactive diterpenoids from Andrographis paniculata: effect of the extraction techniques on extract composition and quantification of three andrographolides using high-performance liquid chromatography.

    PubMed

    Kumar, Satyanshu; Dhanani, Tushar; Shah, Sonal

    2014-10-01

    Andrographis paniculata (Burm.f.) wall.ex Nees (Acanthaceae) or Kalmegh is an important medicinal plant finding uses in many Ayurvedic formulations. Diterpenoid compounds andrographolides (APs) are the main bioactive phytochemicals present in leaves and herbage of A. paniculata. The efficiency of supercritical fluid extraction (SFE) using carbon dioxide was compared with the solid-liquid extraction techniques such as solvent extraction, ultrasound-assisted solvent extraction and microwave-assisted solvent extraction with methanol, water and methanol-water as solvents. Also a rapid and validated reverse-phase high-performance liquid chromatography-diode array detection method was developed for the simultaneous determination of the three biologically active compounds, AP, neoandrographolide and andrograpanin, in the extracts of A. paniculata. Under the best SFE conditions tested for diterpenoids, which involved extraction at 60°C and 100 bar, the extractive efficiencies were 132 and 22 µg/g for AP and neoandrographolide, respectively. The modifier percentage significantly affected the extraction efficiency. PMID:24170124

  9. In vivo and in vitro metabolites from the main diester and monoester diterpenoid alkaloids in a traditional chinese herb, the aconitum species.

    PubMed

    Zhang, Min; Peng, Chong-Sheng; Li, Xiao-Bo

    2015-01-01

    Diester diterpenoid alkaloids (DDAs), such as aconitine (AC), mesaconitine (MA), and hypaconitine (HA), are both pharmacologically active compounds and toxic ingredients in a traditional Chinese herb, the Aconitum species. Many DDA metabolism studies have been performed to explore mechanisms for reducing toxicity in these compounds and in Aconitum species extracts for safe clinical administration. In this review, we summarize recent progress on the metabolism of toxic AC, MA, and HA and corresponding monoester diterpenoid alkaloids (MDAs) in the gastrointestinal tract and liver in different animal species and humans in vivo and/or in vitro, where these alkaloids are primarily metabolized by cytochrome P450 enzymes, carboxylesterases, and intestinal bacteria, which produces phase I metabolites, ester hydrolysed products, and lipoalkaloids. Furthermore, we classify metabolites detected in the blood and urine, where the aforementioned metabolites are absorbed and excreted. Less toxic MDAs and nontoxic alcohol amines are the primary DDA metabolites detected in the blood. Most other DDAs metabolites produced in the intestine and liver detected in the urine have not been reported in the blood. We propose an explanation for this nonconformity. Finally, taking AC, for instance, we generalize a process of toxicity reduction in the body after oral AC administration for the first time. PMID:25705235

  10. A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis paniculata in Human Plasma and Its Application to a Pilot Study.

    PubMed

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Satayavivad, Jutamaad

    2016-01-01

    Andrographis paniculata contains four major active diterpenoids, including andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4), which exhibit differences in types and/or degrees of their pharmacological activity. Previous pharmacokinetic studies in humans reported only the parameters of compound 1 and its analytical method in human plasma. The purpose of this study was to develop a simple, sensitive, and selective liquid chromatography tandem-mass spectrometry technique for the simultaneous determination of all four major active diterpenoids in the A. paniculata product in human plasma. These four diterpenoids in plasma samples were extracted by a simple protein precipitation method with methanol and separated on a Kinetex C18 column using a gradient system with a mobile phase of acetonitrile and water. The liquid chromatography tandem-mass spectrometry was performed in the negative mode, and the multiple reaction monitoring mode was used for the quantitation. The method showed a good linearity over a wide concentration range of 2.50-500 ng/mL for 1 and over the range of 1.00-500 ng/mL for the other diterpenoids with a correlation coefficient R(2) > 0.995. The lower limit of quantification of 1 was found to be 2.50 ng/mL, while those of the other diterpenoids were 1.00 ng/mL. The intraday and interday accuracy (relative error) ranged from 0.03 % to 10.03 %, and the intraday and interday precisions (relative standard deviation) were in the range of 2.05-9.67 %. The extraction recovery (86.54-111.56 %) with a relative standard deviation of 2.78-8.61 % and the matrix effect (85.15-112.36 %) were within the acceptance criteria. Moreover, these four major active diterpenoids were stable in plasma samples at the studied storage conditions with a relative error ≤-9.79 % and a relative standard deviation ≤ 9.26 %. Hence, this present method was successfully validated