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Sample records for lactones isolated frm

  1. Long Chain N-acyl Homoserine Lactone Production by Enterobacter sp. Isolated from Human Tongue Surfaces

    PubMed Central

    Yin, Wai-Fong; Purmal, Kathiravan; Chin, Shenyang; Chan, Xin-Yue; Chan, Kok-Gan

    2012-01-01

    We report the isolation of N-acyl homoserine lactone-producing Enterobacter sp. isolate T1-1 from the posterior dorsal surfaces of the tongue of a healthy individual. Spent supernatants extract from Enterobacter sp. isolate T1-1 activated the biosensor Agrobacterium tumefaciens NTL4(pZLR4), suggesting production of long chain AHLs by these isolates. High resolution mass spectrometry analysis of these extracts confirmed that Enterobacter sp. isolate T1-1 produced a long chain N-acyl homoserine lactone, namely N-dodecanoyl-homoserine lactone (C12-HSL). To the best of our knowledge, this is the first isolation of Enterobacter sp., strain T1-1 from the posterior dorsal surface of the human tongue and N-acyl homoserine lactones production by this bacterium. PMID:23202161

  2. Characterization of N-Acylhomoserine Lactones Produced by Bacteria Isolated from Industrial Cooling Water Systems.

    PubMed

    Okutsu, Noriya; Morohoshi, Tomohiro; Xie, Xiaonan; Kato, Norihiro; Ikeda, Tsukasa

    2015-01-01

    The cooling water systems are used to remove heat generated in the various industries. Biofouling of the cooling water systems causes blocking of condenser pipes and the heat exchanger tubes. In many Gram-negative bacteria, N-acylhomoserine lactone (AHL) are used as quorum-sensing signal molecule and associated with biofilm formation. To investigate the relationship between quorum sensing and biofouling in the cooling water system, we isolated a total of 192 bacterial strains from the five cooling water systems, and screened for AHL production. Seven isolates stimulated AHL-mediated purple pigment production in AHL reporter strain Chromobacterium violaceum CV026 or VIR07. Based on their 16S rRNA gene sequences, AHL-producing isolates were assigned to Aeromonas hydrophila, Lysobacter sp., Methylobacterium oryzae, and Bosea massiliensis. To the best of our knowledge, B. massiliensis and Lysobacter sp. have not been reported as AHL-producing species in the previous researches. AHLs extracted from the culture supernatants of B. massiliensis and Lysobacter sp. were identified by liquid chromatography-mass spectrometry. AHLs produced by B. massiliensis were assigned as N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL), and N-(3-oxooctanoyl)-L-homoserine lactone (3-oxo-C8-HSL). AHLs produced by Lysobacter sp. were assigned as N-decanoyl-L-homoserine lactone (C10-HSL) and N-(3-oxodecanoyl)-L-homoserine lactone (3-oxo-C10-HSL). This is the first report of identification of AHLs produced by B. massiliensis and Lysobacter sp. isolated from the cooling water system. PMID:26729121

  3. Characterization of N-Acylhomoserine Lactones Produced by Bacteria Isolated from Industrial Cooling Water Systems

    PubMed Central

    Okutsu, Noriya; Morohoshi, Tomohiro; Xie, Xiaonan; Kato, Norihiro; Ikeda, Tsukasa

    2015-01-01

    The cooling water systems are used to remove heat generated in the various industries. Biofouling of the cooling water systems causes blocking of condenser pipes and the heat exchanger tubes. In many Gram-negative bacteria, N-acylhomoserine lactone (AHL) are used as quorum-sensing signal molecule and associated with biofilm formation. To investigate the relationship between quorum sensing and biofouling in the cooling water system, we isolated a total of 192 bacterial strains from the five cooling water systems, and screened for AHL production. Seven isolates stimulated AHL-mediated purple pigment production in AHL reporter strain Chromobacterium violaceum CV026 or VIR07. Based on their 16S rRNA gene sequences, AHL-producing isolates were assigned to Aeromonas hydrophila, Lysobacter sp., Methylobacterium oryzae, and Bosea massiliensis. To the best of our knowledge, B. massiliensis and Lysobacter sp. have not been reported as AHL-producing species in the previous researches. AHLs extracted from the culture supernatants of B. massiliensis and Lysobacter sp. were identified by liquid chromatography-mass spectrometry. AHLs produced by B. massiliensis were assigned as N-hexanoyl-l-homoserine lactone (C6-HSL), N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL), and N-(3-oxooctanoyl)-l-homoserine lactone (3-oxo-C8-HSL). AHLs produced by Lysobacter sp. were assigned as N-decanoyl-l-homoserine lactone (C10-HSL) and N-(3-oxodecanoyl)-l-homoserine lactone (3-oxo-C10-HSL). This is the first report of identification of AHLs produced by B. massiliensis and Lysobacter sp. isolated from the cooling water system. PMID:26729121

  4. Activation of antioxidant response element in mouse primary cortical cultures with sesquiterpene lactones isolated from Tanacetum parthenium

    PubMed Central

    Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A.; De Vos, Ric C.H.; Todorović, Slađana; Banjanac, Tijana; Verpoorte, Rob; Johnson, Jeffrey A.

    2012-01-01

    Tanacetum parthenium (Asteraceae) produces biologically active sesquiterpene lactones (SL). Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate a series of genes termed the antioxidant response element (ARE). Activation of the Nrf2/ARE may be useful for the treatment of neurodegenerative disease. In this study we isolated 11 sesquiterpene lactones from T. parthenium with centrifugal partition chromatography and semi-preparative HPLC. Compounds were screened in-vitro for their ability to activate the ARE on primary mouse cortical cultures as well as for their toxicity towards the cultures. All sesquiterpene lactones containing the α-methylene-γ-lactone moiety were able to activate the ARE although a number of compounds displayed significant cellular toxicity towards the cultures. The structure activity relationship of the sesquiterpene lactones indicate that the guaianolides isolated were more active and less toxic then the germacranolides. PMID:22923197

  5. Acyl-homoserine lactones produced by Pantoea sp. isolated from the "maize white spot" foliar disease.

    PubMed

    Pomini, Armando M; Paccola-Meirelles, Luzia D; Marsaioli, Anita J

    2007-02-21

    The "maize white spot" foliar disease is a problem of increasing importance to Brazilian maize crops. A bacterium isolated from water-soaked lesions from infected maize leaves was pathogenic in biological assays in vivo. It was identified as a Gram-negative, nonsporulating, facultative anaerobic bacterium, belonging to the genus Pantoea. Chemical study of the extracts from bacterial cultivation media allowed the identification of (S)-(-)-N-butanoyl-homoserine lactone and trace amounts of N-hexanoyl-homoserine lactone, widely recognized quorum-sensing signaling substances employed in cell-to-cell communication systems. The absolute configuration of natural (S)-(-)-N-butanoyl-homoserine lactone was determined by gas chromatography-flame ionization detection with a chiral stationary phase and by comparison of circular dichroism spectroscopic data with enantiopure synthetic substances. Biological evaluations with reporter Agrobacterium tumefaciens NTL4(pZLR4) were carried out with synthetic and natural products and also with extracts from maize leaves contaminated with the isolated bacterium, as well as from healthy leaves. PMID:17256964

  6. Genotoxic effects of erioflorin acetate and erioflorin methacrylate: Sesquiterpene lactones isolated from Podanthus ovatifolius Lag. (Compositae)

    SciTech Connect

    Cea, G.; Alarcon, M.; Weigert, G.; Sepulveda, R. )

    1990-01-01

    Three major sesquiterpene lactones: eriflorin methacrylate (EM), erioflorin acetate (EA), and ovatifolin acetate (OA) have been isolated from neutral extracts of Podanthus ovatifolius, and all of them have been shown to exhibit antineoplastic properties as tested in standard KB human epidermoid carcinoma of the nasopharynx assay procedures. In the present study the authors report in vivo induction of micronuclei in bone-marrow mice polychromatic erythrocytes (MPCE) by EM, and EA. Chemicals can be screened for chromosome breaking ability by measuring the frequency of erythrocytes with micronuclei derived from acentric chromosomal fragments or lagging chromosomes. This assay has also been described for genotoxicity studies in several mammalian tissues other than polychromatic erythrocytes.

  7. Pantoea sp. isolated from tropical fresh water exhibiting N-acyl homoserine lactone production.

    PubMed

    Tan, Wen-Si; Muhamad Yunos, Nina Yusrina; Tan, Pui-Wan; Mohamad, Nur Izzati; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    N-Acyl homoserine lactone (AHL) serves as signaling molecule for quorum sensing (QS) in Gram-negative bacteria to regulate various physiological activities including pathogenicity. With the aim of isolating freshwater-borne bacteria that can cause outbreak of disease in plants and portrayed QS properties, environmental water sampling was conducted. Here we report the preliminary screening of AHL production using Chromobacterium violaceum CV026 and Escherichia coli [pSB401] as AHL biosensors. The 16S rDNA gene sequence of isolate M009 showed the highest sequence similarity to Pantoea stewartii S9-116, which is a plant pathogen. The isolated Pantoea sp. was confirmed to produce N-3-oxohexanoyl-L-HSL (3-oxo-C6-HSL) through analysis of high resolution mass tandem mass spectrometry. PMID:25197715

  8. Pantoea sp. Isolated from Tropical Fresh Water Exhibiting N-Acyl Homoserine Lactone Production

    PubMed Central

    Tan, Wen-Si; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    N-Acyl homoserine lactone (AHL) serves as signaling molecule for quorum sensing (QS) in Gram-negative bacteria to regulate various physiological activities including pathogenicity. With the aim of isolating freshwater-borne bacteria that can cause outbreak of disease in plants and portrayed QS properties, environmental water sampling was conducted. Here we report the preliminary screening of AHL production using Chromobacterium violaceum CV026 and Escherichia coli [pSB401] as AHL biosensors. The 16S rDNA gene sequence of isolate M009 showed the highest sequence similarity to Pantoea stewartii S9-116, which is a plant pathogen. The isolated Pantoea sp. was confirmed to produce N-3-oxohexanoyl-L-HSL (3-oxo-C6-HSL) through analysis of high resolution mass tandem mass spectrometry. PMID:25197715

  9. Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng.

    PubMed

    An, Ya-Nan; Zhang, Xue; Zhang, Tian-Yuan; Zhang, Meng-Yue; Qian-Zhang; Deng, Xiao-Yu; Zhao, Feng; Zhu, Ling-Juan; Wang, Guan; Zhang, Jie; Zhang, Yi-Xuan; Liu, Bo; Yao, Xin-Sheng

    2016-01-01

    Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1-5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS. PMID:27271722

  10. Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng

    PubMed Central

    An, Ya-Nan; Zhang, Xue; Zhang, Tian-Yuan; Zhang, Meng-Yue; Qian-Zhang; Deng, Xiao-Yu; Zhao, Feng; Zhu, Ling-Juan; Wang, Guan; Zhang, Jie; Zhang, Yi-Xuan; Liu, Bo; Yao, Xin-Sheng

    2016-01-01

    Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1–5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7–12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher’s method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2–4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2–4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS. PMID:27271722

  11. Iron limitation enhances acyl homoserine lactone (AHL) production and biofilm formation in clinical isolates of Acinetobacter baumannii

    PubMed Central

    Modarresi, Farzan; Azizi, Omid; Shakibaie, Mohammad Reza; Motamedifar, Mohammad; Mosadegh, Ellahe; Mansouri, Shahla

    2015-01-01

    Abstract Acinetobacter baumannii is an important source of infections in intensive care units (ICUs) of our hospitals in Kerman, Iran and the most frequently isolated strains produce biofilm. There is a little information about role of iron (Fe) levels on acyl homoserine lactone (AHL) production and biofilm formation in this microorganism. In the present study, we investigated the influence of iron-III limitation on AHL, siderophore, catechol and virulence factors in the biofilm forming clinical strains of A. baumannii. A total of 65 non-duplicated multidrug resistance (MDR) strains of A. baumannii were isolated from patients in ICUs of 2 hospitals in Kerman, Iran. Antibiotic susceptibility, siderophore and other iron chelators, hemolysis, cell twitching motility, capsule, gelatinase and DNase were studied. Presence of quorum sensing, LuxI and LuxR genes was detected by multiplex-PCR. AHL activity quantified by colorimetric method and the functional groups were determined by Fourier Transform Infra-Red Spectroscopy (FT-IR). Biofilm formation was detected by microtiter plate technique. All of the isolates were resistant to third generation of cephalosporins, ciprofloxacin, levofloxacin, tetracycline, whereas, 78% and 81% were resistant to amikacin and carbapenems, respectively. The siderophore activity was highest at 20 μM Fe3+ (70%); however, it decreased to 45% as concentration of Fe3+ increased to 80 μM. Furthermore, screening of the isolates for LuxI and LuxR genes showed that presence of both genes required in the isolates with high AHL activity. FT-IR analysis indicated C=O bond of the lactone ring and primary amides. Significantly, a higher amount of AHL (70%) was detected in the presence of low concentration of iron-III (20 μM); as iron concentration increased to 80 μM, the AHL activity was reduced to 40% (P ≤ 0.05). All the isolates exhibited twitching motility and had a capsule. No any gelatinase or DNase activity was detected. Quantification of

  12. Complete Genome Sequence of Chryseobacterium sp. Strain StRB126, an N-Acylhomoserine Lactone-Degrading Bacterium Isolated from Potato Root

    PubMed Central

    Wang, Wen-Zhao; Someya, Nobutaka; Ikeda, Tsukasa

    2014-01-01

    Chryseobacterium sp. strain StRB126 was isolated from a potato root and showed N-acylhomoserine lactone-degrading activity. Here, we present the complete 5,503,743-bp genome sequence of StRB126, which has a G+C content of 35.6% and carries 4,828 protein-coding genes, six rRNA operons, and 80 tRNA genes. PMID:25291777

  13. Centrifugal partition chromatography elution gradient for isolation of sesquiterpene lactones and flavonoids from Anvillea radiata.

    PubMed

    Destandau, Emilie; Boukhris, Meryem Alaoui; Zubrzycki, Sandrine; Akssira, Mohamed; Rhaffari, Lhoucine El; Elfakir, Claire

    2015-03-15

    An innovative procedure coupling pressurized solvent extraction and centrifugal partition chromatography (CPC) used in linear gradient elution mode was developed to isolate two pure germacranolides (9α-hydroxyparthenolide and 9β-hydroxyparthenolide) and to separate flavonoids (nepetin, isorhamnetin and jaceosidin) and chlorophyll pigments from aerial parts of Anvillea radiata (Coss.&Durieu). The two main germacranolides recovered using this method represent 2 and 5% of the dried plant material respectively. These molecules were extracted using accelerated solvent extraction with chloroform. After optimization of the CPC method, a two-phase solvent system composed of heptane/ethyl acetate/methanol/water (1:5:1:5 v/v/v/v) was employed in descending mode to isolate the germacranolides. Then the lower phase of a heptane/ethyl acetate/methanol/water (6:5:6:5 v/v/v/v) system was pumped in descending mode to generate a linear elution gradient, progressively decreasing the mobile phase polarity, that enabled the flavonoid compounds to be separated in the same run. The efficiency of the preparative separation was controlled through RP-HPLC analysis of the obtained fractions using UV, evaporative light scattering and mass spectrometry detection. The structural identification of the two germacranolides purified over 99% was established by (1)H NMR and (13)C NMR. The least abundant flavonoids were identified by mass spectrometry. PMID:25647341

  14. In vitro antioxidant and in vivo prophylactic effects of two gamma-lactones isolated from Grewia tiliaefolia against hepatotoxicity in carbon tetrachloride intoxicated rats.

    PubMed

    Khadeer Ahamed, Mohamed B; Krishna, Venkatarangaiah; Dandin, Chethan J

    2010-04-10

    Grewia tiliaefolia is widely used in traditional Indian medicines to cure jaundice, biliousness, dysentery and the diseases of blood. Bioassay-guided fractionation of methanolic extract of the G. tiliaefolia bark has resulted in the isolation of D-erythro-2-hexenoic acid gamma-lactone (EHGL) and gulonic acid gamma-lactone (GAGL). Hepatoprotective activity of the methanolic extract and the isolated constituents were evaluated against CCl(4)-induced hepatotoxicity in rats. The treatment with methanolic extract, EHGL and GAGL at oral doses of 100, 150 and 60 mg/kg respectively with concomitant CCl(4) intraperitoneal injection (1 ml/kg) significantly reduced the elevated plasma levels of aminotransferases, alkaline phosphatase and the incidence of liver necrosis compared with the CCl(4)-injected group without affecting the concentrations of serum bilirubin and hepatic markers. EHGL and GAGL significantly inhibited the elevated levels of thiobarbituric acid reactive substances and glutathione in liver homogenates. Histology of the liver tissues of the extract and isolated constituents treated groups showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the normal control. The results revealed that the hepatoprotective activity of EHGL is significant as similar to the standard drug silymarin. To clarify the influence of the extract and isolated constituents on the protection of oxidative-hepatic damage, we examined in vitro antioxidant properties of the test compounds. The extract and the constituents showed significant free radical scavenging activity. These results suggest that the extract as well as the constituents could protect the hepatocytes from CCl(4)-induced liver damage perhaps, by their anti-oxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl(4). PMID:20064503

  15. Investigation of N-acyl homoserine lactone (AHL) molecule production in Gram-negative bacteria isolated from cooling tower water and biofilm samples.

    PubMed

    Haslan, Ezgi; Kimiran-Erdem, Ayten

    2013-09-01

    In this study, 99 Gram-negative rod bacteria were isolated from cooling tower water, and biofilm samples were examined for cell-to-cell signaling systems, N-acyl homoserine lactone (AHL) signal molecule types, and biofilm formation capacity. Four of 39 (10 %) strains isolated from water samples and 14 of 60 (23 %) strains isolated from biofilm samples were found to be producing a variety of AHL signal molecules. It was determined that the AHL signal molecule production ability and the biofilm formation capacity of sessile bacteria is higher than planktonic bacteria, and there was a statistically significant difference between the AHL signal molecule production of these two groups (p < 0.05). In addition, it was found that bacteria belonging to the same species isolated from cooling tower water and biofilm samples produced different types of AHL signal molecules and that there were different types of AHL signal molecules in an AHL extract of bacteria. In the present study, it was observed that different isolates of the same strains did not produce the same AHLs or did not produce AHL molecules, and bacteria known as AHL producers did not produce AHL. These findings suggest that detection of signal molecules in bacteria isolated from cooling towers may contribute to prevention of biofilm formation, elimination of communication among bacteria in water systems, and blockage of quorum-sensing controlled virulence of these bacteria. PMID:23250628

  16. Sesquiterpene lactones from neurolaena oaxacana

    PubMed

    Passreiter; Sandoval-Ramirez; Wright

    1999-08-01

    Twelve sesquiterpene lactones, two new (1 and 2) and 10 known neurolenin-type germacranolides and furanoheliangolides (3-12) were isolated from Neurolaena oaxacana, and their structures were elucidated by NMR and GC-MS analysis. The chemotaxonomic importance of these findings is discussed. As N. lobata is used against dysenteries, neurolenin B (4) and a mixture of the neurolenins C (5) and D (6) were tested against Entamoeba histolytica and Giardia intestinalis. PMID:10479310

  17. Sesquiterpene lactones isolated from Elephantopus scaber L. inhibits human lymphocyte proliferation and the growth of tumour cell lines and induces apoptosis in vitro.

    PubMed

    Geetha, B S; Nair, Mangalam S; Latha, P G; Remani, P

    2012-01-01

    This study was designed to isolate the compounds responsible for the cytotoxic properties of South Indian Elephantopus scaber L. and further investigate their effects on quiescent and proliferating cells. Bioassay-guided isolation of the whole plant of chloroform extract of South Indian Elephantopus scaber afforded the known sesquiterpene lactone, deoxyelephantopin, and isodeoxyelephantopin whose structures were determined by spectroscopic methods. These compounds caused a dose dependent reduction in the viability of L-929 tumour cells in 72 h culture (IC(50) value of 2.7 μg/mL and 3.3 μg/mL) by the cell viability assay. Both the compounds act selectively on quiescent and PHA-stimulated proliferating human lymphocytes and inhibited tritiated thymidine incorporation into cellular DNA of DLA tumour cells. The compound deoxyelephantopin at a concentration of 3 μg/mL caused maximum apoptotic cells. It also exhibited significant in vivo antitumour efficacy against DLA tumour cells. The results, therefore, indicate that the antiproliferative property of deoxyelephantopin and isodeoxyelephantopin could be used in regimens for treating tumors with extensive proliferative potencies. PMID:22500104

  18. Codonolactone, a sesquiterpene lactone isolated from Chloranthus henryi Hemsl, inhibits breast cancer cell invasion, migration and metastasis by downregulating the transcriptional activity of Runx2.

    PubMed

    Wang, Wei; Chen, Bin; Zou, Ruolan; Tu, Xiuying; Tan, Songlin; Lu, Hong; Liu, Zhaojie; Fu, Jianjiang

    2014-11-01

    Metastasis is the most insidious aspect of breast cancer, but effective strategies to control this malignant process are still lacking. In previous studies, we screened over 200 extracts from plants of genus Chloranthaceae by bioactivity-guided fractionation, and found that Codonolactone (CLT) exhibited potential antimetastatic properties in breast cancer cells. This sesquiterpene lactone was isolated from Chloranthus henryi Hemsl, and is also found in other medical herbs, such as Codonopsis pilosula, Atractylodes macrocephala Koidz and others. Here, we report that CLT inhibited the ability of invasion and migration in metastatic breast cancer cells. Furthermore, CLT exhibited significant suppression on formation of lung metastatic foci of breast cancer in vivo. We next investigated the mechanism of CLT-induced metastasis inhibitory effects in breast cancer cells. A significant inhibition on activity and expression of MMP-9 and MMP-13 was observed. Moreover, data from western blotting, Runx2 transcription factor assay and chromatin immunoprecipitation assay showed that binding ability of Runx2 to sequences of the mmp-13 promoter was inhibited by CLT. Collectively, these findings suggested that the antimetastatic properties of CLT in breast cancer were due to the inhibition of MMPs, which might be associated with a downregulation of Runx2 transcriptional activity. PMID:25190326

  19. Antimicrobial activity of sesquiterpene lactones isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm

    PubMed Central

    2012-01-01

    Background Costus speciosus (Koen ex.Retz.) Sm (Costaceae) is an Indian ornamental plant which has long been used medicinally in traditional systems of medicine. The plant has been found to possess diverse pharmacological activities. Rhizomes are used to treat pneumonia, rheumatism, dropsy, urinary diseases, jaundice, skin diseases and leaves are usedto treat mental disorders. Method Antibacterial and antifungal activities were tested using Disc diffusion method and Minimum Inhibitory Concentration (MIC). Column chromatography was used to isolate compounds from hexane extract. X-ray crystallography technique and GC-MS analysis were used to identify the compounds Results Antibacterial and antifungal activities were observed in hexane, chloroform, ethyl acetate and methanol extracts. Hexane extract of C.speciosus showed good activity against tested fungi also. Two sesquiterpenoid compounds were isolated (costunolide and eremanthin) from the hexane extract. Both the compounds did not inhibit the growth of tested bacteria. But, both the compounds inhibited the tested fungi. The compound costunolide showed significant antifungal activity. The MIC values of costunolide were; 62.5 μg/ml against Trichophyton mentagrophytes, 62. μg/ml against T. simii, 31.25 μg/ml against T. rubrum 296, 62.5 μg/ml against T. rubrum 57, 125 μg/ml against Epidermophyton floccosum, 250 μg/ml against Scopulariopsis sp, 250 μg/ml against Aspergillus niger, 125 μg/ml against Curvulari lunata, 250 μg/ml against Magnaporthe grisea. Conclusion Hexane extract showed promising antibacterial and antifungal activity. The isolated compound costunolide showed good antifungal activity. PMID:22397713

  20. Neutron guides at the FRM-II

    NASA Astrophysics Data System (ADS)

    Aschauer, H.; Fleischmann, A.; Schanzer, C.; Steichele, E.

    2000-06-01

    The new research reactor FRM-II in Garching will be equipped with thermal, cold and (optional) very cold neutron guides. The main system in a specially designed beam tube (SR-1) looks onto the cold source and consists of six primary guides of cross-section 120×60 mm 2 (2 guides), 170×60 mm 2 (2) and 170×50 mm 2, respectively. These guides enter a neutron guide hall of 53×26 m 2 experimental area, some of the guides can be lengthened into the old reactor hall of the old “Atom-Ei”. The guides will be coated with either Ni-58 or super-mirror (mostly m=2, 3.5 in focussing sections near the instruments). For optimum background conditions the guides are designed for a short length of direct sight by coating at least the garland side with super-mirror and/or subdividing the width by thin mirror plates into narrower channels. In order to obtain many “endposition” places the primary beams are subdivided in height or width and individual beams are obtained by beam benders. One of the guides, which provides a high-resolution TOF-spectrometer, is double-bent S-shaped in order to get a sharp cut-off at short wavelength. A second pair of cold neutron guides will be installed in beam tube SR-4. A pair of thermal guides for two diffractometers in the experimental hall of the reactor will be installed at beam tube SR-8. Similar to the TGV at ILL a vertical guide can be installed in the vertical cold source to guide very cold neutrons into the reactor hall in first floor.

  1. Croceicoccus naphthovorans sp. nov., a polycyclic aromatic hydrocarbons-degrading and acylhomoserine-lactone-producing bacterium isolated from marine biofilm, and emended description of the genus Croceicoccus.

    PubMed

    Huang, Yili; Zeng, Yanhua; Feng, Hao; Wu, Yuehong; Xu, Xuewei

    2015-05-01

    A polycyclic aromatic hydrocarbons-degrading and acylhomoserine-lactone-producing marine bacterium, designated strain PQ-2(T), was isolated from marine biofilm collected from a boat shell at a harbour of Zhoushan island in Zhejiang Province, PR China. Strain PQ-2(T) is Gram-stain-negative, yellow-pigmented, non-motile and short rod-shaped. Optimal growth of strain PQ-2(T) was observed at 32 °C, at pH 7.0 and in 2% (w/v) NaCl. The 16S rRNA gene sequence of strain PQ-2(T) showed highest similarity to Croceicoccus marinus E4A9(T) (96.3%) followed by Novosphingobium malaysiense MUSC 273(T) (95.6%) and Altererythrobacter marinus H32(T) (95.6%). Phylogenetic analysis with all species of the family Erythrobacteraceae with validly published names revealed that strain PQ-2(T) formed a phyletic line with Croceicoccus marinus E4A9(T) that was distinct from other members of the family Erythrobacteraceae . The sole respiratory quinone was ubiquinone 10 (Q-10). The predominant fatty acids were C18 : 1ω7c, C17 : 1ω6c and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The genomic DNA G+C content was 61.7 mol%. In the polar lipid profile, phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, one unidentified phospholipid and one sphingoglycolipid were the major compounds; and another sphingoglycolipid was present in a minor amount. Based on the genotypic and phenotypic data, strain PQ-2(T) represents a novel species of the genus Croceicoccus , for which the name Croceicoccus naphthovorans sp. nov. is proposed. The type strain is PQ-2(T) ( =CGMCC 1.12805(T) =NBRC 110381(T)). In addition, emended descriptions for the genus Croceicoccus and the species C. marinus are given. PMID:25713040

  2. Hydrostatic countercurrent chromatography and ultra high pressure LC: Two fast complementary separation methods for the preparative isolation and the analysis of the fragrant massoia lactones.

    PubMed

    Urbain, Aurélie; Corbeiller, Pierre; Aligiannis, Nektarios; Halabalaki, Maria; Skaltsounis, Alexios-Leandros

    2010-05-01

    Using a one-step preparative hydrostatic countercurrent chromatography method, the fragrant massoia lactones were purified from the crude massoia bark oil, in less than 3 h. The fractionation was performed with the biphasic solvent system c-hexane-methanol-water (10:9:1, v/v/v), leading to target compounds with purity over 96%, as determined by GC-MS and ultra high pressure LC-MS analyses. Together with C-10, C-12 and C-14 massoia lactones, two other aromatic compounds used in perfumes, benzyl benzoate and benzyl salicylate, were also obtained as pure compounds. In parallel, an easy and efficient ultra high pressure LC method was developed for the ultra-fast analysis of massoia lactones, as an alternative to long GC-MS methods. PMID:20235136

  3. Sesquiterpene lactones and phenylpropanoids from Cosmos pringlei.

    PubMed

    Mata, Rachel; Rivero-Cruz, Isabel; Rivero-Cruz, Blanca; Bye, Robert; Timmermann, Barbara N

    2002-07-01

    Activity-directed fractionation of a phytotoxic extract from Cosmos pringlei led to the isolation of three new compounds, namely, 1'-isovaleroyloxy-4-O-isobutyryleugenol (1), zaluzanin C isobutyrate (2), and zaluzanin C isovalerate (3). In addition, mokko lactone, 1'-isobutiroyloxy-4-O-isobutyryleugenol (4), dehydrocostus lactone (5), costunolide (6), 15-isovaleroyloxycostunolide (7), 15-isobutiroyloxycostunolide (8), 1',2'-epoxy-3',4'-di-isobutyryl-Z-coniferyl alcohol, and 3beta-hydroxy-5alpha-pregn-16-en-20-one were obtained. The structures of the new compounds were established by spectral methods. Compounds 5-7 caused inhibition of radicle growth of seedlings of Amaranthus hypochondriacus. PMID:12141867

  4. Inhibition of growth, migration and invasion of human bladder cancer cells by antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, and its molecular mechanisms.

    PubMed

    Chiu, Kun-Yuan; Wu, Chun-Chi; Chia, Chi-Hao; Hsu, Shih-Lan; Tzeng, Yew-Min

    2016-04-10

    Bladder cancer is the ninth most common cancer around the world, and is a severe urological cancer irrespective of sex. Approximately 65% of the bladder cancers will recur following surgery; with more than 20% of those patients showing an advanced and metastatic stage, with reducing prognosis. Metastasis causes the most death of bladder cancer yet current therapeutic options remain limited. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, has been identified as a strong cytotoxic agent against lung and metastatic breast cancer cells; however, the effects and mechanisms of antrocin on cancer growth and metastasis remain largely unclear. This study showed that treatment with cytotoxic concentration of antrocin induced both intrinsic and extrinsic apoptotic pathways in human bladder cancer 5637 cells, evidenced by increase of Fas, DR5, Bax expression and caspase-3, -8 and -9 activation. Exposure to non-cytotoxic concentrations of antrocin significantly inhibited cell growth, migration, and invasion, which was associated with decreased phosphorylation of focal adhesion kinase (FAK) and paxillin. Antrocin also reduced subcellular distribution of FAK and paxillin at the focal adhesion contacts of the cell periphery site, and disrupted the formation of filopodia and lamellipodia. Moreover, antrocin increased epithelial-to-mesenchymal transition-related gene E-cadherin and decreased vimentin expression. Real-time PCR analysis showed that antrocin downregulated the expression of mRNA of several MMPs, including MMP-2. Moreover, the phosphorylation of ERK and c-Fos were also attenuated by antrocin. Data from chromatin immunoprecipitation assay demonstrated that antrocin decreased the DNA binding activity of c-Fos to the upstream/enhancer region of MMP-2 promoter, an action likely to result in the reducing MMP-2 expression. Overall, this is the first study which demonstrates that antrocin-inhibited migration and invasion of bladder cancer cells is partly

  5. A Possible Role for FRM-1, a C. elegans FERM Family Protein, in Embryonic Development

    PubMed Central

    Choi, Boram; Kang, Junsu; Park, Yang-Seo; Lee, Junho; Cho, Nam Jeong

    2011-01-01

    FRM-1 is a member of the FERM protein superfamily containing a FERM domain, which is a highly conserved protein- protein interaction module found in most eukaryotes. Although FRM-1 is thought to be involved in linking intracellular proteins to membrane proteins, the specific role for FRM-1 remains to be elucidated. In an effort to explore the biological function of FRM-1, we examined the phenotype of frm-1(tm4168) mutant worms. We observed that frm-1(tm4168) worms have a delayed hatching phenotype. Twelve hours after being laid, when virtually all wild-type eggs had hatched, only 64% of frm-1(tm4168) eggs had hatched. About 3% of frm-1(tm4168) eggs failed to hatch, even 3 days after they had been laid. We also found that frm-1(tm4168) mutants displayed a temperature-sensitive sterility phenotype. About 13% of frm-1(tm4168) worms were unable to produce eggs or produced nonviable eggs at 25℃. In contrast, less than 1% of wild-type animals were sterile at this temperature. At 20℃, neither the mutant nor wild type appeared to be sterile. Western blot analysis indicates that FRM-1 is expressed throughout the developmental stages with the strongest expression at the egg stage. Immunostaining experiments revealed that FRM-1 is mainly localized to the plasma membrane of most if not all cells at an early embryonic stage and to the plasma membrane of P cells during the late embryonic stages. GFP fusion experiments showed that FRM-1 can be expressed in the pharynx and intestine at the larval and adult stages. Our data suggest that FRM-1 may participate in diverse biological processes, including embryonic development. PMID:21448586

  6. An alternative LEU design for the FRM-II

    SciTech Connect

    Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

    1997-02-01

    The Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm[sup 3] and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance (8 x 10[sup 14] n/cm[sup 2]/s in the reflector). LEU silicide fuel with 4.5 g/cm[sup 3] has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. Computer models for the HEU and LEU designs have been exchanged between TUM and ANL and discrepancies have been resolved. The following issues are addressed: qualification of HEU and LEU silicide fuels, stability of the fuel plates, gamma heating in the heavy water reflector, a hypothetical accident involving the configuration of the reflector, a loss of primary coolant flow transient due to an interrupted power supply, the radiological consequences of larger fission product and plutonium inventories in the LEU core, and cost and schedule. Calculations were also done to address the possibility that new high density LEU fuels could be developed that would allow conversion of the TUM HEU design to LEU fuel. Based on the excellent results for the Alternative LEU Design that were obtained in these analyses, the RERTR Program concludes that all of the major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II have been successfully resolved and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility.

  7. An alternative LEU design for the FRM-II

    SciTech Connect

    Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

    1996-12-01

    The Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm{sup 3} and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance. LEU silicide fuel with 4.5 g/cm{sup 3} has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. The following issues raised by TUM were addressed in Ref. 1: qualification of HEU and LEU silicide fuels, gamma heating in the heavy water reflector, radiological consequences of larger fission product and plutonium inventories in the LEU core, and cost and schedule. The conclusions of these analyses are summarized below. This paper addresses three additional safety issues that were raised by TUM in Ref. 2: stability of the involute fuel plates, a hypothetical accident involving the configuration of the reflector, and a loss of primary coolant flow transient due to an interrupted power supply. Based on the excellent results for the Alternative LEU Design that were obtained in these analyses, the RERTR Program concludes that all of the major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II have been successfully resolved and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility.

  8. Insights into the Genome Sequences of an N-Acyl Homoserine Lactone Molecule Producing Two Pseudomonas spp. Isolated from the Arctic

    PubMed Central

    Dharmaprakash, Akhilandeswarre; Reghunathan, Dinesh; Sivakumar, Krishnakutty C.; Prasannakumar, Manoj

    2016-01-01

    We report for the first time the draft genome sequence of two psychrotrophic Pseudomonas species, Pseudomonas simiae RGCB 73 and Pseudomonas brenneri RGCB 108, from the Arctic that produce more than one acyl homoserine lactone molecule of varied N-acyl length. The study confirms the presence of a LuxR-LuxI (type) mediated quorum-sensing system in both the Pseudomonas species and enables us to understand the role of quorum sensing in their survival in extremely cold environments. PMID:27491995

  9. Pinostrobin and Cajanus lactone isolated from Cajanus cajan (L.) leaves inhibits TNF-α and IL-1β production: in vitro and in vivo experimentation.

    PubMed

    Patel, Neeraj K; Bhutani, Kamlesh K

    2014-06-15

    The tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) inhibitory activities of Cajanus cajan (leaves) crude methanolic extract, its fractions and its phytochemical constituents were evaluated in lipopolysaccharide (LPS) stimulated RAW 264.7 and J774A.1 cells. Phytochemical investigation of the active ethyl acetate (CCE) and n-butanol (CCB) fractions of C. cajan L. leaves yielded 14 compounds. It was observed that both pinostrobin (9) and cajanus lactone (4) were found to be most active in inhibiting TNF-α (IC50<22 μM) and IL-1β (IC50<40 μM) whereas compounds 2, 3, 5-8, 10 and 14 showed moderate and mild effects (IC50=35.50-81.22 μM for TNF-α and 38.23-89.10 μM for IL-1β) in both the cell lines. Furthermore, at dose of 20mg/kg, both pinostrobin (9) and cajanus lactone (4) were found to reduce LPS-induced TNF-α levels by 48.6% and 55.0% respectively and IL-1β levels by 53.1% and 41.8% respectively in Sprague Dawley (SD) rats. These findings suggest that C. cajan L. leaves can be developed as an effective herbal remedy for the treatment and prevention of inflammation or associated ailments. PMID:24680612

  10. New sesquiterpene lactones from Ambrosia cumanensis Kunth.

    PubMed

    Jimenez-Usuga, Nora Del Socorro; Malafronte, Nicola; Cotugno, Roberta; De Leo, Marinella; Osorio, Edison; De Tommasi, Nunziatina

    2016-09-01

    Eleven sesquiterpene lactones, including three new natural products (1-3), were isolated from the n-butanolic extract of Ambrosia cumanensis Kunth. aerial parts. The structure of all isolated compounds was elucidated by 1D- and 2D-NMR, and MS analyses. All compounds were tested for their antiproliferative activity on HeLa, Jurkat, and U937 cell lines. Compound 3, 2,3-dehydropsilostachyn C, showed cytotoxic activity with different potency in all cell lines. By means of flow cytometric studies, compound 3 was demonstrated to induce in Jurkat cells a G2/M cell cycle block, while in U937 elicited both cytostatic and cytotoxic responses. PMID:27491754

  11. N-Acylhomoserine lactones involved in quorum sensing control the type VI secretion system, biofilm formation, protease production, and in vivo virulence in a clinical isolate of Aeromonas hydrophila

    PubMed Central

    Khajanchi, Bijay K.; Sha, Jian; Kozlova, Elena V.; Erova, Tatiana E.; Suarez, Giovanni; Sierra, Johanna C.; Popov, Vsevolod L.; Horneman, Amy J.; Chopra, Ashok K.

    2009-01-01

    In this study, we delineated the role of N-acylhomoserine lactone(s) (AHLs)-mediated quorum sensing (QS) in the virulence of diarrhoeal isolate SSU of Aeromonas hydrophila by generating a double knockout ΔahyRI mutant. Protease production was substantially reduced in the ΔahyRI mutant when compared with that in the wild-type (WT) strain. Importantly, based on Western blot analysis, the ΔahyRI mutant was unable to secrete type VI secretion system (T6SS)-associated effectors, namely haemolysin coregulated protein and the valine-glycine repeat family of proteins, while significant levels of these effectors were detected in the culture supernatant of the WT A. hydrophila. In contrast, the production and translocation of the type III secretion system (T3SS) effector AexU in human colonic epithelial cells were not affected when the ahyRI genes were deleted. Solid surface-associated biofilm formation was significantly reduced in the ΔahyRI mutant when compared with that in the WT strain, as determined by a crystal violet staining assay. Scanning electron microscopic observations revealed that the ΔahyRI mutant was also defective in the formation of structured biofilm, as it was less filamentous and produced a distinct exopolysaccharide on its surface when compared with the structured biofilm produced by the WT strain. These effects of AhyRI could be complemented either by expressing the ahyRI genes in trans or by the exogeneous addition of AHLs to the ΔahyRI/ahyR+ complemented strain. In a mouse lethality experiment, 50 % attenuation was observed when we deleted the ahyRI genes from the parental strain of A. hydrophila. Together, our data suggest that AHL-mediated QS modulates the virulence of A. hydrophila SSU by regulating the T6SS, metalloprotease production and biofilm formation. PMID:19729404

  12. The comparative efficacy of abamectin, monepantel and an abamectin/derquantel combination against fourth-stage larvae of a macrocyclic lactone-resistant Teladorsagia spp. isolate infecting sheep.

    PubMed

    George, S D; George, A J; Stein, P A; Rolfe, P F; Hosking, B C; Seewald, W

    2012-08-13

    Anthelmintic resistance by gastrointestinal nematodes of sheep continues to be an issue of global interest. While the recent introduction in some countries of one or two new anthelmintic classes (amino-acetonitrile derivatives [AAD] and spiroindoles [SI]) has been welcomed, it is important that there is no relaxation in parasite control and the management of drug resistance. Monepantel (an AAD) was the first new anthelmintic to be approved for use (New Zealand, 2009) and was followed a year later in the same country by a combination of derquantel (a SI) and abamectin. The present study determined the efficacy of the new anthelmintic products and abamectin against fourth-stage larvae of macrocyclic lactone-resistant Teladorsagia spp. in lambs. Efficacies were calculated by comparing post-mortem nematode burdens of treated animals with those of untreated control sheep, and were 98.5, 86.3 and 34.0% for monepantel, abamectin/derquantel and abamectin, respectively. The nematode burdens of monepantel- and abamectin/derquantel-treated sheep were significantly lower than those sheep treated with abamectin and the untreated controls. Similarly, the burden of the monepantel group was significantly lower than that of the abamectin/derquantel group. These findings provide an opportunity to reinforce the recommendation that farmers and animal health advisors need to know the resistance status of nematode populations on subject farms to ensure effective control programs are designed and implemented. Such control programs should include an appropriate choice of anthelmintic(s), monitoring parasite burdens for correct timing of treatments, and pasture management to reduce larval challenge balanced with the maintenance of drug-susceptible populations in refugia. PMID:22459111

  13. Variecolactol: A New Sesterterpene Lactone from the Sclerotia of Aspergillus auricomus (Guegen) Saito

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Variecolactol (1), a new sesterterpene lactone related to variecolin (2), has been isolated from the organic extracts of Aspergillus auricomus. Structure determination of this compound was achieved primarily through HMQC, HMBC, and NOESY experiments. The known compounds dihydropenicillic acid (3) ...

  14. Optimization of the hot pressing parameters to fabricate the fiber reinforced material (FRM)

    SciTech Connect

    Takahashi, Kunio; Onzawa, Tadao

    1995-11-01

    When hot pressing is used to fabricate the fiber reinforced materials (FRM), the deformation and the adhesion of the matrix foil must be completed and the thickness of the reaction layer at the matrix/fiber interface must be smaller than the critical value derived from the Ochiai`s theory. A simulation model was proposed to predict the deformation of matrix foils, where plastic and creep deformations were taken into account. These calculations provide a consistent and unified interpretation of experimental data for Ti-matrix FRM, while the creep constants of Ti are known. A method is proposed to estimate the creep constants from some experimental trial for the matrix materials whose creep constants are unknown. By using this method, to types of Ti{sub 3}Al matrix FRM were formed to demonstrate the applicability of the algorithm. The tensile strength of the FRM was examined.

  15. Fluorinated β-Lactones and Poly(β-hydroxyalkanoate)s: Synthesis via Epoxide Carbonylation and Ring-Opening Polymerization

    PubMed Central

    Kramer, John W.

    2008-01-01

    Efficient and mild reaction conditions were developed for the catalytic carbonylation of fluorinated epoxides to their corresponding β-lactones. Six new lactones with fluorinated side chains were prepared in high isolated yields. These lactones were polymerized to form a series of new poly(β-hydroxyalkanoate)s with fluorinated side chains, and their properties were examined with respect to their hydrocarbon analogs. Finally, copolymerizations were performed with fluorinated lactones and β-butyrolactone, which resulted in tapered copolymers rather than the expected random copolymers. PMID:19606203

  16. Neocosmospora sp.-derived resorcylic acid lactones with in vitro binding capacity for human opioid and cannabinoid receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcyclic acid lactones, neocosmosin A (2), neocosmosin B (3) and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5) and monorden (6) were also ...

  17. Chania multitudinisentens gen. nov., sp. nov., an N-acyl-homoserine-lactone-producing bacterium in the family Enterobacteriaceae isolated from landfill site soil.

    PubMed

    Ee, Robson; Madhaiyan, Munusamy; Ji, Lianghui; Lim, Yan-Lue; Nor, Nuruddin Muhammad; Tee, Kok-Keng; Chen, Jian-Woon; Yin, Wai-Fong

    2016-06-01

    Phylogenetic and taxonomic characterization was performed for bacterium RB-25T, which was isolated from a soil sample collected in a former municipal landfill site in Puchong, Malaysia. Growth occurred at 20-37 °C at pH 5-8 but not in the presence of 9 % (w/v) NaCl or higher. The principal fatty acids were C16:0, C18:1ω7c and summed feature 3 (C16:1ω7c and/or iso-C15:0 2-OH). Ubiquinone-8 was the only isoprenoid quinone detected. Polar lipid analysis revealed the presence of phospholipid, phosphoaminolipid, phosphatidylethanolamine, phosphatidylglycerol and one unidentified aminolipid. DNA G+C content was 50.9 mol% phylogenetic analysis based on 16S rRNA gene sequence showed that strain RB-25T formed a distinct lineage within the family Enterobacteriaceae of the class Gammaproteobacteria. It exhibited a low level of 16S rRNA gene sequence similarity with its phylogenetic neighbours Pantoea rwandensis LMG 26275T (96.6 %), Rahnella aquatilis CIP 78.65T (96.5 %), Pectobacterium betavasculorum ATCC 43762T (96.4 %), Pantoea rodasii LMG 26273T (96.3 %), Gibbsiella dentisursi NUM 1720T (96.3 %) and Serratia glossinae C1T (96.2 %). Multilocus sequence analyses based on fusA, pyrG, rplB, rpoB and sucA sequences showed a clear distinction of strain RB-25T from the most closely related genera. Isolate RB-25T could also be distinguished from members of these genera by a combination of the DNA G+C content, respiratory quinone system, fatty acid profile, polar lipid composition and other phenotypic features. Strain RB-25T represents a novel species of a new genus, for which the name Chaniamultitudinisentens gen. nov., sp. nov. is proposed. The type strain is RB-25T (=DSM 28811T=LMG 28304T). PMID:26978486

  18. Two new aliphatic lactones from the fruits of Coriandrum sativum L.

    PubMed Central

    2012-01-01

    Background The present paper describes the isolation and characterization of two new aliphatic δ-lactones along with three glycerides and n-nonadecanyl cetoleate from the fruits of Coriandrum sativum L. (Apiaceae). The structures of all the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical reactions. Results Phytochemical investigation of the methanolic extract of C. sativum L. (Apiaceae) fruits resulted in the isolation of two new aliphatic δ-lactones characterized as 2α-n-heptatriacont-(Z)-3-en-1,5-olide (1) (coriander lactone) and 2α-n-tetracont-(Z,Z)-3,26-dien-18α-ol-1,5-olide (2) (hydroxy coriander lactone) together with glyceryl-1,2-dioctadec-9,12-dienoate-3-octadec-9-enoate (3); glyceryl-1,2,3-trioctadecanoate (4); n-nonadecanyl-n-docos-11-enoate (5) and oleiyl glucoside (6). Conclusions Phytochemical investigation of the methanolic extract of C. sativum gave coriander lactone and hydroxy coriander lactone as the new phytoconstituents. PMID:22800677

  19. Trichodermaerin: a diterpene lactone from Trichoderma asperellum.

    PubMed

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

    2014-04-01

    The title compound, C20H28O3, known as 'trichodermaerin' [systematic name: (4E)-4,9,15,16,16-penta-methyl-6-oxa-tetra-cyclo-[10.3.1.0(1,10).0(5,9)]hexa-dec-4-ene-7,13-dione], is a diterpene lactone which was isolated from Trichoderma asperellum. The structure has a tetra-cycic 6-5-7-5 ring system, with the cyclo-hexa-none ring adopting a twisted half-chair conformation and the cyclo-pentane ring adopting a half-chair conformation, whereas the cyclo-heptene and tetra-hydro-furan-anone rings are in chair and envelope (with the methyl-substituted C atom as the flap) conformations, respectively. The three-dimensional architecture is stabilized by C-H⋯O inter-actions. PMID:24826124

  20. Estimating FRM PM10 sampler performance characteristics using particle size analysis and collocated TSP and PM10 samplers: Cotton gins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the US, regional air quality compliance with national ambient air quality standards (NAAQS) for particulate matter (PM) is based on concentration measurements taken by federal reference method (FRM) samplers. The EPA specifies the performance criteria for the FRM samplers. These criteria for the ...

  1. Cytotoxic sesquiterpene lactones from the aerial parts of Inula aucheriana.

    PubMed

    Gohari, Ahmad Reza; Mosaddegh, Mahmoud; Naghibi, Farzaneh; Eslami-Tehrani, Bahara; Pirani, Atefeh; Hamzeloo-Moghadam, Maryam; Read, Roger W

    2015-01-01

    Inula aucheriana DC is a member of the family Asteraceae which is known to produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide (stevin) and 14-acetoxy-1β,5α,7αH-4β-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy-1β,5α,7αH-4β-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay to demonstrate cytotoxic activity with IC50 values of (56.6, 19.0), (39.0, 11.8), and (55.7, 15.3) μg/mL against HepG-2, MCF-7 and A-549 cells, respectively. The cytotoxic activity of the two evaluated sesquiterpene lactones partly explains the cytotoxic activity that was previously observed for the extracts of Inula aucheriana. The isolated compounds could be further investigated in cancer research studies. PMID:25993354

  2. 14-Methylpentadecano-15-lactone (muscolide): a new macrocyclic lactone from the oil of Angelica archangelica L.

    PubMed

    Lopes, Daíse; Strobl, Herbert; Kolodziejczyk, Paul

    2004-12-01

    The chemical composition of seed and root oils from Angelica archangelica L. was investigated. Analyses were performed by GC/MS and GC using two columns of different polarities (polyethylene glycol (DB-Wax) and 5% phenyl/95% polydimethylsiloxane (HP-5)), for the separation of several co-eluting components. A total of 58 compounds were identified, accounting for 96.3% (seed) and 93.5% (root) of the oils, respectively. A high content of beta-phellandrene (74.7%) was found in Angelica seed oil. Root oil contained a larger amount of macrocyclic lactones (1.3%) in comparison to the seed oil (0.4%). Different harvest dates produced only slight changes in the root-oil composition. In root oil harvested in summer, the beta-phellandrene content increased by ca. 36%, but no significant changes in the relative compositions of other components were observed. Fresh root oils were collected in five fractions (constant time intervals) during steam distillation (see Table). The highest-boiling fraction contained 9.3% of macrocyclic lactones such as tridecano-13-lactone (5.0%), 12-methyltridecano-13-lactone (0.4%), tetradecano-14-lactone (0.1%), pentadecano-15-lactone (3.5%), 14-methylpentadecano-15-lactone (1; trace), hexadecano-16-lactone (trace), and heptadecano-17-lactone (0.2%). This is the first report of the occurrence of 14-methylpentadecano-15-lactone (muscolide; 1) in a natural product. PMID:17191826

  3. Sesquiterpenoids Lactones: Benefits to Plants and People

    PubMed Central

    Chadwick, Martin; Trewin, Harriet; Gawthrop, Frances; Wagstaff, Carol

    2013-01-01

    Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans. Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments. This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage. Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualities for future crop production are discussed. PMID:23783276

  4. 21 CFR 184.1318 - Glucono delta-lactone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glucono delta-lactone. 184.1318 Section 184.1318... GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or D-glucono-1,5-lactone, is the cyclic 1,5-intramolecular ester...

  5. Cytotoxic Sesquiterpene Lactones from Kauna lasiophthalma Griseb

    PubMed Central

    Maldonado, Eliana M.; Svensson, Daniel; Oredsson, Stina M.; Sterner, Olov

    2014-01-01

    Two new eudesmane derivatives (3 and 8) were isolated from the ethanol extract of the aerial parts of Kaunia lasiophthalma Griseb, together with 14 known eudesmane, germacrane, and guaiane sesquiterpenes, and four flavones. The structures and relative configurations of all the compounds were established by NMR spectroscopy and high-resolution mass spectrometry. The anticancer activity of sesquiterpenes 1, 3, 6–9, 11, 12, 14, and 16 was evaluated in vitro with the breast cancer cell lines HCC1937, JIMT-1, L56Br-C1, MCF-7, and SK-BR-3, and compared with the cytotoxicity in the non-cancerous breast epithelial cell line MCF-10A. All compounds were found to possess anticancer activity, and compound 1 was the most potent in all of the investigated cancer cell lines with IC50 values ranging between 2.0 and 6.2 μM. In order to demonstrate the importance of the α-methylene-γ-lactone/ester moiety present in all compounds for the effects on the cells, the methyl cysteine adduct 21 was prepared from 9 and found to be inactive or considerably less potent. PMID:24634851

  6. Immunotoxic sesquiterpene lactone from Carpesium rosulatum Miq.

    PubMed

    Moon, Hyung-In; Zee, Okpyo

    2011-06-01

    The whole plants of Carpesium rosulatum were chloroform extracted and the isolated sesquiterpene lactones and immunotoxicity effects were studied. The structures and stereochemistry of these compounds were established on the basis of analysis of spectra including mp, [α](D)(25), IR, UV, EI-MS, MS, (1)H-NMR, (13)C-NMR and some chemical transformations as follows: 1 (4β,10α-dihydroxy-guaia-8α,12-olide), 2 (4β,10α-dihydroxy-1(2),11 (13)-guaiadien -8α,12-olide), 3 (3β,8β-dihydroxy-1α,5α-guaian-10(14)-ene-6α,12-olide). 4 (2β,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide) The chloroform extracted had a significant toxic effect against early fourth-stage larvae of Aedes aegypti L with an LC(50) value of 13.11 ppm and an LC(90) value of 20.33 ppm. The results could be useful in search for newer, safer, and more effective natural immunotoxicity agents against A. aegypti. PMID:20738151

  7. Cytotoxic Sesquiterpene Lactones from Kauna lasiophthalma Griseb.

    PubMed

    Maldonado, Eliana M; Svensson, Daniel; Oredsson, Stina M; Sterner, Olov

    2014-03-01

    Two new eudesmane derivatives (3 and 8) were isolated from the ethanol extract of the aerial parts of Kaunia lasiophthalma Griseb, together with 14 known eudesmane, germacrane, and guaiane sesquiterpenes, and four flavones. The structures and relative configurations of all the compounds were established by NMR spectroscopy and high-resolution mass spectrometry. The anticancer activity of sesquiterpenes 1, 3, 6-9, 11, 12, 14, and 16 was evaluated in vitro with the breast cancer cell lines HCC1937, JIMT-1, L56Br-C1, MCF-7, and SK-BR-3, and compared with the cytotoxicity in the non-cancerous breast epithelial cell line MCF-10A. All compounds were found to possess anticancer activity, and compound 1 was the most potent in all of the investigated cancer cell lines with IC50 values ranging between 2.0 and 6.2 μM. In order to demonstrate the importance of the α-methylene-γ-lactone/ester moiety present in all compounds for the effects on the cells, the methyl cysteine adduct 21 was prepared from 9 and found to be inactive or considerably less potent. PMID:24634851

  8. Transient analyses for HEU and LEU designs of the FRM-II.

    SciTech Connect

    Hanan, N. A.

    1998-10-14

    An Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm{sup 3} and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance (8 x 10{sup 14} n/cm{sup 2}-s in the reflector). LEU silicide fuel with 4.5 g/cm{sup 3} has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. Several issues raised by TUM have been addressed in Refs. 1-4. The conclusions of these analyses are summarized below. In this paper, two typical design basis transients are analyzed: control rod withdrawal at different power levels and loss of primary flow. The results show that the HEU and the LEU cores behave in a similar manner and both have excellent safety margins. Based on the excellent results for the Alternative LEU Design that were obtained in all analyses, the RERTR Program reiterates its conclusion that there are no major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility.

  9. SPHERES, Juelich's high-flux neutron backscattering spectrometer at FRM II

    SciTech Connect

    Wuttke, Joachim; Budwig, Alfred; Drochner, Matthias; Kaemmerling, Hans; Kayser, Franz-Joseph; Kleines, Harald; Ossovyi, Vladimir; Pardo, Luis Carlos; Prager, Michael; Richter, Dieter; Schneider, Gerald J.; Schneider, Harald; Staringer, Simon

    2012-07-15

    SPHERES is a third-generation neutron backscattering spectrometer, located at the 20 MW German neutron source FRM II and operated by the Juelich Centre for Neutron Science. It offers an energy resolution (fwhm) better than 0.65 {mu}eV, a dynamic range of {+-} 31 {mu}eV, and a signal-to-noise ratio of up to 1750:1.

  10. The time-of-flight spectrometer with cold neutrons at the FRM-II

    NASA Astrophysics Data System (ADS)

    Zirkel, A.; Roth, S.; Schneider, W.; Neuhaus, J.; Petry, W.

    2000-03-01

    We are presenting a design study of the new cold-time-of-flight spectrometer to be built at the FRM-II. Monte Carlo techniques were used to optimize the flux at the sample position and to calculate the elastic energy resolution. A doubly focusing neutron guide is used to enhance the intensity on the sample. Magnetic bearings and carbon fiber composite disks will give access to very high chopper speeds, thereby considerably increasing the overall performance of the instrument.

  11. Dendocarbin A: a sesquiterpene lactone from Drimys winteri.

    PubMed

    Paz Robles, Cristian; Burgos, Viviana; Suarez, Sebastián; Baggio, Ricardo

    2014-11-01

    The natural compound dendocarbin A, C15H22O3, is a sesquiterpene lactone isolated for the first time from Drimys winteri for var chilensis. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ and its X-ray crystal structure confirmed the S/R character of the chiral centres at C-5/C-10 and C-9/C-11, respectively. The α-OH group at C-11 was found to be involved in intermolecular hydrogen bonding, defining chains along the <100> 2₁ screw axis. PMID:25370095

  12. Sesquiterpenoid Lactones in Tanacetum huronense Inhibit Human Glioblastoma Cell Proliferation.

    PubMed

    Dissanayake, Amila A; Bejcek, Bruce E; Zhang, Chuan-Rui; Nair, Muraleedharan G

    2016-05-01

    Tanacetum huronense (Lake Huron tansy), which is native to the upper Midwest region of USA and Canada, was examined for the presence of anticancer compounds using an in vitro human tumor cell proliferation inhibition assay, with glioblastoma derived cell line U-87 MG. Bioassay-directed purification of the ethyl acetate extract of the aerial portion of this plant identified six active sesquiterpenoid lactones (1-6). Among these, compounds 5 and 6 are new structural analogs. One of the most abundant isolates, tanacin (4), exhibited the greatest inhibition with an IC50 value of 4.5 μg/mL. PMID:27319121

  13. Identification of unsaturated N-acylhomoserine lactones in bacterial isolates of Rhodobacter sphaeroides by liquid chromatography coupled to electrospray ionization-hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Cataldi, Tommaso R I; Bianco, Giuliana; Abate, Salvatore; Losito, Ilario

    2011-07-15

    The identification of two unsaturated N-acylhomoserine lactones (AHLs) produced by Rhodobacter sphaeroides bacteria, based on liquid chromatography (LC) coupled to a hybrid quadrupole linear ion trap (LTQ)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometer upon electrospray ionization (ESI), is presented. Besides the confirmation of the signaling molecule already described in the literature, i.e. (Z)-N-tetradec-7-enoyl-homoserine lactone (C(14:1)-HSL), we have discovered the occurrence, at low, yet significant levels, of another monounsaturated compound, C(12:1) -HSL, which may extend the number of small diffusible chemical signals known for R. sphaeroides. Both unsaturated AHLs were identified by high-resolution FTICR mass spectrometry in extracts of bacterial culture media and the occurrence of a C=C bond was assessed upon their conversion into bromohydrins. Collision-induced dissociation (CID) spectra were then collected on the LTQ mass analyzer. A careful comparison of tandem MS spectra of monounsaturated (i.e., C(12:1)-HSL and C(14:1)-HSL) and saturated AHLs (i.e. C(12)-HSL and C(14)-HSL) led to the emphasis of two series of product ions, exhibiting 14 Da spaced m/z ratios. Both series were referred to progressive fragmentations at the aliphatic end of the AHL acyl chains, followed by neutral losses of terminal alkenes (i.e. CH(2)=CH(CH(2))(n)H). In particular, the series located at the higher end of the explored m/z range (>200 Da), observed only for monounsaturated species, enabled the location of the C=C bond between carbons 7 and 8 of the acyl chain. PMID:21638357

  14. Pseudomonas cremoricolorata Strain ND07 Produces N-acyl Homoserine Lactones as Quorum Sensing Molecules

    PubMed Central

    Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Koh, Chong-Lek; Sam, Choon-Kook; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    Quorum sensing (QS) is a bacterial cell-to-cell communication system controlling QS-mediated genes which is synchronized with the population density. The regulation of specific gene activity is dependent on the signaling molecules produced, namely N-acyl homoserine lactones (AHLs). We report here the identification and characterization of AHLs produced by bacterial strain ND07 isolated from a Malaysian fresh water sample. Molecular identification showed that strain ND07 is clustered closely to Pseudomonas cremoricolorata. Spent culture supernatant extract of P. cremoricolorata strain ND07 activated the AHL biosensor Chromobacterium violaceum CV026. Using high resolution triple quadrupole liquid chromatography-mass spectrometry, it was confirmed that P. cremoricolorata strain ND07 produced N-octanoyl-l-homoserine lactone (C8-HSL) and N-decanoyl-l-homoserine lactone (C10-HSL). To the best of our knowledge, this is the first documentation on the production of C10-HSL in P. cremoricolorata strain ND07. PMID:24984061

  15. Cytotoxic sesquiterpene lactones from aerial parts of Xanthium sibiricum.

    PubMed

    Wang, Lun; Wang, Jing; Li, Fu; Liu, Xin; Chen, Bin; Tang, Ya-Xiong; Wang, Ming-Kui

    2013-05-01

    Chemical investigation of the aerial parts of Xanthium sibiricum led to the isolation of four new xanthanolide-type sesquiterpene lactones, including two xanthanolide dimers, pungiolide D (1) and pungiolide E (2), and two xanthanolide monomers, 8-epi-xanthatin-1α,5α-epoxide (3) and 1β-hydroxyl-5α-chloro-8-epi-xanthatin (4), together with four known compounds, pungiolide A (5), 8-epi-xanthatin-1β,5β-epoxide (6), xanthatin (7), and 11α,13-dihydro-8-epi-xanthatin (8). The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Pungiolide D (1) displayed an unusual structure featuring a 5/5/6-fused tricyclic system in the unit B. Compound 4 was shown to be a rare sesquiterpene lactone containing halogen, and its absolute configuration was determined by X-ray crystallographic analysis. The evaluation of the cytotoxic activities of the isolated new compounds against the SNU387 liver and A-549 lung human cancer cell lines showed that compound 4 possessed significant in vitro cytotoxicity with an IC50 value of 5.1 µM against SNU387 liver cells. PMID:23702839

  16. Mechanisms of lactone hydrolysis in acidic conditions.

    PubMed

    Gómez-Bombarelli, Rafael; Calle, Emilio; Casado, Julio

    2013-07-19

    The acid-catalyzed hydrolysis of linear esters and lactones was studied using a hybrid supermolecule-polarizable continuum model (PCM) approach including up to six water molecules. The compounds studied included two linear esters, four β-lactones, two γ-lactones, and one δ-lactone: ethyl acetate, methyl formate, β-propiolactone, β-butyrolactone, β-isovalerolactone, diketene (4-methyleneoxetan-2-one), γ-butyrolactone, 2(5H)-furanone, and δ-valerolactone. The theoretical results are in good quantitative agreement with the experimental measurements reported in the literature and also in excellent qualitative agreement with long-held views regarding the nature of the hydrolysis mechanisms at molecular level. The present results help to understand the balance between the unimolecular (A(AC)1) and bimolecular (A(AC)2) reaction pathways. In contrast to the experimental setting, where one of the two branches is often occluded by the requirement of rather extreme experimental conditions, we have been able to estimate both contributions for all the compounds studied and found that a transition from A(AC)2 to A(AC)1 hydrolysis takes place as acidity increases. A parallel work addresses the neutral and base-catalyzed hydrolysis of lactones. PMID:23731203

  17. A novel bioassay for high-throughput screening microorganisms with N-acyl homoserine lactone degrading activity.

    PubMed

    Liu, Pengfu; Gao, Yang; Huang, Wei; Shao, Zongze; Shi, Jiping; Liu, Ziduo

    2012-05-01

    A novel biosensor strain (Escherichia coli ALM403) that responded to N-acyl homoserine lactone (AHL) was constructed using a luxR-Plux cassette as a regulatory sequence and β-mannanase as a reporter gene. Dinitrosalicylic acid method was used to detect the response of the sensor strain to N-acyl homoserine lactone. By investigating the response to a range of concentrations of N-β-oxooctanoyl-L-homoserine lactone (OOHL), it was demonstrated that the expression of mannanase in E. coli ALM403 could be greatly enhanced by OOHL and resulted in an assayable phenotype. A high-throughput screening approach was developed to isolate AHL-degrading microorganisms, and a marine Halomonas sp. S66-4 showing a marked AHL-degrading ability was successfully isolated. In conclusion, the bioassay system provided a simple and efficient approach to isolate AHL-degrading bacteria. PMID:22528649

  18. 21 CFR 184.1318 - Glucono delta-lactone.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Glucono delta-lactone. 184.1318 Section 184.1318... Listing of Specific Substances Affirmed as GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or...

  19. 21 CFR 184.1318 - Glucono delta-lactone.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glucono delta-lactone. 184.1318 Section 184.1318... Listing of Specific Substances Affirmed as GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or...

  20. Rotatable multifunctional load frames for neutron diffractometers at FRM II—design, specifications and applications

    NASA Astrophysics Data System (ADS)

    Hoelzel, M.; Gan, W. M.; Hofmann, M.; Randau, C.; Seidl, G.; Jüttner, Ph.; Schmahl, W. W.

    2013-05-01

    Novel tensile rigs have been designed and manufactured at the research reactor Heinz Maier-Leibnitz (FRM II, Garching near Munich). Besides tensile and compressive stress, also torsion can be applied. The unique Eulerian cradle type design (ω, χ, and φ axis) allows orienting the stress axis with respect to the scattering vector. Applications of these tensile rigs at our neutron diffractometers enable various investigations of structural changes under mechanical load, e.g. crystallographic texture evolution, stress-induced phase transformations or lattice expansion, and the anisotropy of mechanical response.

  1. Structural and Sensory Characterization of Novel Sesquiterpene Lactones from Iceberg Lettuce.

    PubMed

    Mai, Franziska; Glomb, Marcus A

    2016-01-13

    Lactuca sativa var. capitate (iceberg lettuce) is a delicious vegetable and popular for its mild taste. Nevertheless, iceberg lettuce is a source of bitter substances, such as the sesquiterpene lactones. Chemical investigations on the n-butanol extract led to the isolation of three novel sesquiterpene lactones. All compounds were isolated by multilayer countercurrent chromatography followed by preparative high-performance liquid chromatography. The structures were verified by means of spectroscopic methods, including NMR and mass spectrometry techniques. For the first time 11ß,13-dihydrolactucin-8-O-sulfate (jaquinelin-8-O-sulfate) was structurally elucidated and identified in plants. In addition, the sesquiterpene lactones cichorioside B and 8-deacetylmatricarin-8-O-sulfate were identified as novel ingredients of iceberg lettuce. Further flowering plants in the daisy family Asteraceae were examined for the above three compounds. At least one of the compounds was identified in nine plants. The comparison between the lettuce butt end and the leaves of five types of the Cichorieae tribe showed an accumulation of the compounds in the butt end. Further experiments addressed the impact of sesquiterpene lactones on color formation and bitter taste. PMID:26727458

  2. A Method of Estimating FRM PM10 Sampler Performance Characteristics Using Particle Size Analysis and Collocated TSP and PM10 Samplers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the US, regional air quality compliance with national ambient air quality standards (NAAQS) for PM10 is based on concentration measurements taken by federal reference method (FRM) PM10 samplers. The EPA specifies the performance characteristics of the FRM PM10 sampler by defining ranges for the p...

  3. Potent Cytotoxic Arylnaphthalene Lignan Lactones from Phyllanthus poilanei

    PubMed Central

    2015-01-01

    Two new (1 and 2) and four known arylnaphthalene lignan lactones (3–6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-α-l-arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase IIα activity. PMID:24937209

  4. Cytotoxic sesquiterpene lactones from Centaurothamnus maximus and Vicoa pentanema.

    PubMed

    Muhammad, Ilias; Takamatsu, Satoshi; Mossa, Jaber S; El-Feraly, Farouk S; Walker, Larry A; Clark, Alice M

    2003-02-01

    The aerial parts of Centaurothamnus maximus yielded three cytotoxic guaianolides, chlorojanerin (1), cynaropicrin (2) and janerin (3). The structure elucidation of 1-3 was based on (1)H and (13)C NMR data, mainly 2D-NMR (1)H-(1)H COSY and (1)H-(13)C HETCOR experiments. Compounds 1-3 showed in vitro cytotoxic activity against human cancer cell lines of malignant melanoma (SK-MEL), epidermoid (KB), ductal (BT-549) and ovarian (SK-OV-3) carcinomas with IC(50) values of 2-6 microgram/mL. In addition, 12 sesquiterpene lactones (4-15), isolated previously from the aerial parts of Vicoa pentanema, were evaluated for cytotoxic and antimicrobial activities. 2alpha- Acetoxy-3beta-hydroxyalantolactone (10) and 8beta-hydroxyparthenolide (14) were found to be the main cytotoxic agents (IC(50) values of 2-6 microgram/mL against SK-MEL, BT-549 and SK-OV-3), while lactones 4, 5, 11 and 15 selectively inhibited the growth of human malignant melanoma (IC(50) value of 3.6-7.3 microgram/mL). Cell aggregation and cell adhesion assays, using HL-60 and HeLa cell lines, evaluated the effect of cytotoxic constituents 1-3, 10 and 14 on immune response and inflammation. PMID:12601682

  5. Study of Research and Development Processes through Fuzzy Super FRM Model and Optimization Solutions

    PubMed Central

    Sârbu, Flavius Aurelian; Moga, Monika; Calefariu, Gavrilă; Boșcoianu, Mircea

    2015-01-01

    The aim of this study is to measure resources for R&D (research and development) at the regional level in Romania and also obtain primary data that will be important in making the right decisions to increase competitiveness and development based on an economic knowledge. As our motivation, we would like to emphasize that by the use of Super Fuzzy FRM model we want to determine the state of R&D processes at regional level using a mean different from the statistical survey, while by the two optimization methods we mean to provide optimization solutions for the R&D actions of the enterprises. Therefore to fulfill the above mentioned aim in this application-oriented paper we decided to use a questionnaire and for the interpretation of the results the Super Fuzzy FRM model, representing the main novelty of our paper, as this theory provides a formalism based on matrix calculus, which allows processing of large volumes of information and also delivers results difficult or impossible to see, through statistical processing. Furthermore another novelty of the paper represents the optimization solutions submitted in this work, given for the situation when the sales price is variable, and the quantity sold is constant in time and for the reverse situation. PMID:25821846

  6. Comparison of the FRM-II HEU design with an alternative LEU design

    SciTech Connect

    Mo, S.C.; Hanan, N.A.; Matos, J.E.

    1995-12-01

    The FRM-II reactor design of the Technical University of Munich has a compact core that utilizes fuel plates containing highly-enriched uranium (HEU, 93%). This paper presents an alternative core design utilizing low-enriched uranium (LEU, <20%) silicide fuel with 4.8 g/cm{sup 3} that provides nearly the same neutron flux for experiments as the HEU design, but has a less favorable fuel cycle economy. If an LEU fuel with a uranium density of 6.0 - 6.5 g/cm{sup 3} were developed, the alternative design would provide the same neutron flux and use the same number of cores per year as the HEU design. The results of this study show that there are attractive possibilities for using LEU fuel instead of HEU fuel in the FRM-II. Further optimization of the LEU design and near-term availability of LEU fuel with a uranium density greater than 4.8 g/cm{sup 3} would enhance the performance of the LEU core. The RERTR Program is ready to exchange information with the Technical University of Munich to resolve any differences that may exist and to identify design modifications that would optimize reactor performance utilizing LEU fuel.

  7. A diastereoselective, nucleophile-promoted aldol-lactonization of ketoacids leading to bicyclic-β-lactones.

    PubMed

    Liu, Gang; Shirley, Morgan E; Romo, Daniel

    2012-03-01

    An improved, tandem acid activation/aldol-lactonization process is described. This more practical protocol shortens reaction times for the construction of bicyclic β-lactones from ketoacids and implements the use of commercially available reagents p-toluenesulfonyl chloride (p-TsCl) as activator and 4-dimethylaminopyridine (4-DMAP) as nucleophilic promoter (Lewis base). Substrates with β-substituents, with respect to the carboxylic acid, consistently showed excellent levels of diastereoselectivity during the bis-cyclization event. PMID:22260519

  8. Chicory cultivars differ in sesquiterpene lactone composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chicory (Cichorium intybus L.) is a valuable forage species for small ruminants because it is nutritious and contains sesquiterpene lactones (SLs) that have anthelmintic activity. Three SLs, lactucin (lac), 8-deoxylactucin (dol), and lactucopicrin (lpic), occur in chicory leaves. Comprehensive dat...

  9. New sesquiterpene lactones, vernonilides A and B, from the seeds of Vernonia anthelmintica in Uyghur and their antiproliferative activities.

    PubMed

    Ito, Takuya; Aimaiti, Simayijiang; Win, Nwet Nwet; Kodama, Takeshi; Morita, Hiroyuki

    2016-08-01

    A new guaianolide sesquiterpene lactone, vernonilide A (1), and a new elemanolide sesquiterpene lactone, vernonilide B (2), were isolated from the seeds of Vernonia anthelmintica, together with three known elemanolide sesquiterpene lactones (3-5). The structures of the isolated compounds were elucidated on the basis of physicochemical evidences. Compounds 1, 3, and 4 showed strong antiproliferative activities against three human cancer cell lines (A549, HeLa, and MDA-MB-231), with IC50 values ranging from 0.10 to 1.00μM. In addition, 5 exhibited significant antiproliferative activities against HeLa and MDA-MB-231 cells, with IC50 values ranging from 1.90 to 2.20μM. The antiproliferative activities of the acetyl derivatives 6 and 7 prepared from 4 and 3, respectively, against the three cell lines were 4-10-fold weaker than the original activities. PMID:27311895

  10. Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi

    PubMed Central

    Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S.; Frank, Fernanda M.; Lombardo, María E.

    2016-01-01

    Trypanosoma cruzi is the causative agent of Chagas’ disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its

  11. Antiplasmodial activities and cytotoxic effects of aqueous extracts and sesquiterpene lactones from Neurolaena lobata.

    PubMed

    François, G; Passreiter, C M; Woerdenbag, H J; Van Looveren, M

    1996-04-01

    Aqueous and lipophilic extracts of Neurolaena lobata (Asteraceae), obtained from Guatemala, were tested against Plasmodium falciparum in vitro. Moreover, sesquiterpene lactones, of the germacranolide and furanoheliangolide type, isolated from N. lobata, were shown to be active against P. falciparum in vitro. In addition to their antiplasmodial activity, their cytotoxic effects on human carcinoma cell lines were evaluated. Structure-activity relationships are discussed. PMID:8657743

  12. Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. II. Structure elucidation.

    PubMed

    Johnson, J H; Tymiak, A A; Bolgar, M S

    1990-08-01

    The structures of janthinocins A, B and C, three novel macrocyclic peptide lactone antibiotics isolated from fermentations of Janthinobacterium lividum, were determined. The janthinocins are of particular interest because they contain three amino acid residues that have not previously been reported in natural products: Each contains erythro-beta-hydroxy-D-leucine while janthinocins A and B also contain beta-hydroxytryptophan and beta-ketotryptophan, respectively. PMID:2211360

  13. A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa.

    PubMed

    Yang, Yong-Fen; Ma, Hong-Mei; Chen, Gang; Wang, Hai-Feng; Xiang, Zheng; Feng, Qing-Mei; Hua, Hui-Ming; Pei, Yue-Hu

    2016-10-01

    A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature. PMID:27156969

  14. Draft Genome Perspective of Staphylococcus saprophyticus Strain SU8, an N-Acyl Homoserine Lactone-Degrading Bacterium.

    PubMed

    Chan, Kok-Gan; Sulaiman, Joanita; Yong, Delicia Ann; Tee, Kok Keng; Yin, Wai-Fong; Priya, Kumutha

    2015-01-01

    Staphylococcus saprophyticus strain SU8 was isolated from a pristine water source in Malaysia and it exhibited degradation of N-hexanoylhomoserine lactone. Here we report the draft genome sequence of S. saprophyticus strain SU8 to further understand its quorum quenching abilities. PMID:26404582

  15. Draft Genome Perspective of Staphylococcus saprophyticus Strain SU8, an N-Acyl Homoserine Lactone-Degrading Bacterium

    PubMed Central

    Sulaiman, Joanita; Yong, Delicia Ann; Tee, Kok Keng; Yin, Wai-Fong; Priya, Kumutha

    2015-01-01

    Staphylococcus saprophyticus strain SU8 was isolated from a pristine water source in Malaysia and it exhibited degradation of N-hexanoylhomoserine lactone. Here we report the draft genome sequence of S. saprophyticus strain SU8 to further understand its quorum quenching abilities. PMID:26404582

  16. Thermodynamic properties of sesquiterpene lactone grossheimin

    NASA Astrophysics Data System (ADS)

    Kasenova, Sh. B.; Atazhanova, G. A.; Sagintaeva, Zh. I.; Kasenov, B. K.; Kishkentaeva, A. S.; Adekenov, S. M.

    2016-08-01

    The enthalpy of dissolution of sesquiterpene lactone grossheimin C15H18O4 is measured using a DAK-I-IA calorimeter at a lactone/ethanol (96%) molar ratios equal to 1 : 18000, 1 : 36000, and 1 : 72000. The standard enthalpy of dissolution of grossheimin in a 96% ethanol solution is calculated based on the resulting data. The temperature dependence of the heat capacity of grossheimin C p ° ˜ f ( T) is studied by means of dynamic calorimetry using a IT-C-400 device in the temperature range of 298.15-423 K. An equation describing this dependence is derived. The standard enthalpies of combustion, melting, and formation of grossheimin are calculated using approximate methods.

  17. Immunobiological properties of sesquiterpene lactones obtained by chemically transformed structural modifications of trilobolide.

    PubMed

    Harmatha, Juraj; Vokáč, Karel; Buděšínský, Miloš; Zídek, Zdeněk; Kmoníčková, Eva

    2015-12-01

    Our previous research on immunostimulatory properties of trilobolide and its structurally related natural analogues isolated from Laser trilobum (L.) Borkh., encouraged us to investigate structurally related guaianolides belonging to a specific group of sesquiterpene lactones with characteristic glycol moiety attached to the lactone ring. Ever increasing attention has been paid to certain guaianolides such as thapsigargin and trilobolide for their promising anti-inflammatory, anticancer, anti-infectious and SERCA inhibitory activities. However, due to their alkylation capabilities, they might be cytotoxic. Search for compounds with preserved immunobiological properties and decreased cytotoxicity led us to transform some of their structural features, particularly those related to their side chain functionality. For this reason, we prepared a series of over 20 various deacylated, acyl modified, or relactonized derivatives of trilobolide. The immunobiological effects were screened in vitro using the rat peritoneal cells primed with lipopolysaccharide. Secretion of interferon-γ (IFN-γ), interleukins (IL) IL-1β, IL-6 and tumour necrosis factor-α (TNF-α) were determined by ELISA, and nitric oxide (NO) production by Griess reagent. Relation between the molecular structure and immunobiological activity was investigated. Acetylation at 7-OH and 11-OH positions of the lactone ring, or acyl modification of the guaianolide functionalities (including relactonization) of trilobolide, led to inability to stimulate secretion of cytokines and production of NO. Interestingly, minor structural changes achieved by catalytic hydrogenation or hydrogenolysis retained the original immunoactivity of trilobolide. It can be concluded that several new chemically transformed sesquiterpene lactones resembling the immunobiological properties of trilobolide or thapsigargin were prepared and identified. The implication of the lactone vicinal diol (glycol) moiety, combined with other structure

  18. Intercalation of lactones into vanadyl phosphate

    NASA Astrophysics Data System (ADS)

    Melánová, Klára; Beneš, Ludvík; Svoboda, Jan; Zima, Vítězslav

    2006-05-01

    Intercalates of vanadyl phosphate with α-methyl-γ-butyrolactone, γ-valerolactone, γ-caprolactone, δ-valerolactone, and ɛ-caprolactone were prepared by a displacement reaction of ethanol-intercalated VOPO4. As follows from the results of elemental analyses and thermogravimetry, intercalates contain about one molecule of the guest per formula unit. The diffractograms of the intercalates show a series of sharp (001) reflections, (200) reflection and some (hkl) lines with low intensity. The tetragonal lattice parameters of the intercalates were calculated. Both δ-valerolactone and ɛ-caprolactone intercalates are stable in air. The intercalates of lactones with side aliphatic chains are less stable. The CO stretching vibration in IR spectra of the intercalates prepared was shifted to lower wavenumbers in comparison with spectra of the pure guests, indicating that lactones are anchored to the host layers by their carbonyl oxygen. Analogously to the arrangement of γ-butyrolactone, also arrangement of molecules of other lactones in the interlayer space of the host layers was proposed.

  19. Reduction of sugar lactones to hemiacetals with lithium triethylborohydride.

    PubMed

    Gonzalez, Cesar; Kavoosi, Sam; Sanchez, Andersson; Wnuk, Stanislaw F

    2016-09-01

    Reduction of ribono-1,4-lactones and gulono-1,4-lactone as well as ribono-1,5-lactone and glucono-1,5-lactones with LTBH (1.2 equiv.) in CH2Cl2 at 0 °C for 30 min provided the corresponding pentose or hexose hemiacetals in high yields. Commonly used in carbohydrate chemistry protecting groups such as trityl, benzyl, silyl, acetals and to some extent acyls are compatible with this reduction. PMID:27341397

  20. Purification and characterization of a novel lactonohydrolase, catalyzing the hydrolysis of aldonate lactones and aromatic lactones, from Fusarium oxysporum.

    PubMed

    Shimizu, S; Kataoka, M; Shimizu, K; Hirakata, M; Sakamoto, K; Yamada, H

    1992-10-01

    A novel lactonohydrolase, an enzyme that catalyzes the hydrolysis of aldonate lactones to the corresponding aldonic acids, was purified 10-fold to apparent homogeneity, with a 61% overall recovery, from Fusarium oxysporum AKU 3702, through a purification procedure comprising DEAE-Sephacel, octyl-Sepharose CL-4B and hydroxyapatite chromatographies and crystallization. The molecular mass of the native enzyme, as estimated by high-performance gel-permeation chromatography, is 125 kDa, and the subunit molecular mass is 60 kDa. The enzyme contains 15.4% (by mass) glucose equivalent of carbohydrate, and about 1 mol calcium/subunit. The enzyme hydrolyzes aldonate lactones, such as D-galactono-gamma-lactone and L-mannono-gamma-lactone, stereospecifically. Furthermore, it can catalyze the asymmetric hydrolysis of D-pantoyl lactone, which is a promising chiral building block for the chemical synthesis of D-pantothenate. These reactions are reversible, and the reaction equilibrium at pH 6.0 has a molar ratio of nearly 1:1 with D-pantoyl lactone and D-pantoic acid. The Km and Vmax for D-galactono-gamma-lactone are 3.6 mM and 1440 U/mg, respectively, and those for D-galactonate are 52.6 mM and 216 U/mg, respectively. The enzyme also irreversibly hydrolyzes several aromatic lactones, such as dihydrocoumarin and homogentisic-acid lactone. PMID:1396712

  1. Heliolactone, a non-sesquiterpene lactone germination stimulant for root parasitic weeds from sunflower.

    PubMed

    Ueno, Kotomi; Furumoto, Toshio; Umeda, Shuhei; Mizutani, Masaharu; Takikawa, Hirosato; Batchvarova, Rossitza; Sugimoto, Yukihiro

    2014-12-01

    Root exudates of sunflower (Helianthus annuus L.) line 2607A induced germination of seeds of root parasitic weeds Striga hermonthica, Orobanche cumana, Orobanche minor, Orobanche crenata, and Phelipanche aegyptiaca. Bioassay-guided purification led to the isolation of a germination stimulant designated as heliolactone. FT-MS analysis indicated a molecular formula of C20H24O6. Detailed NMR spectroscopic studies established a methylfuranone group, a common structural component of strigolactones connected to a methyl ester of a C14 carboxylic acid via an enol ether bridge. The cyclohexenone ring is identical to that of 3-oxo-α-ionol and the other part of the molecule corresponds to an oxidized carlactone at C-19. It is a carlactone-type molecule and functions as a germination stimulant for seeds of root parasitic weeds. Heliolactone induced seed germination of the above mentioned root parasitic weeds, while dehydrocostus lactone and costunolide, sesquiterpene lactones isolated from sunflower root exudates, were effective only on O. cumana and O. minor. Heliolactone production in aquacultures increased when sunflower seedlings were grown hydroponically in tap water and decreased on supplementation of the culture with either phosphorus or nitrogen. Costunolide, on the other hand, was detected at a higher concentration in well-nourished medium as opposed to nutrient-deficient media, thus suggesting a contrasting contribution of heliolactone and the sesquiterpene lactone to the germination of O. cumana under different soil fertility levels. PMID:25446236

  2. Cytotoxic and Pro-apoptotic Activities of Sesquiterpene Lactones from Inula britannica.

    PubMed

    Xiang, Ping; Guo, Xin; Han, Yang-Yang; Gao, Jin-Ming; Tang, Jiang-Jiang

    2016-01-01

    In this study, five known sesquiterpene lactones (STL) with an α-methylene-γ-lactone motif, including two eudesmanolides, 1β-hydroxyalantolactone (1) and ivangustin (2), and three 1,10-seco-eudesmanolides, 1-O-acetylbritannilactone (3), 1,6-O,O-diacetylbritannilactone (4), and 6α-O-(2- methylbutyryl)britannilactone (5) were isolated from the flower heads of the medicinal plant Inula britannica. Their structures were characterized by spectroscopic methods. X-ray data of 2 is reported for the first time. Among them, eudesmanolides 1 and 2 exhibited remarkable cytotoxicity against HEp2, SGC-7901 and HCT116 human cancer cell lines, comparable with etoposide (Vp-16) used as reference drug. Furthermore, treatment of HEp2 cells with 1 induced apoptosis associated with cleaved procaspase-3 and PARP. The biological assays carried out with normal cells (CHO) revealed that all sesquiterpenes were weakly selective against the cancer cell lines tested. PMID:26996005

  3. POWTEX Neutron Diffractometer at FRM II - New Perspectives for In-Situ Rock Deformation Analysis

    NASA Astrophysics Data System (ADS)

    Walter, J. M.; Stipp, M.; Ullemeyer, K.; Klein, H.; Leiss, B.; Hansen, B. T.; Kuhs, W. F.

    2012-04-01

    In Geoscience quantitative texture analysis here defined as the quantitative analysis of the crystallographic preferred orientation (CPO), is a common tool for the investigation of fabric development in mono- and polyphase rocks, their deformation histories and kinematics. Bulk texture measurements also allow the quantitative characterisation of the anisotropic physical properties of rock materials. A routine tool to measure bulk sample volumes is neutron texture diffraction, as neutrons have large penetration capabilities of several cm in geological sample materials. The new POWTEX (POWder and TEXture) Diffractometer at the neutron research reactor FRM II in Garching, Germany is designed as a high-intensity diffractometer by groups from the RWTH Aachen, Forschungszentrum Jülich and the University of Göttingen. Complementary to existing neutron diffractometers (SKAT at Dubna, Russia; GEM at ISIS, UK; HIPPO at Los Alamos, USA; D20 at ILL, France; and the local STRESS-SPEC and SPODI at FRM II) the layout of POWTEX is focused on fast time-resolved experiments and the measurement of larger sample series as necessary for the study of large scale geological structures. POWTEX is a dedicated beam line for geoscientific research. Effective texture measurements without sample tilting and rotation are possible firstly by utilizing a range of neutron wavelengths simultaneously (Time-of-Flight technique) and secondly by the high detector coverage (9.8 sr) and a high flux (~1 - 107 n/cm2s) at the sample. Furthermore the instrument and the angular detector resolution is designed also for strong recrystallisation textures as well as for weak textures of polyphase rocks. These instrument characteristics allow in-situ time-resolved texture measurements during deformation experiments on rocksalt, ice and other materials as large sample environments will be implemented at POWTEX. The in-situ deformation apparatus is operated by a uniaxial spindle drive with a maximum axial load of

  4. Discovery of new lactones in sweet cream butter oil.

    PubMed

    Sarrazin, Elise; Frerot, Eric; Bagnoud, Alain; Aeberhardt, Kasia; Rubin, Mark

    2011-06-22

    Sweet cream butter oil was analyzed to identify new volatile compounds that may contribute to its flavor, with an emphasis on lactones. The volatile part of butter oil was obtained by using short-path distillation. As some previously unknown lactones were detected in this first extract, it was fractionated further. The fatty acids were removed, and the extract was fractionated by flash chromatography. Three lactonic fractions possessing a creamy, buttery, and fatty character were investigated in depth by gas chromatography (GC) and mass spectrometry (MS) (EI and CI) and high-resolution GC-time-of-flight MS. Many lactones were identified by their mass fragmentation and by comparison with reference materials synthesized during this work. Six γ-lactones, five δ-lactones, and one ε-lactone were identified for the first time in butter oil, seven of them for the first time in a natural product. The possible contribution of these new lactones to the aroma of butter oil is briefly discussed. PMID:21599018

  5. Involvement of Acylated Homoserine Lactones (AHLs) of Aeromonas sobria in Spoilage of Refrigerated Turbot (Scophthalmus maximus L.)

    PubMed Central

    Li, Tingting; Cui, Fangchao; Bai, Fengling; Zhao, Guohua; Li, Jianrong

    2016-01-01

    One quorum sensing strain was isolated from spoiled turbot. The species was determined by 16S rRNA gene analysis and classical tests, named Aeromonas sobria AS7. Quorum-sensing (QS) signals (N-acyl homoserine lactones (AHLs)) were detected by report strains and their structures were further determined by GC-MS. The activity changes of AHLs on strain growth stage as well as the influence of different culture conditions on secretion activity of AHLs were studied by the punch method. The result indicated that strain AS7 could induce report strains to produce typical phenotypic response. N-butanoyl-dl-homoserine lactone (C4–HSL), N-hexanoyl-dl-homoserine lactone (C6–HSL), N-octanoyl-dl-homoserine lactone (C8–HSL), N-decanoyl-dl-homoserine lactone (C10–HSL), N-dodecanoyl-dl-homoserine lactone (C12–HSL) could be detected. The activities of AHLs were density-dependent and the max secretion level was at pH 8, sucrose culture, 1% NaCl and 32 h, respectively. The production of siderophore in strain AS7 was regulated by exogenous C8–HSL, rather than C6–HSL. Exogenous C4–HSL and C8–HSL accelerated the growth rate and population density of AS7 in turbot samples under refrigerated storage. However, according to the total viable counts and total volatile basic nitrogen (TVB-N) values of the fish samples, exogenous C6–HSL did not cause spoilage of the turbot fillets. In conclusion, our results suggested that QS was involved in the spoilage of refrigerated turbot. PMID:27420072

  6. Involvement of Acylated Homoserine Lactones (AHLs) of Aeromonas sobria in Spoilage of Refrigerated Turbot (Scophthalmus maximus L.).

    PubMed

    Li, Tingting; Cui, Fangchao; Bai, Fengling; Zhao, Guohua; Li, Jianrong

    2016-01-01

    One quorum sensing strain was isolated from spoiled turbot. The species was determined by 16S rRNA gene analysis and classical tests, named Aeromonas sobria AS7. Quorum-sensing (QS) signals (N-acyl homoserine lactones (AHLs)) were detected by report strains and their structures were further determined by GC-MS. The activity changes of AHLs on strain growth stage as well as the influence of different culture conditions on secretion activity of AHLs were studied by the punch method. The result indicated that strain AS7 could induce report strains to produce typical phenotypic response. N-butanoyl-dl-homoserine lactone (C₄-HSL), N-hexanoyl-dl-homoserine lactone (C₆-HSL), N-octanoyl-dl-homoserine lactone (C₈-HSL), N-decanoyl-dl-homoserine lactone (C10-HSL), N-dodecanoyl-dl-homoserine lactone (C12-HSL) could be detected. The activities of AHLs were density-dependent and the max secretion level was at pH 8, sucrose culture, 1% NaCl and 32 h, respectively. The production of siderophore in strain AS7 was regulated by exogenous C₈-HSL, rather than C₆-HSL. Exogenous C₄-HSL and C₈-HSL accelerated the growth rate and population density of AS7 in turbot samples under refrigerated storage. However, according to the total viable counts and total volatile basic nitrogen (TVB-N) values of the fish samples, exogenous C₆-HSL did not cause spoilage of the turbot fillets. In conclusion, our results suggested that QS was involved in the spoilage of refrigerated turbot. PMID:27420072

  7. Greensporones: Resorcylic Acid Lactones from an Aquatic Halenospora sp.

    PubMed Central

    2015-01-01

    Fourteen new resorcylic acid lactones (1–14) were isolated from an organic extract of a culture of a freshwater aquatic fungus Halenospora sp. originating from a stream in North Carolina. The structures were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configuration of one representative member of the compounds (7) was assigned using X-ray crystallography of an analogue that incorporated a heavy atom, whereas for compounds 8–11, a modified Mosher’s ester method was utilized. The relative configurations of compounds 12–14 were determined on the basis of NOE data. Compounds 12–14 were proposed as artifacts produced by intramolecular cycloetherification of the ε-hydroxy-α,β-unsaturated ketone moieties of the parent compounds during the purification processes. The isolated compounds, except for 8 and 12, were tested against the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compound 5 was the most potent, with IC50 values of 2.9 and 7.5 μM, respectively. The compounds were evaluated as TAK1–TAB1 inhibitors but were found to be inactive. PMID:25093280

  8. High-resolution neutron powder diffractometer SPODI at research reactor FRM II

    NASA Astrophysics Data System (ADS)

    Hoelzel, M.; Senyshyn, A.; Juenke, N.; Boysen, H.; Schmahl, W.; Fuess, H.

    2012-03-01

    SPODI is a high-resolution thermal neutron diffractometer at the research reactor Heinz Maier-Leibnitz (FRM II) especially dedicated to structural studies of complex systems. Unique features like a very large monochromator take-off angle of 155° and a 5 m monochromator-sample distance in its standard configuration achieve both high-resolution and a good profile shape for a broad scattering angle range. Two dimensional data are collected by an array of 80 vertical position sensitive 3He detectors. SPODI is well suited for studies of complex structural and magnetic order and disorder phenomena at non-ambient conditions. In addition to standard sample environment facilities (cryostats, furnaces, magnet) specific devices (rotatable load frame, cell for electric fields, multichannel potentiostat) were developed. Thus the characterisation of functional materials at in-operando conditions can be achieved. In this contribution the details of the design and present performance of the instrument are reported along with its specifications. A new concept for data reduction using a 2 θ dependent variable height for the intensity integration along the Debye-Scherrer lines is introduced.

  9. Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

    PubMed

    Hegazy, Mohamed-Elamir F; Ibrahim, Abeer Y; Mohamed, Tarik A; Shahat, Abdelaaty A; El Halawany, Ali M; Abdel-Azim, Nahla S; Alsaid, Mansour S; Paré, Paul W

    2016-01-01

    Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site. PMID:26441064

  10. Lactones 12. Enzymatic lactonization of gamma, delta-epoxy esters by the apple fruit and Jerusalem artichoke bulb.

    PubMed

    Olejniczak, Teresa; Mironowicz, Agnieszka; Wawrzeńczyk, Czesław

    2003-06-01

    The enzymatic lactonization of three acyclic gamma, delta-epoxy esters (ethyl 3,7-dimethyl-4,5-epoxyoctanoate, ethyl 3,7,7-trimethyl-4,5-epoxyoctanoate, and ethyl 3,3,7-trimethyl-4,5-epoxyoctanoate) by apple fruit (Malus silvestris) and Jerusalem artichoke bulb (Helianthus tuberosus L.) was investigated. The substrates were transformed into a mixture of isomeric delta-hydroxy-gamma-lactones and gamma-hydroxy-delta-lactones. The gamma-lactones (yields ranging from 45-70%) predominated over delta-lactones (yields ranging from 8-40%). The composition of the product mixture depended on the structure of substrate as well as the biocatalyst. The enzymatic system in these biocatalysts also exhibited diastereoselectivity and enantioselectivity. PMID:12818229

  11. Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T Lymphocyte (Jurkat) Cells via the Activation of c-Jun n-terminal Kinase Phosphorylation.

    PubMed

    Iranshahy, Milad; Tayarani-Najaran, Zahra; Kasaian, Jamal; Ghandadi, Morteza; Emami, Seyed Ahmad; Asili, Javad; Chandran, Jima N; Schneider, Bernd; Iranshahi, Mehrdad

    2016-02-01

    Infrared-guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C. concolor. The structures of these compounds were elucidated by one-dimensional and two-dimensional nuclear magnetic resonance techniques, as well as high-resolution mass spectrometry. The purified and characterized compounds were subjected to cytotoxicity assay. The sesquiterpene lactones desoxyjanerin and rhaserolide showed significant cytotoxic activities against five different cancer cell lines and the normal human embryonic kidney cell line. Rhaserolide was chosen to evaluate the possible mechanism of action. Western blot analysis revealed that rhaserolide could induce apoptosis in Jurkat cells via the activation of c-Jun n-terminal kinase phosphorylation. PMID:26581585

  12. Development of Acid Functional Groups and Lactones During the Thermal Degradation of Wood and Wood Components

    USGS Publications Warehouse

    Rutherford, David W.; Wershaw, Robert L.; Reeves, James B., III

    2008-01-01

    Black carbon (pyrogenic materials including chars) in soils has been recognized as a substantial portion of soil organic matter, and has been shown to play a vital role in nutrient cycling; however, little is known concerning the properties of this material. Previous studies have largely been concerned with the creation of high-surface-area materials for use as sorbents. These materials have been manufactured at high temperature and have often been activated. Chars occurring in the environment can be formed over a wide range of temperature. Because it is extremely difficult to isolate black carbon once it has been incorporated in soils, chars produced in the laboratory under controlled conditions can be used to investigate the range of properties possible for natural chars. This report shows that charring conditions (temperature and time) have substantial impact on the acid functional group and lactone content of chars. Low temperatures (250?C) and long charring times (greater than 72 hours) produce chars with the highest acid functional group and lactone content. The charring of cellulose appears to be responsible for the creation of the acid functional group and lactones. The significance of this study is that low-temperature chars can have acid functional group contents comparable to humic materials (as high as 8.8 milliequivalents per gram). Acid functional group and lactone content decreases as charring temperature increases. The variation in formation conditions expected under natural fire conditions will result in a wide range of sorption properties for natural chars which are an important component of soil organic matter. By controlling the temperature and duration of charring, it is possible to tailor the sorption properties of chars, which may be used as soil amendments.

  13. Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones).

    PubMed

    Ann, Jihyae; Yoon, Suyoung; Baek, Jisoo; Kim, Da Hye; Lewin, Nancy E; Hill, Colin S; Blumberg, Peter M; Lee, Jeewoo

    2015-01-27

    DAG-lactones afford a synthetically accessible, high affinity platform for probing structure activity relationships at the C1 regulatory domain of protein kinase C (PKC). Given the central role of PKC isoforms in cellular signaling, along with their differential biological activities, a critical objective is the design of isoform selective ligands. Here, we report the synthesis of a series of DAG-lactones varying in their side chains, with a particular focus on linoleic acid derivatives. We evaluated their selectivity for PKC epsilon versus PKC alpha both under standard lipid conditions (100% phosphatidylserine, PS) as well as in the presence of a nuclear membrane mimetic lipid mixture (NML). We find that selectivity for PKC epsilon versus PKC alpha tended to be enhanced in the presence of the nuclear membrane mimetic lipid mixture and, for our lead compound, report a selectivity of 32-fold. PMID:25437619

  14. POWTEX Neutron Diffractometer at FRM II - New Perspectives in Rock Deformation and Recrystallisation Analysis

    NASA Astrophysics Data System (ADS)

    Walter, J. M.; Stipp, M.; Ullemeyer, K.; Klein, H.; Leiss, B.; Hansen, B.; Kuhs, W. F.

    2011-12-01

    Neutron diffraction has become a routine method in Geoscience for the quantitative analysis of crystallographic preferred orientations (CPOs) and for (experimental) powder diffraction. Quantitative texture analysis is a common tool for the investigation of fabric development in mono- and polyphase rocks, their deformation histories and kinematics. Furthermore the quantitative characterization of anisotropic physical properties by bulk texture measurements can be achieved due to the high penetration capabilities of neutrons. To cope with increasing needs for beam time at neutron diffraction facilities with the corresponding technical characteristics and equipment, POWTEX (POWder and TEXture Diffractometer) is designed as a high-intensity diffractometer at the neutron research reactor FRM II in Garching, Germany by groups from the RWTH Aachen, Forschungszentrum Jülich and the University of Göttingen. Complementary to existing neutron diffractometers (SKAT at Dubna, Russia; GEM at ISIS, UK; HIPPO at Los Alamos, USA; D20 at ILL, France; and the local STRESS-SPEC and SPODI at FRM II) the layout of POWTEX is focused on fast (texture) measurements for either time-resolved experiments or the measurement of larger sample series as necessary for the study of large scale geological structures. By utilizing a range of neutron wavelengths simultaneously (TOF-technique), a high flux (~1 x 107 n/cm2s) and a high detector coverage ( 9.8 sr) effective texture measurements without sample tilting and rotation are possible. Furthermore the instrument and the angular detector resolution is sufficient for strong recrystallisation textures as well as weak textures of polyphase rocks. Thereby large sample environments will be implemented at POWTEX allowing in-situ time-resolved texture measurements during deformation experiments on rocksalt, ice and other materials. Furthermore a furnace for 3D-recrystallisation analysis of single grains will be realized complementary to the furnace

  15. Chemical and Biological Investigation of Olive Mill Waste Water - OMWW Secoiridoid Lactones.

    PubMed

    Vougogiannopoulou, Konstantina; Angelopoulou, Maria T; Pratsinis, Harris; Grougnet, Raphaël; Halabalaki, Maria; Kletsas, Dimitris; Deguin, Brigitte; Skaltsounis, Leandros A

    2015-08-01

    Olive mill waste water is the major byproduct of the olive oil industry containing a range of compounds related to Olea europaea and olive oil constituents. Olive mill waste water comprises an important environmental problem in olive oil producing countries, but it is also a valuable material for the isolation of high added value compounds. In this study, an attempt to investigate the secoiridoid content of olive mill waste water is described with the aid of ultrahigh-performance liquid chromatography-electrospray ionization (±)-high-resolution mass spectrometry and centrifugal partition chromatography methods. In total, seven secoiridoid lactones were isolated, four of which are new natural products. This is the first time that a conjugate of hydroxytyrosol and a secoiridoid lactone has been isolated from olive mill waste water and structurally characterized. Furthermore, the range of isolated compounds allowed for the proposal of a hypothesis for the biotransformation of olive secoiridoids during the production of olive mill waste water. Finally, the ability of the representative compounds to reduce the intracellular reactive oxygen species was assessed with the dichlorofluorescein assay in conjunction with the known antioxidant agent hydroxytyrosol. PMID:26218340

  16. In Vitro Antiplasmodial Activity of Sesquiterpene Lactones from Ambrosia tenuifolia

    PubMed Central

    Sülsen, V.; Gutierrez Yappu, D.; Laurella, L.; Anesini, C.; Gimenez Turba, A.; Martino, V.; Muschietti, L.

    2011-01-01

    The in vitro antiplasmodial activity of Ambrosia tenuifolia organic extract and its isolated sesquiterpene lactones, psilostachyin and peruvin, has been evaluated against Plasmodium falciparum F32 and W2 strains. The cytotoxicity of both compounds was determined on lymphoid cells, and their corresponding selectivity indexes (SIs) were calculated. Peruvin was the most active compound on F32 strain of P. falciparum with a 50% inhibitory concentration value (IC50) of 0.3 μg/mL (1.1 μM) whereas psilostachyin showed activity on both strains (IC50 = 0.6 (2.1 μM) and 1.8 μg/mL (6.4 μM)). Fifty percent cytotoxic concentration (CC50) values (48 h) were 6.8 μg/mL (24.3 μM) and 10.0 μg/mL (37.9 μM) for psilostachyin and peruvin, respectively. PMID:21716685

  17. Varioxiranols I-L, new lactones from a sponge-associated Emericella variecolor fungus.

    PubMed

    Wu, Qi; Long, Hai-Lin; Liu, Dong; Proksch, Peter; Lin, Wen-Han

    2015-01-01

    Chemical examination of the sponge-associated fungus Emericella variecolor resulted in the isolation of four new lactones namely varioxiranols I-L(1-4)with different scaffolds, together with asteltoxin (5) and asteltoxin B (6). The structure elucidation of new compounds was accomplished by spectroscopic analysis, while the absolute configurations were determined by computed circular dichroism (ECD) and induced CD effects. Antitumor activities of these compounds were evaluated against different tumor cell lines, while the result indicated that the new compounds showed moderate cytotoxic activity against a panel of tumor cell lines. PMID:26700546

  18. [A new lactone derivative from plant endophytic fungus Periconia sp. F-31].

    PubMed

    Zhang, De-wu; Liu, Ji-mei; Chen, Ri-dao; Zhang, Min; Yu, Li-yan; Wu, Jun; Dai, Jun-gui

    2015-06-01

    To investigate the secondary metabolites of endophytic fungi Pericinia sp. F-31. Column chromatography on silica gel, Sephadex LH-20 and semi-preparative HPLC were used to separate and purify the compounds. Two compounds were isolated from the fermentation broth of Periconia sp. Their structures were identified as 5-(1-hydroxyhexyl) -6-methyl-2H-pyran-2-one (1) and 2-(3-hydroxy-4-methylphenyl) -propanoic acid (2). Compound 1 was a new lactone compound, compound 2 was new natural product, and the NMR data of compound 2 was reported for the first time. PMID:26591523

  19. Synergistic insecticidal mode of action between sesquiterpene lactones and a phototoxin, alpha-terthienyl.

    PubMed

    Guillet, G; Harmatha, J; Waddell, T G; Philogène, B J; Arnason, J T

    2000-02-01

    The synergistic insecticidal action of characteristic defensive substances produced by the plant family Asteraceae was investigated under controlled laboratory conditions. Sesquiterpene lactones isolated from Asteraceae that may form, through a Michael addition process, conjugates with glutathione were administered in a meridic diet to a herbivorous insect, Manduca sexta. By administering sesquiterpenes, variable in vivo reduced glutathione levels were observed in the insect larvae. When the Asteraceae-derived photooxidant alpha-terthienyl was co-administered, lipid peroxidation and larval mortality were significantly enhanced in the treated groups of insects with lowered in vivo glutathione levels. PMID:10687381

  20. New spiral γ-lactone enantiomers from the plant endophytic fungus Pestalotiopsis foedan.

    PubMed

    Yang, Xiao-Long; Li, Zhuang-Zhuang

    2013-01-01

    (-)-(4S, 8S)-Foedanolide (1a) and (+)-(4R, 8R)-foedanolide (1b), a pair of new spiro-γ-lactone enantiomers, were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis foedan by HPLC using a chiral column, achieving over 7% ee. Their structures and absolute configurations were determined on the basis of extensive analysis of NMR spectra combined with computational methods via calculation of the electronic circular dichroism (ECD) and optical rotation (OR). Compounds 1a and 1b showed moderate activities against HeLa, A-549, U-251, HepG2 and MCF-7 tumor cell lines. PMID:23434873

  1. Variability of sesquiterpene lactones in Neurolaena lobata of different origin.

    PubMed

    Passreiter, C M; Aldana, B E

    1998-06-01

    Leaves of Neurolaena lobata (L.) R. Br. originating from Guatemala, were analyzed using HPLC for their qualitative and quantitative sesquiterpene lactone contents. Significant differences in the individual amounts of neurolenins and furanoheliangolides were found between four natural populations. When plants were cultivated on proving fields at two different localities in Guatemala, their sesquiterpene lactone patterns matched the natural population, but differed quantitatively. The meaning of these differences for the use of N. lobata in traditional medicine and its cultivation is discussed. PMID:17253261

  2. 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

  3. Novel Reporter for Identification of Interference with Acyl Homoserine Lactone and Autoinducer-2 Quorum Sensing

    PubMed Central

    Weiland-Bräuer, Nancy; Pinnow, Nicole

    2014-01-01

    Two reporter strains were established to identify novel biomolecules interfering with bacterial communication (quorum sensing [QS]). The basic design of these Escherichia coli-based systems comprises a gene encoding a lethal protein fused to promoters induced in the presence of QS signal molecules. Consequently, these E. coli strains are unable to grow in the presence of the respective QS signal molecules unless a nontoxic QS-interfering compound is present. The first reporter strain designed to detect autoinducer-2 (AI-2)-interfering activities (AI2-QQ.1) contained the E. coli ccdB lethal gene under the control of the E. coli lsrA promoter. The second reporter strain (AI1-QQ.1) contained the Vibrio fischeri luxI promoter fused to the ccdB gene to detect interference with acyl-homoserine lactones. Bacteria isolated from the surfaces of several marine eukarya were screened for quorum-quenching (QQ) activities using the established reporter systems AI1-QQ.1 and AI2-QQ.1. Out of 34 isolates, two interfered with acylated homoserine lactone (AHL) signaling, five interfered with AI-2 QS signaling, and 10 were demonstrated to interfere with both signal molecules. Open reading frames (ORFs) conferring QQ activity were identified for three selected isolates (Photobacterium sp., Pseudoalteromonas sp., and Vibrio parahaemolyticus). Evaluation of the respective heterologously expressed and purified QQ proteins confirmed their ability to interfere with the AHL and AI-2 signaling processes. PMID:25527543

  4. Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones

    PubMed Central

    Geyer, Joachim; Janko, Christina

    2012-01-01

    P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA-gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug concentrations that otherwise would induce neurological toxicity. A 4-bp deletion mutation exists in the MDR1 gene of many dog breeds such as the Collie and the Australian Shepherd, which results in the expression of a non-functional P-glycoprotein and is associated with multiple drug sensitivity. Accordingly, dogs with homozygous MDR1 mutation are in general prone to neurotoxicity by macrocyclic lactones due to their increased brain penetration. Nevertheless, treatment of these dogs with macrocyclic lactones does not inevitably result in neurological symptoms, since, the safety of treatment highly depends on the treatment indication, dosage, route of application, and the individual compound used as outlined in this review. Whereas all available macrocyclic lactones can safely be administered to MDR1 mutant dogs at doses usually used for heartworm prevention, these dogs will experience neurological toxicity following a high dose regimen which is common for mange treatment in dogs. Here, we review and discuss the neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs. PMID:22039792

  5. Absolute configuration and antimicrobial activity of acylhomoserine lactones.

    PubMed

    Pomini, Armando M; Marsaioli, Anita J

    2008-06-01

    (S)-N-Heptanoylhomoserine lactone is an uncommon acyl odd-chain natural product employed by many Gram-negative bacteria as a signaling substance in chemical communication mechanisms known as quorum sensing. The absolute configuration determination of the metabolite produced by the phytopathogen Pantoea ananatis Serrano is reported herein. As with all other substances of this class, the lactone moiety possesses S configuration, corroborating the hypothesis that it shares the same biosynthetic pathway as the (S)-N-hexanoylhomoserine lactone and also that some LuxI homologues can accept both hexanoyl- and heptanoyl-ACP as precursors. Evaluation of the antimicrobial activity of enantiomeric acylhomoserine lactones against three Gram-positive bacteria (Bacillus cereus, B. subtilis, and Staphylococcus aureus) revealed important features between absolute configuration and antimicrobial activity. The N-heptanoylhomoserine lactone was considerably less active than the 3-oxo derivatives. Surprisingly, non-natural (R)-N-(3-oxo-octanoyl)homoserine lactone was as active as the S enantiomer against B. cereus, while the synthetic racemic product was less active than either enantiomer. PMID:18465897

  6. N-acyl homoserine lactone-producing Pseudomonas putida strain T2-2 from human tongue surface.

    PubMed

    Chen, Jian-Woon; Chin, Shenyang; Tee, Kok Keng; Yin, Wai-Fong; Choo, Yeun Mun; Chan, Kok-Gan

    2013-01-01

    Bacterial cell-to-cell communication (quorum sensing) refers to the regulation of bacterial gene expression in response to changes in microbial population density. Quorum sensing bacteria produce, release and respond to chemical signal molecules called autoinducers. Bacteria use two types of autoinducers, namely autoinducer-1 (AI-1) and autoinducer-2 (AI-2) where the former are N-acylhomoserine lactones and the latter is a product of the luxS gene. Most of the reported literatures show that the majority of oral bacteria use AI-2 for quorum sensing but rarely the AI-1 system. Here we report the isolation of Pseudomonas putida strain T2-2 from the oral cavity. Using high resolution mass spectrometry, it is shown that this isolate produced N-octanoylhomoserine lactone (C8-HSL) and N-dodecanoylhomoserine lactone (C12-HSL) molecules. This is the first report of the finding of quorum sensing of P. putida strain T2-2 isolated from the human tongue surface and their quorum sensing molecules were identified. PMID:24084113

  7. L-pantoyl lactone dehydrogenase from Rhodococcus erythropolis: genetic analyses and application to the stereospecific oxidation of L-pantoyl lactone.

    PubMed

    Si, Dayong; Urano, Nobuyuki; Nozaki, Shinya; Honda, Kohsuke; Shimizu, Sakayu; Kataoka, Michihiko

    2012-07-01

    The 1,2-propanediol (1,2-PD) inducible membrane-bound L-pantoyl lactone (L-PL) dehydrogenase (LPLDH) has been isolated from Rhodococcus erythropolis AKU2103 (Kataoka et al. in Eur J Biochem 204:799, 1992). Based on the N-terminal amino acid sequence of LPLDH and the highly conserved amino acid sequence in homology search results, the LPLDH gene (lpldh) was cloned. The gene consists of 1,179 bases and encodes a protein of 392 amino acid residues. The deduced amino acid sequence showed high similarity to the proteins of the FMN-dependent α-hydroxy acid dehydrogenase/oxidase family. The overexpression vector pKLPLDH containing lpldh with its upstream region (1,940 bp) was constructed and introduced into R. erythropolis AKU2103. The recombinant R. erythropolis AKU2103 harboring pKLPLDH showed six times higher LPLDH activity than the wild-type strain. Conversion of L-PL to ketopantoyl lactone was achieved with 92% or 80% conversion yield when the substrate concentration was 0.768 or 1.15 M, respectively. Stereoinversion of L-PL to D-PL was also carried out by using the combination of recombinant R. erythropolis AKU2103 harboring pKLPLDH and ketopantoic acid-reducing Escherichia coli. PMID:22398860

  8. Characterisation and optimisation of the new Prompt Gamma-ray Activation Analysis (PGAA) facility at FRM II

    NASA Astrophysics Data System (ADS)

    Canella, Lea; Kudějová, Petra; Schulze, Ralf; Türler, Andreas; Jolie, Jan

    2011-04-01

    At the research reactor Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II) a new Prompt Gamma-ray Activation Analysis (PGAA) facility was installed. The instrument was originally built and operating at the spallation source at the Paul Scherrer Institute in Switzerland. After a careful re-design in 2004-2006, the new PGAA instrument was ready for operation at FRM II. In this paper the main characteristics and the current operation conditions of the facility are described. The neutron flux at the sample position can reach up 6.07×1010 [cm-2 s-1], thus the optimisation of some parameters, e.g. the beam background, was necessary in order to achieve a satisfactory analytical sensitivity for routine measurements. Once the optimal conditions were reached, detection limits and sensitivities for some elements, like for example H, B, C, Si, or Pb, were calculated and compared with other PGAA facilities. A standard reference material was also measured in order to show the reliability of the analysis under different conditions at this instrument.

  9. Characterization of quorum sensing and quorum quenching soil bacteria isolated from Malaysian tropical montane forest.

    PubMed

    Chong, Teik-Min; Koh, Chong-Lek; Sam, Choon-Kook; Choo, Yeun-Mun; Yin, Wai-Fong; Chan, Kok-Gan

    2012-01-01

    We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis. PMID:22666062

  10. Studies on zoapatle, II. Leucanthanolide, a novel sesquiterpene lactone from Montanoa leucantha ssp. leucantha.

    PubMed

    Oshima, Y; Wong, S M; Konno, C; Cordell, G A; Waller, D P; Soejarto, D D; Fong, H H

    1986-01-01

    A sesquiterpene lactone given the trivial name leucanthanolide, from the Mexican zoapatle plant (Montanoa leucantha), long used as an herbal remedy, was isolated and was found to have cytotoxicity but no uterine activity. The compound was isolated from the fraction containing zoapatanol, a substance being investigated for its ability to induce menses, abortion and labor. The compound has a molecular formula of C19H2606, a 5-membered lactone ring, an ester group, and a germacradienolide skeleton. It was evaluated for abortifacient activity in pregnant guinea pigs by intraperitoneal injection on day 22 of gestation. 3 of 5 animals had abnormal fetuses, but there was no evidence of early uterine activity. Cytotoxic testing in vitro was done on KB and P-388 test systems in cell culture. The ED50 of leucanthanolide was 0.57 mcg/ml (KB) and 0.93 (P-388). In comparison, the ethyl acetate fraction had an ED50 of 1.35 mcg/ml and 5.2 mcg/ml respectively. PMID:3814249

  11. The Joint Action of Sesquiterpene Lactones from Leaves as an Explanation for the Activity of Cynara cardunculus.

    PubMed

    Rial, Carlos; García, Benito F; Varela, Rosa M; Torres, Ascensión; Molinillo, José M G; Macías, Francisco A

    2016-08-24

    The work described herein is a continuation of a previous study centered on the bioprospect of cardoon (Cynara cardunculus) leaf extracts through the isolation of secondary metabolites with phytotoxic activity. Chromatographic fractionations of the ethyl acetate extract and spectroscopic analysis showed that the majority of the components were sesquiterpene lactones. Of these compounds, aguerin B, grosheimin, and cynaropicrin were very active on etiolated wheat coleoptile, standard target species, and weed growth. The joint action of binary mixtures of these three active sesquiterpene lactones and one nonactive compound (11,13-dihydroxy-8-desoxygrosheimin) was studied. The activities of fixed-ratio mixtures were assessed on wheat coleoptile. The results can be interpreted with respect to a reference model by considering dose-response analyses and isobolograms with linear regression analyses. A total of 17 binary mixtures at different levels of inhibition (ED25, ED50, and ED75) were studied, and predominantly they responded additively (25). Deviations from additivity included seven synergistic responses and two antagonistic responses. The joint action of major sesquiterpene lactones isolated from C. cardunculus can explain the activities observed in extracts and fractions. The results reported here reiterate the utility of the wheat coleoptile bioassay as a quick tool to detect potential synergistic effects in binary mixtures. PMID:27487046

  12. Biosynthesis of sesquiterpene lactones in pyrethrum (Tanacetum cinerariifolium).

    PubMed

    Ramirez, Aldana M; Saillard, Nils; Yang, Ting; Franssen, Maurice C R; Bouwmeester, Harro J; Jongsma, Maarten A

    2013-01-01

    The daisy-like flowers of pyrethrum (Tanacetum cinerariifolium) are used to extract pyrethrins, a botanical insecticide with a long history of safe and effective use. Pyrethrum flowers also contain other potential defense compounds, particularly sesquiterpene lactones (STLs), which represent problematic allergenic residues in the extracts that are removed by the pyrethrum industry. The STLs are stored in glandular trichomes present on the pyrethrum achenes, and have been shown to be active against herbivores, micro-organisms and in the below-ground competition with other plants. Despite these reported bioactivities and industrial significance, the biosynthetic origin of pyrethrum sesquiterpene lactones remains unknown. In the present study, we show that germacratrien-12-oic acid is most likely the central precursor for all sesquiterpene lactones present in pyrethrum. The formation of the lactone ring depends on the regio- (C6 or C8) and stereo-selective (α or β) hydroxylation of germacratrien-12-oic acid. Candidate genes implicated in three committed steps leading from farnesyl diphosphate to STL and other oxygenated derivatives of germacratrien-12-oic acid were retrieved from a pyrethrum trichome EST library, cloned, and characterized in yeast and in planta. The diversity and distribution of sesquiterpene lactones in different tissues and the correlation with the expression of these genes are shown and discussed. PMID:23741445

  13. Discovery of Pantoea rodasii Strain ND03 that Produces N-(3-Oxo-hexanoyl)-l-homoserine Lactone

    PubMed Central

    Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    Proteobacteria use quorum sensing to regulate target gene expression in response to population density. Quorum sensing (QS) is achieved via so-called signalling molecules and the best-studied QS signalling system uses N-acyl homoserine lactones (AHLs). This study aimed to identify and characterize the production of AHLs by a bacterium ND03 isolated from a Malaysian tropical rainforest waterfall. Molecular identification showed that ND03 is a Pantoea sp. closely related to Pantoea rodasii. We used Chromobacterium violaceum CV026, an AHL biosensor for preliminary AHL production screening and then used high resolution triple quadrupole liquid chromatography-mass spectrometry, to confirm that P. rodasii strain ND03 produced N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). To the best of our knowledge, this is the first report for such a discovery in P. rodasii strain ND03. PMID:24859023

  14. Production of acylated homoserine lactone by a novel marine strain of Proteus vulgaris and inhibition of its swarming by phytochemicals.

    PubMed

    Biswa, Pramal; Doble, Mukesh

    2014-10-01

    A marine strain of Proteus vulgaris capable of activating multiple acylated homoserine lactone (AHL)-based reporter cultures was isolated. The cognate signal molecule was characterized as octanoyl homoserine lactone (OHL) and its production was observed to be growth dependent, with maximum production (5.675 µg l(-1)) at 24 h growth. The strain exhibited swarming, but its motility was not affected upon addition of pure OHL or culture supernatant. Phytochemicals such as quercitin and berberine chloride inhibited OHL production and reduced swarming. FliA, the predominantly upregulated protein during swarming, was considered as a possible target for these inhibitors, and docking of the two most active and two least active inhibitors to this protein suggested preferential binding of the former set of compounds. Apart from adding new evidence to AHL production in Proteus vulgaris, active inhibitors shortlisted from this study could help in identifying lead compounds to act against this opportunistic pathogen of the respiratory and gastrointestinal tract. PMID:25012967

  15. Sesquiterpene lactones from Inula falconeri, a plant endemic to the Himalayas, as potential anti-inflammatory agents.

    PubMed

    Cheng, Xiangrong; Zeng, Qi; Ren, Jie; Qin, Jiangjiang; Zhang, Shoude; Shen, Yunheng; Zhu, Jiaxian; Zhang, Fei; Chang, Ruijie; Zhu, Yan; Zhang, Weidong; Jin, Huizi

    2011-11-01

    A phytochemical investigation of Inula falconeri, a plant endemic to the Himalayas, afforded 10 new sesquiterpenoids and 26 known sesquiterpene lactones, including those bearing guaiane, pseudoguaiane, xanthane, eudesmane, germacrane, rare secocaryophyllane, chromolaevane, and carabrane frameworks. The structures were elucidated via spectroscopic analysis and compared with data from literature. All the isolates were assessed for their inhibitory effects against LPS-induced nitric oxide production in RAW264.7 macrophages. Compounds 4, 11, 24, and 31 showed stronger inhibitory activities than the positive control with IC(50) values of 0.13, 0.07, 0.11, and 0.11 μM, respectively. These studies also led to a better understanding of the structure-activity relationships for the sesquiterpene lactone family of compounds. PMID:21924800

  16. Discovery of Pantoea rodasii strain ND03 that produces N-(3-Oxo-hexanoyl)-L-homoserine lactone.

    PubMed

    Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    Proteobacteria use quorum sensing to regulate target gene expression in response to population density. Quorum sensing (QS) is achieved via so-called signalling molecules and the best-studied QS signalling system uses N-acyl homoserine lactones (AHLs). This study aimed to identify and characterize the production of AHLs by a bacterium ND03 isolated from a Malaysian tropical rainforest waterfall. Molecular identification showed that ND03 is a Pantoea sp. closely related to Pantoea rodasii. We used Chromobacterium violaceum CV026, an AHL biosensor for preliminary AHL production screening and then used high resolution triple quadrupole liquid chromatography-mass spectrometry, to confirm that P. rodasii strain ND03 produced N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL). To the best of our knowledge, this is the first report for such a discovery in P. rodasii strain ND03. PMID:24859023

  17. Seasonal variation in sesquiterpene lactone concentration and composition of forage chicory (Cichorium intybus L.) cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chicory (Cichorium intybus L.) herbage contains sesquiterpene lactones that are believed to help control gastrointestinal nematodes in small ruminants. Because the anthelmintic effect could be related to both total sesquiterpene lactone concentration and the proportions of the principal constituent...

  18. Quorum sensing inhibitory potential and molecular docking studies of sesquiterpene lactones from Vernonia blumeoides.

    PubMed

    Aliyu, Abubakar Babando; Koorbanally, Neil Anthony; Moodley, Brenda; Singh, Parvesh; Chenia, Hafizah Yousuf

    2016-06-01

    The increasing incidence of multidrug-resistant Gram-negative bacterial pathogens has focused research on the suppression of bacterial virulence via quorum sensing inhibition strategies, rather than the conventional antimicrobial approach. The anti-virulence potential of eudesmanolide sesquiterpene lactones previously isolated from Vernonia blumeoides was assessed by inhibition of quorum sensing and in silico molecular docking. Inhibition of quorum sensing-controlled violacein production in Chromobacterium violaceum was quantified using violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum and Agrobacterium tumefaciens biosensor systems. Inhibition of violacein production was concentration-dependent, with ⩾90% inhibition being obtained with ⩾2.4mgml(-1) of crude extracts. Violacein inhibition was significant for the ethyl acetate extract with decreasing inhibition being observed with dichloromethane, hexane and methanol extracts. Violacein inhibition ⩾80% was obtained with 0.071mgml(-1) of blumeoidolide B in comparison with ⩾3.6mgml(-1) of blumeoidolide A. Agar diffusion double ring assays indicated that only the activity of the LuxI synthase homologue, CviI, was modulated by blumeoidolides A and B, and V. blumeoides crude extracts, suggesting that quorum sensing signal synthesis was down-regulated or competitively inhibited. Finally, molecular docking was conducted to explore the binding conformations of sesquiterpene lactones into the binding sites of quorum sensing regulator proteins, CviR and CviR'. The computed binding energy data suggested that the blumeoidolides have a tendency to inhibit both CviR and CviR' with varying binding affinities. Vernonia eudesmanolide sesquiterpene lactones have the potential to be novel therapeutic agents, which might be important in reducing virulence and pathogenicity of drug-resistant bacteria in

  19. Sesquiterpene Lactones from Gynoxys verrucosa and their Anti-MRSA Activity

    PubMed Central

    Ordóñez, Paola E.; Quave, Cassandra L.; Reynolds, William F.; Varughese, Kottayil I.; Berry, Brian; Breen, Philip J.; Malagón, Omar; Smeltzer, Mark S.; Compadre, Cesar M.

    2011-01-01

    Ethnopharmacological relevance Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Materials and Methods The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of G. verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of G. verrucosa extracts and its purified constituents was determined against six clinical isolates including S. aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Results Compound 1 has very low activity, while compound 2 has moderate activity with MIC50s between 49 and195 μg/mL. The extract of G. verrucosa has weak activity with MIC50s between 908 and 3290 μg/mL. Conclusions We are reporting the full assignment of the 1H-NMR and 13C-NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plants extracts, does not explain the use of G. verrucosa in traditional medicine for the treatment of wounds and skin infections. PMID:21782013

  20. Operon for Biosynthesis of Lipstatin, the Beta-Lactone Inhibitor of Human Pancreatic Lipase

    PubMed Central

    Bai, Tingli; Zhang, Daozhong; Lin, Shuangjun; Long, Qingshan; Wang, Yemin; Ou, Hongyu; Kang, Qianjin; Deng, Zixin; Liu, Wen

    2014-01-01

    Lipstatin, isolated from Streptomyces toxytricini as a potent and selective inhibitor of human pancreatic lipase, is a precursor for tetrahydrolipstatin (also known as orlistat, Xenical, and Alli), the only FDA-approved antiobesity medication for long-term use. Lipstatin features a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-β-lactone structure with an N-formyl-l-leucine group attached as an ester to the 5-hydroxy group. It has been suggested that the α-branched 3,5-dihydroxy fatty acid β-lactone moiety of lipstatin in S. toxytricini is derived from Claisen condensation between two fatty acid substrates, which are derived from incomplete oxidative degradation of linoleic acid based on feeding experiments. In this study, we identified a six-gene operon (lst) that was essential for the biosynthesis of lipstatin by large-deletion, complementation, and single-gene knockout experiments. lstA, lstB, and lstC, which encode two β-ketoacyl–acyl carrier protein synthase III homologues and an acyl coenzyme A (acyl-CoA) synthetase homologue, were indicated to be responsible for the generation of the α-branched 3,5-dihydroxy fatty acid backbone. Subsequently, the nonribosomal peptide synthetase (NRPS) gene lstE and the putative formyltransferase gene lstF were involved in decoration of the α-branched 3,5-dihydroxy fatty acid chain with an N-formylated leucine residue. Finally, the 3β-hydroxysteroid dehydrogenase-homologous gene lstD might be responsible for the reduction of the β-keto group of the biosynthetic intermediate, thereby facilitating the formation of the unique β-lactone ring. PMID:25239907

  1. Long-chain acyl-homoserine lactones from Methylobacterium mesophilicum: synthesis and absolute configuration.

    PubMed

    Pomini, Armando M; Cruz, Pedro L R; Gai, Cláudia; Araújo, Welington L; Marsaioli, Anita J

    2009-12-01

    The acyl-homoserine lactones (acyl-HSLs) produced by Methylobacterium mesophilicum isolated from orange trees infected with the citrus variegated chlorosis (CVC) disease have been studied, revealing the occurrence of six long-chain acyl-HSLs, i.e., the saturated homologues (S)-N-dodecanoyl (1) and (S)-N-tetradecanoyl-HSL (5), the uncommon odd-chain N-tridecanoyl-HSL (3), the new natural product (S)-N-(2E)-dodecenoyl-HSL (2), and the rare unsaturated homologues (S)-N-(7Z)-tetradecenoyl (4) and (S)-N-(2E,7Z)-tetradecadienyl-HSL (6). The absolute configurations of all HSLs were determined as 3S. Compounds 2 and 6 were synthesized for the first time. Antimicrobial assays with synthetic acyl-HSLs against Gram-positive bacterial endophytes co-isolated with M. mesophilicum from CVC-infected trees revealed low or no antibacterial activity. PMID:19919062

  2. Relationship between Menthiafolic Acid and Wine Lactone in Wine.

    PubMed

    Giaccio, Joanne; Curtin, Chris D; Sefton, Mark A; Taylor, Dennis K

    2015-09-23

    Menthiafolic acid (6-hydroxy-2,6-dimethylocta-2,7-dienoic acid, 2a) was quantified by GC-MS in 28 white wines, 4 Shiraz wines, and for the first time in 6 white grape juice samples. Menthiafolic acid was detected in all but one of the wine samples at concentrations ranging from 26 to 342 μg/L and in the juice samples from 16 to 236 μg/L. Various model fermentation experiments showed that some menthiafolic acid in wine could be generated from the grape-derived menthiafolic acid glucose ester (2b) during alcoholic and malolactic fermentation. Samples containing high concentrations of menthiafolic acid were also analyzed by enantioselective GC-MS and were shown to contain this compound in predominantly the (S)-configuration. Enantioselective analysis of wine lactone (1) in one of these samples, a four-year-old Chardonnay wine showed, for the first time, the presence of the 3R,3aR,7aS isomer of wine lactone (1b), which is the enantiomer of the form previously reported as the sole isomer present in young wine samples. The weakly odorous 3R,3aR,7aS 1b form comprised 69% of the total wine lactone in the sample. On the basis of the enantioselectivity of the hydrolytic conversion of menthiafolic acid to wine lactone at pH 3.0 determined previously and the relative proportions of (R)- and (S)-menthiafolic acid in the Chardonnay wine, the predicted ratio of wine lactone enantiomers that would be formed from hydrolysis at ambient temperature of the menthiafolic acid present in this wine was close to the ratio measured, which was consistent with menthiafolic acid being the major or sole precursor to wine lactone in this sample. PMID:26321591

  3. A New Search for the Atomic EDM of 129Xe at FRM-II (Munich Research Reactor)

    NASA Astrophysics Data System (ADS)

    Singh, Jaideep; Fierlinger, Peter; Kraegeloh, Eva; Kuchler, Florian; Lins, Tobias; Marino, Mike; Meinel, Jonas; Neissen, Benjamin; Stuiber, Stefan; Burghoff, Martin; Fan, Isaac; Kilian, Wolfgang; Knappe-Grueneberg, Silvia; Schnabel, Allard; Seifert, Frank; Trahms, Lutz; Voigt, Jens; Chupp, Tim; Degenkolb, Skyler; Gong, Fei; Sachdeva, Natasha; Babcock, Earl

    2014-09-01

    Electric dipole moments (EDMs) arise due to the breaking of time-reversal or, equivalently, CP -symmetry. Although all searches have so far only set upper limits on EDMs, the motivation for more sensitive searches is stronger than ever. The present limit of 6 ×10-27 e * cm (95% CL) for the 129Xe EDM helps constrain CP -violating parameters within nuclei. A new effort at FRM-II incorporating a 3He comagnetometer can potentially improve this limit by over three orders of magnitude. The noble gas mixture is polarized by spin-exchange optical pumping and then transferred into a high-performance magnetically shielded room. A SQUID magnetometer array measures the precession frequencies in the presence of applied electric- & magnetic-fields. Recent test runs indicate that the experiment is capable of an EDM sensitivity of 10-28 e * cm in one day.

  4. A New Search for the Atomic EDM of 129 Xe at FRM-II (Munich Research Reactor)

    NASA Astrophysics Data System (ADS)

    Kuchler, Florian; Fierlinger, Peter; Kraegeloh, Eva; Lins, Tobias; Marino, Mike; Meinel, Jonas; Niessen, Benjamin; Stuiber, Stefan; Burghoff, Martin; Fan, Isaac; Kilian, Wolfgang; Knappe-Grueneberg, Silvia; Schnabel, Allard; Seifert, Frank; Trahms, Lutz; Voigt, Jens; Chupp, Tim; Degenkolb, Skyler; Gong, Fei; Sachdeva, Natasha; Babcock, Earl; Singh, Jaideep

    2015-04-01

    Electric dipole moments (EDMs) arise due to the breaking of time-reversal or, equivalently, CP-symmetry. Although all searches have so far only set upper limits on EDMs, the motivation for more sensitive searches is stronger than ever. The present limit of 6 × 10-27 e*cm (95 % CL) for the 129 Xe EDM helps constrain CP-violating parameters within nuclei. A new effort at FRM-II incorporating a 3 He comagnetometer can potentially improve this limit by over three orders of magnitude. The noble gas mixture is polarized by spin-exchange optical pumping and then transferred into a high-performance magnetically shielded room. A SQUID magnetometer array measures the precession frequencies in the presence of applied electric- and magnetic-fields. Recent test runs indicate that the experiment is capable of an EDM sensitivity of 10-28 e*cm in one day.

  5. Genepolide, a sesterpene gamma-lactone with a novel carbon skeleton from mountain wormwood (Artemisia umbelliformis).

    PubMed

    Appendino, Giovanni; Taglialatela-Scafati, Orazio; Romano, Adriana; Pollastro, Federica; Avonto, Cristina; Rubiolo, Patrizia

    2009-03-27

    The sesterpene gamma-lactone genepolide (5) has been isolated from a Swiss horticultural variety of mountain wormwood (Artemisia umbelliformis) developed as a thujones-free alternative to native Western Alps wormwoods for the production of liqueurs. Genepolide is the formal Diels-Alder adduct of the exomethylene-gamma-lactone costunolide (2) and the diene myrcene (6), two poorly reactive partners in cycloaddition reactions, and its structure was elucidated through a combination of spectroscopic methods. An investigation on the thermal stability of mixtures of 2 and 6, as well as considerations on the sensitivity of 2 to Brønsted and Lewis acids, suggests that 5 is a genuine natural product and that the Swiss chemotype of A. umbelliformis contains Diels-Alderase enzymatic activity that is lacking in native mountain wormwoods from Western Alps. Remarkable differences in thermal and acid-catalyzed reactions of the cyclodecadiene moiety of 2 and 5 suggest that quaternarization at C-11 has far-reaching effects on the reactivity of their homoconjugated medium-sized diene system. The wide occurrence of this structural motif in sesquiterpenoids makes this issue worth a systematic investigation. PMID:19053512

  6. Cytotoxic and apoptotic effects of leptocarpin, a plant-derived sesquiterpene lactone, on human cancer cell lines.

    PubMed

    Bosio, Claudia; Tomasoni, Giacomo; Martínez, Rolando; Olea, Andrés F; Carrasco, Héctor; Villena, Joan

    2015-12-01

    Sesquiterpene lactones have attracted much attention in drug research because they present a series of biological activities such as anticancer, antifungal, anti-inflammatory, antimicrobial and antioxidant. Leptocarpin (LTC) is a sesquiterpene lactone isolated from a native Chilean plant, Leptocarpha rivularis, which has been widely used in traditional medicine by Mapuche people. Previous work has demonstrated that LTC decreases cell viability of cancer cell lines. In this contribution, we analyze the mechanism of LTC cytotoxicity on different cancer cell lines. The results show that in all cases LTC induces an apoptotic process and inhibition of NF-κB. Apoptosis has been confirmed by observing condensation of chromatin, nuclear fragmentation, release of cytochrome c into the cytosol, and increasing of caspase-3 activity. It has also been found that LTC is an effective inhibitor of NF-κB, which suggests that leptocarpin-induced cytotoxicity involves in some degree the inhibition of NF-κB signaling pathway. The concentration at which LTC inhibits NF-κB activity to the control level is similar or even lower than that found for parthenolide and others sesquiterpene lactones. These results indicate that leptocarpine is a very interesting molecule that could be considered as therapeutic agent for cancer treatment. PMID:26562779

  7. Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).

    PubMed

    Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M

    2015-11-01

    Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety. PMID:26412035

  8. Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana

    PubMed Central

    Barrera, Patricia; Sülsen, Valeria P.; Lozano, Esteban; Rivera, Mónica; Beer, María Florencia; Tonn, Carlos; Martino, Virginia S.; Sosa, Miguel A.

    2013-01-01

    Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host's cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes. We first observed that the antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of the compounds, suggesting that lactones may react with intracellular sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, significantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these findings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act by another mechanism. PMID:23861697

  9. Oxidative conversion of δ-sultones to γ-lactones

    PubMed Central

    Liyanage, Duminda S.; Jungong, Christian S.; Novikov, Alexei V.

    2015-01-01

    Delta-sultones, prepared by C-H insertion, can be oxidatively converted to gamma-lactones by treatment with t-BuOK/t-BuOOH. An intermediate in the synthesis of (−)-eburnamonin was prepared using this approach. PMID:26085691

  10. Enantioselective synthesis of isotopically labeled homocitric acid lactone.

    PubMed

    Moore, Jared T; Hanhan, Nadine V; Mahoney, Maximillian E; Cramer, Stephen P; Shaw, Jared T

    2013-11-15

    A concise synthesis of homocitric acid lactone was developed to accommodate systematic placement of carbon isotopes (specifically (13)C) for detailed studies of this cofactor. This new route uses a chiral allylic alcohol, available in multigram quantities from enzymatic resolution, as a starting material, which transposes asymmetry through an Ireland-Claisen rearrangement. PMID:24180620

  11. Mechanisms of lactone hydrolysis in neutral and alkaline conditions.

    PubMed

    Gómez-Bombarelli, Rafael; Calle, Emilio; Casado, Julio

    2013-07-19

    The neutral and base-catalyzed hydrolysis of nine carboxylic acid esters was studied using a hybrid supermolecule-PCM approach including six explicit water molecules. The molecules studied included two linear esters, four β-lactones, two γ-lactones, and one δ-lactone: ethyl acetate and methyl formate, β-propiolactone, β-butyrolactone, β-isovalerolactone, diketene (4-methyleneoxetan-2-one), γ-butyrolactone, 2(5H)-furanone, and δ-valerolactone. DFT and ab initio methods were used to analyze the features of the various possible hydrolysis mechanisms. For all compounds, reasonable to very good qualitative and quantitative agreement with experimental work was found, and evidence is provided to support long-standing hypotheses regarding the role of solvent molecule as a base catalyst. In addition, novel evidence is presented for the existence of an elimination-addition mechanism in the basic hydrolysis of diketene. A parallel work addresses the acid-catalyzed hydrolysis of lactones. PMID:23758295

  12. Lactones in 193 nm resists: What do they do?

    NASA Astrophysics Data System (ADS)

    Ito, Hiroshi; Truong, Hoa D.; Brock, Phil J.

    2008-03-01

    Lactones are almost ubiquitously employed in 193 nm resists to increase the polarity of hydrophobic alicyclic polymers. What else do lactones do in 193 nm resists? We studied the behavior of methacrylate (MA) resists consisting of different protecting groups, hexafluoroalcohols, and norbornane lactone methacrylate (NLM, 2-oxo-3-oxatricyclo[4.2.1.04,8]nonan-5-yl methacrylate). When the protecting group is large [ethylcyclooctyl (ECO) and methyladamantyl (MAd)], thinning of the resist film that occurs in highly exposed areas upon postexposure bake (PEB) is significantly smaller than what is expected from the polymer composition. When the concentration of isopropylhexafluoroalcohol methacrylate (iPrHFAMA) is increased in the ECOMA-NLM polymer, the thinning increases and reaches 100% of theory and the ECOMA-norbornenehexafluoroalcohol methacrylate (NBHFAMA) resist loses quantitative thickness in highly-exposed areas upon PEB at 90 °C. This indicates that small lactones which are more basic than esters can trap deprotection fragments especially when the protecting group is large. Such entrapment was detected by IR spectroscopy and also observed at temperatures as high as 200 °C in thermogravimetric analysis (TGA). Incorporation of lactone appears to decrease the bake temperature sensitivity and the sensitivity of the resist perhaps due to trapping of photochemically generated acids by basic lactone. The lactone ring can be hydrolyzed during aqueous base development but does not seem to affect the dissolution rate, indicating that hydrolysis occurs in aqueous base solution after dissolution. Poly(methacrylic acid-NLM) dissolves as fast as poly(methacrylic acid) in 0.26 N tetramethylammonium hydroxide (TMAH) aqueous solution. While exposed P(ECOMA 47-NLM 53) resist dissolves in 0.26 N developer at about the same rate as authentically prepared poly(methacrylic acid 47-NLM 53), the dissolution rate of highly-exposed P(MAdMA 44-NLM 56) resist is much slower, indicating

  13. A New Antimicrobial Prenylated Benzo-lactone from the Rhizome of Cissus cornifolia

    PubMed Central

    Musa, Aliyu M.; Tajuddeen, Nasir; Idris, Abdullahi Y.; Rafindadi, Abdurahman Y.; Abdullahi, Musa I.; Aliyu, Abubakar B.; Abdullahi, Mikhail S.; Ibrahim, Mohammed A.

    2015-01-01

    Background: Medicinal plants remain one of the largest reservoirs of new bioactive compounds. In this study, a new prenylated benzo-lactone (4, 6-dihydroxy-5-methoxy-3-(1, 2, 3, 4, 5-pentahydroxypentyl)-2-benzofuran-1(3H)-one) was isolated from the acetone extracts of the rhizome of Cissus cornifolia. The antimicrobial activity of the compound was evaluated against some microorganisms including Staphylococcus aureus, Salmonella typhi, and Candida albicans. Materials and Methods: The acetone extracts of the rhizome of C. cornifolia was separated and purified by various chromatographic techniques. The structure of the isolated compound was characterized by analysis of spectral data including one and two-dimensional nuclear magnetic resonance. Results: The isolated compound was characterized as (4, 6-dihydroxy-5-methoxy-3-(1, 2, 3, 4, 5-pentahydroxypentyl)-2-benzofuran-1(3H)-one), it showed activity against 6 out of 10 tested clinical isolates of some microorganisms including S. aureus, S. typhi, and C. albicans. The inhibition zones ranged between 17 mm and 25 mm. The inhibition zones observed compare favorably with the positive control used. Conclusion: The compound could serve as a lead for the development of more potent antimicrobial agent. To the best of our knowledge, this is the first report of the isolation and characterization as well as antimicrobial screening of the compound. PMID:26692751

  14. Conversion of a Benzofuran Ester to an Amide through an Enamine Lactone Pathway: Synthesis of HCV Polymerase Inhibitor GSK852A.

    PubMed

    Bowman, Roy K; Bullock, Kae M; Copley, Royston C B; Deschamps, Nicole M; McClure, Michael S; Powers, Jeremiah D; Wolters, Andy M; Wu, Lianming; Xie, Shiping

    2015-10-01

    HCV NS5B polymerase inhibitor GSK852A (1) was synthesized in only five steps from ethyl 4-fluorobenzoylacetate (3) in 46% overall yield. Key to the efficient route was the synthesis of the highly functionalized benzofuran core 15 from the β-keto ester in one pot and the efficient conversion of ester 6 to amide 19 via enamine lactone 22. Serendipitous events led to identification of the isolable enamine lactone intermediate 22. Single crystal X-ray diffraction and NMR studies supported the intramolecular hydrogen bond shown in enamine lactone 22. The hydrogen bond was considered an enabler in the proposed pathway from ester 6 to enamine lactone 22 and its rearrangement to amide 19. GSK852A (1) was obtained after reductive amination and mesylation with conditions amenable to the presence of the boronic acid moiety which was considered important for the desirable pharmacokinetics of 1. The overall yield of 46% in five steps was a significant improvement to the previous synthesis from the same β-keto ester in 5% yield over 13 steps. PMID:26355847

  15. A new lanostane-type triterpene and sesquiterpene lactones from Vernonia leopoldii and their in vitro cytotoxicity.

    PubMed

    Marzouk, Amani M; Abd Elhalim, Osama B

    2016-04-01

    Investigation of the aerial parts of Vernonia leopoldii (Sch. Bip.) Vatke afforded a new lanostane-type triterpene along with known hirsutinolide-type sesquiterpene lactones and flavonoid glycosides, all are identified for the first time in this species. The new compound was identified as lanost-3β, 23S-dihydroxy-22(31)-ene. The structures of the isolated compounds were elucidated based on spectroscopic evidence. The hirsutinolides and the triterpene were evaluated for their cytotoxicity against four human cancer cell lines using MTT assay. PMID:26207920

  16. Frequency of FRM1 premutations in a consecutive newborn Manitoba population of PCR of Guthrie blood spots

    SciTech Connect

    Dawson, A.J.; Chudley, A.E.; Chodirker, B.

    1994-09-01

    We have analyzed the frequency of premutations of the FRM1 gene in 3000 X chromosomes of 1000 male and 1000 female consecutive newborn Guthrie blood spots in an unlinked, anonymous survey. The CGG repeat sizes were calculated by measuring the length of products of the PCR reaction based on the molecular size of labeled markers in a denaturing sequencing gel assay. For consistent PCR amplification a DNA microextraction was necessary, including a phenol/chloroform series. In our population, the CGG repeat ranged from 9-106 but 96% of alleles had fewer than 40 repeats. The most frequent allele was a repeat of 28. Approximately 2.7% of alleles had CGG repeats ranging from 40-49 and 0.36% of alleles had repeats ranging from 50-59. The frequency of alleles {ge}60 repeats in the Manitoba population is approximately 0.18%. The use of Guthrie blood spots for population screening of fra(X) premutations is not recommended. The necessity of a phenol/chloroform DNA microextraction is tedious and time consuming. The low yield of DNA (-250 ng) does not allow for re-analysis by Southern blot of apparently homozygous females and may result in an underestimate of premutation carrier status.

  17. Evaluation of novel lactone derivatives for chemically amplified EUV resists

    NASA Astrophysics Data System (ADS)

    Tanaka, Hiroyasu; Mizusaka, Tetsuhiko; Tanagi, Hiroyuki; Furukawa, Kikuo; Yamamoto, Hiroki; Kozawa, Takahiro

    2015-03-01

    EUV lithography is the most favorable process for high volume manufacturing of semiconductor devices beyond 1X nm half-pitch at present. Many efforts have revealed effective proton sources in acid generation in EUV resists, and the effective proton generation and the control of the generated acid diffusion are required to improve the breakthrough of the resolution ? line width roughness ? sensitivity(RLS) trade-off. To clarify the lithographic performance of these derivatives, we synthesized the acrylic ter/tetrapolymers containing novel lactone derivatives - LCHO and LAATB - as model photopolymers and exposed the resist samples based on these polymers to EUV and EB radiation. On the basis of the lithographic performances of these photoresists, we evaluated the characteristics of lactone derivatives upon exposure to EUV radiation. We discuss the relationship between the chemical structures of these derivatives and lithographic performance.

  18. Dispersant additives derived from lactone modified amido-amine adducts

    SciTech Connect

    Gutierrez, A.; Lundberg, R.D.

    1990-10-16

    This patent describes a lactone modified dispersant additive. It comprises one adduct of a polyolefin of 300 to 10,000 number average molecular weight substituted with at least 0.8 (e.g., from about 1 to 4) dicarboxylic acid producing moieties (preferably acid or anhydride moieties) per polyolefin molecule, an amido-amine or thioamido-amine characterized by being a reaction product of at least a polyamine and an alpha, beta-unsaturated compound.

  19. Lactonic Sophorolipids Increase Tumor Burden in Apcmin+/- Mice

    PubMed Central

    Callaghan, Breedge; Lydon, Helen; Roelants, Sophie L. K. W.; Van Bogaert, Inge N. A.; Marchant, Roger; Banat, Ibrahim M.; Mitchell, Christopher A.

    2016-01-01

    Sophorolipids (SL) are amphiphilic biosurfactant molecules consisting of a disaccharide sophorose with one fatty acid at the C1 position and optional acetylation at the C6’and C6” positions. They exist in a closed ring lactonic (LSL) or open acidic (ASL) structure Sophorolipids are produced in crude mixtures in economically viable amounts by the yeast Starmerella bombicola and used in a variety of consumer products. Varying levels of anti- proliferative and anti-cancer activity of crude sophorolipid mixtures are described in a number of tumor cell lines in vitro. However, significant inter-study variation exists in the composition of sophorolipid species as well as other biologically active compounds in these mixtures, which makes interpretation of in vitro and in vivo studies difficult. We produced a 96% pure C18:1 lactonic sophorolipid that dose-dependently reduces the viability of colorectal cancer, as well as normal human colonic and lung cell lines in vitro. Oral administration of vehicle-only; or lactonic sophorolipids (50 mg/kg for 70 days), to Apcmin+/- mice resulted in an increase in the number (55.5 ± 3.3 vs 70.50 ± 7.8: p < 0.05) and size (modal size 2mm vs 4mm) of intestinal polyps. Lactonic administration resulted in a systematic effect via reduced hematocrit (49.5 ± 1.0 vs 28.2 ± 2.0 vs: p<0.03) and splenomegaly (0.56 ± 0.03g vs 0.71 ± 0.04g; p<0.01) confirming exacerbation of disease progression in this model. PMID:27271048

  20. Lactonic Sophorolipids Increase Tumor Burden in Apcmin+/- Mice.

    PubMed

    Callaghan, Breedge; Lydon, Helen; Roelants, Sophie L K W; Van Bogaert, Inge N A; Marchant, Roger; Banat, Ibrahim M; Mitchell, Christopher A

    2016-01-01

    Sophorolipids (SL) are amphiphilic biosurfactant molecules consisting of a disaccharide sophorose with one fatty acid at the C1 position and optional acetylation at the C6'and C6" positions. They exist in a closed ring lactonic (LSL) or open acidic (ASL) structure Sophorolipids are produced in crude mixtures in economically viable amounts by the yeast Starmerella bombicola and used in a variety of consumer products. Varying levels of anti- proliferative and anti-cancer activity of crude sophorolipid mixtures are described in a number of tumor cell lines in vitro. However, significant inter-study variation exists in the composition of sophorolipid species as well as other biologically active compounds in these mixtures, which makes interpretation of in vitro and in vivo studies difficult. We produced a 96% pure C18:1 lactonic sophorolipid that dose-dependently reduces the viability of colorectal cancer, as well as normal human colonic and lung cell lines in vitro. Oral administration of vehicle-only; or lactonic sophorolipids (50 mg/kg for 70 days), to Apcmin+/- mice resulted in an increase in the number (55.5 ± 3.3 vs 70.50 ± 7.8: p < 0.05) and size (modal size 2mm vs 4mm) of intestinal polyps. Lactonic administration resulted in a systematic effect via reduced hematocrit (49.5 ± 1.0 vs 28.2 ± 2.0 vs: p<0.03) and splenomegaly (0.56 ± 0.03g vs 0.71 ± 0.04g; p<0.01) confirming exacerbation of disease progression in this model. PMID:27271048

  1. Languages and dialects: bacterial communication beyond homoserine lactones.

    PubMed

    Brameyer, Sophie; Bode, Helge B; Heermann, Ralf

    2015-09-01

    Gram-negative bacteria use N-acyl homoserine lactones (acyl-HSLs) for communication, predominantly mediated by LuxR-type receptors. Recent studies uncovered aryl-HSLs, α-pyrones and dialkylresorcinols as further chemical languages of Gram-negative bacteria. These findings extend the number of bacterial signaling molecules and suggest that cell-cell communication goes far beyond acyl-HSL signaling in nature. PMID:26231578

  2. New sesquiterpene lactones from sunflower root exudate as germination stimulants for Orobanche cumana.

    PubMed

    Raupp, Frank M; Spring, Otmar

    2013-11-01

    Orobanche cumana is a serious threat for cultivation of sunflower in Europe and Asia. Germination of the parasite is induced by metabolites released from the host root system. The first germination stimulant from sunflower root exudate was recently identified as dehydrocostus lactone, a sesquiterpene lactone. Bioassay-guided fractionation of root exudates now showed the release of additional sesquiterpene lactones. Besides dehydrocostus lactone, costunolide, tomentosin, and 8-epixanthatin were purified and identified spectroscopically. All four compounds induced germination of O. cumana at nano- to micromolar concentrations. Costunolide and dehydrocostus lactone concentrations above 1 μM reduced the activity, and application of 100 μM inhibited germination irreversibly. Seeds of Phelipanche ramosa could not be induced with costunolide. O. cumana seeds also germinated with GR24, a synthetic strigolactone. No bioactive fraction of sunflower contained compounds of this type. This supports previous findings that sesquiterpene lactones instead of strigolactones trigger the sunflower/O. cumana interaction. PMID:24117219

  3. Lipase-mediated deacetylation and oligomerization of lactonic sophorolipids.

    PubMed

    Hu, Yongmei; Ju, Lu-Kwang

    2003-01-01

    The direct enzymatic polymerization of lactonic sophorolipids (SLs) was investigated with four lipases, including porcine pancreatic lipase (PPL), immobilized Mucor miehei lipase (MML), lyophilized Candida antarctica lipase (Fraction B, CAL-B), and lyophilized Pseudomonas sp. lipase (PSL). Several organic solvents, covering a wide range of polarity, were compared for suitability as the reaction medium. Isopropyl ether and toluene were found most effective. According to the quantification and structure identification by HPLC and LC-MS, the reaction proceeded with the formation of monoacetylated lactonic SLs and the subsequent conversion of the intermediates to oligomers and polymers, presumably through ring-opening polymerization. Temperature was found to have significant effects on the reaction. Both the conversion of reactant SLs and the subsequent formation of oligomers and polymers from the intermediates were faster at 60 degrees C than at 50 degrees C. The substrate selectivity among the three dominant reactant SLs also differed with the temperature. The conversion rate increased with the ring size of the lactones at 60 degrees C, but it decreased with the size at 50 degrees C. PMID:12675564

  4. Molecular identification of tuliposide B-converting enzyme: a lactone-forming carboxylesterase from the pollen of tulip.

    PubMed

    Nomura, Taiji; Murase, Tatsunori; Ogita, Shinjiro; Kato, Yasuo

    2015-07-01

    6-Tuliposides A (PosA) and B (PosB), which are the major secondary metabolites in tulip (Tulipa gesneriana), are enzymatically converted to the antimicrobial lactonized aglycons, tulipalins A (PaA) and B (PaB), respectively. We recently identified a PosA-converting enzyme (TCEA) as the first reported member of the lactone-forming carboxylesterases. Herein, we describe the identification of another lactone-forming carboxylesterase, PosB-converting enzyme (TCEB), which preferentially reacts with PosB to give PaB. This enzyme was isolated from tulip pollen, which showed high PosB-converting activity. Purified TCEB exhibited greater activity towards PosB than PosA, which was contrary to that of the TCEA. Novel cDNA (TgTCEB1) encoding the TCEB was isolated from tulip pollen. TgTCEB1 belonged to the carboxylesterase family and was approximately 50% identical to the TgTCEA polypeptides. Functional characterization of the recombinant enzyme verified that TgTCEB1 catalyzed the conversion of PosB to PaB with an activity comparable with the native TCEB. RT-qPCR analysis of each part of plant revealed that TgTCEB1 transcripts were limited almost exclusively to the pollen. Furthermore, the immunostaining of the anther cross-section using anti-TgTCEB1 polyclonal antibody verified that TgTCEB1 was specifically expressed in the pollen grains, but not in the anther cells. N-terminal transit peptide of TgTCEB1 was shown to function as plastid-targeted signal. Taken together, these results indicate that mature TgTCEB1 is specifically localized in plastids of pollen grains. Interestingly, PosB, the substrate of TgTCEB1, accumulated on the pollen surface, but not in the intracellular spaces of pollen grains. PMID:25997073

  5. Acyl-Homoserine Lactone Production Is More Common among Plant-Associated Pseudomonas spp. than among Soilborne Pseudomonas spp.†

    PubMed Central

    Elasri, Miena; Delorme, Sandrine; Lemanceau, Philippe; Stewart, Gordon; Laue, Bridget; Glickmann, Eric; Oger, Phil M.; Dessaux, Yves

    2001-01-01

    A total of 137 soilborne and plant-associated bacterial strains belonging to different Pseudomonas species were tested for their ability to synthesize N-acyl-homoserine lactones (NAHL). Fifty-four strains synthesized NAHL. Interestingly, NAHL production appears to be more common among plant-associated than among soilborne Pseudomonas spp. Indeed, 40% of the analyzed Pseudomonas syringae strains produced NAHL which were identified most often as the short-chain NAHL, N-hexanoyl-l-homoserine lactone, N-(3-oxo-hexanoyl)-homoserine lactone, and N-(3-oxo-octanoyl)-l-homoserine lactone (no absolute correlation between genomospecies of P. syringae and their ability to produce NAHL could be found). Six strains of fluorescent pseudomonads, belonging to the species P. chlororaphis, P. fluorescens, and P. putida, isolated from the plant rhizosphere produced different types of NAHL. In contrast, none of the strains isolated from soil samples were shown to produce NAHL. The gene encoding the NAHL synthase in P. syringae pv. maculicola was isolated by complementation of an NAHL-deficient Chromobacterium mutant. Sequence analysis revealed the existence of a luxI homologue that we named psmI. This gene is sufficient to confer NAHL synthesis upon its bacterial host and has strong homology to psyI and ahlI, two genes involved in NAHL production in P. syringae pv. tabaci and P. syringae pv. syringae, respectively. We identified another open reading frame that we termed psmR, transcribed convergently in relation to psmI and partly overlapping psmI; this gene encodes a putative LuxR regulatory protein. This gene organization, with luxI and luxR homologues facing each other and overlapping, has been found so far only in the enteric bacteria Erwinia and Pantoea and in the related species P. syringae pv. tabaci. PMID:11229911

  6. The fumigant and repellent activity of aliphatic lactones against Pediculus humanus capitis (Anoplura: Pediculidae).

    PubMed

    Toloza, Ariel Ceferino; Zygadlo, Julio; Mougabure-Cueto, Gastón; Zerba, Eduardo; Faillaci, Silvina; Picollo, María Inés

    2006-02-01

    New alternative insecticides are necessary for the chemical control of head lice. In this study the fumigant knockdown time 50% (KT50) and repellency index (RI) of three aliphatic lactones was compared with two essential oils and DDVP, against permethrin-resistance Pediculus humanus capitis from Argentina. In the fumigant assay, none of the lactones were effective compared to the highest activity of eucalyptus (KT50 15.53 m). In the repellency test, the three lactones were equally or more effective (RI ranging from 60.50 to 76.68) than the positive control (piperonal). These lactones are promising as head lice repellents. PMID:16699710

  7. Endophytic Actinomycetes: A Novel Source of Potential Acyl Homoserine Lactone Degrading Enzymes

    PubMed Central

    Chankhamhaengdecha, Surang; Hongvijit, Suphatra; Srichaisupakit, Akkaraphol; Charnchai, Pattra; Panbangred, Watanalai

    2013-01-01

    Several Gram-negative pathogenic bacteria employ N-acyl-L-homoserine lactone (HSL) quorum sensing (QS) system to control their virulence traits. Degradation of acyl-HSL signal molecules by quorum quenching enzyme (QQE) results in a loss of pathogenicity in QS-dependent organisms. The QQE activity of actinomycetes in rhizospheric soil and inside plant tissue was explored in order to obtain novel strains with high HSL-degrading activity. Among 344 rhizospheric and 132 endophytic isolates, 127 (36.9%) and 68 (51.5%) of them, respectively, possessed the QQE activity. The highest HSL-degrading activity was at 151.30 ± 3.1 nmole/h/mL from an endophytic actinomycetes isolate, LPC029. The isolate was identified as Streptomyces based on 16S  rRNA gene sequence similarity. The QQE from LPC029 revealed HSL-acylase activity that was able to cleave an amide bond of acyl-side chain in HSL substrate as determined by HPLC. LPC029 HSL-acylase showed broad substrate specificity from C6- to C12-HSL in which C10HSL is the most favorable substrate for this enzyme. In an in vitro pathogenicity assay, the partially purified HSL-acylase efficiently suppressed soft rot of potato caused by Pectobacterium carotovorum ssp. carotovorum as demonstrated. To our knowledge, this is the first report of HSL-acylase activity derived from an endophytic Streptomyces. PMID:23484156

  8. N-acyl homoserine lactones in diverse Pectobacterium and Dickeya plant pathogens: diversity, abundance, and involvement in virulence.

    PubMed

    Crépin, Alexandre; Beury-Cirou, Amélie; Barbey, Corinne; Farmer, Christine; Hélias, Valérie; Burini, Jean-François; Faure, Denis; Latour, Xavier

    2012-01-01

    Soft-rot bacteria Pectobacterium and Dickeya use N-acyl homoserine lactones (NAHSLs) as diffusible signals for coordinating quorum sensing communication. The production of NAHSLs was investigated in a set of reference strains and recently-collected isolates, which belong to six species and share the ability to infect the potato host plant. All the pathogens produced different NAHSLs, among which the 3-oxo-hexanoyl- and the 3-oxo-octanoyl-L-homoserine lactones represent at least 90% of total produced NAHSL-amounts. The level of NAHSLs varied from 0.6 to 2 pg/cfu. The involvement of NAHSLs in tuber maceration was investigated by electroporating a quorum quenching vector in each of the bacterial pathogen strains. All the NAHSL-lactonase expressing strains produced a lower amount of NAHSLs as compared to those harboring the empty vector. Moreover, all except Dickeya dadantii 3937 induced a lower level of symptoms in potato tuber assay. Noticeably, aggressiveness appeared to be independent of both nature and amount of produced signals. This work highlights that quorum sensing similarly contributed to virulence in most of the tested Pectobacterium and Dickeya, even the strains had been isolated recently or during the past decades. Thus, these key regulatory-molecules appear as credible targets for developing anti-virulence strategies against these plant pathogens. PMID:22737020

  9. N-Acyl Homoserine Lactones in Diverse Pectobacterium and Dickeya Plant Pathogens: Diversity, Abundance, and Involvement in Virulence

    PubMed Central

    Crépin, Alexandre; Beury-Cirou, Amélie; Barbey, Corinne; Farmer, Christine; Hélias, Valérie; Burini, Jean-François; Faure, Denis; Latour, Xavier

    2012-01-01

    Soft-rot bacteria Pectobacterium and Dickeya use N-acyl homoserine lactones (NAHSLs) as diffusible signals for coordinating quorum sensing communication. The production of NAHSLs was investigated in a set of reference strains and recently-collected isolates, which belong to six species and share the ability to infect the potato host plant. All the pathogens produced different NAHSLs, among which the 3-oxo-hexanoyl- and the 3-oxo-octanoyl-l-homoserine lactones represent at least 90% of total produced NAHSL-amounts. The level of NAHSLs varied from 0.6 to 2 pg/cfu. The involvement of NAHSLs in tuber maceration was investigated by electroporating a quorum quenching vector in each of the bacterial pathogen strains. All the NAHSL-lactonase expressing strains produced a lower amount of NAHSLs as compared to those harboring the empty vector. Moreover, all except Dickeya dadantii 3937 induced a lower level of symptoms in potato tuber assay. Noticeably, aggressiveness appeared to be independent of both nature and amount of produced signals. This work highlights that quorum sensing similarly contributed to virulence in most of the tested Pectobacterium and Dickeya, even the strains had been isolated recently or during the past decades. Thus, these key regulatory-molecules appear as credible targets for developing anti-virulence strategies against these plant pathogens. PMID:22737020

  10. Homoserine Lactones, Methyl Oligohydroxybutyrates, and Other Extracellular Metabolites of Macroalgae-Associated Bacteria of the Roseobacter Clade: Identification and Functions.

    PubMed

    Ziesche, Lisa; Bruns, Hilke; Dogs, Marco; Wolter, Laura; Mann, Florian; Wagner-Döbler, Irene; Brinkhoff, Thorsten; Schulz, Stefan

    2015-09-21

    Twenty-four strains of marine Roseobacter clade bacteria were isolated from macroalgae and investigated for the production of quorum-sensing autoinducers, N-acylhomoserine lactones (AHLs). GC/MS analysis of the extracellular metabolites allowed us to evaluate the release of other small molecules as well. Nineteen strains produced AHLs, ranging from 3-OH-C10:0-HSL (homoserine lactone) to (2E,11Z)-C18:2-HSL, but no specific phylogenetic or ecological pattern of individual AHL occurrence was observed when cluster analysis was performed. Other identified compounds included indole, tropone, methyl esters of oligomers of 3-hydroxybutyric acid, and various amides, such as N-9-hexadecenoylalanine methyl ester (9-C16:1-NAME), a structural analogue of AHLs. Several compounds were tested for their antibacterial and antialgal activity on marine isolates likely to occur in the habitat of the macroalgae. Both AHLs and 9-C16:1-NAME showed high antialgal activity against Skeletonema costatum, whereas their antibacterial activity was low. PMID:26212108

  11. Gene expression of ABC transporters in Cooperia oncophora after field and laboratory selection with macrocyclic lactones.

    PubMed

    Tydén, Eva; Skarin, Moa; Höglund, Johan

    2014-12-01

    The most widespread helminth parasites of grazing cattle in northern Europe are the gastrointestinal nematodes Ostertagia ostertagi and Cooperia oncophora. Heavy reliance on the use of macrocyclic lactone (ML) in cattle has led to world-wide emergence of resistance to this drug class in C. oncophora. There is evidence that members of the ATP-binding cassette (ABC) transporter family, such as P-glycoproteins (P-gp) and multidrug-resistant proteins (MRP), play a role in resistance to ML. In this study gene expression of Con-pgp9, Con-pgp11, Con-pgp12, Con-pgp16 and Con-mrp1 was examined in two isolates of C. oncophora sharing the same genetic background but exposed to ML differently. For isolate one (Laboratory-selected), adult worms were recovered before and after treatment with ML in vivo. For isolate two (Field-selected), adult worms were collected from tracer animals that had never received anthelmintics themselves. One group grazed together with untreated animals and one group grazed with animals that received suppressive prophylactic treatment with ML at monthly intervals for up to two consecutive grazing seasons. Real-time PCR data demonstrated differences in gene expression after ML selection, with the highest constitutive expression levels for Con-pgp16 and Con-mrp1. Remarkably, the same pattern of increasing expression levels of the ABC transport genes was observed in both Laboratory- and Field-selected isolates, despite the Field-selected isolate not being directly exposed to ML. The higher expression levels of ABC transporters observed in the Field-selected isolate was thus not a response to direct exposure to ML, but rather appeared to reflect a genetic characteristic inherited from worms in the previous generation which had survived exposure to ML in the co-grazing treated animals. PMID:25619799

  12. Metabolism of 4-Hydroxy-7-oxo-5-heptenoic Acid (HOHA) Lactone by Retinal Pigmented Epithelial Cells.

    PubMed

    Wang, Hua; Linetsky, Mikhail; Guo, Junhong; Yu, Annabelle O; Salomon, Robert G

    2016-07-18

    4-Hydroxy-7-oxo-5-heptenic acid (HOHA)-lactone is a biologically active oxidative truncation product released (t1/2 = 30 min at 37 °C) by nonenzymatic transesterification/deacylation from docosahexaenoate lipids. We now report that HOHA-lactone readily diffuses into retinal pigmented epithelial (RPE) cells where it is metabolized. A reduced glutathione (GSH) Michael adduct of HOHA-lactone is the most prominent metabolite detected by LC-MS in both the extracellular medium and cell lysates. This molecule appeared inside of ARPE-19 cells within seconds after exposure to HOHA-lactone. The intracellular level reached a maximum concentration at 30 min and then decreased with concomitant increases in its level in the extracellular medium, thus revealing a unidirectional export of the reduced GSH-HOHA-lactone adduct from the cytosol to extracellular medium. This metabolism is likely to modulate the involvement of HOHA-lactone in the pathogenesis of human diseases. HOHA-lactone is biologically active, e.g., low concentrations (0.1-1 μM) induce secretion of vascular endothelial growth factor (VEGF) from ARPE-19 cells. HOHA-lactone is also a precursor of 2-(ω-carboxyethyl)pyrrole (CEP) derivatives of primary amino groups in proteins and ethanolamine phospholipids that have significant pathological and physiological relevance to age-related macular degeneration (AMD), cancer, and wound healing. Both HOHA-lactone and the derived CEP can contribute to the angiogenesis that defines the neovascular "wet" form of AMD and that promotes the growth of tumors. While GSH depletion can increase the lethality of radiotherapy, because it will impair the metabolism of HOHA-lactone, the present study suggests that GSH depletion will also increase levels of HOHA-lactone and CEP that may promote recurrence of tumor growth. PMID:27355557

  13. Biosynthesis of ascorbic acid in kidney bean. L-galactono-gamma-lactone dehydrogenase is an intrinsic protein located at the mitochondrial inner membrane

    PubMed

    Siendones; Gonzalez-Reyes; Santos-Ocana; Navas; C rdoba F

    1999-07-01

    Hypocotyls of kidney beans (Phaseolus vulgaris L.) accumulated ascorbate after preincubation with a number of possible precursors, mainly L-galactono-gamma-lactone (L-GL) and L-gulono-gamma-lactone. The increase in the intracellular ascorbate concentration was parallel to the high stimulation of the L-GL dehydrogenase (L-GLD) activity measured in vitro using L-GL as a substrate and cytochrome c as an electron acceptor. Cell fractionation using a continuous linear Percoll gradient demonstrated that L-GLD is associated with mitochondria; therefore, pure mitochondria were isolated and subjected to detergent treatment to separate soluble from membrane-linked proteins. L-GLD activity was mainly associated with the detergent phase, suggesting that a membrane-intrinsic protein is responsible for the ascorbic acid biosynthetic activity. Subfractionation of mitochondria demonstrated that L-GLD is located at the inner membrane. PMID:10398727

  14. Silylene transfer to α-keto esters and application to the synthesis of γ-lactones

    PubMed Central

    Howard, Brett E.; Woerpel, K. A.

    2009-01-01

    Disubstituted α-hydroxy acids have been synthesized by metal-catalyzed silylene transfer to α-keto esters. A range of substituents are tolerated in the transformation with the exception of branched groups at the vinylic position. The α-hydroxy acid products can be converted into γ-lactones using a variety of lactonization conditions. PMID:20625460

  15. Piperitone-derived saturated lactones: synthesis and aphid behavior-modifying activity.

    PubMed

    Grudniewska, Aleksandra; Dancewicz, Katarzyna; Białońska, Agata; Wawrzeńczyk, Czesław; Gabryś, Beata

    2013-04-10

    Two racemic and two enantiomeric pairs of new saturated lactones with the p-menthane system were obtained. The lactones were synthesized from racemic and enantiomerically enriched cis- and trans-piperitols, which were obtained from piperitone. The structures of the compounds were confirmed by spectroscopic data. The antifeedant activity of piperitone to Myzus persicae was studied, and the biological consequences of structural modifications of piperitone, that is, lactonization and chiral center configuration, were examined as well. The behavioral responses of M. persicae to piperitone and piperitone-derived saturated lactones were investigated to reveal the biological background of their deterrent activity. Piperitone appeared rather neutral or weakly deterrent to aphids. The introduction of a lactone moiety into a piperitone molecule dramatically changed its biological activity. All piperitone-derived lactones evoked negative aphid responses. However, the deterrent activity of individual compounds varied in potency, the time of expression, and the duration of the effect, depending on the spatial structure of the lactone. Lactones (1R,3S,6R)-3-isopropyl-6-methyl-9-oxabicyclo[4.3.0]nonan-8-one and trans-3-isopropyl-6-methyl-9-oxabicyclo[4.3.0]nonan-8-one showed the broadest ranges and the highest potencies and durabilities of deterrent activity to M. persicae: they acted immediately after application, caused a cessation of probing before aphids reached phloem elements, and decreased the quality of phloem sap. PMID:23477664

  16. Sesquiterpene lactone composition of wild and cultivated sunflowers and biological activity against an insect pest

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sesquiterpene lactones in sunflowers, Helianthus spp., are important to interactions with pathogens, weeds and insects. Across a broad range of H. annuus, differences in composition of sesquiterpene lactones extracted from florets were found between wild and cultivated sunflowers, but also between d...

  17. Synthetic method and biological activities of cis-fused alpha-methylene gamma-lactones.

    PubMed

    Higuchi, Yohsuke; Shimoma, Fumito; Ando, Masayoshi

    2003-06-01

    A reliable method was developed for the synthesis of cis-fused alpha-methylene gamma-lactones via alpha-methyl gamma-lactones. Bromination of alpha-methyl gamma-lactones with LDA/CBr(4) or TMSOTf/PTAB and successive dehydrobromination with DBU or TBAF of the resulting alpha-bromo-alpha-methyl gamma-lactones gave the desired alpha-methylene gamma-lactones in high yield. This method was successfully applied to the synthesis of biologically active compounds. alpha-Methylene gamma-lactone derivatives 1c, 2c, 4c, and 17 showed cell growth inhibitory activity to P388 lymphocytic leukemia. They also showed significant activities to crop diseases. Thus, alpha-methylene gamma-lactone 1c showed preventive activity in controlling scab of apple caused by Venturia inaequalis. alpha-Methylene gamma-lactones 2c, 4c, 17, and 18 also showed significant preventive activities in controlling damping off of cucumber caused by Pythium aphanidermatum. PMID:12828467

  18. Comparative performance of macrocyclic lactones against large strongyles in horses.

    PubMed

    Toscan, G; Cezar, A S; Pereira, R C F; Silva, G B; Sangioni, L A; Oliveira, L S S; Vogel, F S F

    2012-12-01

    Several formulations of macrocyclic lactones (abamectin, ivermectin, moxidectin), including ivermectin combined with pyrantel (tetrahydropyrimidine) and ivermectin combined with praziquantel (pyrazinoisoquinolin derivative), were tested regarding their efficacy to control gastrointestinal nematodes of horses on a stud farm in southern Brazil. In addition, we tested a pharmaceutically produced generic paste containing ivermectin 4%. Similar formulations of avermectins had different efficacies measured by reduction of EPG. Levels of efficacy of the tested drugs varied against Strongylus edentatus, S. equinus and S. vulgaris. The generic paste (ivermectin 4%) was less effective than the conventional drugs. PMID:22580448

  19. Direct Acylation of Carrier Proteins with Functionalized β-Lactones

    PubMed Central

    Amoroso, Jon W.; Borketey, Lawrence S.; Prasad, Gitanjeli

    2014-01-01

    As the key component of many biosynthetic assemblies, acyl-carrier proteins offer a robust entry point for introduction of small molecule probes and pathway intermediates. Current labeling strategies primarily rely on modifications to the phosphopantetheine cofactor or its biosynthetic precursors followed by attachment to the apo form of a given carrier protein. As a greatly simplified alternative, direct and selective acylation of holo-acyl-carrier proteins using readily accessible β-lactones as electrophilic partners for the phosphopantetheine-thiol has been demonstrated. PMID:20433156

  20. Regulation of acylated homoserine lactones (AHLs) in beef by spice marination.

    PubMed

    Gopu, Venkadesaperumal; Shetty, Prathapkumar Halady

    2016-06-01

    Quorum sensing (QS) is a signaling mechanism used by bacteria to communicate each other through the release of auto-inducing signaling molecules. Despite the fact that bacteria regulate its phenotypes by QS mechanism, their potential role in meat spoilage is not yet elucidated. In the current study, beef samples were analyzed for its microbial association and for the presence of N-acyl-homoserine-lactone (AHLs) throughout the storage experiments. Isolates were screened for AHLs production and selected spices were screened for their quorum sensing inhibitory (QSI) activity. In addition, effect of spices on AHLs production of Y. enterocolitica was quantified through high performance thin layer chromatography (HP-TLC). Outcome showed that microbial association of beef mainly consists of lactic acid bacteria (LAB) and Enterobacteriaceae. Samples stored at both aerobic and modified atmospheric packaging (MAP) exhibited higher counts whereas; marinated samples stored at MAP exhibited the lowest. It was found that out of 35 isolates Y. enterocolitica induced reporter strain CV026 and its cell-free supernatant contained 26.36 nM/100 ml of AHLs when compared to standard. Among the tested spices, C. cyminum exhibited pronounced results by significantly reducing the AHLs concentration up to 47.75 %. Findings revealed the presence of quorum molecules (AHLs) in beef meat throughout the spoilage process and spices can acts as quorum quenchers to influence the spoilage rate by reducing AHLs production. PMID:27478224

  1. Insecticidal and repellant activities of polyacetylenes and lactones derived from Atractylodes lancea rhizomes.

    PubMed

    Chen, Hai-Ping; Zheng, Li-Shi; Yang, Kai; Lei, Ning; Geng, Zhu-Feng; Ma, Ping; Cai, Qian; Du, Shu-Shan; Deng, Zhi-Wei

    2015-04-01

    During a screening program for new agrochemicals from Chinese medicinal herbs and local wild plants, the petroleum ether (PE) extract of Atractylodes lancea (Thunb.) rhizomes was found to possess repellent and contact activities against Tribolium castaneum adults. Bioactivity-directed chromatographic separation of PE extract on repeated silica-gel columns led to the isolation of two polyacetylenes, atractylodin and atractylodinol (1 and 2, resp.), and two lactones, atractylenolides II and III (3 and 4, resp.). The structures of the compounds were elucidated based on NMR spectra. The four isolated compounds were evaluated for their insecticidal and repellent activities against T. castaneum. Atractylodin exhibited strong contact activity against T. castaneum adults with a LD50 value of 1.83 μg/adult. Atractylodin and atractylenolide II also possessed strong repellenct activities against T. castaneum adults. After 4-h exposure, >90% repellency was achieved with atractylodin at a low concentration of 0.63 μg/cm(2) . The results indicated that atractylodin (1) and atractylenolide II (3) have a good potential as a source for natural repellents, and 1 has the potential to be developed as natural insecticide. PMID:25879503

  2. Antiplasmodial Activity of Aporphine Alkaloids and Sesquiterpene Lactones from Liriodendron tulipifera L

    PubMed Central

    Graziose, Rocky; Rathinasabapathy, Thirumurugan; Lategan, Carmen; Poulev, Alexander; Smith, Peter J; Grace, Mary; Lila, Mary Ann; Raskin, Ilya

    2010-01-01

    Aim of the study The objective of this study was to isolate and characterize the active constituents of the traditionally used antimalarial plant Liriodendron tulipifera by antiplasmodial-assay guided fractionation. Materials and methods Bark and leaves were extracted with solvents of increasing polarity. Fractions were generated using flash chromatography, counter current chromatography and preparative HPLC and subjected to in vitro antiplasmodial and cytotoxicity assays. Active fractions were subjected to further fractionation until pure compounds were isolated, for which the IC50 values were calculated. Results and discussion Six known aporphine alkaloids, asimilobine (1), norushinsunine (2), norglaucine (3), liriodenine (4), anonaine (5) and oxoglaucine (6) were found to be responsible for the antiplasmodial activity of the bark. Leaves yielded two known sesquiterpene lactones, peroxyferolide (7) and lipiferolide (8) with antiplasmodial activity. The antiplasmodial activity of (2) (IC50 = 29.6 μg/ml), (3) (IC50 = 22.0 μg/ml), (6) (IC50= 9.1 μg/mL), (7) (IC50 = 6.2 μg/ml) and (8) (IC50 = 1.8 μg/ml) are reported for the first time. Conclusion This work supports the historical use of Liriodendron tulipifera as an antimalarial remedy of the United States and characterizes its antiplasmodial constituents. PMID:20826204

  3. New Perspectives for In-Situ Rock Deformation and Recrystallisation Analysis - POWTEX Neutron Diffractometer at FRM II Garching, Germany

    NASA Astrophysics Data System (ADS)

    Walter, Jens M.; Randau, Christian; Stipp, Michael; Leiss, Bernd; Ullemeyer, Klaus; Klein, Helmut; Hansen, Bent T.; Kuhs, Werner F.

    2013-04-01

    For the investigation of fabric development in mono- and polyphase rocks and their deformation kinematics the quantitative analysis of the crystallographic preferred orientation (CPO) is a common tool. Furthermore, bulk texture measurements also allow the quantitative characterisation of the anisotropic physical properties of rocks. As neutrons have large penetration capabilities of several cm in geological sample materials neutron diffraction is a strong tool for geoscientific texture analysis. The new POWTEX (POWder and TEXture) Diffractometer at the neutron research reactor FRM II in Garching, Germany is designed as a high-intensity (~1 x 107 n/cm2s) time-of-flight diffractometer. The combination of high flux, the utilization of wavelength frames (TOF) and the large detector coverage ( 9.8 sr) allow fast and effective texture measurements. As the cylindrical detector provides sufficient angular resolution also for sharp recrystallisation textures, POWTEX offers unique possibilities for in-situ time-resolved texture measurements during deformation and recrystallisation experiments on rock materials as large sample environments can be placed inside the detector system. The in-situ deformation apparatus is a new design to minimize shadowing effects inside the cylindrical detector and is operated by a uniaxial spindle drive with a maximum axial load of 250 kN. The HT deformation experiments will be carried out in uniaxial compression or extension and an upgrade to triaxial deformation conditions is envisaged. The apparatus can alternatively be used for ice deformation by inserting a cryostat cell for temperatures down to 77 K with a triaxial apparatus allowing also simple shear experiments. Strain rates range between 10-8 and 10-3 s-1 reaching to at least 50 % axial strain. The deformation apparatus is designed for continuous long-term deformation experiments and can be exchanged between in-situ and ex-situ placements during continuous operation inside and outside

  4. Lactone modified viscosity modifiers useful in oleaginous compositions

    SciTech Connect

    Gutierrez, A.; Lundberg, R.D.

    1990-06-12

    This patent describes a lactone modified reaction product useful as a viscosity index improver additive for lubricating oil compositions. It comprises: the reaction produce of: oil soluble ethylene copolymer comprising within the range of about 15 to 90 wt.% ethylene and about 10 to 85 wt.% of one or more C{sub 3} to C{sub 28} alpha-olefin, having a number average molecular weight within a range of about 15,000 to 500,000 and grafted with ethylenically unsaturated C{sub 4}--C{sub 10} monocarboxylic acid or anhydride or C{sub 4}--C{sub 0} dicarboxylic acid or anhydride wherein the carboxylic acid groups or anhydride groups are located on vicinal carbon atoms; amine selected from the group consisting of amines having at least two primary amine groups and amines having at least one primary amine group and at least one secondary amine group; long chain hydrocarbyl substituted succinic anhydride or acid having 25 to 400 carbon atoms; and lactone.

  5. Copolymerization of carbon dioxide and butadiene via a lactone intermediate.

    PubMed

    Nakano, Ryo; Ito, Shingo; Nozaki, Kyoko

    2014-04-01

    Although carbon dioxide has attracted broad interest as a renewable carbon feedstock, its use as a monomer in copolymerization with olefins has long been an elusive endeavour. A major obstacle for this process is that the propagation step involving carbon dioxide is endothermic; typically, attempted reactions between carbon dioxide and an olefin preferentially yield olefin homopolymerization. Here we report a strategy to circumvent the thermodynamic and kinetic barriers for copolymerizations of carbon dioxide and olefins by using a metastable lactone intermediate, 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one, which is formed by the palladium-catalysed condensation of carbon dioxide and 1,3-butadiene. Subsequent free-radical polymerization of the lactone intermediate afforded polymers of high molecular weight with a carbon dioxide content of 33 mol% (29 wt%). Furthermore, the protocol was applied successfully to a one-pot copolymerization of carbon dioxide and 1,3-butadiene, and one-pot terpolymerizations of carbon dioxide, butadiene and another 1,3-diene. This copolymerization technique provides access to a new class of polymeric materials made from carbon dioxide. PMID:24651200

  6. Detection of Quorum Sensing Activity in the Multidrug-Resistant Clinical Isolate Pseudomonas aeruginosa Strain GB11

    PubMed Central

    Cheng, Huey Jia; Ee, Robson; Cheong, Yuet Meng; Tan, Wen-Si; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    A multidrug-resistant clinical bacteria strain GB11 was isolated from a wound swab on the leg of a patient. Identity of stain GB11 as Pseudomonas aeruginosa was validated by using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Detection of the production of signaling molecules, N-acylhomoserine lactones (AHLs), was conducted using three different bacterial biosensors. A total of four different AHLs were found to be produced by strain GB11, namely N-butyryl homoserine lactone (C4-HSL), N-hexanoylhomoserine lactone (C6-HSL), N-octanoyl homoserine lactone (C8-HSL) and N-3-oxo-dodecanoylhomoserine lactone (3-oxo-C12-HSL) using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Of these detected AHLs, 3-oxo-C12-HSL was found to be the most abundant AHL produced by P. aeruginosa GB11. PMID:25019635

  7. Easy access to aroma active unsaturated γ-lactones by addition of modified titanium homoenolate to aldehydes.

    PubMed

    Frerot, Eric; Bagnoud, Alain

    2011-04-27

    The homo-Reformatsky reaction, in which a metal homoenolate of an ester is added to an aldehyde, was adapted to produce γ-lactones from unsaturated, enolizable aldehydes. By use of titanium homoenolate, 11 different γ-lactones were synthesized in one step with moderate to good yields from readily available aldehydes. In particular, this procedure allowed the rapid preparation of a series of C(12) unsaturated γ-lactones differing in the position and configuration of the double bond. These reference compounds will be used to identify previously unknown lactones in butter oil. The chromatographic, spectral, and sensory descriptions of the synthesized lactones are provided. PMID:21395335

  8. A dyf-7 haplotype causes sensory neuron defects and is associated with macrocyclic lactone resistance worldwide in the nematode parasite Haemonchus contortus.

    PubMed

    Urdaneta-Marquez, Ludmel; Bae, Seong Han; Janukavicius, Patrick; Beech, Robin; Dent, Joseph; Prichard, Roger

    2014-12-01

    Heavy reliance on macrocyclic lactones to treat parasitic nematodes has resulted in the evolution of widespread drug resistance that threatens human and animal health. Management strategies have been proposed that would slow the rise of resistance, however testing these strategies has been hampered by the lack of identified strong-effect resistance markers in parasites. We show that the Caenorhabditis elegans gene Cel_dyf-7, necessary for amphid sensory neuron development, also confers macrocyclic lactone sensitivity. In the sheep parasite Haemonchus contortus: (i) strains selected for macrocyclic lactone resistance were enriched in a Hco_dyf-7 haplotype that was rare in the drug-naïve population, (ii) the resistant haplotype correlated with the sensory neuron defects, and (iii) the resistant haplotype was associated with decreased Hco_dyf-7 expression. Resistant field isolates of H. contortus from five continents were enriched for the resistant haplotype, demonstrating the relevance of the Hco_dyf-7 haplotype to practise and indicating that it is a locus of strong effect. Hemizygosity resulting from sex linkage of dyf-7 likely contributes to the rise of resistance in treated populations. PMID:25224687

  9. Towards the industrialization of new biosurfactants: Biotechnological opportunities for the lactone esterase gene from Starmerella bombicola.

    PubMed

    Roelants, Sophie L K W; Ciesielska, Katarzyna; De Maeseneire, Sofie L; Moens, Helena; Everaert, Bernd; Verweire, Stijn; Denon, Quenten; Vanlerberghe, Brecht; Van Bogaert, Inge N A; Van der Meeren, Paul; Devreese, Bart; Soetaert, Wim

    2016-03-01

    Although sophorolipids (SLs) produced by S. bombicola are a real showcase for the industrialization of microbial biosurfactants, some important drawbacks are associated with this efficient biological process, e.g., the simultaneous production of acidic and lactonic SLs. Depending on the application, there is a requirement for the naturally produced mixture to be manipulated to give defined ratios of the components. Recently, the enzyme responsible for the lactonization of SLs was discovered. The discovery of the gene encoding this lactone esterase (sble) enabled the development of promising S. bombicola strains producing either solely lactonic (using a sble overexpression strain described in this paper: oe sble) or solely acidic SLs (using a sble deletion strain, which was recently described, but not characterized yet: Δsble). The new S. bombicola strains were used to investigate the production processes (fermentation and purification) of either lactonic or acidic SLs. The strains maintain the high inherent productivities of the wild-type or even perform slightly better and thus represent a realistic industrial opportunity. 100% acidic SLs with a mixed acetylation pattern were obtained for the Δsble strain, while the inherent capacity to selectively produce lactonic SLs was significantly increased (+42%) for the oe sble strain (99% lactonic SLs). Moreover, the regulatory effect of citrate on lactone SL formation for the wild-type was absent in this new strain, which indicates that it is more robust and better suited for the industrial production of lactonic SLs. Basic parameters were determined for the purified SLs, which confirm that the two new strains produce molecules with distinctive properties of which the application potential can now easily be investigated independently. PMID:26301720

  10. Synthesis, characterization and antiproliferative activity of β-aryl-δ-iodo-γ-lactones

    NASA Astrophysics Data System (ADS)

    Wzorek, Alicja; Gawdzik, Barbara; Gładkowski, Witold; Urbaniak, Mariusz; Barańska, Anita; Malińska, Maura; Woźniak, Krzysztof; Kempińska, Katarzyna; Wietrzyk, Joanna

    2013-09-01

    A convenient pathway for the synthesis of new of β-aryl-δ-iodo-γ-lactones is described. The synthetic route led to both cis and trans isomers which were separated by column chromatography or crystallization. The structures of synthesized compounds were confirmed by spectroscopic methods: IR, NMR and HR-MS. For lactones with naphthyl ring (6e and 7e) the crystal structures were also obtained. The lactones were screened for biological evaluation against cancer line HL-60 (human promyelocytic leukemia). The tests showed that the presence of substituent at the benzene ring does not significantly affect the antiproliferative activity of the compound.

  11. Deacylation reactions of 20-acetyl dinorcholanic lactones and 20,23-diacetyl furost-22-enes.

    PubMed

    Hernández-Linares, Ma Guadalupe; Sandoval-Ramírez, Jesús; Meza-Reyes, Socorro; Montiel-Smith, Sara; Fernández-Herrera, María A; Bernès, Sylvain

    2010-03-01

    We report the deacylation of (20R)-20-acetyl-23,24-dinorcholanic lactones by hydrazine hydrate, under microwave irradiation in high yields. The elimination of the 20-acetyl group proceeded with retention of configuration which contrast with other proved deacylation methods that yield a mixture of diastereoisomers. In this way, unnatural (20R)-23,24-dinorcholanic lactones can be produced rapidly on a large scale. Both (20R)- and (20S)-lactones were prepared starting from diosgenin, hecogenin and sarsasapogenin, in 72-80% overall yields. PMID:20034505

  12. How do the macrocyclic lactones kill filarial nematode larvae?

    PubMed

    Wolstenholme, Adrian J; Maclean, Mary J; Coates, Ruby; McCoy, Ciaran J; Reaves, Barbara J

    2016-09-01

    The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system. PMID:27279086

  13. Antihyperlipidemic activity of sesquiterpene lactones and related compounds.

    PubMed

    Hall, I H; Lee, K H; Starnes, C O; Muraoka, O; Sumida, Y; Waddell, T G

    1980-06-01

    Some naturally occurring pseudoguaianolides and germacranolides as well as synthetic related compounds were observed to be antihyperlipidemic agents in mice. Several of these compounds at a dose of 20 mg/kg/day resulted in lowering of serum cholesterol by approximately 30% and of serum triglycerides by approximately 25%. Thiol-bearing enzymes of lipid synthesis, i.e., acetyl-CoA, citrate-lyase, acetyl-CoA synthetase, and beta-hydroxy-beta-methylglutaryl-CoA reductase, were inhibited by these agents in vitro, supporting the premise that these agents alkylate thiol nucleophiles by a Michael-type addition. The alpha-methylene-gamma-lactone moiety, the beta-unsubstituted cyclopentenone ring, and the alpha-epoxycyclopentanone system of these compounds appeared to be responsible for the lowering of serum lipids. PMID:7205585

  14. Acyl-Homoserine Lactone Quorum Sensing in the Roseobacter Clade

    PubMed Central

    Zan, Jindong; Liu, Yue; Fuqua, Clay; Hill, Russell T.

    2014-01-01

    Members of the Roseobacter clade are ecologically important and numerically abundant in coastal environments and can associate with marine invertebrates and nutrient-rich marine snow or organic particles, on which quorum sensing (QS) may play an important role. In this review, we summarize current research progress on roseobacterial acyl-homoserine lactone-based QS, particularly focusing on three relatively well-studied representatives, Phaeobacter inhibens DSM17395, the marine sponge symbiont Ruegeria sp. KLH11 and the dinoflagellate symbiont Dinoroseobacter shibae. Bioinformatic survey of luxI homologues revealed that over 80% of available roseobacterial genomes encode at least one luxI homologue, reflecting the significance of QS controlled regulatory pathways in adapting to the relevant marine environments. We also discuss several areas that warrant further investigation, including studies on the ecological role of these diverse QS pathways in natural environments. PMID:24402124

  15. Oxyuris equi: lack of efficacy in treatment with macrocyclic lactones.

    PubMed

    Wolf, Denis; Hermosilla, Carlos; Taubert, Anja

    2014-03-17

    Whilst anthelminthic resistance of small strongyles is well documented, anthelmintic failures against infections with Oxyuris equi have scarcely been published so far. We describe two cases of equine oxyurosis and the anthelminthic failure of macrocyclic lactones (moxidectin, ivermectin) resulting in persistent O. equi infections with continuous egg shedding. The horses were kept in two different herds in the federal state of Hessia, Germany. Herd A kept two geldings: an 8-year-old Welsh-Cob-Mix and a 7-year-old Haflinger. Herd B was composed of four animals: 2 Connemara-mares, 31 and 19 years old, one 18-year-old Connemara-gelding and a 27-year-old Norwegian Fjord mare. All animals had a case history of various anthelmintic treatments with macrocyclic lactones (moxidectin and ivermectin alternating irregulary) in 2010 and 2011, nonetheless, they continued to shed O. equi nematodes and eggs. Animals were treated anew with moxidectin by members of the institute and were continuously monitored on a daily base by adhesive tape samples. Follow-up examinations for the reappearance of eggs were performed for 30 days in Herd A and 57 days in Herd B. In total, recurrence of O. equi egg shedding was detected in three out of six horses within 1-4 weeks after treatment. In both herds accompanying horses sharing the same stable and paddock remained negative for detection of O. equi-eggs or worms throughout the whole observation period. This is the first report in Europe showing inefficacy of commercial ivermectin compounds and furthermore the first report at all documenting ineffectiveness of moxidectin compounds in the treatment of O. equi-infections in horses indicating a possible development of resistance or confirming an existing incomplete oxyuricidal efficacy. PMID:24472770

  16. Antifouling and Fungicidal Resorcylic Acid Lactones from the Sea Anemone-Derived Fungus Cochliobolus lunatus.

    PubMed

    Liu, Qing-Ai; Shao, Chang-Lun; Gu, Yu-Cheng; Blum, Mathias; Gan, Li-She; Wang, Kai-Ling; Chen, Min; Wang, Chang-Yun

    2014-03-25

    Three new 14-membered resorcylic acid lactones, cochliomycins D-F, 1-3, and eight known analogues, 4-11, were isolated from the sea anemone-derived fungus Cochliobolus lunatus. Compounds 1-4 are diastereomers differing from each other by the absolute configurations of the 4',5'-diol chiral centers. The absolute configurations of 1-4 were established by the CD exciton chirality method and TDDFT ECD calculations. In antifouling assays, 1, 3-6, and 6a exhibited potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite at nontoxic concentrations, with EC50 values ranging from 1.82 to 22.5 μg/mL. Noticeably, fungicide whole-plant assays indicated that 6 showed excellent activity on the Plasmopara viticola preventative test at 6 ppm and concentration-dependent activity on the Phytophthora infestans preventative application at 200, 60, and 20 ppm. Preliminary structure-activity relationships are also discussed. PMID:24635109

  17. Effect of the sesquiterpene lactone incomptine A in the energy metabolism of Entamoeba histolytica.

    PubMed

    Velázquez-Domínguez, José; Marchat, Laurence A; López-Camarillo, Cesar; Mendoza-Hernández, Guillermo; Sánchez-Espíndola, Esther; Calzada, Fernando; Ortega-Hernández, Alfredo; Sánchez-Monroy, Virginia; Ramírez-Moreno, Esther

    2013-11-01

    Entamoeba histolytica is the causative agent of human amoebiasis, which mainly affects developing countries. Although several drugs are effective against E. histolytica trophozoites, the control of amoebiasis requires the development of new and better alternative therapies. Medicinal plants have been the source of new molecules with remarkable antiprotozoal activity. Incomptine A isolated from Decachaeta incompta leaves, is a sesquiterpene lactone of the heliangolide type which has the major in vitro activity against E. histolytica trophozoites. However the molecular mechanisms involved in its antiprotozoal activity are still unknown. Using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry (ESI-MS/MS) analysis, we evidenced that 21 E. histolytica proteins were differentially expressed in response to incomptine A treatment. Notably, three glycolytic enzymes, namely enolase, pyruvate:ferredoxin oxidoreductase and fructose-1,6-biphosphate aldolase, were down-regulated. Moreover, ultrastructural analysis of trophozoites through electronic microscopy showed an increased number of glycogen granules. Taken together, our data suggested that incomptine A could affect E. histolytica growth through alteration of its energy metabolism. PMID:23994114

  18. Antiproliferative and Antimalarial Sesquiterpene Lactones from Piptocoma antillana from Puerto Rico [1

    PubMed Central

    Liu, Yixi; Rakotondraibe, L. Harinantenaina; Brodie, Peggy J.; Wiley, Jessica D.; Cassera, Maria B.; Goetz, Michael; Kingston, David G. I.

    2015-01-01

    Bioassay-directed fractionation of an antiproliferative ethanol extract of the leaves and twigs of Piptocoma antillana (Asteraceae) afforded two new goyazensolide-type sesquiterpene lactones named 5-O-methyl-5-epiisogoyazensolide (1) and 15-O-methylgoyazensolide (2), together with the known compounds 1-oxo-3,10-epoxy-8-(2-methylacryloxy)-15-acetoxygermacra-2,4,11(13)-trien-6(12)-olide (3) and 5-epiisogoyazensolide (4). The structure elucidation of all compounds was carried out based on NMR and mass spectroscopic data analyses. The relative and absolute configurations of all the isolated compounds were determined from their CD and NOESY NMR spectra. Compounds 1–4 showed moderately potent antiproliferative activities against A2780 ovarian cancer cells, with IC50 values of 1.5±0.5, 0.6±0.3, 1.62±0.05, and 1.56±0.04 µM, respectively. They also displayed antimalarial activity against Plasmodium falciparum, with IC50 values of 6.2 ± 0.5, 2.2 ± 0.5, 8.0 ±0.4, and 9.0±0.6 µM, respectively. PMID:25522525

  19. Analysis of amino acid substitutions in AraC variants that respond to triacetic acid lactone.

    PubMed

    Frei, Christopher S; Wang, Zhiqing; Qian, Shuai; Deutsch, Samuel; Sutter, Markus; Cirino, Patrick C

    2016-04-01

    The Escherichia coli regulatory protein AraC regulates expression of ara genes in response to l-arabinose. In efforts to develop genetically encoded molecular reporters, we previously engineered an AraC variant that responds to the compound triacetic acid lactone (TAL). This variant (named "AraC-TAL1") was isolated by screening a library of AraC variants, in which five amino acid positions in the ligand-binding pocket were simultaneously randomized. Screening was carried out through multiple rounds of alternating positive and negative fluorescence-activated cell sorting. Here we show that changing the screening protocol results in the identification of different TAL-responsive variants (nine new variants). Individual substituted residues within these variants were found to primarily act cooperatively toward the gene expression response. Finally, X-ray diffraction was used to solve the crystal structure of the apo AraC-TAL1 ligand-binding domain. The resolved crystal structure confirms that this variant takes on a structure nearly identical to the apo wild-type AraC ligand-binding domain (root-mean-square deviation 0.93 Å), suggesting that AraC-TAL1 behaves similar to wild-type with regard to ligand recognition and gene regulation. Our results provide amino acid sequence-function data sets for training and validating AraC modeling studies, and contribute to our understanding of how to design new biosensors based on AraC. PMID:26749125

  20. Draft genome sequence of Citrobacter freundii strain ST2, a γ-proteobacterium that produces N-acylhomoserine lactones.

    PubMed

    Wang, Yan; Zhou, Jin

    2015-12-01

    Citrobacter freundii strain ST2, isolated from the algae bloom sample, possesses an N-acylhomoserine lactone (AHL) production activity that secretes short-chain AHL molecules. In this study, we sequenced the complete genome of C. freundii strain ST2 to understand the molecular regulation of the AHL system and to search for the AHL gene in this bacterium. The results show that the genome size is 4.89 Mb with a G + C content of 51.96%. 4626 function proteins were predicted and 3647 proteins were assigned to COG functional categories. A predicted AHL-coding gene LuxR was found at contig 4 and the length was 1541 bp. The strain temporary deposited at Shenzhen Public Platform of Screening & Application of Marine Microbial Resources (Shenzhen, China), and the genome sequence can be accessed at GenBank under the accession no. LJSQ00000000. PMID:26697383

  1. Two cytotoxic sesquiterpene lactones from the leaves of Xanthium strumarium and their in vitro inhibitory activity on farnesyltransferase.

    PubMed

    Kim, Young Sup; Kim, Jeoung Seob; Park, Sung-Hee; Choi, Sang-Un; Lee, Chong Ock; Kim, Seong-Kie; Kim, Young-Kyoon; Kim, Sung Hoon; Ryu, Shi Yong

    2003-04-01

    Two xanthanolide sesquiterpene lactones, 8- epi-xanthatin (1) and 8- epi-xanthatin epoxide (2), isolated from the leaves of Xanthium strumarium (Compositae), demonstrated a significant inhibition on the proliferation of cultured human tumor cells, i. e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro. They were also found to inhibit the farnesylation process of human lamin-B by farnesyltransferase (FTase), in a dose-dependent manner in vitro (IC 50 value was calculated as 64 and 58 microM, respectively). Due to the relatively high concentrations of 1 and 2 required to obtain an FTase inhibition as compared with those necessary for a cytotoxic effect on tumor cells, it remains unclear whether a relationship between these two activities exists. PMID:12709909

  2. Sesquiterpene Lactone Composition of Wild and Cultivated Sunflowers and Biological Activity against an Insect Pest.

    PubMed

    Prasifka, Jarrad R; Spring, Otmar; Conrad, Jürgen; Cook, Leonard W; Palmquist, Debra E; Foley, Michael E

    2015-04-29

    Sesquiterpene lactones in sunflowers, Helianthus spp., are important to interactions with pathogens, weeds, and insects. Across a broad range of Helianthus annuus, differences in composition of sesquiterpene lactones extracted from disc florets were found between wild and cultivated sunflowers and also between distinct groups of inbreds used to produce sunflower hybrids. Discriminant function analysis showed the presence and relative abundance of argophyllone B, niveusin B, and 15-hydroxy-3-dehydrodesoxyfruticin were usually (75%) effective at classifying wild sunflowers, cultivated inbreds, and hybrids. Argophyllone B reduced the larval mass of the sunflower moth, Homeosoma electellum, by >30%, but only at a dose greater than that found in florets. Low doses of mixed extracts from cultivated florets produced a similar (≈40%) reduction in larval mass, suggesting combinations of sesquiterpene lactones act additively. Although the results support a role for sesquiterpene lactones in herbivore defense of cultivated sunflowers, additional information is needed to use these compounds purposefully in breeding. PMID:25853587

  3. Diastereoselective synthesis of tetrahydrofurans via mead reductive cyclization of keto-beta-lactones derived from the tandem Mukaiyama aldol lactonization (TMAL) process.

    PubMed

    Mitchell, T Andrew; Romo, Daniel

    2007-11-23

    The development of a diastereoselective, three-step strategy for the construction of substituted tetrahydrofurans from alkenyl aldehydes based on the tandem Mukaiyama aldol-lactonization process and Mead reductive cyclization of keto beta-lactones is reported. Stereochemical outcomes of the TMAL process are consistent with models established for Lewis acid-mediated additions to alpha-benzyloxy and beta-silyloxy aldehydes while reductions of the five-membered oxocarbenium ions are consistent with Woerpel's models. Further rationalization for observed high diastereoselectivity in reductions of alpha-silyloxy 5-membered oxocarbenium ions based on stereoelectronic effects are posited. A diagnostic trend for coupling constants of gamma-benzyloxy beta-lactones was observed that should enable assignment of the relative configuration of these systems. PMID:17973527

  4. Diastereoselective Synthesis of Tetrahydrofurans via Mead Reductive Cyclization of Keto-β-Lactones Derived from the Tandem Mukaiyama Aldol Lactonization (TMAL) Process

    PubMed Central

    Mitchell, T. Andrew; Romo, Daniel

    2008-01-01

    The development of a diastereoselective, three-step strategy for the construction of substituted tetrahydrofurans from alkenyl aldehydes based on the tandem Mukaiyama aldol-lactonization process and Mead reductive cyclization of keto β-lactones is reported. Stereochemical outcomes of the TMAL process are consistent with models established for Lewis acid-mediated additions to α-benzyloxy and β-silyloxy aldehydes while reductions of the five-membered oxocarbenium ions are consistent with Woerpel’s models. Further rationalization for observed high diastereoselectivity in reductions of α-silyloxy 5-membered oxocarbenium ions based on stereoelectronic effects are posited. A diagnostic trend for coupling constants of γ-benzyloxy β-lactones was observed that should enable assignment of the relative configuration of these systems. PMID:17973527

  5. Copper-Catalyzed Amino Lactonization and Amino Oxygenation of Alkenes Using O-Benzoylhydroxylamines.

    PubMed

    Hemric, Brett N; Shen, Kun; Wang, Qiu

    2016-05-11

    A copper-catalyzed amino lactonization of unsaturated carboxylic acids has been achieved as well as the analogous intermolecular three-component amino oxygenation of olefins. The transformation features mild conditions and a remarkably broad substrate scope, offering a novel and efficient approach to construct a wide range of amino lactones as well as 1,2-amino alcohol derivatives. Mechanistic studies suggest that the reaction proceeds via a distinctive O-benzoylhydroxylamine-promoted electrophilic amination of alkenes. PMID:27114046

  6. Sesquiterpene lactone stereochemistry influences herbivore resistance and plant fitness in the field

    PubMed Central

    Ahern, Jeffrey R.; Whitney, Kenneth D.

    2014-01-01

    Background and Aims Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant–herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field. Methods Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness. Key Results The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide. Conclusions To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories

  7. Influence of cultivation site on sesquiterpene lactone composition of forage chicory (Cichorium intybus L.).

    PubMed

    Foster, Joyce G; Clapham, William M; Belesky, David P; Labreveux, Maria; Hall, Marvin H; Sanderson, Matt A

    2006-03-01

    The forage potential of chicory (Cichorium intybus L.) has not been realized in southern West Virginia (WV) because ruminants are reluctant to consume the herbage. Chicory contains bitter sesquiterpene lactones that can adversely impact palatability. This study was undertaken to determine whether sesquiterpene lactone concentrations in chicory grown in southern WV differ from those in chicory grown in central Pennsylvania (PA) where chicory is grazed readily. Herbage was collected in 1997 and 1998 from cultivars Grasslands Puna (Puna), INIA le Lacerta (Lacerta), and Forage Feast established at research sites near State College, PA, and Beckley, WV. The total concentration of sesquiterpene lactones in WV-grown cultivars was 0.58% (dry matter basis) in Puna, 0.59% in Lacerta, and 0.79% in Forage Feast in 1997 and ranged from 1.03 (Lacerta) to 1.52% (Forage Feast) in 1998. In PA-grown cultivars, sesquiterpene lactones represented 0.16 (Puna), 0.18 (Lacerta), and 0.27% (Forage Feast) of the forage dry matter in 1997 and ranged from 0.32 (Lacerta) to 0.55% (Forage Feast) in 1998. Concentrations of lactucin, lactucopicrin, and total sesquiterpene lactones in Forage Feast exceeded those in the other cultivars grown at the same site. The lowest concentrations of lactucopicrin and total sesquiterpene lactones observed among WV-grown cultivars were higher (2-fold or more) than the highest concentrations present in cultivars grown the same year in PA. Mineral analyses of soils from the two cultivation sites indicate that P availability may influence sesquiterpene lactone composition of chicory herbage. Results provide a foundation for future studies of environmental effects on sesquiterpene lactone composition and palatability of chicory herbage. PMID:16506832

  8. Pharmacokinetics, tissue distribution, and the lactone/carboxylate equilibrium of hydroxycamptothecin delivered via aerosol in mice.

    PubMed

    Hu, Wei; Zhang, Chao; Hu, Wenjin; Fang, Yun; Hou, Wenjie

    2012-10-01

    Aerosol delivery is a route which is advantageous to the therapy of pulmonary diseases, such as lung cancer. The pharmacokinetics and tissue distribution after aerosol delivery of carboxylate form of hydroxycamptothecin (C-HCPT) were investigated. The concentrations of the three different types (lactone, carboxylate and the total of both forms) of HCPT were measured by HPLC analysis. The initial experiment showed no evident difference between lactone and carboxylate in the lungs during the aerosol treatment, compared with the HCPT content in plasma. The AUC(inf) value of lactone in the lungs was higher than that of carboxylate, which was 138,176.00 min ng g⁻¹ and 128,460.00 min ng g⁻¹, respectively. Meanwhile, AUC(inf) in the plasma during the entire treatment indicated that the lactone content was always at a lower level, and the carboxylate form tended to predominate, as shown by the lactone/carboxylate (L/C) equilibrium. The tissue distribution results showed that the lactone proportion in the liver increased up to the maximum value of 69.69% after aerosol administration, whereas the mean L/C equilibrium index for the liver was 2.07±1.06, and the C(max) and AUC(0-∞) values of the total HCPT were highest in the tissues. Based on these results we speculated that the initial wholly carboxylate form of the HCPT atomized liquid did not influence the transformation to lactone form. Moreover, the deposition of the total HCPT and lactone was higher in the lungs and other tissues than in the plasma after the aerosol treatment. This study will be beneficial to the therapy of pulmonary carcinoma. PMID:22858157

  9. Optimization of a partially non-magnetic primary radiation. shielding for the triple-axis spectrometer PANDA at the Munich high-flux reactor FRM-II

    NASA Astrophysics Data System (ADS)

    Pyka, N. M.; Noack, K.; Rogov, A.

    Monte Carlo simulations have been used to optimize the monochromator shielding of the polarized cold-neutron triple-axis spectrometer PANDA at the Munich high-flux reactor FRM-II. By using the Monte Carlo program MCNP-4B, the density of the total spectrum of incoming neutrons and γ radiation from the beam tube SR-2 has been determined during the three-dimensional diffusion process in different types of heavy concrete and other absorbing material. Special attention has been paid to build a compact and highly efficient shielding, partially non-magnetic, with a total biological radiation dose of less than 10 μSv/h at its outsides. Especially considered was the construction of an albedo reducer, which serves to reduce the background in the experiment outside the shielding.

  10. Germa-gamma-lactones as novel inhibitors of bacterial urease activity.

    PubMed

    Amtul, Zareen; Follmer, Cristian; Mahboob, Sumera; Atta-Ur-Rahman; Mazhar, Muhammad; Khan, Khalid M; Siddiqui, Rafat A; Muhammad, Sajjad; Kazmi, Syed A; Choudhary, Mohammad Iqbal

    2007-05-01

    Organogermanium compounds have been used as pharmacological agents. However, very few reports are available on the synthesis and antibacterial activities of lactones containing organogermaniums. The purpose of the present investigation was to determine the effects of different lactone-substituted organogermaniums on bacterial growth and their urease activity. We report synthesis of 12 germa-gamma-lactones (GeL) and their antimicrobial activities against several bacterial pathogens. Antibacterial action of all GeL was highly selective against Gram-negative bacilli, particularly Proteus mirabilis, an important pathogen infecting the urinary tract. Furthermore, our data indicate that 8-quinoline derivatives were more potent against P. mirabilis than 2-methyl-8-quinoline. For example, the beta-(o-methylphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone and beta-(o-methoxyphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone were maximally active with MIC(90) of 61 and 94 microM, respectively. In vitro studies demonstrated a linear correlation between antibacterial activity and inhibition of P. mirabilis urease enzyme. Further kinetic analyses revealed that inhibition occurred in a noncompetitive and concentration-dependent manner with the minimum IC(50) of 31 microM for beta-(o-methoxyphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone. In conclusion, these findings suggest that GeL have potential to be developed as antimicrobial agents against P. mirabilis infection. PMID:17367756

  11. Interaction of macrocyclic lactones with a Dirofilaria immitis P-glycoprotein.

    PubMed

    Mani, Thangadurai; Bourguinat, Catherine; Keller, Kathy; Ashraf, Shoaib; Blagburn, Byron; Prichard, Roger K

    2016-09-01

    Dirofilaria immitis, a filarial nematode, causes dirofilariasis or heartworm disease in dogs, cats and wild canids. Effective prevention of the disease is mainly by the use of the macrocyclic lactone class of drugs as heartworm preventives, and no other class of drugs is effective for preventing infection. Macrocyclic lactones have been used for prevention of heartworm infection for more than 26years. However, prevention has been compromised by the development of resistance in recent years. The mechanism of macrocyclic lactone resistance in D. immitis has yet to be established. In other parasitic nematodes, P-glycoproteins (PGPs) have been implicated in macrocyclic lactone resistance. The presence of two polymorphic loci on D. immitis P-glycoprotein-11 (Dim-pgp-11) correlated with loss of efficacy of macrocyclic lactone anthelmintics, suggesting that PGPs may be involved in macrocyclic lactone resistance in D. immitis. We have identified the full length of Dim-Pgp-11 cDNA, expressed it in mammalian cells, and studied the functional activity of the expressed protein. We have characterised its interaction with the four macrocyclic lactone preventives, ivermectin, selamectin, moxidectin and milbemycin oxime, using the transport of different fluorescent substrates. The inhibitory effect of these macrocyclic lactones on the transport of two fluorophore probes, Rhodamine 123 and Hoechst 33342, by Dim-PGP-11 has been studied. The avermectins, ivermectin and selamectin, markedly inhibited Rhodamine 123 transport in a concentration-dependent and saturable manner, whereas the milbemycins, moxidectin and milbemycin oxime, were found to have different inhibition profiles with Rhodamine 123 transport. However, both avermectins and milbemycin preventives inhibited the transport of Hoechst 33342 by Dim-PGP-11 in a concentration-dependent and apparently saturable manner, although differences existed in terms of efficiency and potency of inhibition between the two sub-classes of

  12. Lactonization and protonation of gluconic acid: a thermodynamicand kinetic study by potentiometry, nmr and esi-ms

    SciTech Connect

    Zhang, Z.; Gibson, P.; Clark, S.B.; Tian, G.; Zanonato, P.; Rao, L.

    2007-01-10

    In acidic aqueous solutions, gluconate protonation is coupled with lactonization of gluconic acid. With the decrease of pC{sub H}, two lactones ({delta}/{gamma}) are sequentially formed. The {delta}-lactone forms more readily than the {gamma}-lactone. In 0.1 M gluconate solutions, if pC{sub H} is above 2.5, only the {delta}-lactone is generated. When pC{sub H} is decreased below 2.0, the formation of the {gamma}-lactone is observable although the {delta}-lactone predominates. At I = 0.1 M NaClO{sub 4} and room temperature, the deprotonation constant of the carboxylic group, using the NMR technique, was determined to be log K{sub a} = 3.30 {+-} 0.02; the {delta}-lactonization constant, by the batch potentiometric titrations, was obtained to be log K{sub L} = - (0.54 {+-} 0.04). Using ESI-MS, the rate constants of the {delta}-lactonization and the hydrolysis at pC{sub H} {approx} 5.0 were estimated to be k{sub 1} = 3.2 x 10{sup -5} s{sup -1} and k{sup -1} = 1.1 x 10{sup -4} s{sup -1}, respectively.

  13. Precursor-directed biosynthesis of novel triketide lactones.

    PubMed

    Regentin, Rika; Kennedy, Jonathan; Wu, Nicholas; Carney, John R; Licari, Peter; Galazzo, Jorge; Desai, Ruchir

    2004-01-01

    Precursor-directed biosynthesis was used to produce different triketide lactones (R-TKLs) in a fermentation process. Plasmids expressing engineered versions of the first subunit of 6-deoxyerythronolide B synthase (DEBS1) fused to the terminal DEBS thioesterase (TE) were introduced into three different Streptomyces strains. The DEBS1 protein fused to TE had either an inactivated ketosynthase domain (KS1 degrees ) or a partial DEBS1 lacking module 1 but containing module 2 (M2+TE). Different synthetic precursors were examined for their effect on R-TKL production. An overproducing strain of S. coelicolor expressing the M2+TE protein was found to be best for production of R-TKLs. Racemic precursors were as effective as enantiomerically pure precursors in the fermentation process. The R group on the precursor significantly affected titer (propyl > chloromethyl > vinyl). The R-TKLs were unstable in fermentation broth at pH 6-8. A two-phase fermentation with a pH shift was implemented to stabilize the products. The fermentation pH initially was controlled at optimal values for cell growth (pH 6.5) and then shifted to 5.5 during production. This doubled peak titers and stabilized the product. Finally, the concentration of synthetic precursor in the fermentation was optimized to improve production. A maximum titer of 500 mg/L 5-chloromethyl-TKL was obtained using 3.5 g/L precursor. PMID:14763833

  14. Bicarbonate promotes a cleavage of lactone ring of dehydroascorbate.

    PubMed

    Koshiishi, I; Mamura, Y; Imanari, T

    1998-02-01

    The half-life of dehydroascorbate (DHA) in human plasma is only a few minutes. This DHA disappearance is caused by a cleavage of lactone ring. Similarly, when DHA was incubated in Dulbecco's modified Eagle's medium (D-MEM), which stood in atmosphere of 5% CO2-95% air, the rapid transformation of DHA into 2,3-diketogulonate (2,3-DKG) is also observed. These observations suggest that both human plasma and D-MEM contain a common component, which promotes the hydrolysis of DHA. In the present study, this component was identified to be bicarbonate which acts as a general base catalyst. Direct evidence for this mechanism was obtained as follows: (1) significant hydrolysis of DHA in the bicarbonate-free D-MEM (pH 7.40) was not observed; (2) hydrolysis of DHA in Tris-HCl buffer at constant pH (7.4) increases with increasing bicarbonate concentration; and (3) significant hydrolysis of DHA in the decarbonated ultrafiltrate of plasma was not observed. These results suggest that DHA hydrolysis may be controlled by the variation of CO2 pressure in circulating blood. PMID:9528661

  15. Short communication: Macrocyclic lactone residues in butter from Brazilian markets.

    PubMed

    Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte

    2015-06-01

    Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues. PMID:25864054

  16. Membrane anchoring of diacylglycerol-lactones substituted with rigid hydrophobic acyl domains correlates with biological activities

    PubMed Central

    Raifman, Or; Kolusheva, Sofiya; Comin, Maria J.; Kedei, Noemi; Lewin, Nancy E.; Blumberg, Peter M.; Marquez, Victor E.; Jelinek, Raz

    2009-01-01

    Summary Synthetic diacylglycerol lactones (DAG-lactones) are effective modulators of critical cellular signaling pathways, downstream of the lipophilic second messenger diacylglycerol, that activate a host of protein kinase C (PKC) isozymes as well as other non-kinase proteins that share with PKC similar C1 membrane-targeting domains. A fundamental determinant of the biological activity of these amphiphilic molecules is the nature of their interactions with cellular membranes. This study characterizes the membrane interactions and bilayer anchoring of a series of DAG-lactones in which the hydrophobic moiety is a “molecular rod”, namely a rigid 4-[2-(R-phenyl)ethynyl]benzoate moiety in the acyl position. Application of assays employing chromatic biomimetic vesicles and biophysical techniques reveals that the mode of membrane anchoring of the DAG-lactone derivatives was markedly affected by the presence of the hydrophobic diphenyl rod and by the size of the functional unit displayed at the terminus of the rod. Two primary mechanisms of interaction were observed: surface binding of the DAG-lactones at the lipid/water interface and deep insertion of the ligands into the alkyl core of the lipid bilayer. These membrane-insertion properties could explain the different patterns of PKC translocation from cytosol to membranes induced by the molecular-rod DAG-lactones. This investigation emphasizes that the side-residues of DAG-lactones, rather than simply conferring hydrophobicity, profoundly influence membrane interactions and in that fashion may further contribute to the diversity of biological actions of these synthetic biomimetic ligands. PMID:19961537

  17. Structure-Based Function Discovery of an Enzyme for the Hydrolysis of Phosphorylated Sugar Lactones

    PubMed Central

    Xiang, Dao Feng; Kolb, Peter; Fedorov, Alexander A.; Xu, Chengfu; Fedorov, Elena V.; Narindoshivili, Tamari; Williams, Howard J.; Shoichet, Brian K.; Almo, Steven C.; Raushel, Frank M.

    2012-01-01

    Two enzymes of unknown function from the cog1735 subset of the amidohydrolase superfamily (AHS), LMOf2365_2620 (Lmo2620) from Listeria monocytogenes str. 4b F2365 and Bh0225 from Bacillus halodurans C-125, were cloned, expressed and purified to homogeneity. The catalytic functions of these two enzymes were interrogated by an integrated strategy encompassing bioinformatics, computational docking to three-dimensional crystal structures, and library screening. The three-dimensional structure of Lmo2620 was determined at a resolution of 1.6 Å with two phosphates and a binuclear zinc center in the active site. The proximal phosphate bridges the binuclear metal center and is 7.1 Å away from the distal phosphate. The distal phosphate hydrogen bonds with Lys-242, Lys-244, Arg-275 and Tyr-278. Enzymes within cog1735 of the AHS have previously been shown to catalyze the hydrolysis of substituted lactones. Computational docking of the high energy intermediate (HEI) form of the KEGG database to the three-dimensional structure of Lmo2620 highly enriched anionic lactones versus other candidate substrates. The active site structure and the computational docking results suggested that probable substrates would likely include phosphorylated sugar lactones. A small library of diacid sugar lactones and phosphorylated sugar lactones was synthesized and tested for substrate activity with Lmo2620 and Bh0225. Two substrates were identified for these enzymes, d-lyxono-1,4-lactone-5-phosphate and l-ribono-1,4-lactone-5-phosphate. The kcat/Km values for the cobalt-substituted enzymes with these substrates are ~105 M−1 s−1. PMID:22313111

  18. A Novel Lactone-Forming Carboxylesterase: Molecular Identification of a Tuliposide A-Converting Enzyme in Tulip1[W

    PubMed Central

    Nomura, Taiji; Ogita, Shinjiro; Kato, Yasuo

    2012-01-01

    Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4-dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa gesneriana). Their lactonized aglycons, tulipalins, function as defensive chemicals due to their biological activities. We recently found that tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins, but the possibility of the presence of several TCE isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE. Here, to prove this hypothesis, TCE was purified from petals, which have the second highest TCE activity after bulbs. The purified enzyme, like the bulb enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A the best substrate, which allowed naming the enzyme tuliposide A-converting enzyme (TCEA), but specific activity and molecular mass differed between the petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding petal TCEA was isolated, and the functional characterization of the recombinant enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs, indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct enzymatic characters between the petal and bulb enzymes. Plastidial localization of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad characteristic of typical carboxylesterases are essential for the catalytic process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member of the lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification. PMID:22474185

  19. A novel lactone-forming carboxylesterase: molecular identification of a tuliposide A-converting enzyme in tulip.

    PubMed

    Nomura, Taiji; Ogita, Shinjiro; Kato, Yasuo

    2012-06-01

    Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4-dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa gesneriana). Their lactonized aglycons, tulipalins, function as defensive chemicals due to their biological activities. We recently found that tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins, but the possibility of the presence of several TCE isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE. Here, to prove this hypothesis, TCE was purified from petals, which have the second highest TCE activity after bulbs. The purified enzyme, like the bulb enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A the best substrate, which allowed naming the enzyme tuliposide A-converting enzyme (TCEA), but specific activity and molecular mass differed between the petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding petal TCEA was isolated, and the functional characterization of the recombinant enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs, indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct enzymatic characters between the petal and bulb enzymes. Plastidial localization of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad characteristic of typical carboxylesterases are essential for the catalytic process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member of the lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification. PMID:22474185

  20. Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.

    PubMed

    Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor

    2013-08-01

    The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 μg/mL reduced LPS-stimulated TNF-α production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9α-hydroxy-8β-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 μM) than the positive control parthenolide (IC50=4.79 μM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. PMID:23747054

  1. Draft Genome Sequence of Jeotgalibacillus soli DSM 23228, a Bacterium Isolated from Alkaline Sandy Soil

    PubMed Central

    Chan, Kok-Gan; Yaakop, Amira Suriaty; Chan, Chia Sing; Ee, Robson; Tan, Wen-Si; Gan, Han Ming

    2015-01-01

    Jeotgalibacillus soli, a bacterium capable of degrading N-acyl homoserine lactone, was isolated from a soil sample in Portugal. J. soli constitutes the only Jeotgalibacillus species isolated from a non-marine source. Here, the draft genome, several interesting glycosyl hydrolases, and its putative N-acyl homoserine lactonases are presented. PMID:25999554

  2. Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis

    PubMed Central

    Ivanescu, Bianca; Miron, Anca; Corciova, Andreia

    2015-01-01

    Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation. PMID:26495156

  3. Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis.

    PubMed

    Ivanescu, Bianca; Miron, Anca; Corciova, Andreia

    2015-01-01

    Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation. PMID:26495156

  4. Acyl-homoserine lactone recognition and response hindering the quorum-sensing regulator EsaR.

    PubMed

    Schu, Daniel J; Scruggs, Jessica M; Geissinger, Jared S; Michel, Katherine G; Stevens, Ann M

    2014-01-01

    During quorum sensing in the plant pathogen Pantoea stewartii subsp. stewartii, EsaI, an acyl-homoserine lactone (AHL) synthase, and the transcription factor EsaR coordinately control capsular polysaccharide production. The capsule is expressed only at high cell density when AHL levels are high, leading to inactivation of EsaR. In lieu of detailed structural information, the precise mechanism whereby EsaR recognizes AHL and is hindered by it, in a response opposite to that of most other LuxR homologues, remains unresolved. Hence, a random mutagenesis genetic approach was designed to isolate EsaR* variants that are immune to the effects of AHL. Error-prone PCR was used to generate the desired mutants, which were subsequently screened for their ability to repress transcription in the presence of AHL. Following sequencing, site-directed mutagenesis was used to generate all possible mutations of interest as single, rather than multiple amino acid substitutions. Eight individual amino acids playing a critical role in the AHL-insensitive phenotype have been identified. The ability of EsaR* variants to bind AHL and the effect of individual substitutions on the overall conformation of the protein were examined through in vitro assays. Six EsaR* variants had a decreased ability to bind AHL. Fluorescence anisotropy was used to examine the relative DNA binding affinity of the final two EsaR* variants, which retained some AHL binding capability but remained unresponsive to it, perhaps due to an inability of the N-terminal domain to transduce information to the C-terminal domain. PMID:25238602

  5. Acyl-Homoserine Lactone Recognition and Response Hindering the Quorum-Sensing Regulator EsaR

    PubMed Central

    Schu, Daniel J.; Scruggs, Jessica M.; Geissinger, Jared S.; Michel, Katherine G.; Stevens, Ann M.

    2014-01-01

    During quorum sensing in the plant pathogen Pantoea stewartii subsp. stewartii, EsaI, an acyl-homoserine lactone (AHL) synthase, and the transcription factor EsaR coordinately control capsular polysaccharide production. The capsule is expressed only at high cell density when AHL levels are high, leading to inactivation of EsaR. In lieu of detailed structural information, the precise mechanism whereby EsaR recognizes AHL and is hindered by it, in a response opposite to that of most other LuxR homologues, remains unresolved. Hence, a random mutagenesis genetic approach was designed to isolate EsaR* variants that are immune to the effects of AHL. Error-prone PCR was used to generate the desired mutants, which were subsequently screened for their ability to repress transcription in the presence of AHL. Following sequencing, site-directed mutagenesis was used to generate all possible mutations of interest as single, rather than multiple amino acid substitutions. Eight individual amino acids playing a critical role in the AHL-insensitive phenotype have been identified. The ability of EsaR* variants to bind AHL and the effect of individual substitutions on the overall conformation of the protein were examined through in vitro assays. Six EsaR* variants had a decreased ability to bind AHL. Fluorescence anisotropy was used to examine the relative DNA binding affinity of the final two EsaR* variants, which retained some AHL binding capability but remained unresponsive to it, perhaps due to an inability of the N-terminal domain to transduce information to the C-terminal domain. PMID:25238602

  6. Trypanocidal Activity of Smallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation

    PubMed Central

    Frank, F. M.; Ulloa, J.; Cazorla, S. I.; Maravilla, G.; Malchiodi, E. L.; Grau, A.; Martino, V.; Catalán, C.; Muschietti, L. V.

    2013-01-01

    In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1), uvedalin (2), and polymatin B (3) by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 μM (1), 1.09 μM (2), and 4.90 μM (3). After a 24 h treatment with 10 μg/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33.4 μM and 25.0 μM against T. cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 μM, 3.34 μM, and 9.02 μM for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 μM (1), 46.8 μM (2), and 147.3 μM (3) and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs. PMID:23840260

  7. Antiplasmodial activity of sesquiterpene lactones and a sucrose ester from Vernonia guineensis Benth. (Asteraceae)

    PubMed Central

    Toyang, Ngeh J.; Krause, Michael A.; Fairhurst, Rick M.; Tane, Pierre; Bryant, Joseph; Verpoorte, Rob

    2013-01-01

    Ethnopharmacological relevance Aqueous preparations of Vernonia guineensis Benth. (Asteraceae) are used in Cameroonian folk medicine as a general stimulant and to treat various illnesses and conditions including malaria, bacterial infections and helminthic infestations. Materials and methods 10-g samples of the leaf and tuber powders of V. guineensis were extracted separately using dichloromethane, methanol and distilled water. The extracts were dried in vacuo and used in bioassays. These extracts and three compounds previously isolated from V. guineensis [vernopicrin (1), vernomelitensin (2) and pentaisovalerylsucrose (3)] were screened for antiplasmodial activity against chloroquine (CQ)-sensitive (Hb3) and CQ-resistant (Dd2) Plasmodium falciparum lines. Results Crude extracts and pure compounds from V. guineensis showed antiplasmodial activity against both Hb3 and Dd2. The IC50 values of extracts ranged from 1.64 – 27.2 μg/ml for Hb3 and 1.82 – 30.0 μg/ml for Dd2; those for compounds 1, 2 and 3 ranged from 0.47 – 1.62 μg/ml (1364 – 1774 nM) for Hb3 and 0.57 – 1.50 μg/ml (1644 – 2332 nM) for Dd2. None of the crude extracts or pure compounds was observed to exert toxic effects on the erythrocytes used to cultivate the P. falciparum lines. Conclusion In Cameroonian folk medicine, V. guineensis may be used to treat malaria in part due to the antiplasmodial activity of sesquiterpene lactones (1, 2), a sucrose ester (3) and perhaps other compounds present in crude plant extracts. Exploring the safety and antiplasmodial efficacy of these compounds in vivo requires further study. PMID:23542146

  8. Anti-angiogenic Activity and Mechanism of Sesquiterpene Lactones from Centipeda minima.

    PubMed

    Huang, Weihuan; Yu, Xiaobin; Liang, Ning; Ge, Wei; Kwok, Hin Fai; Lau, Clara Bik-San; Li, Yaolan; Chung, Hau Yin

    2016-04-01

    Centipeda minima is a Chinese herbal medicine used in the treatment of various diseases including cancer. An ethanol extract of the herb, its four fractions with different polarities, and two volatile oils prepared by steam distillation (SD) and supercritical fluid extraction (SFE) were investigated for their anti-angiogenic activity in a wild-type zebrafish model using a quantitative endogenous alkaline phosphatase (EAP) assay. The SFE oil displayed potent anti-angiogenic activity. Fifteen sesquiterpene lactones (SLs; compounds 1-15) isolated from the SFE oil were evaluated for their anti-angiogenic effect. Results revealed that pseudoguaianolide type SLs (1-8) inhibited vessel formation in the zebrafish embryos while guaianolide type SLs (9-15) showed little effect. Among the active ones, 6-O-angeloylenolin (1), a major component of SFE oil, possessed the strongest effect by reducing vessel formation in zebrafish embryos to 40% of the control value at 29.7 µM. Further study using the Tg (fli1a:EGFP) y1-type zebrafish model revealed that it blocked both intersegmental blood vessels (ISVs) and subintestinal vessels plexus (SIVs) formation in zebrafish embryos. Real-time polymerase chain reaction assay on the wild-type zebrafish embryos suggested that 6-O-angeloylenolin affected multiple molecular targets related to angiogenesis including VEGF receptor, angiopoietin, and its receptors. Taken together, our findings demonstrate that C. minima possesses anti-angiogenic activity, and 6-O-angeloylenolin is a promising candidate for the development of an anti-angiogenic agent. PMID:27396185

  9. Quorum Sensing Activity of Mesorhizobium sp. F7 Isolated from Potable Water

    PubMed Central

    Yong, Pei-Ling; Chan, Kok-Gan

    2014-01-01

    We isolated a bacterial isolate (F7) from potable water. The strain was identified as Mesorhizobium sp. by 16S rDNA gene phylogenetic analysis and screened for N-acyl homoserine lactone (AHL) production by an AHL biosensor. The AHL profile of the isolate was further analyzed using high resolution triple quadrupole liquid chromatography mass spectrometry (LC/MS) which confirmed the production of multiple AHLs, namely, N-3-oxo-octanoyl-L-homoserine lactone (3-oxo-C8-HSL) and N-3-oxo-decanoyl-L-homoserine lactone (3-oxo-C10-HSL). These findings will open the perspective to study the function of these AHLs in plant-microbe interactions. PMID:25177734

  10. Quorum Sensing Activity of Enterobacter asburiae Isolated from Lettuce Leaves

    PubMed Central

    Lau, Yin Yin; Sulaiman, Joanita; Chen, Jian Woon; Yin, Wai-Fong; Chan, Kok-Gan

    2013-01-01

    Bacterial communication or quorum sensing (QS) is achieved via sensing of QS signaling molecules consisting of oligopeptides in Gram-positive bacteria and N-acyl homoserine lactones (AHL) in most Gram-negative bacteria. In this study, Enterobacteriaceae isolates from Batavia lettuce were screened for AHL production. Enterobacter asburiae, identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was found to produce short chain AHLs. High resolution triple quadrupole liquid chromatography mass spectrometry (LC/MS) analysis of the E. asburiae spent supernatant confirmed the production of N-butanoyl homoserine lactone (C4-HSL) and N–hexanoyl homoserine lactone (C6-HSL). To the best of our knowledge, this is the first report of AHL production by E. asburiae. PMID:24152877

  11. Quorum Quenching Bacillus sonorensis Isolated from Soya Sauce Fermentation Brine

    PubMed Central

    Yin, Wai-Fong; Tung, Hun-Jiat; Sam, Choon-Kook; Koh, Chong-Lek; Chan, Kok-Gan

    2012-01-01

    An N-acylhomoserine lactone (AHL)-degrading bacterial strain, L62, was isolated from a sample of fermentation brine of Chinese soya sauce by using rich medium agar supplemented with soya sauce (10% v/v). L62, a rod-shaped Gram positive bacterium with amylolytic activity, was phylogentically related to Bacillus sonorensis by 16S ribosomal DNA and rpoB sequence analyses. B. sonorensis L62 efficiently degraded N-3-oxohexanoyl homoserine lactone and N-octanoylhomoserine lactone. However, the aiiA homologue, encoding an autoinducer inactivation enzyme catalyzing the degradation of AHLs, was not detected in L62, suggesting the presence of a different AHL-degrading gene in L62. To the best of our knowledge, this is the first report of AHL-degrading B. sonorensis from soya sauce liquid state fermentation. PMID:22666018

  12. In vitro analysis of the anthelmintic activity of forage chicory (Cichorium intybus L.) sesquiterpene lactones against a predominatly Haemonchus contortus egg population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The anthelmintic activity of chicory (Cichorium intybus L.) herbage has been attributed to sesquiterpene lactones. Chicory leaves contain significant amounts of lactucin (LAC), 8-deoxylactucin (DOL), and lactucopicrin (LPIC), but the proportions of these three sesquiterpene lactones vary among fora...

  13. Zr[bis(salicylidene)ethylenediaminato]-mediated Baeyer–Villiger oxidation: Stereospecific synthesis of abnormal and normal lactones

    PubMed Central

    Watanabe, Akira; Uchida, Tatsuya; Irie, Ryo; Katsuki, Tsutomu

    2004-01-01

    Baeyer–Villiger oxidation of racemic bicyclic cyclobutanones with Zr[bis(salicylidene)ethylenediaminato] (salen) complex 1 as catalyst in the presence of a urea-hydrogen peroxide adduct was found to proceed enantiospecifically. The enantiotopos selection in the oxidation was governed primarily by the Zr(salen) catalyst, although migratory aptitude (methine > methylene > methyl) in Baeyer–Villiger oxidation affected the selection to a varied extent, depending on the substrate structures; one enantiomer of cyclobutanones gave exclusively a normal lactone expected from the migratory aptitude, and the other enantiomer gave an abnormal lactone preferentially, the formation of which is counter to the migratory aptitude. Furthermore, the rates of abnormal lactone formation were found to be faster than those of normal lactone formation in most of the oxidations examined. For example, the enantiomer of racemic bicyclo[3.2.0]heptan-6-one giving an abnormal lactone reacted 2.2 times faster than the other enantiomer giving a normal lactone. To our knowledge, this example of chemocatalytic Baeyer–Villiger oxidation giving an abnormal lactone in preference to a normal lactone has been previously unreported. This unusual behavior is likely to be attributable to strict control of stereoelectronic demand in Baeyer–Villiger oxidation and chiral recognition by complex 1. PMID:15073326

  14. Thermoregulation of N-Acyl Homoserine Lactone-Based Quorum Sensing in the Soft Rot Bacterium Pectobacterium atrosepticum▿

    PubMed Central

    Latour, Xavier; Diallo, Stéphanie; Chevalier, Sylvie; Morin, Danièle; Smadja, Bruno; Burini, Jean-François; Haras, Dominique; Orange, Nicole

    2007-01-01

    The psychrotolerant bacterium Pectobacterium atrosepticum produces four N-acyl homoserine lactones under a wide range of temperatures. Their thermoregulation differs from that of the exoenzyme production, described as being under quorum-sensing control. A mechanism involved in this thermoregulation consists of controlling N-acyl homoserine lactones synthase production at a transcriptional level. PMID:17468275

  15. Lipase-catalyzed ring-opening polymerization of lactones to polyesters and its mechanistic aspects.

    PubMed

    Namekawa, S; Suda, S; Uyama, H; Kobayashi, S

    1999-01-01

    Lipase catalysis induced a ring-opening polymerization of lactones with different ring-sizes. Small-size (four-membered) and medium-size lactones (six- and seven-membered) as well as macrolides (12-, 13-, 16-, and 17-membered) were subjected to lipase-catalyzed polymerization. The polymerization behaviors depended primarily on the lipase origin and the monomer structure. The macrolides showing much lower anionic polymerizability were enzymatically polymerized faster than epsilon-caprolactone. The granular immobilized lipase derived from Candida antartica showed extremely efficient catalysis in the polymerization of epsilon-caprolactone. Single-step terminal functionalization of the polyester was achieved by initiator and terminator methods. The enzymatic polymerizability of lactones was quantitatively evaluated by Michaelis-Menten kinetics. PMID:10416661

  16. A New Acyl-homoserine Lactone Molecule Generated by Nitrobacter winogradskyi

    PubMed Central

    Shen, Qiuxuan; Gao, Jie; Liu, Jun; Liu, Shuangjiang; Liu, Zijun; Wang, Yinghuan; Guo, Baoyuan; Zhuang, Xuliang; Zhuang, Guoqiang

    2016-01-01

    It is crucial to reveal the regulatory mechanism of nitrification to understand nitrogen conversion in agricultural systems and wastewater treatment. In this study, the nwiI gene of Nitrobacter winogradskyi was confirmed to be a homoserine lactone synthase by heterologous expression in Escherichia coli that synthesized several acyl-homoserine lactone signals with 7 to 11 carbon acyl groups. A novel signal, 7, 8-trans-N-(decanoyl) homoserine lactone (C10:1-HSL), was identified in both N. winogradskyi and the recombined E. coli. Furthermore, this novel signal also triggered variances in the nitrification rate and the level of transcripts for the genes involved in the nitrification process. These results indicate that quorum sensing may have a potential role in regulating nitrogen metabolism. PMID:26965192

  17. Neuroprotective effects of a sesquiterpene lactone and flavanones from Paulownia tomentosa Steud. against glutamate-induced neurotoxicity in primary cultured rat cortical cells.

    PubMed

    Kim, Soo-Ki; Cho, Sang-Buem; Moon, Hyung-In

    2010-12-01

    The neuroprotective effects of Paulownia tomentosa against glutamate-induced neurotoxicity were studied in primary cultured rat cortical cells. It was found that the aqueous extract of this medicinal plant significantly attenuated glutamate-induced toxicity. In order to clarify the mechanism(s) underlying this neuroprotective effect, the active fractions and components were isolated and identified. Five compounds were isolated as the methanol extracts from air-dried flowers of P. tomentosa. Isoatriplicolide tiglate exhibited significant neuroprotective activity against glutamate-induced toxicity at concentrations ranging from 1 μM to 10 μM, and exhibited cell viability of approximately 43-78%. Therefore, the neuroprotective effect of P. tomentosa might be due to the inhibition of glutamate-induced toxicity by the sesquiterpene lactone derivative it contains. PMID:20683844

  18. Synthesis and Antifeedant Activity of Racemic and Optically Active Hydroxy Lactones with the p-Menthane System.

    PubMed

    Grudniewska, Aleksandra; Kłobucki, Marek; Dancewicz, Katarzyna; Szczepanik, Maryla; Gabryś, Beata; Wawrzeńczyk, Czesław

    2015-01-01

    Two racemic and two enantiomeric pairs of new δ-hydroxy-γ-lactones based on the p-menthane system were prepared from racemic and optically active cis- and trans-piperitols. The Johnson-Claisen rearrangement of the piperitols, epoxidation of the γδ-unsaturated esters, and acidic lactonization of the epoxy esters were described. The structures of the compounds were confirmed spectroscopically. The antifeedant activities of the hydroxy lactones and racemic piperitone were evaluated against three insect pests: lesser mealworm, Alphitobius diaperinus (Panzer); Colorado potato beetle, Leptinotarsa decemlineata (Say); and peach-potato aphid, Myzus persicae (Sulz.). The chemical transformation of piperitone by the introduction of a lactone moiety and a hydroxy group changed its antifeedant properties. Behavioral bioassays showed that the feeding deterrent activity depended on the insect species and the structure of the compounds. All hydroxy lactones deterred the settling of M. persicae. Among chewing insects, the highest sensitivity showed A. diaperinus adults. PMID:26132506

  19. Synthesis and Antifeedant Activity of Racemic and Optically Active Hydroxy Lactones with the p-Menthane System

    PubMed Central

    Grudniewska, Aleksandra; Kłobucki, Marek; Dancewicz, Katarzyna; Szczepanik, Maryla; Gabryś, Beata; Wawrzeńczyk, Czesław

    2015-01-01

    Two racemic and two enantiomeric pairs of new δ-hydroxy-γ-lactones based on the p-menthane system were prepared from racemic and optically active cis- and trans-piperitols. The Johnson-Claisen rearrangement of the piperitols, epoxidation of the γδ-unsaturated esters, and acidic lactonization of the epoxy esters were described. The structures of the compounds were confirmed spectroscopically. The antifeedant activities of the hydroxy lactones and racemic piperitone were evaluated against three insect pests: lesser mealworm, Alphitobius diaperinus (Panzer); Colorado potato beetle, Leptinotarsa decemlineata (Say); and peach-potato aphid, Myzus persicae (Sulz.). The chemical transformation of piperitone by the introduction of a lactone moiety and a hydroxy group changed its antifeedant properties. Behavioral bioassays showed that the feeding deterrent activity depended on the insect species and the structure of the compounds. All hydroxy lactones deterred the settling of M. persicae. Among chewing insects, the highest sensitivity showed A. diaperinus adults. PMID:26132506

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

    PubMed

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

    2015-10-01

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

  1. Purification and identification of antimicrobial sesquiterpene lactones from yacon (Smallanthus sonchifolius) leaves.

    PubMed

    Lin, Fengqiu; Hasegawa, Morifumi; Kodama, Osamu

    2003-10-01

    The extraction of yacon [Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson; Asteraceae] leaves and chromatographic separation yielded two new antibacterial melampolide-type sesquiterpene lactones, 8beta-tigloyloxymelampolid-14-oic acid methyl ester and 8beta-methacryloyloxymelampolid-14-oic acid methyl ester, as well as the four known melampolides, sonchifolin, uvedalin, enhydrin and fluctuanin. The newly identified compound, 8beta-methacryloyloxymelampolid-14-oic acid methyl ester, exhibited potent antimicrobial activity against Bacillus subtilis and Pyricularia oryzae, while 8beta-tigloyloxymelampolid-14-oic acid methyl ester showed lower activity. Fluctuanin exhibited the strongest antibacterial activity against B. subtilis among these six sesquiterpene lactones. PMID:14586103

  2. 19-Benzo-yloxy-13,16-seco-ent-beyeran 13,16-lactone.

    PubMed

    Cai, Jin; Zha, Xiaoming

    2010-01-01

    The title compound, C(27)H(34)O(5), a beyerane-type diterpenoid prepared by peroxidation and benzoyl-ation of isosteviol, contains a fused six-membered ring system. The O atoms of the benzoic ester and the lactone are disordered with occupancy ratios of 0.6 (4):0.4 (4) and 0.6 (2):0.4 (2), respectively. Three cyclo-hexane rings have chair conformations, whereas the remaining lactone ring adopts a half-chair conformation. PMID:21522644

  3. Production of N-acylhomoserine lactone signal molecules by gram-negative soil-borne and plant-associated bacteria.

    PubMed

    Veselova, M; Kholmeckaya, M; Klein, S; Voronina, E; Lipasova, V; Metlitskaya, A; Mayatskaya, A; Lobanok, E; Khmel, I; Chernin, L

    2003-01-01

    Quorum-sensing control mediated by N-acylhomoserine lactone (AHL) signal molecules has been established as a key feature in the regulation of various metabolic traits in many bacteria. Approximately 300 strains representing 6 genera and 18 species of soil-borne and plant-associated Gram-negative bacteria isolated in various regions of the former USSR using two reporter systems were screened for AHL production. The production was observed in 17.5% of the screened bacterial strains. Positive response was detected in all of the 14 tested strains of Erwinia herbicola, in 41 of the 239 strains of Pseudomonas species; in all 5 strains of Xanthomonas ampelina, X. campestris pv. malvacearum, pv. translucens, pv. vesicatoria and in one strain of Pantoea stewartii. AHL assay of 41 strains of X. maltophilia (syn. Stenotrophomonas maltophilia) isolated from soils with Chromobacterium violaceum reporter has revealed no strains synthesizing these signal molecules; 26 strains analyzed with Agrobacterium tumefaciens reporter showed the same result. PMID:15058194

  4. Molecular targets and mechanisms of cancer prevention and treatment by withaferin a, a naturally occurring steroidal lactone.

    PubMed

    Vyas, Avani R; Singh, Shivendra V

    2014-01-01

    The plants used in Ayurvedic medicine, which has been practiced in India for thousands of years for the treatment of a variety of disorders, are rich in chemicals potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is one such medicinal plant whose anticancer value was realized over four decades ago after isolation of a crystalline steroidal compound (withaferin A) from the leaves of this shrub. The root and leaf extracts of W. somnifera are shown to confer protection against chemically-induced cancers in experimental rodents, and retard tumor xenograft growth in athymic mice. Anticancer effect of W. somnifera is generally attributable to steroidal lactones collectively referred to as withanolides. Withaferin A (WA) appears most active against cancer among structurally divergent withanolides isolated from the root or leaf of W. somnifera. Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models. This review summarizes the key in vivo preclinical studies demonstrating anticancer effects of WA. Molecular targets and mechanisms likely contributing to the anticancer effects of WA are also discussed. Finally, challenges in clinical development of WA for the prevention and treatment of cancer are highlighted. PMID:24046237

  5. Cytotoxicity of the Sesquiterpene Lactones Neoambrosin and Damsin from Ambrosia maritima Against Multidrug-Resistant Cancer Cells

    PubMed Central

    Saeed, Mohamed; Jacob, Stefan; Sandjo, Louis P.; Sugimoto, Yoshikazu; Khalid, Hassan E.; Opatz, Till; Thines, Eckhard; Efferth, Thomas

    2015-01-01

    Multidrug resistance is a prevailing phenomenon leading to chemotherapy treatment failure in cancer patients. In the current study two known cytotoxic pseudoguaianolide sesquiterpene lactones; neoambrosin (1) and damsin (2) that circumvent MDR were identified. The two cytotoxic compounds were isolated using column chromatography, characterized using 1D and 2D NMR, MS, and compared with literature values. The isolated compounds were investigated for their cytotoxic potential using resazurin assays and thereafter confirmed with immunoblotting and in silico studies. MDR cells overexpressing ABC transporters (P-glycoprotein, BCRP, ABCB5) did not confer cross-resistance toward (1) and (2), indicating that these compounds are not appropriate substrates for any of the three ABC transporters analyzed. Resistance mechanisms investigated also included; the loss of the functions of the TP53 and the mutated EGFR. The HCT116 p53-/- cells were sensitive to 1 but resistant to 2. It was interesting to note that resistant cells transfected with oncogenic ΔEGFR exhibited hypersensitivity CS toward (1) and (2) (degrees of resistances were 0.18 and 0.15 for (1) and (2), respectively). Immunoblotting and in silico analyses revealed that 1 and 2 silenced c-Src kinase activity. It was hypothesized that inhibition of c-Src kinase activity may explain CS in EGFR-transfected cells. In conclusion, the significant cytotoxicity of 1 and 2 against different drug-resistant tumor cell lines indicate that they may be promising candidates to treat refractory tumors. PMID:26617519

  6. Optimizing a neutron-beam focusing device for the direct geometry time-of-flight spectrometer TOFTOF at the FRM II reactor source

    NASA Astrophysics Data System (ADS)

    Rasmussen, N. G.; Simeoni, G. G.; Lefmann, K.

    2016-04-01

    A dedicated beam-focusing device has been designed for the direct geometry thermal-cold neutron time-of-flight spectrometer TOFTOF at the neutron facility FRM II (Garching, Germany). The prototype, based on the compressed Archimedes' mirror concept, benefits from the adaptive-optics technology (adjustable supermirror curvature) and the compact size (only 0.5 m long). We have simulated the neutron transport across the entire guide system. We present a detailed computer characterization of the existing device, along with the study of the factors mostly influencing the future improvement. We have optimized the simulated prototype as a function of the neutron wavelength, accounting also for all relevant features of a real instrument like the non-reflecting side edges. The results confirm the "chromatic" displacement of the focal point (flux density maximum) at fixed supermirror curvature, and the ability of a variable curvature to keep the focal point at the sample position. Our simulations are in excellent agreement with theoretical predictions and the experimentally measured beam profile. With respect to the possibility of a further upgrade, we find that supermirror coatings with m-values higher than 3.5 would have only marginal influence on the optimal behaviour, whereas comparable spectrometers could take advantage of longer focusing segments, with particular impact for the thermal region of the neutron spectrum.

  7. [Effects of coriaria lactone on the concentration of intracellular free calcium of rat hippocampal neurons].

    PubMed

    Lai, Xiaohui; Zhang, Qin; Zhou, Dong

    2008-08-01

    We instituted an investigation to elucidate the role of Ca2+ and calcium channels in epileptogenesis and to analyze the mechanism by which coriaria lactone (CL) regulates intracellular Ca2+ concentration. The hippocampal neurons of Sprague-Dawley rats (post natal days 7 to 14) were acutely isolated and loaded with calcium-sensitive fluorescent indicator Fluo-3/AM. Intracellular calcium concentration ([Ca2+]i) changes were measured using laser scanning confocal microscopy. The study included five groups, namely the CL group, the NiCl2 plus CL group, the Nifedipine plus CL group, the NiCl2+ Nifedipine plus CL group, and the control group. The results indicated that 20 microl/ml CL induced a significant increase of [Ca2+]i in hippocampal neurons when compared to the control (P < 0.01), the mean fluorescent intensity of intracellular calcium displaying an increase from 5.46 +/- 2.37 to 34.03 +/- 3.45. Although the increase of relative intracellular fluorescent intensity was delayed by 3 or 4 minutes in the NiCl2 plus CL group, the Nifedipine plus CL group, and the NiCl2+ Nifedipine plus CL group, yet the use to 20 microl/ml CL in these 3 groups caused a significant ascending level of the fluorescent intensities (from 3.94 +/- 1.75 to 30.18 +/- 4.22; from 3.38 +/- 1.11 to 36.39 +/- 3.97; from 3.05 +/- 1.02 to 28.05 +/- 2.71), and the effect was comparable to that observed in the CL group (P > 0.05). So CL can increase [Ca2+]i in acutely isolated rat hippocampal neurons. This effect can be delayed but can not be completely blocked by NiCl2 and Nifedipine. These findings indicate that CL can increase [Ca2+]i by other means besides T- and L-type voltage-gated calcium channels, and that CL can increase the excitability of neurons and play a role in the epileptogenesis process. PMID:18788307

  8. Transformation of a series of saturated isomeric steroidal diols by Aspergillus tamarii KITA reveals a precise stereochemical requirement for entrance into the lactonization pathway.

    PubMed

    Hunter, A Christy; Collins, Catherine; Dodd, Howard T; Dedi, Cinzia; Koussoroplis, Salomé-Juliette

    2010-11-01

    Four isomers of 5α-androstan-3,17-diol have been transformed by the filamentous fungus Aspergillus tamarii, an organism which has the ability to convert progesterone to testololactone in high yield through an endogenous four step enzymatic pathway. The only diol handled within the lactonization pathway was 5α-androstan-3α,17β-diol which, uniquely underwent oxidation of the 17β-alcohol to the 17-ketone prior to its Baeyer-Villiger oxidation and the subsequent production of 3α-hydroxy-17a-oxa-D-homo-5α-androstan-17-one. This demonstrated highly specific stereochemical requirements of the 17β-hydroxysteroid dehydrogenase for oxidation of this specific steroidal diol to occur. In contrast, the other three diols were transformed within the hydroxylation pathway resulting in functionalization at C-11β. Only 5α-androstan-3β,17α-diol could bind to the hydroxylase in multiple binding modes undergoing monohydroxylation in 6β and 7β positions. Evidence from this study has indicated that hydroxylation of saturated steroidal lactones may occur following binding of ring-D in its open form in which an α-alcohol is generated with close spatial parity to the C-17α hydroxyl position. All metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR and DEPT analysis and further characterized using infra-red, elemental analysis and accurate mass measurement. PMID:20832471

  9. GacS-dependent regulation of enzymic and antifungal activities and synthesis of N-acylhomoserine lactones in rhizospheric strain Pseudomonas chlororaphis 449.

    PubMed

    Veselova, M; Lipasova, V; Protsenko, M A; Buza, N; Khmel, I A

    2009-09-01

    Pseudomonas chlororaphis strain 449 isolated from the rhizosphere of maize suppresses numerous plant pathogens in vitro. The strain produces phenazine antibiotics and synthesizes at least three types of quorum sensing signaling molecules, N-acylhomoserine lactones. Here we have shown that the rhizospheric P. chlororaphis strains 449, well known strain 30-84 as well as two other P. chlororaphis strains exhibit polygalacturonase activity. Using mini-Tn5 transposon mutagenesis, four independent mutants of strain P. chlororaphis 449 with insertion of mini-Tn5 Km2 in gene gacS of two-component GacA-GacS system of global regulation were selected. All these mutant strains were deficient in production of extracellular proteinase(s), phenazines, N-acylhomoserine lactones synthesis, and did not inhibit the growth of G(+) bacteria in comparison with the wild type strain. The P. chlororaphis 449-06 gacS (-) mutant studied in greater detail was deficient in polygalacturonase, pectin methylesterase activities, swarming motility and antifungal activity. It is the first time the involvement of GacA-GacS system in the regulation of enzymes of pectin metabolism, polygalacturonase and pectin methylesterase, was demonstrated in fluorescent pseudomonads. PMID:19937212

  10. Biosynthesis of Germacrene A Carboxylic Acid in Chicory Roots. Demonstration of a Cytochrome P450 (+)-Germacrene A Hydroxylase and NADP+-Dependent Sesquiterpenoid Dehydrogenase(s) Involved in Sesquiterpene Lactone Biosynthesis

    PubMed Central

    de Kraker, Jan-Willem; Franssen, Maurice C. R.; Dalm, Marcella C. F.; de Groot, Aede; Bouwmeester, Harro J.

    2001-01-01

    Sprouts of chicory (Cichorium intybus), a vegetable grown in the dark, have a slightly bitter taste associated with the presence of guaianolides, eudesmanolides, and germacranolides. The committed step in the biosynthesis of these compounds is catalyzed by a (+)-germacrene A synthase. Formation of the lactone ring is the postulated next step in biosynthesis of the germacrene-derived sesquiterpene lactones. The present study confirms this hypothesis by isolation of enzyme activities from chicory roots that introduce a carboxylic acid function in the germacrene A isopropenyl side chain, which is necessary for lactone ring formation. (+)-Germacrene A is hydroxylated to germacra-1(10),4,11(13)-trien-12-ol by a cytochrome P450 enzyme, and is subsequently oxidized to germacra-1(10),4,11(13)-trien-12-oic acid by NADP+-dependent dehydrogenase(s). Both oxidized germacrenes were detected as their Cope-rearrangement products elema-1,3,11(13)-trien-12-ol and elema-1,3,11(13)-trien-12-oic acid, respectively. The cyclization products of germacra-1(10),4,11(13)-trien-12-ol, i.e. costol, were also observed. The (+)-germacrene A hydroxylase is inhibited by carbon monoxide (blue-light reversible), has an optimum pH at 8.0, and hydroxylates β-elemene with a modest degree of enantioselectivity. PMID:11299372

  11. Developmental and Environmental Effects on Sesquiterpene Lactones in Cultivated Arnica montana L.

    PubMed

    Todorova, Milka; Trendafilova, Antoaneta; Vitkova, Antonina; Petrova, Maria; Zayova, Ely; Antonova, Daniela

    2016-08-01

    The amount of sesquiterpene lactones and the lactone profile of Arnica montana L. in flowering and seed formation stages in vitro and in vivo propagated from seeds of German, Ukrainian, and Austrian origin and grown in two experimental fields were studied. It was found that in vitro propagated 2-year plants in full flowering stage accumulated higher amount of lactones in comparison to in vivo propagated 3-year plants and to the seed formation stage, respectively. Helenalins predominated in in vivo propagated 2-year or in vitro propagated 3-year plants. 2-Methylbutyrate (2MeBu) was the principal ester in the samples with prevalence of helenalins, while isobutyrate (iBu) was the major one in the samples with predominance of 11,13-dihydrohelenalins. The results revealed that the environmental conditions on Vitosha Mt. are more suitable for cultivation of A. montana giving higher content of lactones. PMID:27368426

  12. Concurrent and supercritical fluid chromatographic analysis of Terpene Lactones and ginkolic acids in Ginko biloba.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Supercritical fluid chromatography was used to resolve and determine ginkgolic acids (GAs) and terpene lactones concurrently in ginkgo plant materials and commercial dietary supplements. Analysis of GAs (C13:0, C15:0, C15:1 and C17:1) was carried out by ESI (-) mass detection. The ESI (-) spectra of...

  13. SELECTIVE HYDROGENATION OF ANHYDRIDES TO LACTONES UNDER SUPERCRITICAL CARBON DIOXIDE MEDIUM

    EPA Science Inventory

    Selective Hydrogenation of Anhydrides to Lactones Under Supercritical Carbon Dioxide Medium

    Endalkachew Sahle-Demessie Unnikrishnan R Pillai
    U.S. EPA , 26 W. Martin Luther King Dr. Cincinnati, OH 45268 Phone: 513-569-7739
    Fax: 513-569-7677
    Abstract:
    Hydrogenat...

  14. Alkene Dioxygenation with Malonoyl Peroxides: Synthesis of γ-Lactones, Isobenzofuranones, and Tetrahydrofurans.

    PubMed

    Alamillo-Ferrer, Carla; Karabourniotis-Sotti, Marianna; Kennedy, Alan R; Campbell, Matthew; Tomkinson, Nicholas C O

    2016-07-01

    Treatment of homoallylic alcohols or carboxylic acids with malonoyl peroxide 1 provides a stereoselective method for the preparation of tetrahydrofurans, γ-lactones, and isobenzofuranones in 44-82% yield and up to 27:1 trans selectivity. Application of this simple and effective heterocyclization in the synthesis of the antidepressant citalopram is also described. PMID:27314605

  15. Anthelmintic potential of chicory forage is influenced by sesquiterpene lactone composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The anthelmintic activity of chicory (Cichorium intybus L.) herbage has been attributed to sesquiterpene lactones (SLs). Chicory leaves contain lactucin (LAC), 8-deoxylactucin (DOL), and lactucopicrin (LPIC), but the amounts of these three SLs vary among cultivars. The objective of this study was...

  16. Enantioselective and collective syntheses of xanthanolides involving a controllable dyotropic rearrangement of cis-β-lactones.

    PubMed

    Ren, Weiwu; Bian, Yichao; Zhang, Ziyang; Shang, Hai; Zhang, Pengtao; Chen, Yuejie; Yang, Zhen; Luo, Tuoping; Tang, Yefeng

    2012-07-01

    Let's swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted γ-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-β-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products. PMID:22674838

  17. In vitro leishmanicidal activities of sesquiterpene lactones from Tithonia diversifolia against Leishmania braziliensis promastigotes and amastigotes.

    PubMed

    de Toledo, Juliano S; Ambrósio, Sergio R; Borges, Carly H G; Manfrim, Viviane; Cerri, Daniel G; Cruz, Angela K; Da Costa, Fernando B

    2014-01-01

    Natural compounds represent a rich and promising source of novel, biologically active chemical entities for treating leishmaniasis. Sesquiterpene lactones are a recognized class of terpenoids with a wide spectrum of biological activities, including activity against Leishmania spp. In this work, a sesquiterpene lactone-rich preparation-a leaf rinse extract (LRE) from Tithonia diversifolia-was tested against promastigote forms of L. braziliensis. The results revealed that the LRE is a rich source of potent leishmanicidal compounds, with an LD50 value 1.5 ± 0.50 µg·mL-1. Therefore, eight sesquiterpene lactones from the LRE were initially investigated against promastigote forms of L. braziliensis. One of them did not present any significant leishmanicidal effect (LD50 > 50 µg·mL-1). Another had a cytotoxic effect against macrophages (4.5 µg·mL-1). The five leishmanicidal compounds with the highest level of selectivity were further evaluated against intracellular parasites (amastigotes) using peritoneal macrophages. Tirotundin 3-O-methyl ether, tagitinin F, and a guaianolide reduced the internalization of parasites after 48 h, in comparison with the negative control. This is the first report on sesquiterpene lactones that have potent leishmanicidal effects on both developmental stages of L. braziliensis. PMID:24830711

  18. Self-Assembly and Lipid Interactions of Diacylglycerol Lactone Derivatives Studied at the Air/Water Interface

    PubMed Central

    Philosof-Mazor, Liron; Volinsky, Roman; Comin, Maria J.; Lewin, Nancy E.; Kedei, Noemi; Blumberg, Peter M.; Marquez, Victor E.; Jelinek, Raz

    2009-01-01

    Synthetic diacylglycerol lactones (DAG-lactones) have been shown to be effective modulators of critical cellular signaling pathways. The biological activity of these amphiphilic molecules depends in part upon their lipid interactions within the cellular plasma membrane. This study explores the thermodynamic and structural features of DAG-lactone derivatives and their lipid interactions at the air/water interface. Surface-pressure/area isotherms and Brewster angle microscopy revealed the significance of specific side-groups attached to the terminus of a very rigid 4-(2-phenylethynyl) benzoyl chain of the DAG-lactones, which affected both the self-assembly of the molecules and their interactions with phospholipids. The experimental data highlight the formation of different phases within mixed DAG-lactone/phospholipid monolayers and underscore the relationship between the two components in binary mixtures of different mole ratios. Importantly, the results suggest that DAG-lactones are predominantly incorporated within fluid phospholipid phases rather than in the condensed phases that form, for example, by cholesterol. Moreover, the size and charge of the phospholipid headgroups do not seem to affect DAG-lactone interactions with lipids. PMID:18788772

  19. Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides

    PubMed Central

    Schirmer, Andreas; Kennedy, Jonathan; Murli, Sumati; Reid, Ralph; Santi, Daniel V.

    2006-01-01

    Resorcylic acid lactones containing a cis-enone are susceptible to Michael addition reactions and are potent inhibitors of several protein kinases. A structural-bioinformatics analysis identified a conserved Cys residue in the ATP-binding site of the kinases reported to be inhibited by cis-enone resorcylic acid lactones but absent in those that are not. Mining of the kinome database revealed that a subset of some 46 kinases contained this Cys residue. Screening a panel of 124 kinases with the resorcylic acid lactone hypothemycin showed that 18 of 19 targets containing the conserved Cys were inhibited. Kinetic analyses showed time-dependent inhibition, a hallmark of covalent inactivation, and biochemical studies of the interaction of extracellular signal-regulated kinase (ERK)2 with hypothemycin confirmed covalent adduct formation. Resorcylic acid lactones are unique among kinase inhibitors in that they target mitogen-activated protein (MAP) kinase pathways at four levels: mitogen receptors, MAP kinase kinase (MEK)1/2 and ERK1/2, and certain downstream ERK substrates. Cell lines dependent on the activation of Tyr kinase mitogen receptor targets of the resorcylic acid lactones were unusually sensitive toward hypothemycin and showed the expected inhibition of kinase phosphorylation due to inhibition of the mitogen receptors and/or MEK1/2 and ERK1/2. Among cells without mitogen receptor targets, those harboring an ERK pathway-activating B-RAF V600E mutation were selectively and potently inhibited by hypothemycin. Hypothemycin also prevented stimulated activation of the p38 cascade through inhibition of the Cys-containing targets MEK3/6 and TGF-β-activated kinase 1 and of the JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) cascade through inhibition of MEK4/7. PMID:16537514

  20. Validation of analytical procedures using HPLC-ELSD to determine six sesquiterpene lactones in Eremanthus species.

    PubMed

    Sousa, João Paulo B; Nogueira, Elídia F; Ferreira, Leandro S; Lopes, Norberto P; Lopes, João Luis C

    2016-03-01

    Eremanthus species display sesquiterpene lactones with therapeutic potential. We are proposing the development of a new analytical method that has been completely validated to qualify Eremanthus species and its main lactones in raw material using HPLC-ELSD. For the sample preparation, 10.0 mg of powdered Eremanthus leaves was extracted with a 5 mL MeOH/H2 O (9:1 v/v) solution containing scopoletin at 140 µg/mL as the internal standard. For the separation of eight compounds, six of which were lactones, one internal (IS) and one secondary standard were performed utilizing monolithic columns with a nonlinear gradient. The selectivity, stability, precision and matrix effects parameters showed values of RSD of <10%. The six lactones and scopoletin (IS) were recovered with a proportion between 74 and 90% with accuracy represented by error at -25.41%. The linear dynamic range was obtained between 10.0 and 310.0 µg/mL for all compounds with r(2)  > 0.9987. The limits of detection and quantitation ranged from 2.00 to 6.79 µg/mL and from 6.00 to 20.40 µg/mL, respectively. Assessing the robustness study, this method can be used in inter-laboratory studies. Using the HPLC-ELSD method, six sesquiterpene lactones including 4β,5-dihydro-2',3'-dihydroxy-15-deoxy-goyazensolide, goyazensolide, 4β,5-dihydro-2',3'-epoxy-15-deoxy-goyazensolide, centratherin, 4β,5-dihydro-15-deoxy-goyazensolide and lychnofolide, were detected and quantified from distinct Eremanthus species, which were collected in different regions. PMID:26234655

  1. Effect of different types of sesquiterpene lactones on the maturation of Rhinella arenarum oocytes.

    PubMed

    Sánchez-Toranzo, G; Zapata-Martínez, J; Catalán, C; Bühler, M I

    2015-06-01

    The sesquiterpene lactones (STLs) are a large class of plant secondary metabolites that are generally found in the Asteraceae family and that have high diversity with respect to chemical structure as well as biological activity. STLs have been classified into different groups, such as guaianolides, germacranolides, and melampolides etc., based on their carboxylic skeleton. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under the stimulus of progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. The purpose of this work was to determine whether sesquiterpene lactones from the germacranolide and melampolide groups act as inhibitor agents on the meiosis of amphibian oocytes in vitro. Results for germacranolides indicated that the addition of deoxyelephantopins caused a high degree of inhibition and that minimolide showed a moderate inhibitory effect, whereas glaucolide A was inactive. Furthermore, the addition of melampolides (uvedalin, enhydrin, polymatin A and polymatin B) showed inhibitory effects. For enhydrin and uvedalin, inhibitory effects were observed at the higher concentrations assayed. The results of this study suggest that the inhibitory activity of the tested sesquiterpene lactones on the meiosis of Rhinella arenarum oocytes is not dependent on the group to which they belong, i.e. not on the carboxylic skeleton, but probably due to the arrangement and type of function groups present in the molecules. All assayed lactones in the germacranolide group showed low toxicity. In contrast, important differences in toxicity were observed for lactones from the melampolide group: enhydrin and uvedalin showed low toxicity, but polymatin A and B were highly toxic. PMID:24522008

  2. Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque.

    PubMed

    Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

    2016-01-01

    Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID:26860259

  3. Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque

    PubMed Central

    Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

    2016-01-01

    Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID:26860259

  4. Protolichesterinic acid derivatives: α-methylene-γ-lactones as potent dual activators of PPARγ and Nrf2 transcriptional factors.

    PubMed

    Le Lamer, Anne-Cécile; Authier, Hélène; Rouaud, Isabelle; Coste, Agnès; Boustie, Joël; Pipy, Bernard; Gouault, Nicolas

    2014-08-15

    PPARγ and Nrf2 are important transcriptional factors involved in many signaling pathways, especially in the anti-infectious response of macrophages. Compounds bearing a Michael acceptor moiety are well known to activate such transcriptional factors, we thus evaluated the potency of α,β-unsaturated lactones synthesized using fluorous phase organic synthesis. Compounds were first screened for their cytotoxicity in order to select lactones for PPARγ and Nrf2 activation evaluation. Among them, two α-methylene-γ-lactones were identified as potent dual activators of PPARγ and Nrf2 in macrophages. PMID:25027935

  5. In Situ Electrostatic Separation of Ambient PM2.5 into Source-Specific Fractions During Collection in a FRM Sampler

    SciTech Connect

    Naresh Shah; Frank E. Huggins; Gerald P. Huffman

    2006-07-31

    Coal combustion is generally viewed as a major source of PM2.5 emissions into the atmosphere. For some time, toxicologists have been asking for an exposure environment enriched with the coal combustion source specific PM{sub 2.5} to conduct meaningful exposure studies to better understand the mechanisms of the adverse health effects of coal combustion specific PM2.5 in the ambient environment. There are several unique characteristics of primary PM generated from coal combustion. In this research project, an attempt has been made to exploit some of the unique properties of PM generated from coal fired power plants to preferentially separate them out from the rest of the primary and secondary PM in the ambient environment. An existing FRM sampler used for monitoring amount of PM{sub 2.5} in the ambient air is modified to incorporate an electrostatic field. A DC corona charging device is also installed at the ambient air inlet to impart positive or negative charge to the PM. Visual Basic software has been written to simulate the lateral movement of PM as it passes through the electrostatic separator under varying operating conditions. The PM samples collected on polycarbonate filters under varying operating conditions were extensively observed for clustering and/or separation of PM in the direction parallel to the electric field. No systematic PM separation was observed under any of the operating conditions. A solution to overcome this kind of turbulence caused remixing has been offered. However, due to major programmatic changes in the DOE UCR program, there are no venues available to further pursue this research.

  6. Lipase-catalyzed synthesis of aliphatic polyesters via copolymerization of lactone, dialkyl diester, and diol.

    PubMed

    Jiang, Zhaozhong

    2008-11-01

    Candida antarctica lipase (CALB) has been successfully used as catalyst for copolymerization of dialkyl diester with diol and lactone to form aliphatic polyesters. The polymerization reactions were performed using a two stage process: first stage oligomerization under low vacuum followed by second stage polymerization under high vacuum. Use of the two-stage process is required to obtain products with high molecular weights at high yields for the following reasons: (i) the first stage reaction ensures that the monomer loss via evaporation is minimized to maintain 1:1 diester to diol stoichiometric ratio, and the monomers are converted to nonvolatile oligomers; (ii) use of high vacuum during the second stage accelerates equilibrium transesterification reactions to transform the oligomers to high molecular weight polymers. Thus, terpolymers of omega-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) with a M w of whole product (nonfractionated) up to 77000 and M w/ M n between 1.7 and 4.0 were synthesized in high yields (e.g., 95% isolated yield). A desirable reaction temperature for the copolymerizations was found to be around 95 degrees C. At 1:1:1 PDL/DES/BD monomer molar ratio, the resultant terpolymers contained equal moles of PDL, succinate, and butylene repeat units in the polymer chains. (1)H and (13)C NMR analyses were used to determine the polyester microstructures. The synthesized PDL-DES-BD terpolymers possessed near random structures with all possible combinations of PDL, succinate, and butylene units via ester linkages in the polymer backbone. Furthermore, thermal stability and crystallinity of a pure PDL-DES-BD terpolymer with 1:1:1 PDL to succinate to butylene unit ratio and M w of 85400 were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The copolyester was found to be a semicrystalline material with a T g of -34 degrees C and a T m of 64 degrees C, which degrades in a single weight loss

  7. Effects of the sesquiterpene lactone parthenolide on prostate tumor-initiating cells: an integrated molecular profiling approach

    PubMed Central

    Kawasaki, Brian T.; Hurt, Elaine M.; Kalathur, Madhuri; Duhagon, Maria Ana; Milner, John A.; Kim, Young S.; Farrar, William L.

    2009-01-01

    Recent evidence suggests tumor-initating cells (TICs), also called cancer stem cells, are responsible for tumor initiation and progression; therefore, they represent an important cell population for development of future anti-cancer therapies. In this study, we show that the sesquiterpene lactone parthenolide (PTL) is cytotoxic to prostate TICs isolated from prostate cancer cell lines: DU145, PC3, VCAP and LAPC4, as well as primary prostate TICs. Furthermore, PTL inhibited TIC-driven tumor formation in mouse xenografts. Using an integrated molecular profiling approach encompassing proteomics, profiles of activated transcription factors and genomics we ascertained the effects of PTL on prostate cancer cells. In addition to the previously described effects of PTL, we determined that the non-receptor tyrosine kinase src, and many src signaling components, including: Csk, FAK, β1-arrestin, FGFR2, PKC, MEK/MAPK, CaMK, ELK-1 and ELK-1-dependent genes are novel targets of PTL action. Furthermore, PTL altered the binding of transcription factors important in prostate cancer including: C/EBP-α, fos related antigen-1 (FRA-1), HOXA-4, c-MYB, SNAIL, SP1, serum response factor (SRF), STAT3, X-box binding protein-1 (XBP1) and p53. In summary, we show PTL is cytotoxic to prostate TICs and describe the molecular events of PTL-mediated cytotoxicity. Therefore, PTL represents a promising therapeutic for prostate cancer treatment. PMID:19204913

  8. Anti-Inflammatory and Cytostatic Activities of a Parthenolide-Like Sesquiterpene Lactone from Cota palaestina subsp. syriaca

    PubMed Central

    Talhouk, Rabih S.; Nasr, Bilal; Fares, Mohamed-Bilal; Ajeeb, Bushra; Nahhas, Rana; Al Aaraj, Lamis; Ghaddar, Tarek H.; Saliba, Najat A.

    2015-01-01

    A sesquiterpene lactone 1-β,10-Epoxy-6-hydroxy-1,10H-inunolide (K100) was isolated through “bioassay-guided fractionation” from Cota palaestina subsp. syriaca, an Eastern Mediterranean endemic plant. K100 inhibited endotoxin- (ET-) induced proinflammatory markers: IL-6, MMP-9, and NO in normal mouse mammary SCp2 Cells. Molecular docking in silico suggested that K100, having highly analogous structure as parthenolide (PTL), an anticancer compound, could bind PTL target proteins at similar positions and with comparable binding affinities. Both compounds, K100 and PTL, inhibited the proliferation and prolonged the S-phase of the cell cycle of breast adenocarcinoma MDA-MB-231 cells grown in 2D cultures. Noncytotoxic concentrations of K100 and PTL decreased the proliferation rate of MDA-MB-231 and shifted their morphology from stellate to spherical colonies in 3D cultures. This was accompanied with a significant increase in the amount of small colonies and a decrease in the amount of large colonies. Moreover, K100 and PTL decreased cellular motility and invasiveness of MDA-MB-231 cells. In summary, these results suggest that K100 exhibits PTL-analogous anti-inflammatory, cytostatic, and antimetastatic effects. PMID:26089941

  9. A New N-Acyl Homoserine Lactone Synthase in an Uncultured Symbiont of the Red Sea Sponge Theonella swinhoei.

    PubMed

    Britstein, Maya; Devescovi, Giulia; Handley, Kim M; Malik, Assaf; Haber, Markus; Saurav, Kumar; Teta, Roberta; Costantino, Valeria; Burgsdorf, Ilia; Gilbert, Jack A; Sher, Noa; Venturi, Vittorio; Steindler, Laura

    2016-02-01

    Sponges harbor a remarkable diversity of microbial symbionts in which signal molecules can accumulate and enable cell-cell communication, such as quorum sensing (QS). Bacteria capable of QS were isolated from marine sponges; however, an extremely small fraction of the sponge microbiome is amenable to cultivation. We took advantage of community genome assembly and binning to investigate the uncultured majority of sponge symbionts. We identified a complete N-acyl-homoserine lactone (AHL)-QS system (designated TswIR) and seven partial luxI homologues in the microbiome of Theonella swinhoei. The TswIR system was novel and shown to be associated with an alphaproteobacterium of the order Rhodobacterales, here termed Rhodobacterales bacterium TS309. The tswI gene, when expressed in Escherichia coli, produced three AHLs, two of which were also identified in a T. swinhoei sponge extract. The taxonomic affiliation of the 16S rRNA of Rhodobacterales bacterium TS309 to a sponge-coral specific clade, its enrichment in sponge versus seawater and marine sediment samples, and the presence of sponge-specific features, such as ankyrin-like domains and tetratricopeptide repeats, indicate a likely symbiotic nature of this bacterium. PMID:26655754

  10. A New N-Acyl Homoserine Lactone Synthase in an Uncultured Symbiont of the Red Sea Sponge Theonella swinhoei

    PubMed Central

    Britstein, Maya; Devescovi, Giulia; Handley, Kim M.; Malik, Assaf; Haber, Markus; Saurav, Kumar; Teta, Roberta; Costantino, Valeria; Burgsdorf, Ilia; Gilbert, Jack A.; Sher, Noa; Venturi, Vittorio

    2015-01-01

    Sponges harbor a remarkable diversity of microbial symbionts in which signal molecules can accumulate and enable cell-cell communication, such as quorum sensing (QS). Bacteria capable of QS were isolated from marine sponges; however, an extremely small fraction of the sponge microbiome is amenable to cultivation. We took advantage of community genome assembly and binning to investigate the uncultured majority of sponge symbionts. We identified a complete N-acyl-homoserine lactone (AHL)-QS system (designated TswIR) and seven partial luxI homologues in the microbiome of Theonella swinhoei. The TswIR system was novel and shown to be associated with an alphaproteobacterium of the order Rhodobacterales, here termed Rhodobacterales bacterium TS309. The tswI gene, when expressed in Escherichia coli, produced three AHLs, two of which were also identified in a T. swinhoei sponge extract. The taxonomic affiliation of the 16S rRNA of Rhodobacterales bacterium TS309 to a sponge-coral specific clade, its enrichment in sponge versus seawater and marine sediment samples, and the presence of sponge-specific features, such as ankyrin-like domains and tetratricopeptide repeats, indicate a likely symbiotic nature of this bacterium. PMID:26655754

  11. Identification of N-acyl homoserine lactones produced by Gluconacetobacter diazotrophicus PAL5 cultured in complex and synthetic media.

    PubMed

    Nieto-Peñalver, Carlos G; Bertini, Elisa V; de Figueroa, Lucía I C

    2012-07-01

    The endophytic diazotrophic Gluconacetobacter diazotrophicus PAL5 was originally isolated from sugarcane (Saccharum officinarum). The biological nitrogen fixation, phytohormones secretion, solubilization of mineral nutrients and phytopathogen antagonism allow its classification as a plant growth-promoting bacterium. The recent genomic sequence of PAL5 unveiled the presence of a quorum sensing (QS) system. QS are regulatory mechanisms that, through the production of signal molecules or autoinducers, permit a microbial population the regulation of the physiology in a coordinated manner. The most studied autoinducers in gram-negative bacteria are the N-acyl homoserine lactones (AHLs). The usage of biosensor strains evidenced the presence of AHL-like molecules in cultures of G. diazotrophicus PAL5 grown in complex and synthetic media. Analysis of AHLs performed by LC-APCI-MS permitted the identification of eight different signal molecules, including C6-, C8-, C10-, C12- and C14-HSL. Mass spectra confirmed that this diazotrophic strain also synthesizes autoinducers with carbonyl substitutions in the acyl chain. No differences in the profile of AHLs could be determined under both culture conditions. However, although the level of short-chain AHLs was not affected, a decrease of 30% in the production of long-chain AHLs could be measured in synthetic medium. PMID:22350020

  12. Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance.

    PubMed

    Bourguinat, Catherine; Lee, Alice C Y; Lizundia, Regina; Blagburn, Byron L; Liotta, Janice L; Kraus, Marc S; Keller, Kathy; Epe, Christian; Letourneau, Louis; Kleinman, Claudia L; Paterson, Tara; Gomez, Elena Carreton; Montoya-Alonso, José Alberto; Smith, Hubert; Bhan, Aron; Peregrine, Andrew S; Carmichael, James; Drake, Jason; Schenker, Rudolf; Kaminsky, Ronald; Bowman, Dwight D; Geary, Timothy G; Prichard, Roger K

    2015-06-15

    Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D. immitis and identified genetic markers that are correlated with, and therefore can predict ML resistance. ML controlled studies showed that LOE strains of D. immitis established infections in dogs despite chemoprophylaxis with oral ivermectin or injectable moxidectin. A whole genome approach was used to search for loci associated with the resistance phenotype. Many loci showed highly significant differences between pools of susceptible and LOE D. immitis. Based on 186 potential marker loci, Sequenom(®) SNP frequency analyses were conducted on 663 individual parasites (adult worms and microfilariae) which were phenotypically characterized as susceptible (SUS), confirmed ML treatment survivors/resistant (RES), or suspected resistant/loss of efficacy (LOE) parasites. There was a subset of SNP loci which appears to be promising markers for predicting ML resistance, including SNPs in some genes that have been associated with ML resistance in other parasites. These data provide unequivocal proof of ML resistance in D. immitis and identify genetic markers that could be used to monitor for ML resistance in heartworms. PMID:25936435

  13. Britannin, a sesquiterpene lactone, inhibits proliferation and induces apoptosis through the mitochondrial signaling pathway in human breast cancer cells.

    PubMed

    Hamzeloo-Moghadam, Maryam; Aghaei, Mahmoud; Fallahian, Faranak; Jafari, Seyyed Mehdi; Dolati, Masoumeh; Abdolmohammadi, Mohammad Hossein; Hajiahmadi, Sima; Esmaeili, Somayeh

    2015-02-01

    Induction of apoptosis in cancer cells can be a promising treatment method in cancer therapy. Naturally derived products had drawn growing attention as agent in cancer therapy. The main target of anticancer drugs may be distinct, but eventually, they lead to identical cell death pathway, which is apoptosis. Here, we indicated that britannin, a sesquiterpene lactone isolated from Asteraceae family, has antiproliferative activity on the MCF-7 and MDA-MB-468 human breast cancer cells. Annexin V/propidium iodide (PI) staining, Hoechst 33258 staining, and caspase-3/9 activity assay confirmed that britannin is able to induce apoptosis in MCF-7 and MDA-MB-468 cells. The Western blot analysis showed that the expression of Bcl-2 was noticeably decreased in response to britannin treatment, while the expression of Bax protein was increased, which were positively correlated with elevated expression of p53. Moreover, britannin also increased reactive oxygen species (ROS) generation which in turn triggered the loss of mitochondrial transmembrane potential (ΔΨm) and the subsequent release of cytochrome c from mitochondria into cytosol. Taken together, these results suggest that britannin inhibits growth of MCF-7 and MDA-MB-468 breast cancer cells through the activation of the mitochondrial apoptotic pathway and may potentially serve as an agent for breast cancer therapy. PMID:25342596

  14. Bacteriocin small of Rhizobium leguminosarum belongs to the class of N-acyl-L-homoserine lactone molecules, known as autoinducers and as quorum sensing co-transcription factors.

    PubMed Central

    Schripsema, J; de Rudder, K E; van Vliet, T B; Lankhorst, P P; de Vroom, E; Kijne, J W; van Brussel, A A

    1996-01-01

    Small bacteriocin was isolated from the culture broth of the gram-negative bacterium Rhizobium leguminosarum, which forms symbiotic nitrogen-fixing root nodules on a number of leguminous plants. The structure of the molecule was elucidated by spectroscopic methods and identified as N-(3R-hydroxy-7-cis-tetradecanoyl)-L-homoserine lactone. The absolute configuration of both asymmetric carbon atoms in the molecule was determined by the use of the chiral solvating agents S-(+)- and R-(-)-2,2,2-trifluoro-1-(9-anthryl)-ethanol. small bacteriocin is structurally related to the quorum sensing co-transcription factors for genes from other bacteria such as Vibrio fischeri, Pseudomonas aeruginosa, Erwinia carotovora, and Agrobacterium tumefaciens which are involved in animal-microbe or plant-microbe interactions. The mechanism of regulation of such interactions by this kind of co-transcription factors is still unknown in R. leguminosarum. PMID:8550454

  15. Synthesis of L-iduronic acid derivatives via [3.2.1] and [2.2.2] L-iduronic lactones from bulk glucose-derived cyanohydrin hydrolysis: a reversible conformationally switched superdisarmed/rearmed lactone route to heparin disaccharides.

    PubMed

    Hansen, Steen U; Dalton, Charlotte E; Baráth, Marek; Kwan, Glenn; Raftery, James; Jayson, Gordon C; Miller, Gavin J; Gardiner, John M

    2015-04-17

    L-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of L-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] L-iduronate lactones. The former is obtained via a 100 g scale synthesis of 3-OBn L-IdoA. A two-step conversion of this mixture provides either pure anomer of the novel [2.2.2] l-iduronate thioglycoside lactones. Both [3.2.1] and [2.2.2] lactones are converted into GlcN-IdoA heparin precursor disaccharides. The [2.2.2] lactone enables a scalable 3-step route from 1 to a new type of highly disarmed O-4 iduronate thioglycoside, which is an effective acceptor with glucoazide thioglycoside donors. The resulting new iduronic [2.2.2] lactone disaccharides are readily rearmed by mild methanolysis to provide GlcN-IdoA thiophenyl disaccharide donors, intercepting their established utility for the assembly of both heparin- and heparan sulfate-like oligosaccharides. The [2.2.2] lactonization acts as a conformational switch to superdisarm iduronate components, reversible by lactone ring opening. In addition, the separated 2,4-diacetates also provide short access to all four anomeric and ring size isomers of l-iduronic acid methyl glycosides, including the first syntheses of the parent idofuranosides. X-ray structures are reported for a [2.2.2] iduronate lactone and examples of both methyl L-idopyranoside and novel methyl-L-idofuranoside systems. PMID:25646641

  16. Conformational analysis of δ-lactones by DFT calculations: the parent compound and its monomethyl and selected dimethyl derivatives.

    PubMed

    Weber, Fabian; Brückner, Reinhard

    2013-01-21

    The static and dynamic stereochemistry of unsubstituted δ-valerolactone, all monomethylated δ-lactones, and all nongeminally dimethylated δ-lactones was explored with the B3LYP functional and def2-TZVPP basis set. A search strategy was employed which allowed the entire conformational space of any (poly-)substituted δ-lactone to be scanned. It allowed the lowest threshold conformational interconversion pathways to be mapped. The latter can be visualized in appealingly intuitive yet unprecedented diagrams. They trace the energy versus a circular abscissa which describes the passage of the molecule through one complete conformation interchange. The respective plot is C(2)-symmetrical for the parent compound, which is achiral, and C(1)-symmetrical for all methylated δ-lactones, which are chiral. PMID:23296596

  17. Effects of α,β-unsaturated lactones on larval survival and gut trypsin as well as oviposition response of Aedes aegypti.

    PubMed

    Barros, Maria Ester S B; Freitas, Juliano C R; Santos, Geanne K N; da Silva, Rayane Cristine Santos; Pontual, Emmanuel V; Paiva, Patrícia M G; Napoleão, Thiago H; Navarro, Daniela M A F; Menezes, Paulo H

    2015-09-01

    Lactones are organic cyclic esters that have been described as larvicides against Aedes aegypti and as components of oviposition pheromone of Culex quinquefasciatus. This work describes the effect of six α,β-unsaturated lactones (5a-5f) on survival of A. aegypti fourth instar larvae (L4). It is also reported the effects of the lactones on L4 gut trypsin activity and oviposition behavior of A. aegypti females. Five lactones were able to kill L4 being the lactones 5a (LC50 of 39.05 ppm), 5e (LC50 of 36.30 ppm) and 5f (LC50 of 40.46 ppm) the most promising larvicides. Only the lactone 5a inhibited L4 gut trypsin activity, with an IC50 of 115.15 µg/mL. Lactones 5a, 5c, 5d and 5e did not exert deterrent or stimulatory effects on oviposition, whereas lactone 5b exhibited a strong deterrent oviposition activity. In conclusion, this work introduces new α,β-unsaturated lactones as promising alternatives to control A. aegypti dissemination. The larvicidal mechanism of the lactone 5a can involve the disruption of proteolysis at larval gut. PMID:26044355

  18. Highly regio- and diastereoselective synthesis of CF3-substituted lactones via photoredox-catalyzed carbolactonization of alkenoic acids.

    PubMed

    Yasu, Yusuke; Arai, Yusuke; Tomita, Ren; Koike, Takashi; Akita, Munetaka

    2014-02-01

    Trifluoromethylative lactonization of both terminal and internal alkenoic acids by photoredox catalysis has been developed. The use of a Ru photocatalyst and Umemoto's reagent as a CF3 source is key in the present carbolactonization. This is the first example of a highly endo- and diastereoselective synthesis of CF3-substituted five-, six-, and seven-membered ring lactones from internal alkenoic acids. PMID:24422891

  19. Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropo-enantioselective Transesterification.

    PubMed

    Yu, Chenguang; Huang, He; Li, Xiangmin; Zhang, Yueteng; Wang, Wei

    2016-06-01

    A solution to the unmet synthetic challenge of achieving highly atropo-enantioselective transesterification of Bringmann's lactones has been realized, employing a chiral bifunctional amine thiourea as promoter. The synergistic activation of the lactones and alcohols/phenols by the respective thiourea and amine groups is crucial for achieving the highly enantioselective, high-yielding dynamic kinetic resolution process. This protocol gives highly optically pure, axially chiral biaryl compounds with a broad substrate scope under mild reaction conditions. PMID:27218264

  20. Comparison between the modes of action of novel meta-diamide and macrocyclic lactone insecticides on the RDL GABA receptor.

    PubMed

    Nakao, Toshifumi; Banba, Shinichi; Hirase, Kangetsu

    2015-05-01

    Macrocyclic lactones, avermectins, and milbemycins are widely used to control arthropods, nematodes, and endo- and ectoparasites in livestock and pets. Their main targets are glutamate-gated chloride channels. Furthermore, macrocyclic lactones reportedly interact with insect RDL γ-aminobutyric acid (GABA) receptors, but their modes of action on insect RDL GABA receptors remain unknown. In this study, we attempted to better understand the modes of action of macrocyclic lactones on RDL GABA receptors. We observed that ivermectin and milbemectin behaved as allosteric agonists of the Drosophila RDL GABA receptor. G336A, G336S, and G336T mutations had profound effects on the activities of ivermectin and milbemectin, and a G336M mutation abolished the allosteric agonist and antagonist activities of these macrocyclic lactones. These results suggest that G336 in TM3 of the Drosophila RDL GABA receptor is important for the binding of macrocyclic lactones. Recently, it has been suggested that a novel RDL GABA receptor antagonist, 3-benzamido-N-(2-bromo-4-perfluoroisopropyl-6-(trifluoromethyl)phenyl)-2-fluorobenzamide (meta-diamide 7), binds to the transmembrane intersubunit pocket near G336 in the Drosophila RDL GABA receptor. Thus, we compared the effects of mutations around G336 and A302 mutations in TM2 on the activities of macrocyclic lactone and meta-diamide 7. The effects of L281C, V340Q, V340N, A302S, and A302N mutations on the activity of meta-diamide 7 differed from those on ivermectin and milbemectin. Molecular modeling studies showed that macrocyclic lactones docked in the intersubunit pocket near G336 in the Drosophila RDL GABA receptor in the open state. In contrast, meta-diamide 7 docked into the Drosophila RDL GABA receptor in the closed state. This suggests that the modes of action of macrocyclic lactone binding to the wild-type Drosophila RDL GABA receptor differ from those of meta-diamide binding. PMID:25987227

  1. Two new sesquiterpene lactones from the fruits of Illicium jiadifengpi.

    PubMed

    Liu, Jifeng; Liu, Feiyan; Zhang, Nenling; Wang, Yafeng; Yang, Lijia; Bi, Yuefeng; Zhang, Yanbing; Liu, Mengqi

    2016-01-01

    Two new seco-prezizaane-type sesquiterpenes, 3,4-dehydroneomajucin (1) and 1,2,3,4-tetradehydroneomajucin (2), were isolated from the fruits of Illicium jiadifengpi. The structure of these compounds was determined using 1D and 2D NMR and ESI-MS. The isolates were evaluated for their anti-hepatitis B virus activities on the Hep G2.2.15 cell line. The inhibitory rates of compounds 1 and 2 on the HBeAg and HBsAg expression were 30.08 ± 3.09% and 11.43 ± 1.92% at a concentrations of 68.00 μM and 7.88 ± 1.21% and 16.96 ± 4.24% at a concentration of 68.50 μM, respectively. PMID:26212001

  2. Fluorine in fragrances: exploring the difluoromethylene (CF2) group as a conformational constraint in macrocyclic musk lactones.

    PubMed

    Corr, Michael J; Cormanich, Rodrigo A; von Hahmann, Cortney N; Bühl, Michael; Cordes, David B; Slawin, Alexandra M Z; O'Hagan, David

    2016-01-01

    The CF2 group is incorporated into specific positions within the lactone ring of the natural musk lactone, (12R)-(+)-12-methyl-13-tridecanolide, a constituent of Angelica root oil, Angelica archangelica L. The approach is taken as it was anticipated that CF2 groups would dictate corner locations in the macrocycle and limit the conformational space available to the lactone. Three fluorine containing lactones are prepared by organic synthesis. One (8) has CF2 groups located at the C-6 and C-9 positions, another (9) with CF2 groups at the C-5 and C-9 positions, and a third (10) with a CF2 group at C-8. Two of the fluorine containing lactones (8 and 10) were sufficiently crystalline to obtain X-ray crystal structures which revealed that the CF2 groups do adopt corner locations. All three lactones were subject to computational analysis at the B3LYP-D3/6-311+G** level to assess the relative energies of different conformers. In all cases, the global minima and most of the lowest energy minima have squared/rectangular geometries and located the CF2 groups at the corners. The lowest energy structures for 8 and 10 closely approximated the observed X-ray structures, suggesting good convergence of theory and experiment in determining relevant low energy conformations. All three compounds retained a pleasant odour suggesting the rings retained sufficient conformational flexibility to access relevant olfactory conformations. PMID:26584449

  3. A β-lactone-based antivirulence drug ameliorates Staphylococcus aureus skin infections in mice.

    PubMed

    Weinandy, Franziska; Lorenz-Baath, Katrin; Korotkov, Vadim S; Böttcher, Thomas; Sethi, Shneh; Chakraborty, Trinad; Sieber, Stephan A

    2014-04-01

    Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi-resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life-threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β-lactone-based molecule demonstrated that antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β-lactone significantly decreased abscess size even when applied 6 h post-infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies. PMID:24678014

  4. [Formation of hydroxylated steroid lactones from Dehydroepiandrosterone by Spicaria fumoso-rosea F-881].

    PubMed

    Lobastova, T G; Khomutov, S M; Donova, M V

    2015-01-01

    The transformation of dehydroepiandrosterone by Spicaria fumoso-rosea VKM F-881 produced 7alpha- and 7beta-hydroxy-dehydroepiandrosterone, 3beta,7alpha-dihydroxy-17a-oxa-D-homo-androst-5-en-17-one, and 3beta,7beta-dihydroxy- 17a-oxa-D-homo-androst-5-en-17-one. The yield of the main product-3beta,7beta-dihydroxy-17a-oxa-D-homo-androst-5-en-17-one-was 49.5-72 mol % at substrate loadings of 5-20 g/L. Lactone formation proceeded through 7alpha- and 7beta-hydroxy derivatives of dehydroepiandrosterone. The structure of the products was determined by mass spectrometry, 1H-NMR spectroscopy, and 13C-NMR spectroscopy. The proposed microbiological method for producing steroid lactones opens prospects for the syn- thesis of novel steroid compounds. PMID:26027352

  5. Anionic ring-opening polymerization of beta-alkoxymethyl-substituted beta-lactones.

    PubMed

    Adamus, Grazyna; Kowalczuk, Marek

    2008-02-01

    We report on anionic ring-opening polymerization (ROP) of racemic beta-(methoxymethyl)-beta-propiolactone (MOMPL) and beta-(ethoxymethyl)-beta-propiolactone (EOMPL) initiated by supramolecular complex of potassium acetate and tetrabutylammonium acetate (Bu4N+ Ac) as well as by tetrabutylammonium hydroxide, respectively. Structure of the resulting polymers has been established at the molecular level by electrospray ionization multistage mass spectrometry (ESI-MS(n)) and has been confirmed by FT-IR, NMR, and GPC analyses. Similar behavior of MOMPL and EOMPL with respect to already-studied beta-alkyl-substituted beta-lactones, e.g., beta-butyrolactone (MPL), has been observed under the conditions of anionic ROP (including observed side reactions leading to unsaturated end groups) and the already-established mechanisms of anionic polymerization of beta-alkyl-substituted beta-lactones are extended on beta-alkoxymethyl-substituted ones. PMID:18179174

  6. Cascade Synthesis of Five-Membered Lactones using Biomass-Derived Sugars as Carbon Nucleophiles.

    PubMed

    Yamaguchi, Sho; Matsuo, Takeaki; Motokura, Ken; Miyaji, Akimitsu; Baba, Toshihide

    2016-06-01

    We report the cascade synthesis of five-membered lactones from a biomass-derived triose sugar, 1,3-dihydroxyacetone, and various aldehydes. This achievement provides a new synthetic strategy to generate a wide range of valuable compounds from a single biomass-derived sugar. Among several examined Lewis acid catalysts, homogeneous tin chloride catalysts exhibited the best performance to form carbon-carbon bonds. The scope and limitations of the synthesis of five-membered lactones using aldehyde compounds are investigated. The cascade reaction led to high product selectivity as well as diastereoselectivity, and the mechanism leading to the diastereoselectivity was discussed based on isomerization experiments and density functional theory (DFT) calculations. The present results are expected to support new approaches for the efficient utilization of biomass-derived sugars. PMID:27061111

  7. The Lactone form of stachybotrydial: a new inhibitor of dihydrofolate reductase from stachybotrys sp. FN298.

    PubMed

    Kwon, Yun-Ju; Sohn, Mi-Jin; Kim, Hyun-Ju; Kim, Won-Gon

    2014-01-01

    Dihydrofolate reductase (DHFR) has been confirmed to be a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Stachybotrys sp. FN298 can inhibit the DHFR of Staphylococcus aureus. Its structure was identified as a lactone form of stachybotrydial using mass spectrometry and nuclear magnetic resonance analysis. This compound inhibited S. aureus DHFR with a half-maximal inhibitory concentration of 41 µM. It also prevented the growth of S. aureus and methicillin-resistant S. aureus (MRSA) with a minimum inhibitory concentration of 32 µg·mL(-1). To our knowledge, this is the first description of a DHFR inhibitor of microbial origin. The inhibitory function of the lactone form of stachybotrydial highlights its potential for development into a new broad-spectrum antibacterial agent and as an agent against MRSA. PMID:25087962

  8. Exogenous Supply of Pantoyl Lactone to Excised Leaves Increases their Pantothenate Levels

    PubMed Central

    RATHINASABAPATHI, BALA; RAMAN, SURESH BABU

    2005-01-01

    • Background and Aims All plants synthesize pantothenate but its synthesis and regulation are not well understood. The aim of this work is to study the effect of exogenous supply of precursor compounds on pantothenate levels in leaves. • Methods Precursor compounds were supplied in solution to excised leaves and the pantothenate content was measured using a microbial method. • Key Results Pantothenate levels in excised leaves of Limonium latifolium, tomato (Lycopersicon esculentum), bean (Phaseolus vulgaris) and grapefruit (Citrus × paradisi) were examined following an exogenous supply of the precursor compounds pantoyl lactone or β-alanine. Significantly higher levels of extractable pantothenate were found when pantoyl lactone was supplied, but not when β-alanine was supplied despite a measurable uptake of β-alanine into the leaf. • Conclusions The results suggested that the pantoate supply may be rate-limiting or regulating pantothenate synthesis in leaves. PMID:15767268

  9. Method to produce water-soluble sugars from biomass using solvents containing lactones

    DOEpatents

    Dumesic, James A.; Luterbacher, Jeremy S.

    2015-06-02

    A process to produce an aqueous solution of carbohydrates that contains C6-sugar-containing oligomers, C6 sugar monomers, C5-sugar-containing oligomers, C5 sugar monomers, or any combination thereof is presented. The process includes the steps of reacting biomass or a biomass-derived reactant with a solvent system including a lactone and water, and an acid catalyst. The reaction yields a product mixture containing water-soluble C6-sugar-containing oligomers, C6-sugar monomers, C5-sugar-containing oligomers, C5-sugar monomers, or any combination thereof. A solute is added to the product mixture to cause partitioning of the product mixture into an aqueous layer containing the carbohydrates and a substantially immiscible organic layer containing the lactone.

  10. Branched-chain fatty acids produced by mutants of Streptomyces fradiae, putative precursors of the lactone ring of tylosin.

    PubMed Central

    Huber, M L; Paschal, J W; Leeds, J P; Kirst, H A; Wind, J A; Miller, F D; Turner, J R

    1990-01-01

    Three branched-chain fatty acids (7-hydroxy-4,6-dimethylnona-2,4-dienoic acid [compound 1], its 7-epimer [compound 2], and 7-keto-4,6-dimethylnona-2,4-dienoic acid [compound 3]) and a ketone (9-hydroxy-6,8-dimethylundeca-4,6-dien-3-one [compound 4]) were isolated from the culture broth of mutants of Streptomyces fradiae which were blocked in the biosynthesis of the macrolide antibiotic tylosin. Two phenotypic classes of mutants of this organism which were blocked in the addition of mycaminose to tylactone (compound 6) accumulated these compounds. These compounds were not produced by mutants which were blocked in lactone synthesis, in steps beyond mycaminose addition, or by the wild-type strain. Synthesis of these compounds, like synthesis of tylosin, was inhibited by the addition of cerulenin. Compounds 1, 2, and 3 were partially interconvertible by these mutants; but they were not produced from the degradation of tylactone and they were not directly incorporated into tylosin by intact cells. The structures of compounds 1 and 2 were equivalent to that of a predicted intermediate (S. Yue, J. S. Duncan, Y. Yamamoto, and C. R. Hutchinson, J. Am. Chem. Soc. 109:1253-1255, 1987) in the biosynthesis of tylactone. The ketone (compound 4) reported previously (N. D. Jones, M. O. Chaney, H. A. Kirst, G. M. Wild, R. H. Baltz, R. L. Hamill, and J. W. Paschal, J. Antibiot. 35:420-425, 1982) appears to be the decarboxylation product of the intermediate following that represented by compound 1. This represents the first report of the isolation of putative precursors of tylactone from tylosin-producing organisms. PMID:2221862

  11. "One-pot" reductive lactone alkylation provides a concise asymmetric synthesis of chiral isoprenoid targets.

    PubMed

    Cao, Jia; Perlmutter, Patrick

    2013-09-01

    An efficient method, based on nucleophilic addition to lactones followed by modified in situ Clemmensen reduction, provides a short synthetic route to chiral isoprenoid targets. The efficacy of this method has been exemplified through the synthesis of several targets including the commercial fragrance Rosaphen, the side chain of Zaragozic acid C, the cotton leaf sex pheromone, and the side chains of vitamin E. PMID:23957629

  12. Lewis Acid Catalyzed Synthesis of α-Trifluoromethyl Esters and Lactones by Electrophilic Trifluoromethylation.

    PubMed

    Katayev, Dmitry; Matoušek, Václav; Koller, Raffael; Togni, Antonio

    2015-12-01

    An electrophilic trifluoromethylation of ketene silyl acetals (KSAs) by hypervalent iodine reagents 1 and 2 has been developed. The reaction proceeds under very mild conditions in the presence of a catalytic amount of trimethylsilyl bis(trifluoromethanesulfonyl)imide (up to 2.5 mol %) as a Lewis acid providing a direct access to a variety of secondary, tertiary, and quaternary α-trifluoromethyl esters and lactones in high yield (up to 98%). PMID:26588788

  13. Stereodivergent Organocatalytic Intramolecular Michael Addition/Lactonization for the Asymmetric Synthesis of Substituted Dihydrobenzofurans and Tetrahydrofurans

    PubMed Central

    Belmessieri, Dorine; de la Houpliere, Alix; Calder, Ewen D D; Taylor, James E; Smith, Andrew D

    2014-01-01

    A stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-(−)-tetramisole hydrochloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r.syn/anti, 99 % eesyn), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r.syn/anti, 99 % eeanti). PMID:24989672

  14. Two lactones in the androconial scent of the lycaenid butterfly Celastrina argiolus ladonides

    NASA Astrophysics Data System (ADS)

    Ômura, Hisashi; Yakumaru, Kazuhisa; Honda, Keiichi; Itoh, Takao

    2013-04-01

    Male adult butterflies of many species have characteristic odors originating from the disseminating organs known as androconia. Despite the fact that androconia exist in several species, there have been few investigations on adult scents from the lycaenid species. Celastrina argiolus ladonides (Lycaenidae) is a common species in Eurasia. We have reported that male adults of this species emit a faint odor, and the major components causing this odor have been newly found in the Insecta. By using field-caught individuals, we determined the chemical nature and location of this odor in the butterfly. Gas chromatography-mass spectrometry (GC-MS) analyses revealed that two lactone compounds, lavender lactone and δ-decalactone, are present in the extracts of males but absent in those of the females. On an average, approximately 50 ng of each compound was found per male. Chiral GC analyses performed using enantiomerically pure standards revealed that the natural lavender lactone was a mixture of two enantiomers with an R/ S ratio of 32:68, whereas the natural δ-decalactone contained only the R-enantiomer. When the analyses were conducted using different parts—forewings, hindwings, and body—of three males, the lactones were more abundantly found on the forewings and hindwings than on the body. Microscopic observation of the wings demonstrated that battledore scales known as androconia are scattered on the upper surface of both the wings of C. argiolus ladonides males. These results indicate that the specialized scales on the wings of males serve as scent-disseminating organs.

  15. Cerinolactone, a hydroxy-lactone derivative from Trichoderma cerinum.

    PubMed

    Vinale, Francesco; Girona, Isabel Arjona; Nigro, Marco; Mazzei, Pierluigi; Piccolo, Alessandro; Ruocco, Michelina; Woo, Sheridan; Rosa, David Ruano; Herrera, Carlos López; Lorito, Matteo

    2012-01-27

    A novel metabolite, 3-hydroxy-5-(6-isopropyl-3-methylene-3,4,4a,5,6,7,8,8a-octahydronaphthalen-2-yl)dihydrofuran-2-one, trivially named cerinolactone (1), has been isolated from culture filtrates of Trichoderma cerinum together with three known butenolides containing the 3,4-dialkylfuran-2(5H)-one nucleus, harzianolide (2), T39butenolide (3), and dehydroharzianolide (4). The structure of 1 was determined by spectroscopic methods, including UV, MS, and 1D and 2D NMR analyses. In vitro tests with the purified compound exhibited activity against Pythium ultimum, Rhizoctonia solani, and Botrytis cinerea. PMID:22196692

  16. Purity Assessment of Aryltetralin Lactone Lignans by Quantitative 1H Nuclear Magnetic Resonance.

    PubMed

    Sun, Yan-Jun; Zhang, Yan-Li; Wang, Yu; Wang, Jun-Min; Zhao, Xuan; Gong, Jian-Hong; Gao, Wei; Guan, Yan-Bin

    2015-01-01

    In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized, including relaxation delay (D1), scan numbers (NS), and pulse angle. 1,4-Dinitrobenzene was used as internal standard (IS), and deuterated dimethyl sulfoxide (DMSO-d6) as the NMR solvent. The purities were calculated by the area ratios of H-2,6 from target analytes vs. aromatic protons from IS. Six aryltetralin lactone lignans (deoxypodophyllotoxin, podophyllotoxin, 4-demethylpodophyllotoxin, podophyllotoxin-7'-O-β-d-glucopyranoside, 4-demethylpodophyllotoxin-7'-O-β-d-glucopyranoside, and 6''-acetyl-podophyllotoxin-7'-O-β -d-glucopyranoside) were analyzed. The analytic results of qHNMR were further validated by high performance liquid chromatography (HPLC). Therefore, the qHNMR method was a rapid, accurate, reliable tool for monitoring the purity of aryltetralin lactone lignans. PMID:26016553

  17. Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States

    PubMed Central

    2012-01-01

    In order to provide a background to current concerns relative to the possible resistance of heartworms to macrocyclic lactones, this review summarizes various studies in which lack of efficacies (LOEs) have been observed in dogs on macrocyclic lactone preventives relative to the United States of America. Some of these studies have been published in the peer-reviewed literature, others have appeared in various reports to the Center for Veterinary Medicine (CVM) of the Food and Drug Administration (FDA) of the USA as New Animal Drug Application (NADA) summaries, and one appeared as a letter to US veterinarians. This review also discusses reports relating to the potential problem of heartworm resistance in microfilariae and third-stage larvae, as well as molecular markers associated with resistance to macrocyclic lactones within Dirofilaria immitis. As more work is being done in this area of great concern relative to the protection of dogs from infection using this class of preventives, it seems timely to summarize what is known about heartworms, their potential resistance to treatment, and the means of selecting for resistance genes in populations of this helminth in the laboratory and in the field. PMID:22776618

  18. Effects of alpha-tocopherol on lactones in beef headspace during storage.

    PubMed

    Watanabe, A; Imanari, M; Higuchi, M; Shiba, N; Yonai, M

    2010-01-01

    We studied the effect of alpha-tocopherol (alpha-Toc) on the production of lactones, a desirable flavor in Wagyu beef (Japanese Black Cattle), in meat headspace. Fresh beef was minced and divided into 4 groups containing different alpha-Toc levels (1.9, 2.7, 6.1, and 10.7 mg/kg) or packed with oxygen absorber. After 10 d of storage at 2 °C, these samples were cooked in distilled water and rendered fat was collected. The headspace of the fat was analyzed with solid-phase microextraction combined with gas chromatography-mass spectrometry. The DB-17MS capillary column led to good separation of aliphatic lactones. Oxygen was important for the development of all lactones during storage. The amounts of gamma-octalactone and gamma-nonalactone decreased linearly with increasing alpha-Toc levels. The effect of alpha-Toc on delta-decalactone, delta-undecalactone, and delta-tetoradecalactone was weaker, and that on delta-hexadecalactone was ambiguous. These observations suggest that oxidation was necessary to develop the flavor of Wagyu beef, and warn that an excessive increase of alpha-Toc could reduce levels of positive flavor components, gamma-octalactone and gamma-nonalactone, in the headspace of Wagyu beef. PMID:21535590

  19. Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States.

    PubMed

    Bowman, Dwight D

    2012-01-01

    In order to provide a background to current concerns relative to the possible resistance of heartworms to macrocyclic lactones, this review summarizes various studies in which lack of efficacies (LOEs) have been observed in dogs on macrocyclic lactone preventives relative to the United States of America. Some of these studies have been published in the peer-reviewed literature, others have appeared in various reports to the Center for Veterinary Medicine (CVM) of the Food and Drug Administration (FDA) of the USA as New Animal Drug Application (NADA) summaries, and one appeared as a letter to US veterinarians. This review also discusses reports relating to the potential problem of heartworm resistance in microfilariae and third-stage larvae, as well as molecular markers associated with resistance to macrocyclic lactones within Dirofilaria immitis. As more work is being done in this area of great concern relative to the protection of dogs from infection using this class of preventives, it seems timely to summarize what is known about heartworms, their potential resistance to treatment, and the means of selecting for resistance genes in populations of this helminth in the laboratory and in the field. PMID:22776618

  20. Improvement of bioelectrochemical property and energy recovery by acylhomoserine lactones (AHLs) in microbial electrolysis cells (MECs)

    NASA Astrophysics Data System (ADS)

    Liu, Wenzong; Cai, Weiwei; Ma, Anzhou; Ren, Ge; Li, Zhiling; Zhuang, Guoqiang; Wang, Aijie

    2015-06-01

    Quorum sensing (QS) has been extensively studied as a cell-cell communication system, where small chemical signal molecules (acylhomoserine lactones, AHLs) can regulate the bacterial communications in bioelectrochemical systems via chemical signaling and electric signaling. In this study, electrochemical activity of bio-anode is substantially promoted by adding two kinds of AHLs with different chain length at the stage of community formation in microbial electrolysis cells (MECs). Hydrogen yield increase is observed by adding of two chain length AHLs, 3-oxo-hexanoyl-homoserine lactone (3OC6-HSL) and 3-oxo-dodecanoyl homoserine lactone (3OC12-HSL). A higher MEC current is acquired with addition of 3OC6-HSL than 3OC12-HSL at a fixed voltage of 0.8 V (vs. SHE). The highest yield is up to 3.8 ± 0.2 mol H2 mol-1 acetate at 10 μM 3OC6-HSL, which is increased 29% over control MECs. Evaluated on applied voltage, energy efficiency is increased to 171.6 ± 21.3% with short chain AHL, however, no significant improvement is performed on energy efficiency and coulombic efficiency with long-chain AHL. The study shows that bioelectrochemical characteristics of MECs varied on the chain length of AHL signal molecules and short-chain AHLs have a more positive effect on electron transfer and energy recovery in MECs.

  1. Acyl-homoserine Lactone from Saccharum × officinarum with Stereochemistry-Dependent Growth Regulatory Activity.

    PubMed

    Olher, Vanessa G A; Ferreira, Nagela P; Souza, Alan G; Chiavelli, Lucas U R; Teixeira, Aline F; Santos, Wanderley D; Santin, Silvana M O; Ferrarese Filho, Osvaldo; Silva, Cleuza C; Pomini, Armando M

    2016-05-27

    Acyl-homoserine lactones (AHLs) are a class of compounds produced by Gram-negative bacteria that are used in a process of chemical communication called quorum sensing. Much is known about how bacteria use these chemical compounds to control the expression of important factors; however, there have been few reports about the presence and effects of AHLs in plants. In this study, the phytochemical study of leaves and culms of sugar cane (Saccharum × officinarum) led to the identification of N-(3-oxo-octanoyl)homoserine lactone. Since the absolute configuration of the natural product could not be determined, both R and S enantiomers of N-(3-oxo-octanoyl)homoserine lactone were synthesized and tested in sugar cane culms. The enantiomers caused changes in the mass and length of buds and roots when used at micromolar concentrations. Using the sugar cane RB96-6928 variety, the S enantiomer increased sprouting of roots more effectively than the R enantiomer. Furthermore, scanning electron microscopy showed that both the R and S enantiomers led to more stretched root cells compared with the control. PMID:27192014

  2. Dehydrocostus lactone is exuded from sunflower roots and stimulates germination of the root parasite Orobanche cumana.

    PubMed

    Joel, Daniel M; Chaudhuri, Swapan K; Plakhine, Dina; Ziadna, Hammam; Steffens, John C

    2011-05-01

    The germination of the obligate root parasites of the Orobanchaceae depends on the perception of chemical stimuli from host roots. Several compounds, collectively termed strigolactones, stimulate the germination of the various Orobanche species, but do not significantly elicit germination of Orobanche cumana, a specific parasite of sunflower. Phosphate starvation markedly decreased the stimulatory activity of sunflower root exudates toward O. cumana, and fluridone - an inhibitor of the carotenoid biosynthesis pathway - did not inhibit the production of the germination stimulant in both shoots and roots of young sunflower plants, indicating that the stimulant is not a strigolactone. We identified the natural germination stimulant from sunflower root exudates by bioassay-driven purification. Its chemical structure was elucidated as the guaianolide sesquiterpene lactone dehydrocostus lactone (DCL). Low DCL concentrations effectively stimulate the germination of O. cumana seeds but not of Phelipanche aegyptiaca (syn. Orobanche aegyptiaca). DCL and other sesquiterpene lactones were found in various plant organs, but were previously not known to be exuded to the rhizosphere where they can interact with other organisms. PMID:21353686

  3. Isolation and characterization of N-acylhomoserine lactonase from the thermophilic bacterium, Geobacillus caldoxylosilyticus YS-8.

    PubMed

    Seo, Myung-Ji; Lee, Beom-Seon; Pyun, Yu-Ryang; Park, Hoon

    2011-01-01

    Geobacillus caldoxylosilyticus YS-8, which was isolated from volcanic soil in Indonesia, was found to degrade various N-acylhomoserine lactones (AHLs) with different lengths and acyl side-chain substitutions over a wide temperature range of 30-70 °C. The purified AHL-degrading enzyme showed a single band of 32 kDa, and its N-terminal amino acid sequence was determined to be ANVIKARPKLYVMDN, tentatively suggesting that the AHL-degrading enzyme was AHL lactonase. The AHL-degrading activity of the purified enzyme was maximized at pH 7.5 and 50 °C, and it retained about 50% of its activity even after a heat treatment at 60 °C for 3 h, exhibiting properties consistent with a thermostable enzyme. The mass spectrometric analysis demonstrated that the AHL-degrading enzyme catalyzed lactone ring opening of N-3-oxohexanoyl-L-homoserine lactone and N-hexanoyl-L-homoserine lactone by hydrolyzing the lactones and working as an AHL lactonase. PMID:21897031

  4. Sesquiterpenoids Isolated from Two Species of the Asteriscus Alliance.

    PubMed

    Triana, Jorge; Eiroa, José Luis; Morales, Manuel; Perez, Francisco J; Brouard, Ignacio; Quintana, José; Ruiz-Estévez, Mercedes; Estévez, Francisco; León, Francisco

    2016-05-27

    Investigation of the aerial parts of two Spanish members of the Asteriscus alliance, Asteriscus graveolens subsp. stenophyllus and Asteriscus schultzii, afforded four new sesquiterpene lactones containing a humulene skeleton (1-4) and one new sesquiterpene lactone of the asteriscanolide type (5). Their chemical structures were determined on the basis of the HRMS and from 1D and 2D NMR spectroscopic studies. Both species showed different profiles of sesquiterpenoid constituents. A. schultzii did not show humulene or asteriscane sesquiterpenes, suggesting a resemblance to the genus Pallenis, another member of the Asteriscus alliance. A literature review on chemical isolates from the Asteriscus alliance supported the placement of A. schultzii in the genus Pallenis. The isolated components (1-5) were assessed for cytotoxicity against the HL-60 and MOLT-3 leukemia cell lines, with compound 1 showing activity in both biological assays (IC50 value range 4.1-5.4 μM). PMID:27145162

  5. The binding of D-gluconohydroximo-1,5-lactone to glycogen phosphorylase. Kinetic, ultracentrifugation and crystallographic studies.

    PubMed Central

    Papageorgiou, A C; Oikonomakos, N G; Leonidas, D D; Bernet, B; Beer, D; Vasella, A

    1991-01-01

    Combined kinetic, ultracentrifugation and X-ray-crystallographic studies have characterized the effect of the beta-glucosidase inhibitor gluconohydroximo-1,5-lactone on the catalytic and structural properties of glycogen phosphorylase. In the direction of glycogen synthesis, gluconohydroximo-1,5-lactone was found to competitively inhibit both the b (Ki 0.92 mM) and the alpha form of the enzyme (Ki 0.76 mM) with respect to glucose 1-phosphate in synergism with caffeine. In the direction of glycogen breakdown, gluconohydroximo-1,5-lactone was found to inhibit phosphorylase b in a non-competitive mode with respect to phosphate, and no synergism with caffeine could be demonstrated. Ultracentrifugation and crystallization experiments demonstrated that gluconohydroximo-1,5-lactone was able to induce dissociation of tetrameric phosphorylase alpha and stabilization of the dimeric T-state conformation. A crystallographic binding study with 100 mM-gluconohydroximo-1,5-lactone at 0.24 nm (2.4 A) resolution showed a major peak at the catalytic site, and no significant conformational changes were observed. Analysis of the electron-density map indicated that the ligand adopts a chair conformation. The results are discussed with reference to the ability of the catalytic site of the enzyme to distinguish between two or more conformations of the glucopyranose ring. PMID:1900987

  6. Genetic and Biochemical Characterization of a Novel Monoterpene ɛ-Lactone Hydrolase from Rhodococcus erythropolis DCL14

    PubMed Central

    van der Vlugt-Bergmans, Cécile J. B; van der Werf, Mariët J.

    2001-01-01

    A monoterpene ɛ-lactone hydrolase (MLH) from Rhodococcus erythropolis DCL14, catalyzing the ring opening of lactones which are formed during degradation of several monocyclic monoterpenes, including carvone and menthol, was purified to apparent homogeneity. It is a monomeric enzyme of 31 kDa that is active with (4R)-4-isopropenyl-7-methyl-2-oxo-oxepanone and (6R)-6-isopropenyl-3-methyl-2-oxo-oxepanone, lactones derived from (4R)-dihydrocarvone, and 7-isopropyl-4-methyl-2-oxo-oxepanone, the lactone derived from menthone. Both enantiomers of 4-, 5-, 6-, and 7-methyl-2-oxo-oxepanone were converted at equal rates, suggesting that the enzyme is not stereoselective. Maximal enzyme activity was measured at pH 9.5 and 30°C. Determination of the N-terminal amino acid sequence of purified MLH enabled cloning of the corresponding gene by a combination of PCR and colony screening. The gene, designated mlhB (monoterpene lactone hydrolysis), showed up to 43% similarity to members of the GDXG family of lipolytic enzymes. Sequencing of the adjacent regions revealed two other open reading frames, one encoding a protein with similarity to the short-chain dehydrogenase reductase family and the second encoding a protein with similarity to acyl coenzyme A dehydrogenases. Both enzymes are possibly also involved in the monoterpene degradation pathways of this microorganism. PMID:11157238

  7. Whole-Genome Sequencing Reveals a New Genospecies of Methylobacterium sp. GXS13, Isolated from Vitis vinifera L. Xylem Sap

    PubMed Central

    Lai, Wan Xin; Gan, Han Ming; Hudson, André O.

    2016-01-01

    The whole-genome sequence of a new genospecies of Methylobacterium sp., named GXS13 and isolated from grapevine xylem sap, is reported and demonstrates potential for methylotrophy, cytokinin synthesis, and cell wall modification. In addition, biosynthetic gene clusters were identified for cupriachelin, carotenoid, and acyl-homoserine lactone using the antiSMASH server. PMID:26847900

  8. Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPARγ-dependent pathway

    PubMed Central

    Ramer, Robert; Mittag, Nadine; Hinz, Burkhard

    2016-01-01

    Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) are well-established agents to treat hyperlipidemic states. Experimental and epidemiological evidence further implies an anticancer effect of these substances. This study investigates the mechanism underlying human lung cancer cell death by lovastatin and the role of the prostaglandin (PG)-synthesizing enzyme cyclooxygenase-2 (COX-2) in this process. In A549 and H358 lung carcinoma cells the lipophilic prodrug lovastatin lactone led to a concentration-dependent decrease of viability and induction of DNA fragmentation, whereas its HMG-CoA-inhibitory, ring-open acid form was inactive in this respect. Apoptotic cell death by lovastatin was accompanied by high intracellular levels of the lactone form, by upregulation of COX-2 mRNA and protein, as well as by increased formation of peroxisome proliferator-activated receptor γ (PPARγ)-activating PGD2 and 15-deoxy-Δ12,14-PGJ2. Cells were significantly less sensitive to lovastatin-induced apoptotic cell death, when the expression or activity of COX-2 was suppressed by siRNA or by the COX-2 inhibitor NS-398. Apoptosis by lovastatin was likewise reversed by the PPARγ antagonist GW9662. Fluorescence microscopy analyses revealed a lovastatin-induced cytosol-to-nucleus translocation of PPARγ that was inhibited by NS-398. Collectively, this study demonstrates COX-2 induction and subsequent COX-2-dependent activation of PPARγ as a hitherto unknown mechanism by which lovastatin lactone induces human lung cancer cell death. PMID:26863638

  9. N-Heterocyclic Carbene-Catalyzed [3 + 4] Annulation of Enals and Alkenyl Thiazolones: Enantioselective Synthesis of Thiazole-Fused ε-Lactones.

    PubMed

    Liang, Zhi-Qin; Yi, Liang; Chen, Kun-Quan; Ye, Song

    2016-06-01

    The bifunctional N-heterocyclic carbene catalyzed [3 + 4] annulation of enals and 5-alkenyl thiazolones was developed, giving the corresponding thiazole-fused ε-lactones in high yields with excellent diastereoselectivties and enantioselectivities. The thiazole-fused ε-lactone could be isomerized to the spirocyclic thiazolone-cyclopentanone without erosion of enantioselectivity. PMID:27159734

  10. DDQ-promoted dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones by a radical ion mechanism.

    PubMed

    Ding, Ye; Huang, Zhangjian; Yin, Jian; Lai, Yisheng; Zhang, Shibo; Zhang, Zhiguo; Fang, Lei; Peng, Sixun; Zhang, Yihua

    2011-09-01

    A novel and facile DDQ-mediated dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones is described. The formation of lactones proceeds by a radical ion mechanism, which has been established by DPPH˙-mediated chemical identification, ESR spectroscopy and an enol intermediate trapping. PMID:21766102

  11. Efficient, solvent-free hydrogenation of α-angelica lactone catalysed by Ru/C at atmospheric pressure and room temperature.

    PubMed

    Al-Shaal, Mohammad G; Hausoul, Peter J C; Palkovits, Regina

    2014-09-14

    The hydrogenation of α-angelica lactone was investigated over Ru/C. A mild protocol was developed, which resulted in full conversion and 96% selectivity toward γ-valerolactone. The reaction network was investigated and α-angelica lactone was employed in the one-pot conversion into 2-methyltetrahydrofuran, demonstrating its superiority as a platform molecule in potential biorefinery schemes. PMID:25027166

  12. Stereodivergent and Protecting-Group-Free Synthesis of the Helicascolide Family: A Rhodium-Catalyzed Atom-Economical Lactonization Strategy.

    PubMed

    Haydl, Alexander M; Berthold, Dino; Spreider, Pierre A; Breit, Bernhard

    2016-05-01

    Natural products of polyketide origin, in particular small-sized lactones often possess a very broad range of impressive biological activities. An efficient way to demonstrate the concise access to six-membered lactones was emphasized as part of a stereodivergent and protecting-group-free synthesis of all three representatives of the helicascolide family. This strategy features an atom-economical and highly diastereoselective rhodium-catalyzed "head-to-tail" lactonization by an intramolecular addition of ω-allenyl-substituted carboxylic acids to terminal allenes, including the selective construction of a new stereocenter in the newly formed core structures. The excellent selectivities with which the helicascolide precursors were obtained are remarkable, thus resulting in an expeditious and highly efficient natural product synthesis. PMID:27043137

  13. Acyl-homoserine lactones from Erwinia psidii R. IBSBF 435T, a guava phytopathogen (Psidium guajava L.).

    PubMed

    Pomini, Armando M; Manfio, Gilson P; Araújo, Welington L; Marsaioli, Anita J

    2005-08-10

    The phytopathogen Erwinia psidii R. IBSBF 435T causes rot in branches, flowers, and fruits of guava (Psidium guajava L.), being responsible for crop losses, and has no effective control. It was demonstrated that this strain produces two compounds [S-(-)-N-hexanoyl and N-heptanoyl-homoserine lactone], both belonging to the class of quorum-sensing signaling substances. A protocol using gas chromatography-flame ionization detection with chiral stationary phase is described for the absolute configuration determination of a natural acyl-homoserine lactone. Biological assays with specific reporter and synthesis of identified substances are also described. This is the first report on the N-heptanoyl-homoserine lactone occurrence in the Erwinia genus. PMID:16076103

  14. Adsorption separation of terpene lactones from Ginkgo biloba L. extract using glass fiber membranes modified with octadecyltrichlorosilane.

    PubMed

    Su, I-Fang; Chen, Li-Jen; Suen, Shing-Yi

    2005-07-01

    In this study porous glass fiber membranes were modified by reaction with octadecyl-trichlorosilane to form C18 hydrophobic membranes. The contact angle and the CH2 vibration bands at 2855 and 2920 cm(-1) found by FTIR measurements verified the successful immobilization of C18 groups on the glass fiber membranes. The resulting C18 hydrophobic membranes were used to adsorb terpene lactones from crude Ginkgo biloba L. extracts. In batch adsorption processes, the modified C18 membranes exhibited a better adsorption performance than commercial C18 solid phase extraction adsorbents. Different desorption solvents were tested and ethyl acetate was found to preferentially desorb terpene lactones from the modified C18 membranes. In flow adsorption experiments at 1 mL/min, terpene lactone contents higher than 6 wt% (the standardized content) could be achieved in the elution step using ethyl acetate. PMID:16116999

  15. A tri-serine tri-lactone scaffold for the quantification of citrate in urine.

    PubMed

    Akdeniz, Ali; Caglayan, Mehmet Gokhan; Anzenbacher, Pavel

    2016-01-31

    Tri-serine tri-lactone based C3 symmetry fluorescent sensors were synthesized. Citrate is shown to bind to sensors, while displaying an increase in fluorescence intensity for the sensor with thiourea and a quenching for the sensor with sulfonamide. Information-rich responses of the sensors enable us to discriminate structurally similar anions, including mono-, di- and tri-carboxylates with 100% correct classification. A simple two-sensor array enables the determination of the concentration of citrate in urine without any sample preparation with high accuracy (error < 2%). PMID:26669653

  16. Origin of Kinetic Resolution of Hydroxy Esters through Catalytic Enantioselective Lactonization by Chiral Phosphoric Acids.

    PubMed

    Changotra, Avtar; Sunoj, Raghavan B

    2016-08-01

    Kinetic resolution is a widely used strategy for separation and enrichment of enantiomers. Using density functional theory computations, the origin of how a chiral BINOL-phosphoric acid catalyzes the selective lactonization of one of the enantiomers of α-methyl γ-hydroxy ester is identified. In a stepwise mechanism, the stereocontrolling transition state for the addition of the hydroxyl group to the si face of the ester carbonyl in the case of the S isomer exhibits a network of more effective noncovalent interactions between the substrate and the chiral catalyst. PMID:27463593

  17. Lovastatin lactone may improve irritable bowel syndrome with constipation (IBS-C) by inhibiting enzymes in the archaeal methanogenesis pathway

    PubMed Central

    Muskal, Steven M.; Sliman, Joe; Kokai-Kun, John; Pimentel, Mark; Wacher, Vince; Gottlieb, Klaus

    2016-01-01

    Methane produced by the methanoarchaeon Methanobrevibacter smithii ( M. smithii) has been linked to constipation, irritable bowel syndrome with constipation (IBS-C), and obesity. Lovastatin, which demonstrates a cholesterol-lowering effect by the inhibition of HMG-CoA reductase, may also have an anti-methanogenesis effect through direct inhibition of enzymes in the archaeal methanogenesis pathway. We conducted protein-ligand docking experiments to evaluate this possibility. Results are consistent with recent clinical findings. METHODS: F420-dependent methylenetetrahydromethanopterin dehydrogenase ( mtd), a key methanogenesis enzyme was modeled for two different methanogenic archaea: M. smithii and Methanopyrus kandleri. Once protein models were developed, ligand-binding sites were identified. Multiple ligands and their respective protonation, isomeric and tautomeric representations were docked into each site, including F420-coenzyme (natural ligand), lactone and β-hydroxyacid forms of lovastatin and simvastatin, and other co-complexed ligands found in related crystal structures. RESULTS: 1) Generally, for each modeled site the lactone form of the statins had more favorable site interactions compared to F420; 2) The statin lactone forms generally had the most favorable docking scores, even relative to the native template PDB ligands; and 3) The statin β-hydroxyacid forms had less favorable docking scores, typically scoring in the middle with some of the F420 tautomeric forms. Consistent with these computational results were those from a recent phase II clinical trial ( NCT02495623) with a proprietary, modified-release lovastatin-lactone (SYN-010) in patients with IBS-C, which showed a reduction in symptoms and breath methane levels, compared to placebo. CONCLUSION: The lactone form of lovastatin exhibits preferential binding over the native-F420 coenzyme ligand in silico and thus could inhibit the activity of the key M. smithii methanogenesis enzyme mtd in vivo

  18. A novel multifunctional metabolic pathway in a marine mollusc leads to unprecedented prostaglandin derivatives (prostaglandin 1,15-lactones).

    PubMed Central

    Di Marzo, V; Cimino, G; Crispino, A; Minardi, C; Sodano, G; Spinella, A

    1991-01-01

    The discovery of high levels of prostaglandin (PG) 1,15-lactones of both the E and F series and their co-existence with PGs has been recently described in the opisthobranch mollusc Tethys fimbria. The present study was undertaken in order to investigate the biosynthesis of these novel natural PG derivatives in vivo using radiolabelled precursors, and to gain a preliminary understanding of their biological role. PGE2 1,15-lactone was shown to be produced from both PGE2 and PGF2 alpha in the mollusc mantle and appeared to be quickly transferred to the mollusc dorsal appendices (cerata). The detachment of the latter during the typical defence behaviour of T. fimbria was accompanied by the conversion of PGE2 and PGE3 1,15-lactones back to the corresponding PGs. Both PGE2 and PGE2 1,15-lactone were also shown to be biosynthesized from arachidonic acid. Lactones of the F series were present as 11-acetyl derivatives in T. fimbria mantle and as 9- and 11-fatty acyl esters in the mollusc egg-mass and reproductive gland, and their biosynthesis from PGF2 alpha was demonstrated in all of these tissues. A multiple biological role of PG 1,15-lactones in T. fimbria defensive behaviour, smooth muscle contraction and egg production/fertilization control is hypothesized. The high amounts of PG derivatives found in T. fimbria and the biosynthetic studies described herein indicate that this marine mollusc may be a useful model for future studies on PG biosynthesis. PMID:1899996

  19. Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6years of macrocyclic lactone use.

    PubMed

    Laing, Roz; Maitland, Kirsty; Lecová, Lenka; Skuce, Philip J; Tait, Andy; Devaney, Eileen

    2016-09-01

    Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class, the macrocyclic lactones, are not known and sensitive diagnostic tools based on molecular markers are not currently available. This prohibits accurate surveillance of resistance or assessment of strategies aimed at controlling its spread. In this study, we examined four UK field populations of Haemonchus contortus, differing in macrocyclic lactone treatment history, for evidence of selection at 'candidate gene' loci identified as determining macrocyclic lactone resistance in previously published research. Individual worms were genotyped at Hc-lgc-37, Hc-glc-5, Hc-avr-14 and Hc-dyf-7, and four microsatellite loci. High levels of polymorphism were identified at the first three candidate gene loci with remarkably little polymorphism at Hc-dyf-7. While some between-population comparisons of individual farms with and without long-term macrocyclic lactone use identified statistically significant differences in allele frequency and/or fixation index at the Hc-lgc-37, Hc-glc-5 or Hc-avr-14 loci, we found no consistent evidence of selection in other equivalent comparisons. While it is possible that different mechanisms are important in different populations or that resistance may be conferred by small changes at multiple loci, our findings suggest that these are unlikely to be major loci conferring macrocyclic lactone resistance on UK farms or suitable for diagnostic marker development. More powerful approaches, using genome-wide or whole genome sequencing, may be required to define macrocyclic lactone resistance loci in such genetically variable populations. PMID:27179994

  20. Chemopreventive activity of sesquiterpene lactones (SLs) from yacon against TPA-induced Raji cells deformation.

    PubMed

    Siriwan, D; Miyawaki, C; Miyamoto, T; Naruse, T; Okazaki, K; Tamura, H

    2011-05-15

    Yacon is a medicinal plant used as a traditional medicine by the natives in South America. In Japan, it becomes popular as a health food. Sesquiterpene Lactones (SLs) from yacon leaves were investigated and the active SLs such as enhydrin, uvedalin and sonchifolin, bearing alpha-methylene-gamma-lactone and epoxides as the active functional groups, were identified by 1H-6000 MHz-NMR. Chemopreventive and cytotoxic activities were determined using different primary screening methods. In this study, all tested SLs strongly inhibited TPA-induced deformed of Raji cells. The IC50 values of yacon SLs from anti-deforming assay were 0.04-0.4 microM. Interestingly, yacon SLs showed more potential of chemo preventive activity than both curcumin and parthenolide. However, the cytotoxicity on Raji cells was observed at high concentration of yacon SLs. The degree of anti-deformation was ranked in order: enhydrin >uvedalin >sonchifolin >parthenolide >curcumin. As according to structure-activity relationship, the high activities of enhydrin, uvedalin and sonchifolin may be due to the 2-methyl-2-butenoate and its epoxide moiety. PMID:22097098

  1. Nitrite-Oxidizing Bacterium Nitrobacter winogradskyi Produces N-Acyl-Homoserine Lactone Autoinducers

    PubMed Central

    Bottomley, Peter J.

    2015-01-01

    Nitrobacter winogradskyi is a chemolithotrophic bacterium that plays a role in the nitrogen cycle by oxidizing nitrite to nitrate. Here, we demonstrate a functional N-acyl-homoserine lactone (acyl-HSL) synthase in this bacterium. The N. winogradskyi genome contains genes encoding a putative acyl-HSL autoinducer synthase (nwi0626, nwiI) and a putative acyl-HSL autoinducer receptor (nwi0627, nwiR) with amino acid sequences 38 to 78% identical to those in Rhodopseudomonas palustris and other Rhizobiales. Expression of nwiI and nwiR correlated with acyl-HSL production during culture. N. winogradskyi produces two distinct acyl-HSLs, N-decanoyl-l-homoserine lactone (C10-HSL) and a monounsaturated acyl-HSL (C10:1-HSL), in a cell-density- and growth phase-dependent manner, during batch and chemostat culture. The acyl-HSLs were detected by bioassay and identified by ultraperformance liquid chromatography with information-dependent acquisition mass spectrometry (UPLC-IDA-MS). The C=C bond in C10:1-HSL was confirmed by conversion into bromohydrin and detection by UPLC-IDA-MS. PMID:26092466

  2. Low-temperature EPR and quantum chemical study of lactone radical cations and their transformations

    NASA Astrophysics Data System (ADS)

    Naumov, S.; Janovský, I.; Knolle, W.; Mehnert, R.; Turin, D. A.

    2005-07-01

    Radical cations of a number of lactones ( β-butyro-, γ-butyro-, γ-valero-, δ-hexano-, δ-valero- and ɛ-capro-) were radiolytically generated in CF 3CCl 3 matrix and investigated by EPR spectroscopy. The primary radical cation of the 4-membered ring β-butyrolactone is unstable even at 77 K and undergoes spontaneous ring opening and fragmentation, leading to the deprotonated neutral (CH 2CHCH 2) rad radical. The stability of the primary carbonyl-centred radical cations of the 5-, 6- and 7-membered lactone rings towards intramolecular H-shift from the C1 in α-position to carbonyl oxygen depends primarily on the ring size, which determines the activation energy of the transformation and distance L(H-O) of the carbonyl oxygen to the nearest H-atom on the ring. The larger the ring, the smaller the L(H-O) and also activation energy of the H-shift, making the transformation of the primary radical cation more feasible. The quantum chemical calculations facilitated the interpretation of the EPR spectra of the secondary radical cations.

  3. Pressure-induced polymerization of carbon monoxide: disproportionation and synthesis of an energetic lactonic polymer

    SciTech Connect

    Evans, W J; Lipp, M J; Yoo, C; Herberg, J L; Maxwell, R S; Nicol, M F

    2005-10-04

    We have studied pressure-induced chemical reactions in carbon monoxide using both a diamond-anvil cell and a modified large volume press. Our spectroscopic data reveal that carbon monoxide disproportionates into molecular CO{sub 2} and a solid lactone-type polymer; photochemically above 3.2 GPa, thermochemically above 5 GPa at 300K, or at 3 GPa and {approx}2000K as achieved by laser heating. The solid product can be recovered at ambient conditions with a high degree of conversion, measured to be up to 95% of the original CO. Its fundamental chemical structure includes {beta}-lactone and conjugated C=C, which can be considered a severely modified polymeric carbon suboxide with open ladders and smaller five-membered rings. The polymer is metastable at ambient conditions, spontaneously liberating CO{sub 2} gases exothermically. We find that the recovered polymer has a high energy density, 1-8 KJ/g, and is very combustible. We estimate the density of recovered CO polymer to be at least 1.65 g/cm cm{sup 3}.

  4. Thermal stability of antiparasitic macrocyclic lactones milk residues during industrial processing.

    PubMed

    Imperiale, F A; Farias, C; Pis, A; Sallovitz, J M; Lifschitz, A; Lanusse, C

    2009-01-01

    The chemical stability of residues of different antiparasitic macrocyclic lactone compounds in milk subjected to thermal treatment was assessed. Concentrations of ivermectin (IVM), moxidectin (MXD) and eprinomectin (EPM) in sheep milk, equivalent to those measured in vivo in milk excretion studies, were subjected to 65 degrees C over 30 min or to 75 degrees C for 15 s. Residue concentrations of IVM, MXD and EPM in milk were measured by high-performance liquid chromatography (HPLC) (fluorescence detection) before and after heat treatment of the drug-fortified milk samples. No evidence of chemical loss was obtained in either of the thermal treatments under evaluation. The stability of the parent compounds in milk was evidenced by the lack of bioconversion products (metabolites) after both thermal treatments. Only very minor changes on drug concentrations were observed at the end of the treatments, which fell within the limits of the variation of the validated analytical method. In conclusion, residue concentrations of macrocyclic lactones are unaffected by industrial-simulated milk thermal procedures. Based on the reported findings, it can be postulated that residue concentrations of IVM, MXD and EPM measured in raw sheep milk may be used to estimate consumer exposure and dietary intake for these veterinary drugs. PMID:19680871

  5. Effects of lactone, ketone, and phenolic compounds on methane production and metabolic intermediates during anaerobic digestion.

    PubMed

    Wikandari, Rachma; Sari, Noor Kartika; A'yun, Qurrotul; Millati, Ria; Cahyanto, Muhammad Nur; Niklasson, Claes; Taherzadeh, Mohammad J

    2015-02-01

    Fruit waste is a potential feedstock for biogas production. However, the presence of fruit flavors that have antimicrobial activity is a challenge for biogas production. Lactones, ketones, and phenolic compounds are among the several groups of fruit flavors that are present in many fruits. This work aimed to investigate the effects of two lactones, i.e., γ-hexalactone and γ-decalactone; two ketones, i.e., furaneol and mesifurane; and two phenolic compounds, i.e., quercetin and epicatechin on anaerobic digestion with a focus on methane production, biogas composition, and metabolic intermediates. Anaerobic digestion was performed in a batch glass digester incubated at 55 °C for 30 days. The flavor compounds were added at concentrations of 0.05, 0.5, and 5 g/L. The results show that the addition of γ-decalactone, quercetin, and epicathechin in the range of 0.5-5 g/L reduced the methane production by 50 % (MIC50). Methane content was reduced by 90 % with the addition of 5 g/L of γ-decalactone, quercetin, and epicathechin. Accumulation of acetic acid, together with an increase in carbon dioxide production, was observed. On the contrary, γ-hexalactone, furaneol, and mesifurane increased the methane production by 83-132 % at a concentration of 5 g/L. PMID:25416476

  6. Two competing reactions of tetrabutylammonium alginate in organic solvents: Amidation versus γ-lactone synthesis.

    PubMed

    Schleeh, Thomas; Madau, Mathieu; Roessner, Dierk

    2016-03-15

    Biocompatibility and thickening properties predetermine alginates as ingredients in food, cosmetic and pharmaceutical products. Further chemical modifications are often desired for a product optimization. The introduction of hydrophobic groups can be realized by employing organic tetrabutylammonium alginate (TBA-Alg) solutions. The synthesis of alginic acid alkyl amides from TBA-Alg with 2-chloro-1-methylpyridinium iodide (CMPI) as a coupling agent, however, has so far not resulted in a high degree of amidation. The analysis of the coupling reaction revealed the formation of mannuronic acid γ-lactone structures, which required a conformation change from (1)C4 to (4)C1. The opening of the γ-lactone required a high excess of butylamine. In the case of CMPI, triethylamine had to be added prior to the coupling agent in order to suppress the assumed alginic acid formation. The degrees of amidation achieved were up to 0.8, and for propylphosphonic anhydride as the coupling agent up to 1. The molecular weights of the alginic acid butyl amide were ≥35kDa. PMID:26794759

  7. Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

    PubMed Central

    Barker Rasmussen, Bastian; Fog Nielsen, Kristian; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C.

    2014-01-01

    Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7) HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria. PMID:25419995

  8. Temperature Behavior of Electric Relaxational Effects due to Ionic Conductivity in Liquid Lactones

    NASA Astrophysics Data System (ADS)

    Świergiel, J.; Jadżyn, J.

    2012-05-01

    This paper concerns the studies of temperature and frequency behavior of the complex impedance, electric modulus, and electric conductivity due to an ionic current in liquid γ-butyrolactone (GBL) and γ-valerolactone (GVL). The frequency of the applied electric stimulus (500 Hz to 5 MHz) corresponds to the static dielectric regime of the lactones. The studies were performed in the temperature range of 263 K to 313 K. It was shown that in the static dielectric case, the dc ionic conductivity ( σ DC) and the static dielectric permittivity {(\\varepsilon_s)} determine the relaxational behavior of the impedance ( Z*) and the electric modulus ( M*) of the molecular liquids and both spectra are of the Debye-type characterized by the same conductivity relaxation time ( τ σ ). Both σ DC and τ σ of GBL and GVL fairly well fulfill an Arrhenius temperature dependence with very similar values of the thermal activation energy {E_{σ_DC} ≈ E_{tau_σ} ≈ 25 kJ . mol^{-1}} . The temperature dependence of the static dielectric permittivity and its temperature derivative is analyzed and interpreted in terms of the dipolar aggregation in the studied lactones.

  9. Synthesis and analysis of thio-, thiono-, and dithio-derivatives of whiskey lactone.

    PubMed

    Schmarr, H G; Eisenreich, W; Engel, K H

    2001-12-01

    Cis- and trans-3-methyl-4-octanolide (1, whiskey lactones) were converted into their thio- (2), thiono- (3), and dithio- (4) derivatives by reaction with phosphorus pentasulfide. The reaction products were characterized by GC-mass spectrometry, (1)H NMR spectroscopy, and GC-olfactometry. Two-dimensional NOESY spectra showed that sulfur is incorporated into the ring with reversal of the absolute configuration at C-4, whereas substitution of the keto-oxygen atom by sulfur occurs with retention of ring configuration. The cis- and trans-pairs of 2, 3, and 4 were separated into enantiomers by GC on heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin and heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin as chiral stationary phases. GC-olfactometry revealed a sweet coconut-like odor for the cis-thio- and pleasant mushroom-like flavors for the cis-thiono- and trans-dithio-derivatives of whiskey lactone. PMID:11743786

  10. Catalytic Asymmetric Synthesis of Ketene Heterodimer β-Lactones: Scope and Limitations.

    PubMed

    Chen, Shi; Ibrahim, Ahmad A; Peraino, Nicholas J; Nalla, Divya; Mondal, Mukulesh; Van Raaphorst, Maxwell; Kerrigan, Nessan J

    2016-09-01

    In this article we describe extensive studies of the catalytic asymmetric heterodimerization of ketenes to give ketene heterodimer β-lactones. The optimal catalytic system was determined to be a cinchona alkaloid derivative (TMS-quinine or Me-quinidine). The desired ketene heterodimer β-lactones were obtained in good to excellent yields (up to 90%), with excellent levels of enantioselectivity (≥90% ee for 33 Z and E isomer examples), good to excellent (Z)-olefin isomer selectivity (≥90:10 for 20 examples), and excellent regioselectivity (only one regioisomer formed). Full details of catalyst development studies, catalyst loading investigations, substrate scope exploration, protocol innovations (including double in situ ketene generation for 7 examples), and an application to a cinnabaramide A intermediate are described. The addition of lithium perchlorate (1-2 equiv) as an additive to the alkaloid catalyst system was found to favor formation of the E isomer of the ketene heterodimer. Ten examples were formed with moderate to excellent (E)-olefin isomer selectivity (74:25 to 97:3) and with excellent enantioselectivity (84-98% ee). PMID:27490092

  11. The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase.

    PubMed

    Reimmann, C; Beyeler, M; Latifi, A; Winteler, H; Foglino, M; Lazdunski, A; Haas, D

    1997-04-01

    The global activator GacA, a highly conserved response regulator in Gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. The gacA gene of Pseudomonas aeruginosa PAO1 was isolated and its role in cell-density-dependent gene expression was characterized. Mutational inactivation of gacA resulted in delayed and reduced formation of the cell-density signal N-butyryl-L-homoserine lactone (BHL), of the cognate transcriptional activator RhIR (VsmR), and of the transcriptional activator LasR, which is known to positively regulate RhIR expression. Amplification of gacA on a multicopy plasmid caused precocious and enhanced production of BHL, RhIR and LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhIR-dependent formation of the cytotoxic compounds pyocyanin and cyanide and the exoenzyme lipase. However, the concentrations of another known cell-density signal of P. aeruginosa, N-oxododecanoyl-L-homoserine lactone, did not always match BHL concentrations. A model accounting for these observations places GacA function upstream of LasR and RhIR in the complex, cell-density-dependent signal-transduction pathway regulating several exoproducts and virulence factors of P. aeruginosa via BHL. PMID:9159518

  12. Ecological roles and release patterns of acylated homoserine lactones in Pseudomonas sp. HF-1 and their implications in bacterial bioaugmentation.

    PubMed

    Wang, Mei-zhen; Zheng, Xin; He, Hong-zhen; Shen, Dong-sheng; Feng, Hua-jun

    2012-12-01

    To enable development of a better bacterial bioaugmentation system for tobacco wastewater treatment, the roles and release patterns of acylated homoserine lactones (AHLs) in Pseudomonas sp. HF-1 were evaluated. Swarming was found to be induced by N-hexanoyl-homoserine lactone (C(6)-HSL) and N-3-oxo-hexanoyl-homoserine lactone (3-oxo-C(6)-HSL); the formation of extracellular polymeric substances (EPS) was induced by 3-oxo-C(6)-HSL, C(6)-HSL and N-3-oxo-octanoyl-homoserine lactone (3-oxo-C(8)-HSL); and biofilm formation was induced by C(6)-HSL and 3-oxo-C(8)-HSL. When the culture conditions were 25°C, pH 5-6, 3% inoculum, 1.5 g L(-1) nicotine and 1% NaCl, the amount of AHLs released was sufficient for quorum sensing of swarming and EPS formation for strain HF-1, which was beneficial to the startup stage during bioaugmentation. When strain HF-1 was cultured at pH 8 in the presence of 1.2-1.8 g L(-1) of nicotine and 1% NaCl, the threshold for quorum sensing of biofilm formation was reached and the bioaugmentation system showed an efficient performance. PMID:23026323

  13. Diastereoselective synthesis of γ-lactones through reaction of enediolates with α,β-unsaturated sulfoxonium salts.

    PubMed

    Peraino, Nicholas J; Wheeler, Kraig A; Kerrigan, Nessan J

    2015-04-01

    Studies of the reaction of lithium enediolates with α,β-unsaturated sulfoxonium salts are described. γ-Lactones were formed in very good to excellent yields (82% → 99% for 11 examples) and with very good to excellent diastereoselectivity (dr >90:10 for 10 examples), favoring the trans-diastereomer. PMID:25783172

  14. Degradation of N-Acyl-l-Homoserine Lactones by Bacillus cereus in Culture Media and Pork Extract▿

    PubMed Central

    Medina-Martínez, Maria Stella; Uyttendaele, Mieke; Rajkovic, Andreja; Nadal, Pol; Debevere, Johan

    2007-01-01

    Degradation of the quorum-sensing signal molecule N-acyl-l-homoserine lactone (AHL) in cocultures was verified with Bacillus cereus and Yersinia enterocolitica in culture medium and in pork extract. Results showed evidence of microbial interaction when the AHL-degrading bacterium and AHL-producing bacterium were cocultured in a food-simulating condition. PMID:17293532

  15. A study of the piezoelectric resonance in organic single crystal: glucuronic acid γ-lactone

    NASA Astrophysics Data System (ADS)

    Saripalli, Ravi Kiran; Chakraborty, Tirthankar; Bhat, H. L.; Elizabeth, Suja

    2016-04-01

    An organic nonlinear optical material, namely glucuronic acid γ-lactone or glucuronolactone, was crystallized from aqueous solution. Crystals of large dimensions and full morphology were obtained by slow-cooling method in a custom-built solution growth setup. CHN analysis and X-ray diffraction confirmed the phase formation in the grown crystal. High-resolution XRD studies followed by Rietveld refinement yielded accurate lattice parameters which compared well with the reported values. UV-Vis spectrum recorded for a b-plate of 2 mm thickness revealed the low UV-cutoff at 250 nm. Dielectric constant and dielectric loss were monitored as a function of frequency. Piezoelectric resonance peaks were observed in the range 0.2-1.5 MHz which are dependent on the plate thickness. The temperature dependence of the resonance peak frequency was studied. Piezoelectric coefficients were estimated by resonance-antiresonance method.

  16. Synthesis and Biological Evaluation of Several Bryostatin Analogues Bearing a Diacylglycerol Lactone C-Ring.

    PubMed

    Baumann, David O; McGowan, Kevin M; Kedei, Noemi; Peach, Megan L; Blumberg, Peter M; Keck, Gary E

    2016-09-01

    As an initial step in designing a simplified bryostatin hybrid molecule, three bryostatin analogues bearing a diacylglycerol lactone-based C-ring, which possessed the requisite pharmacophores for binding to protein kinase C (PKC) together with a modified bryostatin-like A- and B-ring region, were synthesized and evaluated. Merle 46 and Merle 47 exhibited binding affinity to PKC alpha with Ki values of 7000 ± 990 and 4940 ± 470 nM, respectively. Reinstallation of the trans-olefin and gem-dimethyl group present in bryostatin 1 in Merle 48 resulted in improved binding affinity, 363 ± 42 nM. While Merle 46 and 47 were only marginally active biologically, Merle 48 showed sufficient activity on the U937 cells to confirm that it was PMA-like for growth and attachment, as predicted by the substitution pattern of its A- and B-rings. PMID:27494208

  17. Biofilm activity and sludge characteristics affected by exogenous N-acyl homoserine lactones in biofilm reactors.

    PubMed

    Hu, Huizhi; He, Junguo; Liu, Jian; Yu, Huarong; Zhang, Jie

    2016-07-01

    This study verified the effect of N-acyl homoserine lactone (AHL) concentrations on mature biofilm systems. Three concentrations of an AHL mixture were used in the batch test. Introducing of 5nM AHLs significantly increased biofilm activity and increased sludge characteristics, which resulted in better pollutant removal performance, whereas exogenous 50nM and 500nM AHLs limited pollutant removal, especially COD and nitrogen removal. To further identify how exogenous signal molecular affects biofilm system nitrogen removal, analyzing of nitrifying bacteria through real-time polymerase chain reaction (RT-PCR) revealed that these additional signal molecules affect nitrifying to total bacteria ratio. In addition, the running state of the system was stable during 15days of operation without an AHL dose, which suggests that the changes in the system due to AHL are irreversible. PMID:27030953

  18. [The effects of alkylhydroxybenzenes on homoserine lactone-induced manifestations of quorum sensing in bacteria].

    PubMed

    Deriabin, D G; Kamaeva, A A; Tolmacheva, A A; Él'-Registan, G I

    2014-01-01

    The effects of four alkylhydroxybenzene (AHB) homologs of different hydrocarbon chain lengths on synthesis of the pigment violacein induced by C6-homoserine lactone (HSL) and biofilm formation by Chromobacterium violaceum NCTC 13274 and on Escherichia coli pAL103 bioluminescence in the presence of C6-oxo-HSL were studied. It was shown that the inhibitory effect of alkylhydroxybenzenes on the growth of C. violaceum increased in the C5-AHB --> C12-AHB series in the absence of this activity in C1-AHB. Sub-inhibitory AHB concentrations reduced violacein production and suppressed biofilm formation. These effects were presented as individual and group regression dependencies between the analyzed parameters. It was shown using the bioluminescent model that the regulatory effects of AHBs are not associated with their direct competition with HSL and that they develop as a result of changes in the sensitivity of bacterial cells to the respective quorum sensing inducer. PMID:25707115

  19. In Vitro Shoot Cultures and Analysis of Steroidal Lactones in Withania coagulans (Stocks) Dunal.

    PubMed

    Jain, Rohit; Kachhwaha, Sumita; Kothari, S L

    2016-01-01

    Withania coagulans (Stocks) Dunal (Solanaceae), also known as 'Panir Bandh' is an important medicinal plant that is extensively used as a home remedy for several diseases in the Indian subcontinent. The plant possesses specific steroidal lactones known as withanolides which show high level of pharmaceutical activity against a broad spectrum of microorganisms. Natural propagation of the plant occurs through Seed but due to unisexual nature of the flowers; chances of Seed setting are very limited and the plant is on the verge of extinction because of overexploitation and reproductive failure. Plant tissue culture techniques offer opportunities for ex situ conservation and mass multiplication of endangered plant species through micropropagation and also enhancement of in vitro biosynthesis of bioactive compounds. In this chapter we present protocols for the mass multiplication of W. coagulans, assessment of clonal fidelity by RAPD, and estimation of bioactive compounds (withanolides) by thin layer chromatography (TLC) and reverse phase HPLC developed in our laboratory. PMID:27108323

  20. Inhibiting N-acyl-homoserine lactone synthesis and quenching Pseudomonas quinolone quorum sensing to attenuate virulence

    PubMed Central

    Chan, Kok-Gan; Liu, Yi-Chia; Chang, Chien-Yi

    2015-01-01

    Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed. PMID:26539190

  1. Mode of action of the sesquiterpene lactone, tenulin, from Helenium amarum against herbivorous insects.

    PubMed

    Arnason, J T; Isman, M B; Philogène, B J; Waddell, T G

    1987-01-01

    Tenulin [1], a sesquiterpene lactone from Helenuim amarum, is a potent antifeedant to the European corn borer Ostrinia nubilalis. At 3 mumol/g in artificial diets, 1 reduced growth and delayed larval development of O. nubilalis and the variegated cutworm Peridroma saucia larvae. An especially pronouned carry-over effect in O. nubilis was substantial reduction in fecundity of adult moths resulting from treated larvae. The LD50 (lethal dose for 50% mortality) of 1 by injection in the migratory grasshopper Melanoplus sanguinipes was 0.88 mumol/insect. Toxicity in M. sanguinipes was antagonized by co-administration of cysteine, suggesting that the cyclopentenone group of tenulin undergoes Michael addition of biological nucleophiles in vivo. This mechanism was partially confirmed by the finding that only tenulin analogues capable of acting as electrophic acceptors had significant antifeedant activity. PMID:3430166

  2. Enzymatic polyketide chain branching to give substituted lactone, lactam, and glutarimide heterocycles.

    PubMed

    Heine, Daniel; Bretschneider, Tom; Sundaram, Srividhya; Hertweck, Christian

    2014-10-20

    Polyketides typically result from head-to-tail condensation of acyl thioesters to produce highly functionalized linear chains. The biosynthesis of the phytotoxin rhizoxin, however, involves a polyketide synthase (PKS) module that introduces a δ-lactone chain branch through Michael addition of a malonyl extender to an α,β-unsaturated intermediate unit. To evaluate the scope of the branching module, polyketide mimics were synthesized and their biotransformation by the reconstituted PKS module from the Rhizopus symbiont Burkholderia rhizoxinica was monitored in vitro. The impact of the type and configuration of the δ-substituents was probed and it was found that amino-substituted surrogates yield the corresponding lactams. A carboxamide analogue was transformed into a glutarimide unit, which can be found in many natural products. Our findings illuminate the biosynthesis of glutarimide-bearing polyketides and also demonstrate the utility of this branching module for synthetic biology. PMID:25214315

  3. Insights into the biosynthesis of 12-membered resorcylic acid lactones from heterologous production in Saccharomyces cerevisiae.

    PubMed

    Xu, Yuquan; Zhou, Tong; Espinosa-Artiles, Patricia; Tang, Ying; Zhan, Jixun; Molnár, István

    2014-05-16

    The phytotoxic fungal polyketides lasiodiplodin and resorcylide inhibit human blood coagulation factor XIIIa, mineralocorticoid receptors, and prostaglandin biosynthesis. These secondary metabolites belong to the 12-membered resorcylic acid lactone (RAL12) subclass of the benzenediol lactone (BDL) family. Identification of genomic loci for the biosynthesis of lasiodiplodin from Lasiodiplodia theobromae and resorcylide from Acremonium zeae revealed collaborating iterative polyketide synthase (iPKS) pairs whose efficient heterologous expression in Saccharomyces cerevisiae provided a convenient access to the RAL12 scaffolds desmethyl-lasiodiplodin and trans-resorcylide, respectively. Lasiodiplodin production was reconstituted in the heterologous host by co-expressing an O-methyltransferase also encoded in the lasiodiplodin cluster, while a glutathione-S-transferase was found not to be necessary for heterologous production. Clarification of the biogenesis of known resorcylide congeners in the heterologous host helped to disentangle the roles that biosynthetic irregularities and chemical interconversions play in generating chemical diversity. Observation of 14-membered RAL homologues during in vivo heterologous biosynthesis of RAL12 metabolites revealed "stuttering" by fungal iPKSs. The close global and domain-level sequence similarities of the orthologous BDL synthases across different structural subclasses implicate repeated horizontal gene transfers and/or cluster losses in different fungal lineages. The absence of straightforward correlations between enzyme sequences and product structural features (the size of the macrocycle, the conformation of the exocyclic methyl group, or the extent of reduction by the hrPKS) suggest that BDL structural variety is the result of a select few mutations in key active site cavity positions. PMID:24597618

  4. Specificity of acyl-homoserine lactone synthases examined by mass spectrometry.

    PubMed

    Gould, Ty A; Herman, Jake; Krank, Jessica; Murphy, Robert C; Churchill, Mair E A

    2006-01-01

    Many gram-negative bacteria produce a specific set of N-acyl-L-homoserine-lactone (AHL) signaling molecules for the purpose of quorum sensing, which is a means of regulating coordinated gene expression in a cell-density-dependent manner. AHLs are produced from acylated acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine by the AHL synthase enzyme. The appearance of specific AHLs is due in large part to the intrinsic specificity of the enzyme for subsets of acyl-ACP substrates. Structural studies of the Pantoea stewartii enzyme EsaI and AHL-sensitive bioassays revealed that threonine 140 in the acyl chain binding pocket directs the enzyme toward production of 3-oxo-homoserine lactones. Mass spectrometry was used to examine the range of AHL molecular species produced by AHL synthases under a variety of conditions. An AHL selective normal-phase chromatographic purification with addition of a deuterated AHL internal standard was followed by reverse-phase liquid chromatography-tandem mass spectrometry in order to obtain estimates of the relative amounts of different AHLs from biological samples. The AHLs produced by wild-type and engineered EsaI and LasI AHL synthases show that intrinsic specificity and different cellular conditions influence the production of AHLs. The threonine at position 140 in EsaI is important for the preference for 3-oxo-acyl-ACPs, but the role of the equivalent threonine in LasI is less clear. In addition, LasI expressed in Escherichia coli produces a high proportion of unusual AHLs with acyl chains consisting of an odd number of carbons. Furthermore, these studies offer additional methods that will be useful for surveying and quantitating AHLs from different sources. PMID:16385066

  5. GABAA receptor cysteinyl mutants and the ginkgo terpenoid lactones bilobalide and ginkgolides.

    PubMed

    Ng, Chiu Chin; Duke, Rujee K; Hinton, Tina; Johnston, Graham A R

    2016-04-15

    The terpenoid lactones from Ginkgo biloba, bilobalide and ginkgolides, have been shown to act as negative modulators at α1β2γ2L GABAA receptors. They have structural features similar to those of the chloride channel blocker picrotoxinin. Unlike picrotoxinin, however they are not known to produce convulsant effects. Using two-electrode voltage clamp electrophysiology, this study compared the effect of mutation of 2', 6' and 15' pore facing M2 domain residues to cysteine on the action of picrotoxinin, bilobalide and ginkgolides at α1β2γ2L GABAA receptors expressed in Xenopus oocytes. Picrotoxinin was affected by mutation differently from the ginkgo terpenoid lactones. Although some of these compounds were affected by the mutation at same position and/or subunit, the changes in their potency were found to be dissimilar. The results suggest that the intracellular pore binding site for picrotoxinin, bilobalide, ginkgolide A, ginkgolide B and ginkgolide C is comprised of 2'β-6'β6'γ, 2'α2'β-6'α6'β, 2'α2'β2'γ-6'β6'γ, 2'α, 2'β2'γ-6'β and 2'α2'β, respectively. Unlike bilobalide and ginkgolides, the inhibitory action of picrotoxinin was not affected by mutations at 15' position. It is proposed that 15'α15'β, 15'β, 15'α15'β and 15'α15'β15'γ forms an extracellular pore binding site for bilobalide, ginkgolide A, ginkgolide B and ginkgolide C, respectively. The lack of convulsant effects of bilobalide, and ginkgolide A and B may be associated in part with their different binding locations within the chloride channel. PMID:26953225

  6. Discovery of a series of aromatic lactones as ALDH1/2-directed inhibitors

    PubMed Central

    Buchman, Cameron D.; Mahalingan, Krishna K.; Hurley, Thomas D.

    2015-01-01

    In humans, the aldehyde dehydrogenase superfamily consists of 19 isoenzymes which mostly catalyze the NAD(P)+-dependent oxidation of aldehydes. Many of these isoenzymes have overlapping substrate specificities and therefore their potential physiological functions may overlap. Thus the development of new isoenyzme-selective probes would be able to better delineate the function of a single isoenyzme and its individual contribution to the metabolism of a particular substrate. This specific study was designed to find a novel modulator of ALDH2, a mitochondrial ALDH isoenzyme most well-known for its role in acetaldehyde oxidation. 53 compounds were initially identified to modulate the activity of ALDH2 by a high-throughput esterase screen from a library of 63,000 compounds. Of these initial 53 compounds, 12 were found to also modulate the oxidation of propionaldehyde by ALDH2. Single concentration measurements at 10 μM compound were performed using ALDH1A1, ALDH1A2, ALDH1A3, ALDH2, ALDH1B1, ALDH3A1, ALDH4A1, and/or ALDH5A1 to determine the selectivity of these 12 compounds towards ALDH2. Four of the twelve compounds shared an aromatic lactone structure and were found to be potent inhibitors of the ALDH1/2 isoenzymes, but have no inhibitory effect on ALDH3A1, ALDH4A1 or ALDH5A1. Two of the aromatic lactones show selectivity within the ALDH1/2 class, and one appears to be selective for ALDH2 compared to all other isoenzymes tested. PMID:25641190

  7. Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK/NF-κB-Dependent Mechanism

    PubMed Central

    Zhao, Yan; Chen, Si-jia; Wang, Jian-cheng; Niu, Hong-xin; Jia, Qian-qian; Chen, Xiao-wen; Du, Xiao-yan; Lu, Lu; Huang, Bo; Zhang, Quan; Chen, Yue; Long, Hai-bo

    2015-01-01

    Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases. PMID:25664142

  8. Selection of the N-Acylhomoserine Lactone-Degrading Bacterium Alteromonas stellipolaris PQQ-42 and of Its Potential for Biocontrol in Aquaculture

    PubMed Central

    Torres, Marta; Rubio-Portillo, Esther; Antón, Josefa; Ramos-Esplá, Alfonso A.; Quesada, Emilia; Llamas, Inmaculada

    2016-01-01

    The production of virulence factors by many pathogenic microorganisms depends on the intercellular communication system called quorum sensing, which involves the production and release of signal molecules known as autoinducers. Based on this, new-therapeutic strategies have emerged for the treatment of a variety of infections, such as the enzymatic degradation of signaling molecules, known as quorum quenching (QQ). In this study, we present the screening of QQ activity amongst 450 strains isolated from a bivalve hatchery in Granada (Spain), and the selection of the strain PQQ-42, which degrades a wide range of N-acylhomoserine lactones (AHLs). The selected strain, identified as Alteromonas stellipolaris, degraded the accumulation of AHLs and reduced the production of protease and chitinase and swimming motility of a Vibrio species in co-cultivation experiments in vitro. In the bio-control experiment, strain PQQ-42 significantly reduced the pathogenicity of Vibrio mediterranei VibC-Oc-097 upon the coral Oculina patagonica showing a lower degree of tissue damage (29.25 ± 14.63%) in its presence, compared to when the coral was infected with V. mediterranei VibC-Oc-097 alone (77.53 ± 13.22%). Our results suggest that this AHL-degrading bacterium may have biotechnological applications in aquaculture. PMID:27242684

  9. Bacterial Growth Stimulation with Exogenous Siderophore and Synthetic N-Acyl Homoserine Lactone Autoinducers under Iron-Limited and Low-Nutrient Conditions

    PubMed Central

    Guan, Le Luo; Onuki, Hiroyuki; Kamino, Kei

    2000-01-01

    The growth of marine bacteria under iron-limited conditions was investigated. Neither siderophore production nor bacterial growth was detected for Pelagiobacter sp. strain V0110 when Fe(III) was present in the culture medium at a concentration of <1.0 μM. However, the growth of V0110 was strongly stimulated by the presence of trace amounts of exogenous siderophore from an alpha proteobacterium, V0902, and 1 nM N-acyl-octanoylhomoserine lactone (C8-HSL), which is known as a quorum-sensing chemical signal. Even though the iron-binding functionality of a hydroxamate siderophore was undetected in the supernatant of V0902, a hydroxamate siderophore was detected in the supernatant of V0110 under the above conditions. These results indicated that hydroxamate siderophore biosynthesis by V0110 began in response to the exogenous siderophore from V0902 when in the presence of C8-HSL; however, C8-HSL production by V0110 and V0902 was not detected. Direct interaction between V0902 and V0110 through siderophore from V0902 was observed in the dialyzing culture. Similar stimulated growth by exogenous siderophore and HSL was also observed in other non-siderophore-producing bacteria isolated from marine sponges and seawater. The requirement of an exogenous siderophore and an HSL for heterologous siderophore production indicated the possibility that cell-cell communication between different species was occurring. PMID:10877770

  10. In vitro and in vivo antileishmania activity of sesquiterpene lactone-rich dichloromethane fraction obtained from Tanacetum parthenium (L.) Schultz-Bip.

    PubMed

    Rabito, Mirela Fulgencio; Britta, Elizandra Aparecida; Pelegrini, Bruna Luiza; Scariot, Débora Botura; Almeida, Mariana Bortholazzi; Nixdorf, Suzana Lucy; Nakamura, Celso Vataru; Ferreira, Izabel Cristina Piloto

    2014-08-01

    The discovery of new treatments for neglected diseases, including leishmaniasis, is a substantial challenge for scientific research. Plant extracts have shown potential in the selective treatment of tropical diseases. The present study evaluated the in vitro and in vivo antileishmania effects of a sesquiterpene lactone-rich dichloromethane fraction (DF) obtained from the aerial parts of Tanacetum parthenium (L.) Schultz-Bip. In vitro studies of the DF indicated an IC50 of 2.40±0.76 μg mL(-1) against the promastigote form and 1.76±0.25 μg mL(-1) against the axenic amastigote form of Leishmania amazonensis. In vivo intramuscular treatment with DF decreased the growth and size of footpad lesions in mice. The DF also significantly decreased the parasite population compared with animals that were treated with the reference drug. Plasma malondialdehyde levels were increased slightly by the DF, attributable to its parthenolide-rich composition that causes cellular apoptosis, compared with the control group, demonstrating treatment efficacy without toxicity or genotoxicity. Because the isolation and purification of plant compounds are costly and time-consuming and generate low yields, extract fractions, such as the DF studied herein, represent a promising alternative for the treatment of leishmaniasis. PMID:24810433

  11. Colochiroside E, an Unusual Non-holostane Triterpene Sulfated Trioside from the Sea Cucumber Colochirus robustus and Evidence of the Impossibility of a 7(8)-Double Bond Migration in Lanostane Derivatives having an 18(16)-Lactone.

    PubMed

    Silchenko, Alexandra S; Kalinovsky, Anatoly I; Avilov, Sergey A; Andryjaschenko, Pelageya V; Dmitrenok, Pavel S; Yurchenko, Ekaterina A; Dolmatov, Igor Yu; Dautov, Salim Sh; Stonik, Valentin A; Kalinin, Vladimir I

    2016-06-01

    The unusual non-holostane triterpene glycoside, colochiroside E (1) was isolated from the sea cucumber Colochirus robustus (Cucumariidae, Dendrochirotida). The structure of 1 was established by analysis of 1D, 2D NMR and HRESI MS data. Colochiroside E (1) belongs to a rare group of glycosylated 9β-H-lanosta-18(16)-lactones and has an unprecedented sulfated trisaccharide carbohydrate chain consisting of two glucose and one xylose units. In contrast with (9β-H)-7(8)-unsaturated holostane glycosides, the 7(8)-double bond in the having (9β-H)-configuration aglycone of colochiroside E is not capable of migration into the 8(9)- and then into the 9(11)-position on treatment with HCl. The formation of a chlorine derivative of 1 was observed under these conditions. PMID:27534106

  12. Are isolated wetlands isolated?

    USGS Publications Warehouse

    Smith, Loren M.; Euliss, Ned H.; Haukos, David A.

    2011-01-01

    While federal regulations during the past 10 years have treated isolated wetlands as unconnected to aquatic resources protected by the Clean Water Act, they provide critical ecosystem services to society that extend well beyond their wetland boundaries. The authors offer well-documented examples from the scientific literature on some of the ecosystem services provided by isolated wetlands to society and other ecosystems.

  13. Effects of acid and lactone forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the induction of MDR1 expression and function in LS180 cells.

    PubMed

    Yamasaki, Daisuke; Nakamura, Tsutomu; Okamura, Noboru; Kokudai, Makiko; Inui, Naoki; Takeuchi, Kazuhiko; Watanabe, Hiroshi; Hirai, Midori; Okumura, Katsuhiko; Sakaeda, Toshiyuki

    2009-05-12

    In the present study, the ability of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), also known as statins, to regulate the gene expression and function of multidrug resistance protein 1 (MDR1/P-glycoprotein) and differences between their acid and lactone forms were examined in human intestinal epithelial LS180 cells. Some statins had the potential to induce the expression of mRNAs for MDR1 and/or CYP3A in either form. The change in the mRNA expression of MDR1 was accompanied by a change in the CsA-dependent intracellular accumulation of rhodamine 123. Simvastatin lactone, but not the acid form, exhibited a strong inductive effect on the mRNA expression of MDR1 and CYP3A in a dose-dependent manner. Sulforaphane significantly suppressed the expression of MDR1 and CYP3A mRNAs induced by atorvastatin lactone, lovastatin acid, and lovastatin lactone, comparable to the control level, and moderately inhibited that by cerivastatin acid, fluvastatin acid and simvastatin lactone. In the case of pitavastatin acid, sulforaphane had no significant effect on the expression of MDR1 mRNA.These results suggested that some statins could induce MDR1 and CYP3A gene expression and these inductive effects differed between the lactone and active hydroxy acid forms, and that PXR-mediated regulation was rarely associated with the mRNA inducibility by pitavastatin acid, unlike that by other statins. PMID:19429419

  14. Biocatalytic Lactone Generation in Genetically Engineered Escherichia coli and Identification of Products by Gas Chromatography-Mass Spectroscopy

    NASA Astrophysics Data System (ADS)

    Slawson, Chad; Stewart, Jon; Potter, Robert

    2001-11-01

    Genetically altered Escherichia coli are used as biocatalysts to produce optically pure lactones from a variety of cyclic ketones as a biotechnology experiment for a biochemistry laboratory. The genetically engineered E. coli bacteria express large amounts of the enzyme cyclohexanone monooxygenase and are therefor capable of converting a variety of ketones into optically pure lactones. Separation by organic extraction and analysis by thin layer chromatography and gas chromatography-mass spectroscopy allows for the direct identification of products. Yield calculations and evaluation of the cost effectiveness of various substrates give students an opportunity to make recommendations and model industrial decision-making. Evaluation of the synthetic process for its environmental impact allows students to consider problems of cost versus environmental concerns. Use of bacterial biocatalysts offers chemistry students an opportunity to work with microorganisms and directly see the utility of genetically altered bacteria for synthetic chemistry.

  15. Synthesis of ethers by GaBr3 -catalyzed reduction of carboxylic acid esters and lactones by siloxanes.

    PubMed

    Biermann, Ursula; Metzger, Jürgen O

    2014-02-01

    Ethers were synthesized by reduction of the respective esters catalyzed by gallium bromide (GaBr3 ) and using siloxanes, preferentially 1,1,3,3-tetramethyldisiloxane, as reductant. Methyl oleate, triglycerides, that is, tributyrine and glyceryl triundec-10-enoate as well as γ- and δ-lactones were converted into the respective ethers in high to moderate yields. γ-Lactones were reduced with high selectivity in the presence of a methyl ester functionality. The reduction has been carried out at room temperature or moderately elevated temperature of up to 60 °C using stoichiometric amounts of the reductant and 0.005-0.01 equiv of GaBr3 as catalyst per ester functionality without any solvent added. After a reaction time of 1-4 h the conversion of the substrate was 100 %. The product was separated from polymeric siloxanes formed as coupled product by simple distillation. PMID:24488681

  16. Nitric Oxide Inhibitory Activity and Absolute Configurations of Arylalkenyl α,β-Unsaturated δ/γ-Lactones from Cryptocarya concinna.

    PubMed

    Yang, Bing-Yuan; Kong, Ling-Yi; Wang, Xiao-Bing; Zhang, Yang-Mei; Li, Rui-Jun; Yang, Ming-Hua; Luo, Jian-Guang

    2016-01-22

    During an ongoing exploration of potential anti-inflammatory agents from medicinal plants, eight new arylalkenyl α,β-unsaturated δ-lactones, cryptoconcatones A-H (1-8), and two unusual arylalkenyl α,β-unsaturated γ-lactones, cryptoconcatones I and J (9 and 10), were identified from the leaves and twigs of Cryptocarya concinna. The structures of these compounds were established based on spectroscopic data (MS, 1D/2D NMR), and their absolute configurations were determined with Riguera's method, the modified Mosher's method, chemical derivatization, and the Snatzke chirality rule. Compounds 4-6 and 8-10 showed inhibitory activity toward nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages, particularly compounds 4 and 8-10, with IC50 values of 3.2, 4.2, 3.4, and 7.5 μM, respectively. PMID:26741483

  17. Synthesis and Structure–Activity Relationships of α-Amino-γ-lactone Ketolides: A Novel Class of Macrolide Antibiotics

    PubMed Central

    2014-01-01

    An efficient synthesis of α-amino-γ-lactone ketolide (3) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLSB-resistant strains of S. pneumoniae and S. pyogenes. In addition, ketolide 11o showed excellent in vitro antibacterial activity against H. influenzae strain as compared to telithromycin. These results indicate that C-21 substituted γ-lactone ketolides have potential as a next generation macrolide antibiotics. PMID:25313326

  18. Biofilm Formation and Quorum-Sensing-Molecule Production by Clinical Isolates of Serratia liquefaciens

    PubMed Central

    Remuzgo-Martínez, Sara; Lázaro-Díez, María; Mayer, Celia; Aranzamendi-Zaldumbide, Maitane; Padilla, Daniel; Calvo, Jorge; Marco, Francesc; Martínez-Martínez, Luis; Icardo, José Manuel; Otero, Ana

    2015-01-01

    Serratia spp. are opportunistic human pathogens responsible for an increasing number of nosocomial infections. However, little is known about the virulence factors and regulatory circuits that may enhance the establishment and long-term survival of Serratia liquefaciens in the hospital environment. In this study, two reporter strains, Chromobacterium violaceum CV026 and VIR24, and high-resolution triple-quadrupole liquid chromatography–mass spectrometry (LC-MS) were used to detect and to quantify N-acyl-homoserine lactone (AHL) quorum-sensing signals in 20 S. liquefaciens strains isolated from clinical samples. Only four of the strains produced sufficient amounts of AHLs to activate the sensors. Investigation of two of the positive strains by high-performance liquid chromatography (HPLC)-MS confirmed the presence of significant amounts of short-acyl-chain AHLs (N-butyryl-l-homoserine lactone [C4-HSL] and N-hexanoyl-l-homoserine lactone [C6-HSL]) in both strains, which exhibited a complex and strain-specific signal profile that included minor amounts of other short-acyl-chain AHLs (N-octanoyl-l-homoserine lactone [C8-HSL] and N-3-oxohexanoyl-l-homoserine lactone [OC6-HSL]) and long-acyl-chain (C10, C12, and C14) AHLs. No correlation between biofilm formation and the production of large amounts of AHLs could be established. Fimbria-like structures were observed by transmission electron microscopy, and the presence of the type 1 fimbrial adhesin gene fimH in all strains was confirmed by PCR. The ability of S. liquefaciens to adhere to abiotic surfaces and to form biofilms likely contributes to its persistence in the hospital environment, increasing the probability of causing nosocomial infections. Therefore, a better understanding of the adherence properties of this species will provide greater insights into the diseases it causes. PMID:25746999

  19. Synthesis of beta-lactones by the regioselective, cobalt and Lewis acid catalyzed carbonylation of simple and functionalized epoxides.

    PubMed

    Lee, J T; Thomas, P J; Alper, H

    2001-08-10

    The PPNCo(CO)(4) and BF(3) x Et(2)O catalyzed carbonylation of simple and functionalized epoxides in DME gives the corresponding beta-lactones regioselectively in good to high yields. The carbonylation occurred selectively at the unsubstituted C-O bond of the epoxide ring, and this reaction tolerates various functional groups such as alkenyl, halide, hydroxy, and alkyl ether. PMID:11485465

  20. Acid-mediated coupling of γ-hydroxybutenolides and aldehydes: Synthesis of a new class of spirocyclic ketal-lactones

    PubMed Central

    Munoz, Alberto; Murelli, Ryan P.

    2012-01-01

    In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf), γ-methyl-γ-hydroxybutenolide reacts with aromatic aldehydes to generate a new class of stereochemically rich spirocyclic ketal-lactones in good yields and with excellent stereoselectivities. We believe that this process takes place through the in situ generation of protoanemonin followed by a Prins reaction. Herein, we describe this discovery, along with substrate scope and preliminary mechanistic studies. PMID:23335822

  1. Synthesis of the glycosidic precursor of isomeric marmelo lactones, volatile components of the quince fruit, Cydonia oblonga.

    PubMed

    Shimizu, Hiroki; Kitahara, Takeshi

    2002-04-01

    The glucosidic precursor of marmelo lactones was synthesized by employing a common intermediate which had been used for the synthesis of the glucosidic precursor of marmelo oxides. The synthesis was performed by modifying the former procedure. Monochloroacetyl was adopted to protect both the glucose and aglycon hydroxyl groups for selective transesterification in the presence of the glycosyl ester. Glycosylation of the aglycon carboxyl group with 1-alpha-bromopermonochloroacetylglucose and final selective alcoholysis yielded the target glucoside. PMID:12036045

  2. The plant pathogen Pantoea ananatis produces N-acylhomoserine lactone and causes center rot disease of onion by quorum sensing.

    PubMed

    Morohoshi, Tomohiro; Nakamura, Yuta; Yamazaki, Go; Ishida, Akio; Kato, Norihiro; Ikeda, Tsukasa

    2007-11-01

    A number of gram-negative bacteria have a quorum-sensing system and produce N-acyl-l-homoserine lactone (AHL) that they use them as a quorum-sensing signal molecule. Pantoea ananatis is reported as a common colonist of wheat heads at ripening and causes center rot of onion. In this study, we demonstrated that P. ananatis SK-1 produced two AHLs, N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). We cloned the AHL-synthase gene (eanI) and AHL-receptor gene (eanR) and revealed that the deduced amino acid sequence of EanI/EanR showed high identity to those of EsaI/EsaR from P. stewartii. EanR repressed the ean box sequence and the addition of AHLs resulted in derepression of ean box. Inactivation of the chromosomal eanI gene in SK-1 caused disruption of exopolysaccharide (EPS) biosynthesis, biofilm formation, and infection of onion leaves, which were recovered by adding exogenous 3-oxo-C6-HSL. These results demonstrated that the quorum-sensing system involved the biosynthesis of EPS, biofilm formation, and infection of onion leaves in P. ananatis SK-1. PMID:17827290

  3. Involvement of N-acyl-L-hormoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens.

    PubMed

    Eberl, L; Winson, M K; Sternberg, C; Stewart, G S; Christiansen, G; Chhabra, S R; Bycroft, B; Williams, P; Molin, S; Givskov, M

    1996-04-01

    Several bacterial species possess the ability to differentiate into highly motile swarmer cells capable of rapid surface colonization. In Serratia liquefaciens, we demonstrate that initiation of swarmer-cell differentiation involves diffusible signal molecules that are released into the growth medium. Using high-performance liquid chromatography (HPLC), high resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, we identified N-butanoyl-L-homoserine lactone (BHL) and N-hex anoyl-L-homoserine lactone (HHL) in cell-free Serratia culture supernatants. BHL and HHL are present in a ratio of approximately 10:1 and their structures were unequivocally confirmed by chemical synthesis. The swrl (swarmer initiation) gene, the predicted translation product of which exhibits substantial homology to the LuxI family of putative N-acyl homoserine lactone (AHL) synthases is responsible for directing synthesis of both BHL and HHL. In an swrl mutant, swarming motility is abolished but can be restored by the addition of an exogenous AHL. These results add swarming motility to the rapidly expanding list of phenotypes known to be controlled through quorum sensing. PMID:8861211

  4. The impact of sesquiterpene lactones and phenolics on sensory attributes: An investigation of a curly endive and escarole germplasm collection.

    PubMed

    Filippo D'Antuono, L; Ferioli, Federico; Manco, Manuela Agata

    2016-05-15

    In the present study, curly endive (Cichorium endivia L. var. crispum) and escarole (Cichorium endivia L. var. latifolium) accessions were investigated for their sensory characters (bitterness, astringency and herbaceous flavour) and acceptance in relation to sesquiterpene lactone and phenolic content. Different facets of the perception of these sensory traits in relation to lactones and phenolics were brought out. Lactucopicrin and kaempferol malonyl glucoside were consistently related to bitterness, astringency and herbaceous flavour perceptions. Overall acceptance was significantly and inversely related mainly to bitterness. The generic statement that sesquiterpene lactones and phenolic compounds are determinants of bitterness and other related sensory characters does not seem to be fully consistent with our data, that indicated how the balance of different compounds affects these traits individually, in a rather complex manner, with a prevailing negative impact of phenolics. Bitter, astringent, and herbaceous perceptions were significantly affected by variety, with curly endive showing on average higher scores in comparison to escarole, with particular respect to bitterness. PMID:26775966

  5. Determination of lactones in wines by headspace solid-phase microextraction and gas chromatography coupled with mass spectrometry.

    PubMed

    Pérez-Olivero, S J; Pérez-Pont, M L; Conde, J E; Pérez-Trujillo, J P

    2014-01-01

    Application of headspace solid-phase microextraction (HS-SPME) coupled with high-resolution gas chromatographic (HRGC) analysis was studied for determining lactones in wines. Six different SPME fibers were tested, and the influence of different factors such as temperature and time of desorption, ionic strength, time of extraction, content of sugar, ethanol, tannins and anthocyanins, and pH and influence of SO2 were studied. The proposed HS-SPME-GC method is an appropriate technique for the quantitative analysis of γ-butyrolactone, γ-hexalactone, trans-whiskey lactone, γ-octalactone, cis-whiskey lactone, γ-nonalactone, γ-decalactone, δ-decalactone, and γ-undecalactone in wines. Method reproducibility and repeatability ranged between 0.6 and 5.2% for all compounds. Detection limit for γ-butyrolactone was 0.17 mg/L and a few μg/L for the rest of the compounds. The optimized method has been applied to several wine samples. PMID:24782943

  6. Determination of Lactones in Wines by Headspace Solid-Phase Microextraction and Gas Chromatography Coupled with Mass Spectrometry

    PubMed Central

    Pérez-Olivero, S. J.; Pérez-Pont, M. L.; Conde, J. E.; Pérez-Trujillo, J. P.

    2014-01-01

    Application of headspace solid-phase microextraction (HS-SPME) coupled with high-resolution gas chromatographic (HRGC) analysis was studied for determining lactones in wines. Six different SPME fibers were tested, and the influence of different factors such as temperature and time of desorption, ionic strength, time of extraction, content of sugar, ethanol, tannins and anthocyanins, and pH and influence of SO2 were studied. The proposed HS-SPME-GC method is an appropriate technique for the quantitative analysis of γ-butyrolactone, γ-hexalactone, trans-whiskey lactone, γ-octalactone, cis-whiskey lactone, γ-nonalactone, γ-decalactone, δ-decalactone, and γ-undecalactone in wines. Method reproducibility and repeatability ranged between 0.6 and 5.2% for all compounds. Detection limit for γ-butyrolactone was 0.17 mg/L and a few μg/L for the rest of the compounds. The optimized method has been applied to several wine samples. PMID:24782943

  7. The Plant Pathogen Pantoea ananatis Produces N-Acylhomoserine Lactone and Causes Center Rot Disease of Onion by Quorum Sensing▿

    PubMed Central

    Morohoshi, Tomohiro; Nakamura, Yuta; Yamazaki, Go; Ishida, Akio; Kato, Norihiro; Ikeda, Tsukasa

    2007-01-01

    A number of gram-negative bacteria have a quorum-sensing system and produce N-acyl-l-homoserine lactone (AHL) that they use them as a quorum-sensing signal molecule. Pantoea ananatis is reported as a common colonist of wheat heads at ripening and causes center rot of onion. In this study, we demonstrated that P. ananatis SK-1 produced two AHLs, N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). We cloned the AHL-synthase gene (eanI) and AHL-receptor gene (eanR) and revealed that the deduced amino acid sequence of EanI/EanR showed high identity to those of EsaI/EsaR from P. stewartii. EanR repressed the ean box sequence and the addition of AHLs resulted in derepression of ean box. Inactivation of the chromosomal eanI gene in SK-1 caused disruption of exopolysaccharide (EPS) biosynthesis, biofilm formation, and infection of onion leaves, which were recovered by adding exogenous 3-oxo-C6-HSL. These results demonstrated that the quorum-sensing system involved the biosynthesis of EPS, biofilm formation, and infection of onion leaves in P. ananatis SK-1. PMID:17827290

  8. Isolation and Asymmetric Total Synthesis of Perforanoid A.

    PubMed

    Lv, Chao; Yan, Xiaohui; Tu, Qian; Di, Yingtong; Yuan, Chunmao; Fang, Xin; Ben-David, Yaacove; Xia, Lei; Gong, Jianxian; Shen, Yuemao; Yang, Zhen; Hao, Xiaojiang

    2016-06-20

    A novel limonoid, perforanoid A, was isolated, and an asymmetric total synthesis was achieved in 10 steps. The key steps are chiral tertiary aminonaphthol mediated enantioselective alkenylation of an aldehyde to an allylic alcohol, Pd-catalyzed coupling of the allylic alcohol with vinyl ether to form the γ-lactone ring, and cyclopentenone ring formation through a Rh-catalyzed Pauson-Khand reaction. Preliminary studies show that perforanoid A is cytotoxic towards HEL, K562, and CB3 tumor cell lines. PMID:27167098

  9. Isolation of AHL-degrading bacteria from micro-algal cultures and their impact on algal growth and on virulence of Vibrio campbellii to prawn larvae.

    PubMed

    Pande, Gde Sasmita Julyantoro; Natrah, Fatin Mohd Ikhsan; Flandez, Ace Vincent Bravo; Kumar, Uday; Niu, Yufeng; Bossier, Peter; Defoirdt, Tom

    2015-12-01

    Inactivation of quorum sensing (QS) signal molecules, such as acylhomoserine lactones (AHLs) of pathogenic bacteria, has been proposed as a novel method to combat bacterial diseases in aquaculture. Despite the importance of micro-algae for aquaculture, AHL degradation by bacteria associated with micro-algal cultures has thus far not been investigated. In this study, we isolated Pseudomonas sp. NFMI-T and Bacillus sp. NFMI-C from open cultures of the micro-algae Tetraselmis suecica and Chaetoceros muelleri, respectively. An AHL degradation assay showed that either monocultures or co-cultures of the isolates were able to degrade the AHL N-hexanoyl-L-homoserine lactone. In contrast, only Bacillus sp. NFMI-C was able to inactivate N-hydroxybutanoyl-L-homoserine lactone, the AHL produced by Vibrio campbellii. The isolated bacteria were able to persist for up to 3 weeks in conventionalized micro-algal cultures, indicating that they were able to establish and maintain themselves within open algal cultures. Using gnotobiotic algal cultures, we found that the isolates did not affect growth of the micro-algae from which they were isolated, whereas a mixture of both isolates increased the growth of Tetraselmis and decreased the growth of Chaetoceros. Finally, addition of Bacillus sp. NFMI-C to the rearing water of giant river prawn (Macrobrachium rosenbergii) larvae significantly improved survival of the larvae when challenged with pathogenic V. campbellii, whereas it had no effect on larval growth. PMID:26344339

  10. Computational study of the acid dissociation of esters and lactones. A case study of diketene.

    PubMed

    Gómez-Bombarelli, Rafael; González-Pérez, Marina; Pérez-Prior, María Teresa; Calle, Emilio; Casado, Julio

    2009-07-17

    A computational study of the aqueous pK(a) of some saturated and unsaturated cyclic and linear esters and ketones was carried out at the DFT-B3LYP 6-31++G(2df,2pd), CBS-Q, and G2 levels, with the integral equation formalism polarizable continuum model for solvation, using a proton exchange mechanism. The influence of unsaturation, position of the double bond, and cyclization were studied. The computational results show that (a) in all cases studied except that of diketene (4-methylene-2-oxetanone), the alpha-beta unsaturated isomer is 20-30 kJ mol(-1) lower in energy that the beta-gamma unsaturated one; (b) alpha-beta unsaturation lowers the pK(a) of an ester approximately 6 units, whereas beta-gamma unsaturation lowers it by approximately 10 units, and cyclization lowers the pK(a) by approximately 3 units. In order to check the predictive power of the methodology, the acid dissociation constant of diketene in water was measured via kinetic study of its base-catalyzed hydrolysis. The pK(a) value obtained (15.2 +/- 0.3) is in keeping with the expected value for a beta-gamma unsaturated beta-lactone. This low value also suggests that deprotonated diketene does not interconvert to a more stable, less acidic alpha-beta unsaturated isomer, which is also consistent with computational results. PMID:19459649

  11. [Gamma-hydroxybutyrate (GHB) and its lactone (GBL) as psychoactive substances].

    PubMed

    Krajewska, Anna; Kwiecień-Obara, Ewelina; Szponar, Jarosław; Majewska, Magdalena; Kołodziej, Małgorzata

    2012-01-01

    Gammabutyrolactone is included in the solvent such as wheel cleaners, pesticides, cosmetics, drugs. After ingestion GBL is converted to gamma-hydroxybutyrate. Both substances are classified as so called "club drugs" and their action is characterized by euphoria, sedation, and induction of retrograde amnesia of events. These activities were basis for the use of GHB and its lactone as rape pill. Acute poisoning with these compounds causes confusion, agitation, ataxia, nausea, vomiting, nystagmus, dyskinesia, hallucinations, coma, irregular breathing, hypothermia, bradycardia, hypotension, convulsions, respiratory paralysis and thus respiratory arrest. These substances carry a risk of development of physical addiction of the hard proceeding of abstinence syndrome. In the USA there is a ban on the sale and promotion of these compounds. In Poland despite the fact that GHB is a controlled substance, there is no regulation of GBL trading. The aim of this paper is to summarize current knowledge regarding the pharmacology, impact on the human body, toxicity, and the effects of chronic abuse of these substances. PMID:23243924

  12. Functional characterization of a soybean growth stimulator Bradyrhizobium sp. strain SR-6 showing acylhomoserine lactone production.

    PubMed

    Ali, Amanat; Ayesha; Hameed, Sohail; Imran, Asma; Iqbal, Mazhar; Iqbal, Javed; Oresnik, Ivan J

    2016-09-01

    A soybean nodule endophytic bacterium Bradyrhizobium sp. strain SR-6 was characterized for production of acyl homoserine lactones (AHLs) as quorum sensing molecules. Mass spectrometry analysis of AHLs revealed the presence of C6-HSL, 3OH-C6-HSL, C8-HSL, C10-HSL, 3oxoC10-HSL, 3oxo-C12-HSL and 3OH-C12-HSL which are significantly different from those reported earlier in soybean symbionts. Purified AHL extracts significantly improved wheat and soybean seedling growth and root hair development along with increased soybean nodulation under axenic conditions. A positive correlation was observed among in vivo nitrogenase and catalase enzyme activities of the strain SR-6. Transmission electron microscopic analysis showed the cytochemical localization of catalase activity within the bacteroids, specifically attached to the peribacteroidal membrane. Root and nodule colonization proved rhizosphere competence of SR-6. The inoculation of SR-6 resulted in increased shoot length (13%), plant dry matter (50%), grain weight (16%), seed yield (20%) and N-uptake (14%) as compared to non-inoculated soybean plants. The symbiotic bacterium SR-6 has potential to improve soybean growth and yield in sub-humid climate of Azad Jammu and Kashmir region of Pakistan. The production and mass spectrometric profiling of AHLs as well as in vivo cytochemical localization of catalase enzyme activity in soybean Bradyrhizobium sp. have never been reported earlier elsewhere before our these investigations. PMID:27242370

  13. New ventures in the genotoxic and cytotoxic effects of macrocyclic lactones, abamectin and ivermectin.

    PubMed

    Molinari, G; Soloneski, S; Larramendy, M L

    2010-01-01

    Abamectin and Ivermectin are 2 closely related members of the Avermectin family of 16-membered macrocyclic lactones derived from the actinomycete Streptomyces avermectinius which exhibit extraordinary anthelmintic activity. They are used worldwide in veterinary and human medicine as well as in agriculture. In the present review we summarized the results published so far for estimating the genotoxicity and cytotoxicity exerted by both compounds in several cellular systems. Although both compounds do not induce in vitro and in vivo gene mutations in either bacterial or mammalian cells, there is no concrete evidence of a clear clastogenic effect exerted both in vitro and in vivo in mammalian cells. However, reports indicating that both anthelmintic agents are able to induce single DNA-strand breaks in vitro and inhibit cell growth either in vitro or in in vivo bioassays, are scarce. Taking into account the similarity of the genotoxicity and cytotoxicity exerted by both antibiotics, and that only Abamectin has been classified so far as a class II toxicity pesticide by the EPA, the necessity of reconsideration for a further hazard evaluation of Ivermectin by an international regulatory agency(ies) is strongly recommended. PMID:20389039

  14. Sensitive quantification of six steroidal lactones in Withania coagulans extract by UHPLC electrospray tandem mass spectrometry.

    PubMed

    Ali, Arslan; Maher, Saima; Khan, Shahid Ali; Chaudhary, M Iqbal; Musharraf, Syed Ghulam

    2015-12-01

    A method for the concurrent determination of six known steroidal lactones (syn. withanolides or withasteroids), namely withaferin A, withanolide H, withanolide K, withanolide A, withacoagulin H, and withanolide J in Withania coagulans extracts was developed. Extracts of Withania species and purified withanolides are considered among the most important natural products used for medicinal purposes. Methanolic extract of plant material was subjected to reverse phase ultra-high performance liquid chromatography (UHPLC) coupled with electrospray (JetStream ESI) triple quadrupole mass spectrometer operated in the Multiple Reaction Monitoring (MRM) mode. Satisfactory separation of withanolide component was achieved within 9 min on UHPLC runtime. The limits of detection (LOD) and the limits of quantitation (LOQs) for the six withanolides ranged between 0.040-4.80 ng/mL, and 0.13-16 ng/mL, respectively. Linear responses were attained for all six withanolides in two orders of magnitude with the linear regression coefficient values ⩾0.998. At the five QC levels inspected, the relative standard deviations (RSD) were found below 5% in most cases. The newly developed method is fast, precise, and sensitive, therefore, the method can be used for high-throughput quantification of various withanolides in W. coagulans extract, and other herbal formulations, derived from W. coagulans. PMID:26459135

  15. Sesquiterpene lactones: Mechanism of antineoplastic activity; relationship of cellular glutathione to cytotoxicity; and disposition

    SciTech Connect

    Grippo, A.A.

    1987-01-01

    Helenalin, a sesquiterpene lactone, inhibited the growth of P388 lymphocytic and L1210 lymphoid leukemia, and Ehrlich ascites and KB carcinoma cells. The L1210 leukemia cells were most sensitive to the cytotoxic effects of helenalin. Helenalin's antineoplastic effects were due to inhibition of DNA synthesis by suppressing the activities of enzymes involved in this biosynthetic pathway; i.e., IMP dehydrogenase, ribonucleoside diphosphate reductase, thioredoxin complex, GSH disulfide oxidoreductase and DNA polymerase {alpha} activities. The relationship of reduced glutathione (GSH) to the cytotoxic effects of helanalin was evaluated. L1210 cells, which were more sensitive to helenalin's toxicity, contained lower basal concentrations of GSH. Helenalin decreased the concentration of reduced glutathione in both L1210 and P388 leukemia cells. Concurrent administration of helanalin with agents reported to raise GSH concentrations did not substantially effect GSH levels, nor were survival times of tumor-bearing mice enhanced. Following intraperitoneal administration of {sup 3}H-plenolin, no radioactive drug and/or metabolite was sequestered in the organs of BDF{sub 1} mice. Approximately 50% of {sup 3}H-plenolin and/or its metabolites were eliminated via urine while lesser amounts of radioactive drug and/or metabolites were eliminated in the feces.

  16. Changes in the Salmonella enterica Enteritidis phenotypes in presence of acyl homoserine lactone quorum sensing signals.

    PubMed

    Campos-Galvão, Maria Emilene Martino; Ribon, Andrea Oliveira Barros; Araújo, Elza Fernandes; Vanetti, Maria Cristina Dantas

    2016-05-01

    Quorum sensing is used by bacteria to coordinate gene expression in response to population density and involves the production, detection and response to extracellular signaling molecules known as autoinducers (AIs). Salmonella does not synthesize the AI-1, acyl homoserine lactone (AHL) common to gram-negative bacteria; however, it has a receptor for AI-1, the SdiA protein. The effect of SdiA in modulating phenotypes of Salmonella has not been elucidated. In this report, we provide evidence that the AIs-1 affect Salmonella enterica serovar Enteritidis behavior by enhancing the biofilm formation and expression of virulence genes under anaerobic conditions. Biofilm formation by Salmonella was detected by the crystal violet method and by scanning electron microscopy. The presence of AHLs, particularly C12-HSL, increased biofilm formation and promoted expression of biofilm formation genes (lpfA, fimF, fliF, glgC) and virulence genes (hilA, invA, invF). Our results demonstrated that AHLs produced by other organisms played an important role in virulence phenotypes of Salmonella Enteritidis. PMID:26662614

  17. Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation.

    PubMed

    Rui, Tian-Qi; Zhang, Liang; Qiao, Hong-Zhi; Huang, Ping; Qian, Shuai; Li, Jun-Song; Chen, Zhi-Peng; Fu, Ting-Ming; Di, Liu-Qing; Cai, Baochang

    2016-01-01

    The aim of this study was to investigate the potential of nanosuspensions (NSs) in improving the dissolution and absorption of poorly water-soluble ginkgo lactones (GLs), including ginkgolide A, ginkgolide B, and ginkgolide C. Liquid GL-NSs were prepared by a combined bottom-up and top-down approach with response surface methodology design, followed by freeze-drying solidification. Physicochemical characterization of the prepared freeze-dried GL-NSs was performed by photon correlation spectroscopy, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. In vitro dissolution and in vivo bioavailability of ginkgolide A, ginkgolide B, and ginkgolide C in freeze-dried GL-NSs were evaluated with GLs coarse powder as control. Their inhibitory effects on platelet aggregation were also comparatively analyzed. GLs existed in an amorphous state in the prepared freeze-dried GL-NSs. The particle size, polydispersity index, zeta potential, and redispersibility index of freeze-dried GL-NSs were around 286 nm, 0.26, -25.19 mV, and 112%, respectively. The particle size reduction resulted in much more rapid and complete dissolution of ginkgolides from GL-NSs than coarse powder. Comparison with GLs coarse powder, freeze-dried GL-NSs showed a significant decreased Tmax, 2-fold higher peak concentration, and 2-fold higher area under plasma concentrations curve for 3 ginkgolides and exhibited significantly higher antiplatelet aggregation effect. PMID:26852855

  18. N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins

    PubMed Central

    Zhao, Guoping; Neely, Aaron M.; Schwarzer, Christian; Lu, Huayi; Whitt, Aaron G.; Stivers, Nicole S.; Burlison, Joseph A.; White, Carl; Machen, Terry E.; Li, Chi

    2016-01-01

    Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule for bacterial communication. C12 has also been reported to induce apoptosis in various types of tumor cells. However, the detailed molecular mechanism of C12-triggerred tumor cell apoptosis is still unclear. In addition, it is completely unknown whether C12 possesses any potential therapeutic effects in vivo. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in tumor cells through inducing mitochondrial membrane permeabilization independent of both pro- and anti-apoptotic Bcl-2 proteins. Importantly, C12 inhibits tumor growth in animals regardless of either pro- or anti-apoptotic Bcl-2 proteins. Furthermore, opposite to conventional chemotherapeutics, C12 requires paraoxonase 2 (PON2) to exert its cytotoxicity on tumor cells in vitro and its inhibitory effects on tumor growth in vivo. Overall, our results demonstrate that C12 inhibits tumor growth independent of both pro- and anti-apoptotic Bcl-2 proteins, and through inducing unique apoptotic signaling mediated by PON2 in tumor cells. PMID:26758417

  19. Localization of sesquiterpene lactone biosynthesis in cells of capitate glandular trichomes of Helianthus annuus (Asteraceae).

    PubMed

    Amrehn, Evelyn; Aschenbrenner, Anna-Katharina; Heller, Annerose; Spring, Otmar

    2016-03-01

    Capitate glandular trichomes (CGT) of sunflower, Helianthus annuus, synthesize bioactive sesquiterpene lactones (STLs) within a short period of only a few days during trichome development. In the current project, the subcellular localization of H. annuus germacrene A monooxygenase (HaGAO), a key enzyme of the STL biosynthesis in sunflower CGT, was investigated. A polyclonal antibody raised against this enzyme was used for immunolabelling. HaGAO was found in secretory and stalk cells of CGT. This correlated with the appearance of smooth endoplasmic reticulum in both cell types. Stalk cells and secretory cells differed in form, size and types of plastids, but both had structures necessary for secretion. No HaGAO-specific immunoreaction was found in sunflower leaf tissue outside of CGT or in developing CGT before the secretory phase had started. Our results indicated that not only secretory cells but also nearly all cells of the CGT were involved in the biosynthesis of STL and that this process was not linked to the presence or absence of a specific type of plastid. PMID:25956500

  20. N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins.

    PubMed

    Zhao, Guoping; Neely, Aaron M; Schwarzer, Christian; Lu, Huayi; Whitt, Aaron G; Stivers, Nicole S; Burlison, Joseph A; White, Carl; Machen, Terry E; Li, Chi

    2016-02-01

    Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule for bacterial communication. C12 has also been reported to induce apoptosis in various types of tumor cells. However, the detailed molecular mechanism of C12-triggerred tumor cell apoptosis is still unclear. In addition, it is completely unknown whether C12 possesses any potential therapeutic effects in vivo. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in tumor cells through inducing mitochondrial membrane permeabilization independent of both pro- and anti-apoptotic Bcl-2 proteins. Importantly, C12 inhibits tumor growth in animals regardless of either pro- or anti-apoptotic Bcl-2 proteins. Furthermore, opposite to conventional chemotherapeutics, C12 requires paraoxonase 2 (PON2) to exert its cytotoxicity on tumor cells in vitro and its inhibitory effects on tumor growth in vivo. Overall, our results demonstrate that C12 inhibits tumor growth independent of both pro- and anti-apoptotic Bcl-2 proteins, and through inducing unique apoptotic signaling mediated by PON2 in tumor cells. PMID:26758417

  1. Synthesis of novel beta-lactone inhibitors of fatty acid synthase.

    PubMed

    Richardson, Robyn D; Ma, Gil; Oyola, Yatsandra; Zancanella, Manuel; Knowles, Lynn M; Cieplak, Piotr; Romo, Daniel; Smith, Jeffrey W

    2008-09-11

    Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and amino ester substitutions were altered and the resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display an increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development. PMID:18710210

  2. Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

    PubMed Central

    Richardson, Robyn D.; Ma, Gil; Oyola, Yatsandra; Zancanella, Manuel; Knowles, Lynn M.; Cieplak, Piotr; Romo, Daniel; Smith, Jeffrey W.

    2011-01-01

    Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a β-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the α- and β-alkyl chains, their chemical composition, and amino ester substitutions were altered and the resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display an increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development. PMID:18710210

  3. Topical Administration of Acylated Homoserine Lactone Improves Epithelialization of Cutaneous Wounds in Hyperglycaemic Rats

    PubMed Central

    Kitamura, Aya; Quinetti, Paes C.; Nakagami, Gojiro; Mugita, Yuko; Oe, Makoto; Noguchi, Hiroshi; Mori, Taketoshi; Sanada, Hiromi

    2016-01-01

    Clinicians often experience delayed epithelialization in diabetic patients, for which a high glucose condition is one of the causes. However, the mechanisms underlying delayed wound closure have not been fully elucidated, and effective treatments to enhance epithelialization in patients with hyperglycaemia have not been established. Here we propose a new reagent, acylated homoserine lactone (AHL), to improve the delayed epithelialization due to the disordered formation of a basement membrane of epidermis in hyperglycaemic rats. Acute hyperglycaemia was induced by streptozotocin injection in this experiment. Full thickness wounds were created on the flanks of hyperglycaemic or control rats. Histochemical and immunohistochemical analyses were performed to identify hyperglycaemia-specific abnormalities in epidermal regeneration by comparison between groups. We then examined the effects of AHL on delayed epithelialization in hyperglycaemic rats. Histological analysis showed the significantly shorter epithelializing tissue (P < 0.05), abnormal structure of basement membrane (fragmentation and immaturity), and hypo- and hyperproliferation of basal keratinocytes in hyperglycaemic rats. Treating the wound with AHL resulted in the decreased abnormalities of basement membrane, normal distribution of proliferating epidermal keratinocytes, and significantly promoted epithelialization (P < 0.05) in hyperglycemic rats, suggesting the improving effects of AHL on abnormal epithelialization due to hyperglycemia. PMID:27404587

  4. Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases

    PubMed Central

    Xu, Yuquan; Zhou, Tong; Zhang, Shuwei; Espinosa-Artiles, Patricia; Wang, Luoyi; Zhang, Wei; Lin, Min; Gunatilaka, A. A. Leslie; Zhan, Jixun; Molnár, István

    2014-01-01

    Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into “build–couple–pair” combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery. PMID:25049383

  5. Topical Administration of Acylated Homoserine Lactone Improves Epithelialization of Cutaneous Wounds in Hyperglycaemic Rats.

    PubMed

    Huang, Lijuan; Minematsu, Takeo; Kitamura, Aya; Quinetti, Paes C; Nakagami, Gojiro; Mugita, Yuko; Oe, Makoto; Noguchi, Hiroshi; Mori, Taketoshi; Sanada, Hiromi

    2016-01-01

    Clinicians often experience delayed epithelialization in diabetic patients, for which a high glucose condition is one of the causes. However, the mechanisms underlying delayed wound closure have not been fully elucidated, and effective treatments to enhance epithelialization in patients with hyperglycaemia have not been established. Here we propose a new reagent, acylated homoserine lactone (AHL), to improve the delayed epithelialization due to the disordered formation of a basement membrane of epidermis in hyperglycaemic rats. Acute hyperglycaemia was induced by streptozotocin injection in this experiment. Full thickness wounds were created on the flanks of hyperglycaemic or control rats. Histochemical and immunohistochemical analyses were performed to identify hyperglycaemia-specific abnormalities in epidermal regeneration by comparison between groups. We then examined the effects of AHL on delayed epithelialization in hyperglycaemic rats. Histological analysis showed the significantly shorter epithelializing tissue (P < 0.05), abnormal structure of basement membrane (fragmentation and immaturity), and hypo- and hyperproliferation of basal keratinocytes in hyperglycaemic rats. Treating the wound with AHL resulted in the decreased abnormalities of basement membrane, normal distribution of proliferating epidermal keratinocytes, and significantly promoted epithelialization (P < 0.05) in hyperglycemic rats, suggesting the improving effects of AHL on abnormal epithelialization due to hyperglycemia. PMID:27404587

  6. Acyl Homoserine Lactones from Culture Supernatants of Pseudomonas aeruginosa Accelerate Host Immunomodulation

    PubMed Central

    Gupta, Ravi Kumar; Chhibber, Sanjay; Harjai, Kusum

    2011-01-01

    The virulence of Pseudomonas aeruginosa is multifactorial and under the control of quorum sensing signals, such as acyl homoserine lactones (AHLs). The importance of these molecules in the establishment of infection has been previously reported. These molecules either improve the virulence potential of P. aeruginosa or modulate the host immune response. To establish the immune modulating potential of quorum sensing signal molecules, previous studies have only used synthetic AHLs. However, there can be differences in the biological properties of synthetic and natural AHLs. The use of naturally extracted AHLs from the culture supernatant of P. aeruginosa is likely to simulate natural conditions more than the use of synthetic AHLs. Therefore, in the present study, the immune modulating potential of synthetic and naturally extracted AHLs was compared using a thymidine uptake assay, immunophenotyping and sandwich ELISA in order to assess mouse T-cell proliferation and production of Th1 and Th2 cytokines. Natural AHLs were able to suppress T-cell proliferation, even at low concentrations, compared to synthetic AHLs. The majority of cells undergoing proliferation were CD4+, as revealed by immunophenotyping. The inhibition of T-cells was stronger with natural AHLs compared to synthetic AHLs. Moreover, the natural AHLs were also able to shift immune responses away from host protective Th1 responses to pathogen protective Th2 responses. PMID:21698201

  7. Quantification of Sesquiterpene Lactones in Asteraceae Plant Extracts: Evaluation of their Allergenic Potential

    PubMed Central

    Salapovic, Helena; Geier, Johannes; Reznicek, Gottfried

    2013-01-01

    Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene group, are important allergens in Asteraceae (Compositae) plants. As a screening tool, the Compositae mix, consisting of five Asteraceae plant extracts with allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is part of several national patch test baseline series. However, the SL content of the Compositae mix may vary due to the source material. Therefore, a simple spectrophotometric method for the quantitative measurement of SLs with the α-methylene-γ-butyrolactone moiety was developed, giving the percentage of allergenic compounds in plant extracts. The method has been validated and five Asteraceae extracts, namely feverfew (Tanacetum parthenium L.), tansy (Tanacetum vulgare L.), arnica (Arnica montana L.), yarrow (Achillea millefolium L.), and German chamomile (Chamomilla recutita L. Rauschert) that have been used in routine patch test screening were evaluated. A good correlation could be found between the results obtained using the proposed spectrophotometric method and the corresponding clinical results. Thus, the introduced method is a valuable tool for evaluating the allergenic potential and for the simple and efficient quality control of plant extracts with allergenic potential. PMID:24106675

  8. N-ACYL HOMOSERINE LACTONe LACTONASE, AiiA, INACTIVATION OF QUORUM-SENSING AGONISTS PRODUCED BY CHLAMYDOMONAS REINHARDTII (CHLOROPHYTA) AND CHARACTERIZATION OF aiiA TRANSGENIC ALGAE(1).

    PubMed

    Rajamani, Sathish; Teplitski, Max; Kumar, Anil; Krediet, Cory J; Sayre, Richard T; Bauer, Wolfgang D

    2011-10-01

    Eukaryotes such as plants and the unicellular green alga Chlamydomonas reinhardtii P. A. Dang. produce and secrete compounds that mimic N-acyl homoserine lactone (AHL) bacterial quorum-sensing (QS) signals and alter QS-regulated gene expression in the associated bacteria. Here, we show that the set of C. reinhardtii signal-mimic compounds that activate the CepR AHL receptor of Burkholderia cepacia are susceptible to inactivation by AiiA, an AHL lactonase enzyme of Bacillus. Inactivation of these algal mimics by AiiA suggests that the CepR-stimulatory class of mimics produced by C. reinhardtii may have a conserved lactone ring structure in common with AHL QS signals. To examine the role of AHL mimic compounds in the interactions of C. reinhardtii with bacteria, the aiiA gene codon optimized for Chlamydomonas was generated for the expression of AiiA as a chimeric fusion with cyan fluorescent protein (AimC). Culture filtrates of transgenic strains expressing the fusion protein AimC had significantly reduced levels of CepR signal-mimic activities. When parental and transgenic algae were cultured with a natural pond water bacterial community, a morphologically distinct, AHL-producing isolate of Aeromonas veronii was observed to colonize the transgenic algal cultures and form biofilms more readily than the parental algal cultures, indicating that secretion of the CepR signal mimics by the alga can significantly affect its interactions with bacteria it encounters in natural environments. The parental alga was also able to sequester and/or destroy AHLs in its growth media to further disrupt or manipulate bacterial QS. PMID:27020200

  9. Quorum sensing activity of a Kluyvera sp. isolated from a Malaysian waterfall.

    PubMed

    Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    In many species of bacteria, the quorum sensing mechanism is used as a unique communication system which allows them to regulate gene expression and behavior in accordance with their population density. N-Acylhomoserine lactones (AHLs) are known as diffusible autoinducer molecules involved in this communication network. This finding aimed to characterize the production of AHL of a bacterial strain ND04 isolated from a Malaysian waterfall. Strain ND04 was identified as Kluyvera sp. as confirmed by molecular analysis of its 16S ribosomal RNA gene sequence. Kluyvera sp. is closely related to the Enterobacteriaceae family. Chromobacterium violaceum CV026 was used as a biosensor to detect the production of AHL by strain ND04. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of strain ND04 showed our isolate produced two AHLs which are N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6 HSL) and N-3-oxo-octanoyl-L-homoserine lactone (3-oxo-C8 HSL). PMID:24815680

  10. Lack of AHL-based quorum sensing in Pseudomonas fluorescens isolated from milk.

    PubMed

    Martins, Maurilio L; Pinto, Uelinton M; Riedel, Kathrin; Vanetti, Maria C D; Mantovani, Hilário C; de Araújo, Elza F

    2014-01-01

    Numerous bacteria coordinate gene expression in response to small signalling molecules in many cases known as acylhomoserine lactones (AHLs), which accumulate as a function of cell density in a process known as quorum sensing. This work aimed to determine if phenotypes that are important to define microbial activity in foods such as biofilm formation, swarming motility and proteolytic activity of two Pseudomonas fluorescens strains, isolated from refrigerated raw milk, are influenced by AHL molecules. The tested P. fluorescens strains did not produce AHL molecules in none of the evaluated media. We found that biofilm formation was dependent on the culture media, but it was not influenced by AHLs. Our results indicate that biofilm formation, swarming motility and proteolytic activity of the tested P. fluorescens strains are not regulated by acyl-homoserine lactones. It is likely that AHL-dependent quorum sensing system is absent from these strains. PMID:25477941

  11. Lack of AHL-based quorum sensing in Pseudomonas fluorescens isolated from milk

    PubMed Central

    Martins, Maurilio L.; Pinto, Uelinton M.; Riedel, Kathrin; Vanetti, Maria C.D.; Mantovani, Hilário C.; de Araújo, Elza F.

    2014-01-01

    Numerous bacteria coordinate gene expression in response to small signalling molecules in many cases known as acylhomoserine lactones (AHLs), which accumulate as a function of cell density in a process known as quorum sensing. This work aimed to determine if phenotypes that are important to define microbial activity in foods such as biofilm formation, swarming motility and proteolytic activity of two Pseudomonas fluorescens strains, isolated from refrigerated raw milk, are influenced by AHL molecules. The tested P. fluorescens strains did not produce AHL molecules in none of the evaluated media. We found that biofilm formation was dependent on the culture media, but it was not influenced by AHLs. Our results indicate that biofilm formation, swarming motility and proteolytic activity of the tested P. fluorescens strains are not regulated by acyl-homoserine lactones. It is likely that AHL-dependent quorum sensing system is absent from these strains. PMID:25477941

  12. 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

  13. In Planta Biocontrol of Pectobacterium atrosepticum by Rhodococcus erythropolis Involves Silencing of Pathogen Communication by the Rhodococcal Gamma-Lactone Catabolic Pathway

    PubMed Central

    Barbey, Corinne; Crépin, Alexandre; Bergeau, Dorian; Ouchiha, Asma; Mijouin, Lily; Taupin, Laure; Orange, Nicole; Feuilloley, Marc; Dufour, Alain; Burini, Jean-François; Latour, Xavier

    2013-01-01

    The virulence of numerous Gram-negative bacteria is under the control of a quorum sensing process based on synthesis and perception of N-acyl homoserine lactones. Rhodococcus erythropolis, a Gram-positive bacterium, has recently been proposed as a biocontrol agent for plant protection against soft-rot bacteria, including Pectobacterium. Here, we show that the γ-lactone catabolic pathway of R. erythropolis disrupts Pectobacterium communication and prevents plant soft-rot. We report the first characterization and demonstration of N-acyl homoserine lactone quenching in planta. In particular, we describe the transcription of the R. erythropolis lactonase gene, encoding the key enzyme of this pathway, and the subsequent lactone breakdown. The role of this catabolic pathway in biocontrol activity was confirmed by deletion of the lactonase gene from R. erythropolis and also its heterologous expression in Escherichia coli. The γ-lactone catabolic pathway is induced by pathogen communication rather than by pathogen invasion. This is thus a novel and unusual biocontrol pathway, differing from those previously described as protecting plants from phytopathogens. These findings also suggest the existence of an additional pathway contributing to plant protection. PMID:23805254

  14. In Planta Biocontrol of Pectobacterium atrosepticum by Rhodococcus erythropolis Involves Silencing of Pathogen Communication by the Rhodococcal Gamma-Lactone Catabolic Pathway.

    PubMed

    Barbey, Corinne; Crépin, Alexandre; Bergeau, Dorian; Ouchiha, Asma; Mijouin, Lily; Taupin, Laure; Orange, Nicole; Feuilloley, Marc; Dufour, Alain; Burini, Jean-François; Latour, Xavier

    2013-01-01

    The virulence of numerous Gram-negative bacteria is under the control of a quorum sensing process based on synthesis and perception of N-acyl homoserine lactones. Rhodococcus erythropolis, a Gram-positive bacterium, has recently been proposed as a biocontrol agent for plant protection against soft-rot bacteria, including Pectobacterium. Here, we show that the γ-lactone catabolic pathway of R. erythropolis disrupts Pectobacterium communication and prevents plant soft-rot. We report the first characterization and demonstration of N-acyl homoserine lactone quenching in planta. In particular, we describe the transcription of the R. erythropolis lactonase gene, encoding the key enzyme of this pathway, and the subsequent lactone breakdown. The role of this catabolic pathway in biocontrol activity was confirmed by deletion of the lactonase gene from R. erythropolis and also its heterologous expression in Escherichia coli. The γ-lactone catabolic pathway is induced by pathogen communication rather than by pathogen invasion. This is thus a novel and unusual biocontrol pathway, differing from those previously described as protecting plants from phytopathogens. These findings also suggest the existence of an additional pathway contributing to plant protection. PMID:23805254

  15. A Highly Productive, Whole-Cell DERA Chemoenzymatic Process for Production of Key Lactonized Side-Chain Intermediates in Statin Synthesis

    PubMed Central

    Ošlaj, Matej; Cluzeau, Jérôme; Orkić, Damir; Kopitar, Gregor; Mrak, Peter; Časar, Zdenko

    2013-01-01

    Employing DERA (2-deoxyribose-5-phosphate aldolase), we developed the first whole-cell biotransformation process for production of chiral lactol intermediates useful for synthesis of optically pure super-statins such as rosuvastatin and pitavastatin. Herein, we report the development of a fed-batch, high-density fermentation with Escherichia coli BL21 (DE3) overexpressing the native E. coli deoC gene. High activity of this biomass allows direct utilization of the fermentation broth as a whole-cell DERA biocatalyst. We further show a highly productive bioconversion processes with this biocatalyst for conversion of 2-substituted acetaldehydes to the corresponding lactols. The process is evaluated in detail for conversion of acetyloxy-acetaldehyde with the first insight into the dynamics of reaction intermediates, side products and enzyme activity, allowing optimization of the feeding strategy of the aldehyde substrates for improved productivities, yields and purities. The resulting process for production of ((2S,4R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl)methyl acetate (acetyloxymethylene-lactol) has a volumetric productivity exceeding 40 g L−1 h−1 (up to 50 g L−1 h−1) with >80% yield and >80% chromatographic purity with titers reaching 100 g L−1. Stereochemical selectivity of DERA allows excellent enantiomeric purities (ee >99.9%), which were demonstrated on downstream advanced intermediates. The presented process is highly cost effective and environmentally friendly. To our knowledge, this is the first asymmetric aldol condensation process achieved with whole-cell DERA catalysis and it simplifies and extends previously developed DERA-catalyzed approaches based on the isolated enzyme. Finally, applicability of the presented process is demonstrated by efficient preparation of a key lactol precursor, which fits directly into the lactone pathway to optically pure super-statins. PMID:23667462

  16. Genome sequencing-assisted identification and the first functional validation of N-acyl-homoserine-lactone synthases from the Sphingomonadaceae family

    PubMed Central

    Gan, Han Ming; Dailey, Lucas K.; Halliday, Nigel; Williams, Paul; Hudson, André O.

    2016-01-01

    Background Members of the genus Novosphingobium have been isolated from a variety of environmental niches. Although genomics analyses have suggested the presence of genes associated with quorum sensing signal production e.g., the N-acyl-homoserine lactone (AHL) synthase (luxI) homologs in various Novosphingobium species, to date, no luxI homologs have been experimentally validated. Methods In this study, we report the draft genome of the N-(AHL)-producing bacterium Novosphingobium subterraneum DSM 12447 and validate the functions of predicted luxI homologs from the bacterium through inducible heterologous expression in Agrobacterium tumefaciens strain NTL4. We developed a two-dimensional thin layer chromatography bioassay and used LC-ESI MS/MS analyses to separate, detect and identify the AHL signals produced by the N. subterraneum DSM 12447 strain. Results Three predicted luxI homologs were annotated to the locus tags NJ75_2841 (NovINsub1), NJ75_2498 (NovINsub2), and NJ75_4146 (NovINsub3). Inducible heterologous expression of each luxI homologs followed by LC-ESI MS/MS and two-dimensional reverse phase thin layer chromatography bioassays followed by bioluminescent ccd camera imaging indicate that the three LuxI homologs are able to produce a variety of medium-length AHL compounds. New insights into the LuxI phylogeny was also gleemed as inferred by Bayesian inference. Discussion This study significantly adds to our current understanding of quorum sensing in the genus Novosphingobium and provide the framework for future characterization of the phylogenetically interesting LuxI homologs from members of the genus Novosphingobium and more generally the family Sphingomonadaceae.

  17. A highly productive, whole-cell DERA chemoenzymatic process for production of key lactonized side-chain intermediates in statin synthesis.

    PubMed

    Ošlaj, Matej; Cluzeau, Jérôme; Orkić, Damir; Kopitar, Gregor; Mrak, Peter; Casar, Zdenko

    2013-01-01

    Employing DERA (2-deoxyribose-5-phosphate aldolase), we developed the first whole-cell biotransformation process for production of chiral lactol intermediates useful for synthesis of optically pure super-statins such as rosuvastatin and pitavastatin. Herein, we report the development of a fed-batch, high-density fermentation with Escherichia coli BL21 (DE3) overexpressing the native E. coli deoC gene. High activity of this biomass allows direct utilization of the fermentation broth as a whole-cell DERA biocatalyst. We further show a highly productive bioconversion processes with this biocatalyst for conversion of 2-substituted acetaldehydes to the corresponding lactols. The process is evaluated in detail for conversion of acetyloxy-acetaldehyde with the first insight into the dynamics of reaction intermediates, side products and enzyme activity, allowing optimization of the feeding strategy of the aldehyde substrates for improved productivities, yields and purities. The resulting process for production of ((2S,4R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl)methyl acetate (acetyloxymethylene-lactol) has a volumetric productivity exceeding 40 g L(-1) h(-1) (up to 50 g L(-1) h(-1)) with >80% yield and >80% chromatographic purity with titers reaching 100 g L(-1). Stereochemical selectivity of DERA allows excellent enantiomeric purities (ee >99.9%), which were demonstrated on downstream advanced intermediates. The presented process is highly cost effective and environmentally friendly. To our knowledge, this is the first asymmetric aldol condensation process achieved with whole-cell DERA catalysis and it simplifies and extends previously developed DERA-catalyzed approaches based on the isolated enzyme. Finally, applicability of the presented process is demonstrated by efficient preparation of a key lactol precursor, which fits directly into the lactone pathway to optically pure super-statins. PMID:23667462

  18. Thiol dependent NF-κB suppression and inhibition of T-cell mediated adaptive immune responses by a naturally occurring steroidal lactone Withaferin A.

    PubMed

    Gambhir, Lokesh; Checker, Rahul; Sharma, Deepak; Thoh, M; Patil, Anand; Degani, M; Gota, Vikram; Sandur, Santosh K

    2015-12-01

    Withaferin A (WA), a steroidal lactone isolated from ayurvedic medicinal plant Withania somnifera, was shown to inhibit tumor growth by inducing oxidative stress and suppressing NF-κB pathway. However, its effect on T-cell mediated adaptive immune responses and the underlying mechanism has not been investigated. Since both T-cell responses and NF-κB pathway are known to be redox sensitive, the present study was undertaken to elucidate the effect of WA on adaptive immune responses in vitro and in vivo. WA inhibited mitogen induced T-cell and B-cell proliferation in vitro without inducing any cell death. It inhibited upregulation of T-cell (CD25, CD69, CD71 and CD54) and B-cell (CD80, CD86 and MHC-II) activation markers and secretion of Th1 and Th2 cytokines. WA induced oxidative stress by increasing the basal ROS levels and the immunosuppressive effects of WA were abrogated only by thiol anti-oxidants. The redox modulatory effects of WA in T-cells were attributed to its ability to directly interact with free thiols. WA inhibited NF-κB nuclear translocation in lymphocytes and prevented the direct binding of nuclear NF-κB to its consensus sequence. MALDI-TOF analysis using a synthetic NF-κB-p50 peptide containing Cys-62 residue suggested that WA can modify the cysteine residue of NF-κB. The pharmacokinetic studies for WA were also carried out and in vivo efficacy of WA was studied using mouse model of Graft-versus-host disease. In conclusion, WA is a potent inhibitor of T-cell responses and acts via a novel thiol dependent mechanism and inhibition of NF-κB pathway. PMID:26408225

  19. EM23, A Natural Sesquiterpene Lactone from Elephantopus mollis, Induces Apoptosis in Human Myeloid Leukemia Cells through Thioredoxin- and Reactive Oxygen Species-Mediated Signaling Pathways

    PubMed Central

    Li, Hongyu; Li, Manmei; Wang, Guocai; Shao, Fangyuan; Chen, Wenbo; Xia, Chao; Wang, Sheng; Li, Yaolan; Zhou, Guangxiong; Liu, Zhong

    2016-01-01

    Elephantopus mollis (EM) is a traditional herbal medicine with multiple pharmacological activities. However, the efficacy of EM in treating human leukemia is currently unknown. In the current study, we report that EM23, a natural sesquiterpene lactone isolated from EM, inhibits the proliferation of human chronic myeloid leukemia (CML) K562 cells and acute myeloid leukemia (AML) HL-60 cells by inducing apoptosis. Translocation of membrane-associated phospholipid phosphatidylserines, changes in cell morphology, activation of caspases, and cleavage of PARP were concomitant with this inhibition. The involvement of the mitochondrial pathway in EM23-mediated apoptosis was suggested by observed disruptions in mitochondrial membrane potential. Mechanistic studies indicated that EM23 caused a marked increase in the level of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine, a ROS scavenger, almost fully reversed EM23-mediated apoptosis. In EM23-treated cells, the expression levels of thioredoxin (Trx) and thioredoxinreductase (TrxR), two components of the Trx system involved in maintaining cellular redox homeostasis, were significantly down-regulated. Concomitantly, Trx regulated the activation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream regulatory targets, the p38, JNK, and ERK MAPKs. EM23-mediated activation of ASK1/MAPKs was significantly inhibited in the presence of NAC. Furthermore, tumor necrosis factor alpha (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) was suppressed by EM23, as suggested by the observed blockage of p65 nuclear translocation, phosphorylation, and reversion of IκBα degradation following EM23 treatment. Taken together, these results provide important insights into the anticancer activities of the EM component EM23 against human CML K562 cells and AML HL-60 cells. PMID:27064563

  20. EM23, A Natural Sesquiterpene Lactone from Elephantopus mollis, Induces Apoptosis in Human Myeloid Leukemia Cells through Thioredoxin- and Reactive Oxygen Species-Mediated Signaling Pathways.

    PubMed

    Li, Hongyu; Li, Manmei; Wang, Guocai; Shao, Fangyuan; Chen, Wenbo; Xia, Chao; Wang, Sheng; Li, Yaolan; Zhou, Guangxiong; Liu, Zhong

    2016-01-01

    Elephantopus mollis (EM) is a traditional herbal medicine with multiple pharmacological activities. However, the efficacy of EM in treating human leukemia is currently unknown. In the current study, we report that EM23, a natural sesquiterpene lactone isolated from EM, inhibits the proliferation of human chronic myeloid leukemia (CML) K562 cells and acute myeloid leukemia (AML) HL-60 cells by inducing apoptosis. Translocation of membrane-associated phospholipid phosphatidylserines, changes in cell morphology, activation of caspases, and cleavage of PARP were concomitant with this inhibition. The involvement of the mitochondrial pathway in EM23-mediated apoptosis was suggested by observed disruptions in mitochondrial membrane potential. Mechanistic studies indicated that EM23 caused a marked increase in the level of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine, a ROS scavenger, almost fully reversed EM23-mediated apoptosis. In EM23-treated cells, the expression levels of thioredoxin (Trx) and thioredoxinreductase (TrxR), two components of the Trx system involved in maintaining cellular redox homeostasis, were significantly down-regulated. Concomitantly, Trx regulated the activation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream regulatory targets, the p38, JNK, and ERK MAPKs. EM23-mediated activation of ASK1/MAPKs was significantly inhibited in the presence of NAC. Furthermore, tumor necrosis factor alpha (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) was suppressed by EM23, as suggested by the observed blockage of p65 nuclear translocation, phosphorylation, and reversion of IκBα degradation following EM23 treatment. Taken together, these results provide important insights into the anticancer activities of the EM component EM23 against human CML K562 cells and AML HL-60 cells. PMID:27064563

  1. Inuloxins A-D, phytotoxic bi-and tri-cyclic sesquiterpene lactones produced by Inula viscosa: potential for broomrapes and field dodder management.

    PubMed

    Andolfi, Anna; Zermane, Nadjia; Cimmino, Alessio; Avolio, Fabiana; Boari, Angela; Vurro, Maurizio; Evidente, Antonio

    2013-02-01

    Four phytotoxic bi- and tri-cyclic sesquiterpene lactones, named inuloxins A-D, were isolated together with the known α-costic acid, from the aerial parts of Inula viscosa (family Asteraceae), a widespread Mediterranean plant well known for its content of pharmacologically active metabolites. The structures of inuloxins A-D were established by spectroscopic and chemical methods and determined to be: (4E,7R*,8R*,10S*)-3-oxo-germacra-4,11(13)-dien-8β-12-olide (A), its 11,13-dihydro analogue (B), (5R*,7R*,8R*,10R*)-1,15-methylene-5β-hydroxy-eudesm-1(15),11(13)-dien-8β-12-olide (C), and (7R*,8R*)-1,4-dimethyl-4-hydroxy-secoeudesm-5(10),11(13)-dien-8β-12-olide (D). The S absolute stereochemistry at C-5 of 5-hydroxyhexan-2-yl side chain of inuloxin D was assigned by applying an advanced Mosher's method. The phytotoxic activity of inuloxins A-D, that of the diazo and monoacetyl derivatives (of inuloxin A and C, resply), as well as that of α-costic acid was evaluated against two parasitic plant species, i.e. crenate broomrape (Orobanche crenata) and field dodder (Cuscuta campestris). Inuloxins A, C and D were the most active on both parasites and caused up to 100% inhibition of the seed germination. Inuloxin B was less active on Cuscuta and completely inactive against Orobanche. The main metabolite α-costic acid had a suppressive effect on the dodder seed germination but had a stimulating action on the broomrape seed germination. These preliminary results allowed to suppose some structure-activity relationships. PMID:23137725

  2. A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells.

    PubMed

    Yeh, Chi-Tai; Huang, Wen-Chien; Rao, Yerra Koteswara; Ye, Min; Lee, Wei-Hwa; Wang, Liang-Shun; Tzeng, David T W; Wu, Chih-Hsiung; Shieh, Yi-Shing; Huang, Chi-Ying F; Chen, Yu-Jen; Hsiao, Michael; Wu, Alexander T H; Yang, Zhen; Tzeng, Yew-Min

    2013-12-01

    Lung cancer is the leading cause of cancer deaths worldwide and current therapies fail to treat this disease in majority of cases. Antrodia camphorata is a medicinal mushroom being widely used as food dietary supplement for cancer prevention. The sesquiterpene lactone antrocin is the most potent among >100 secondary metabolites isolated from A. camphorata. However, the molecular mechanisms of antrocin-mediated anticancer effects remain unclear. In this study, we found that antrocin inhibited cell proliferation in two non-small-cell lung cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC50 = 0.75 μM) and H1975 (gefitnib-resistant mutant T790M, IC50 = 0.83 μM). Antrocin dose dependently suppressed colony formation and induced apoptosis as evidenced by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies indicated that antrocin downregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We further demonstrated that antrocin suppressed both constitutively activated and interleukin 6-induced STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition is found to be achieved through the suppression of JAK2 and interaction between STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased microRNA let-7c expression and suppressed STAT signaling. The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells. Such dual interruption of JAK2 and STAT3 pathways also induced downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression. In vivo intraperitoneal administration of antrocin significantly suppressed the growth of lung cancer tumor xenografts. Our results indicate that antrocin may be a potential therapeutic agent for human lung cancer cells through constitutive inhibition of JAK2/STAT3 pathway. PMID:23880305

  3. The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission.

    PubMed

    Balaich, Jared N; Mathias, Derrick K; Torto, Baldwyn; Jackson, Bryan T; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B; Cheseto, Xavier; Foster, Woodbridge A; Dinglasan, Rhoel R

    2016-04-01

    Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect onPlasmodiumblood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofPlasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin againstP. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. PMID:26787692

  4. Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia

    PubMed Central

    Schwarzer, Christian; Fu, Zhu; Patanwala, Maria; Hum, Lauren; Lopez-Guzman, Mirielle; Illek, Beate; Kong, Weidong; Lynch, Susan V.; Machen, Terry E.

    2014-01-01

    Pseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis CF) patients, a process regulated by quorum sensing molecules including N-(3-oxododecanoyl)-L-homoserine lactone, C12. C12 (10–100 μM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CFΔF508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (Δψmito) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca2+ and ER-targeted GFP and oxidized contents into the cytosol). Effects began within 5 minutes and were complete in 1–2 hrs. C12 caused similar activation of caspases and release of cytoC from mitos in Calu-3 (wtCFTR, bronchial gland) cells, showing that C12-triggered responses occurred similarly in different airway epithelial types. C12 had nearly identical effects on three key aspects of the apoptosis response (caspase 3/7, depolarization of Δψmito and reduction of redox potential in the ER) in JME and CFTR-corrected JME cells (adenoviral expression), showing that CFTR was likely not an important regulator of C12-triggered apoptosis in airway epithelia. Exposure of airway cultures to biofilms from PAO1wt caused depolarization of Δψmito and increases in Cacyto like 10–50 μM C12. In contrast, biofilms from PAO1ΔlasI (C12 deficient) had no effect, suggesting that C12 from P. aeruginosa biofilms may contribute to accumulation of apoptotic cells that cannot be cleared from CF lungs. A model to explain the effects of C12 is proposed. PMID:22233488

  5. Influence of food system conditions on N-acyl-L-homoserine lactones production by Aeromonas spp.

    PubMed

    Medina-Martínez, M S; Uyttendaele, M; Demolder, V; Debevere, J

    2006-12-01

    Eleven of 13 Aeromonas strains were shown to produce AHLs. Results of TLC showed that N-butanoyl-L-homoserine lactone (C4-HSL) was the main AHL produced in LB medium at 30 degrees C. The influence of different carbon sources, temperature, pH values and salt concentrations on AHL production was determined in eight A. hydrophila and one A. caviae strain. Additionally a quantitative study of C4-HSL production by A. hydrophila strain 519 under different conditions was performed. Positive results were found in the AHL induction assay for some Aeromonas strains in cultures in LB agar incubated at 12 degrees C after 72-96 h. The induction of the sensor strains by Aeromonas spp. occurred in LB medium supplemented with all carbon sources in a concentration of 0.5%. The production of C4-HSL by A. hydrophila 519 was found until 3.5% (w/v) of NaCl. For pHs close to the neutrality the C4-HSL production by A. hydrophila was evident after 24-48 h of incubation. A. hydrophila 519 produced C4-HSL under anaerobic conditions. Also, the AHL production by Aeromonas strains was studied in simulate agar of shrimp, fish and some vegetables. The production of AHLs was evident by almost all the test strains in shrimp simulated agar. In fish agar only for one of three fish species tested, positive results were found. Induction assay in vegetables simulated agar showed principally negative results, probably because of the presence of inhibitory compounds in these vegetables. PMID:16797762

  6. Characterization of Haemonchus contortus P-glycoprotein-16 and its interaction with the macrocyclic lactone anthelmintics.

    PubMed

    Godoy, P; Che, H; Beech, R N; Prichard, R K

    2015-11-01

    Anthelmintic resistance in veterinary nematodes, including Haemonchus contortus, has become a limitation to maintaining high standards of animal health. Resistance in this parasite, to all drug families including the macrocyclic lactones (MLs) is a serious issue worldwide. Mechanisms of resistance to the MLs appear to be complex and to include the elimination of these compounds by ABC transporter-like proteins present in nematodes. In order to investigate the potential involvement of ABC transporters in ML resistance in H. contortus, we have characterized the functionality of the ABC transporter H. contortus P-glycoprotein-16 (Hco-PGP-16) expressed in mammalian cells. This has included a study of its interaction with different MLs, including the avermectins, abamectin (ABA) and ivermectin (IVM), and the milbemycin, moxidectin (MOX). Hco-PGP-16 transport activity was studied using the fluorophore Rhodamine 123 (Rho 123). Transfected cells expressing Hco-PGP-16 accumulated less than 50% of Rho 123 than control cells, suggesting an active transport of this tracer dye by Hco-PGP-16. The influence of the MLs on the Rho123 transport by Hco-PGP-16 was then investigated. A marked inhibition of Rho123 transport by ABA and IVM was observed. In contrast, MOX showed less effect on inhibition of Rho123 transport by Hco-PGP-16, and the inhibition was not saturable. The difference in the interaction of the avermectins and MOX with Hco-PGP-16 may help explain the slower rate of development of resistance to MOX compared with the avermectins in H. contortus. PMID:26657092

  7. Rapid acyl-homoserine lactone quorum signal biodegradation in diverse soils.

    PubMed

    Wang, Ya-Juan; Leadbetter, Jared Renton

    2005-03-01

    Signal degradation impacts all communications. Although acyl-homoserine lactone (acyl-HSL) quorum-sensing signals are known to be degraded by defined laboratory cultures, little is known about their stability in nature. Here, we show that acyl-HSLs are biodegraded in soils sampled from diverse U.S. sites and by termite hindgut contents. When amended to samples at physiologically relevant concentrations, 14C-labeled acyl-HSLs were mineralized to 14CO2 rapidly and, at most sites examined, without lag. A lag-free turf soil activity was characterized in further detail. Heating or irradiation of the soil prior to the addition of radiolabel abolished mineralization, whereas protein synthesis inhibitors did not. Mineralization exhibited an apparent Km of 1.5 microM acyl-HSL, ca. 1,000-fold lower than that reported for a purified acyl-HSL lactonase. Under optimal conditions, acyl-HSL degradation proceeded at a rate of 13.4 nmol x h(-1) x g of fresh weight soil(-1). Bioassays established that the final extent of signal inactivation was greater than for its full conversion to CO2 but that the two processes were well coupled kinetically. A most probable number of 4.6 x 10(5) cells . g of turf soil(-1) degraded physiologically relevant amounts of hexanoyl-[1-14C]HSL to 14CO2. It would take chemical lactonolysis months to match the level of signal decay achieved in days by the observed biological activity. Rapid decay might serve either to quiet signal cross talk that might otherwise occur between spatially separated microbial aggregates or as a full system reset. Depending on the context, biological signal decay might either promote or complicate cellular communications and the accuracy of population density-based controls on gene expression in species-rich ecosystems. PMID:15746331

  8. Fenugreek lactone attenuates palmitate-induced apoptosis and dysfunction in pancreatic β-cells

    PubMed Central

    Gong, Jing; Dong, Hui; Jiang, Shu-Jun; Wang, Ding-Kun; Fang, Ke; Yang, De-Sen; Zou, Xin; Xu, Li-Jun; Wang, Kai-Fu; Lu, Fu-Er

    2015-01-01

    AIM: To investigate the effect of fenugreek lactone (FL) on palmitate (PA)-induced apoptosis and dysfunction in insulin secretion in pancreatic NIT-1 β-cells. METHODS: Cells were cultured in the presence or absence of FL and PA (0.25 mmol/L) for 48 h. Then, lipid droplets in NIT-1 cells were observed by oil red O staining, and the intracellular triglyceride content was measured by colorimetric assay. The insulin content in the supernatant was determined using an insulin radio-immunoassay. Oxidative stress-associated parameters, including total superoxide dismutase, glutathione peroxidase and catalase activity and malondialdehyde levels in the suspensions were also examined. The expression of upstream regulators of oxidative stress, such as protein kinase C-α (PKC-α), phospho-PKC-α and P47phox, were determined by Western blot analysis and real-time PCR. In addition, apoptosis was evaluated in NIT-1 cells by flow cytometry assays and caspase-3 viability assays. RESULTS: Our results indicated that compared to the control group, PA induced an increase in lipid accumulation and apoptosis and a decrease in insulin secretion in NIT-1 cells. Oxidative stress in NIT-1 cells was activated after 48 h of exposure to PA. However, FL reversed the above changes. These effects were accompanied by the inhibition of PKC-α, phospho-PKC-α and P47phox expression and the activation of caspase-3. CONCLUSION: FL attenuates PA-induced apoptosis and insulin secretion dysfunction in NIT-1 pancreatic β-cells. The mechanism for this action may be associated with improvements in levels of oxidative stress. PMID:26730156

  9. LuxR homolog-independent gene regulation by acyl-homoserine lactones in Pseudomonas aeruginosa.

    PubMed

    Chugani, Sudha; Greenberg, Everett Peter

    2010-06-01

    Pseudomonas aeruginosa quorum control of gene expression involves three LuxR-type signal receptors LasR, RhlR, and QscR that respond to the LasI- and RhlI-generated acyl-homoserine lactone (acyl-HSL) signals 3OC12-HSL and C4-HSL. We found that a LasR-RhlR-QscR triple mutant responds to acyl-HSLs by regulating at least 37 genes. LuxR homolog-independent activation of the representative genes antA and catB also occurs in the wild type. Expression of antA was influenced the most by C10-HSL and to a lesser extent by other acyl-HSLs, including the P. aeruginosa 3OC12-HSL and C4-HSL signals. The ant and cat operons encode enzymes for the degradation of anthranilate to tricarboxylic acid cycle intermediates. Our results indicate that LuxR homolog-independent acyl-HSL control of the ant and cat operons occurs via regulation of antR, which codes for the transcriptional activator of the ant operon. Although P. aeruginosa has multiple pathways for anthranilate synthesis, one pathway-the kynurenine pathway for tryptophan degradation-is required for acyl-HSL activation of the ant operon. The kynurenine pathway is also the critical source of anthranilate for energy metabolism via the antABC gene products, as well as the source of anthranilate for synthesis of the P. aeruginosa quinolone signal. Our discovery of LuxR homolog-independent responses to acyl-HSLs provides insight into acyl-HSL signaling. PMID:20498077

  10. Bromoenol Lactone Attenuates Nicotine-Induced Breast Cancer Cell Proliferation and Migration

    PubMed Central

    Calderon, Lindsay E.; Liu, Shu; Arnold, Nova; Breakall, Bethany; Rollins, Joseph; Ndinguri, Margaret

    2015-01-01

    Objectives Calcium independent group VIA phospholipase A2 (iPLA2β) and Matrix Metalloproteinase-9 (MMP-9) are upregulated in many disease states; their involvement with cancer cell migration has been a recent subject for study. Further, the molecular mechanisms mediating nicotine-induced breast cancer cell progression have not been fully investigated. This study aims to investigate whether iPLA2β mediates nicotine-induced breast cancer cell proliferation and migration through both in-vitro and in-vivo techniques. Subsequently, the ability of Bromoenol Lactone (BEL) to attenuate the severity of nicotine-induced breast cancer was examined. Method and Results We found that BEL significantly attenuated both basal and nicotine-induced 4T1 breast cancer cell proliferation, via an MTT proliferation assay. Breast cancer cell migration was examined by both a scratch and transwell assay, in which, BEL was found to significantly decrease both basal and nicotine-induced migration. Additionally, nicotine-induced MMP-9 expression was found to be mediated in an iPLA2β dependent manner. These results suggest that iPLA2β plays a critical role in mediating both basal and nicotine-induced breast cancer cell proliferation and migration in-vitro. In an in-vivo mouse breast cancer model, BEL treatment was found to significantly reduce both basal (p<0.05) and nicotine-induced tumor growth (p<0.01). Immunohistochemical analysis showed BEL decreased nicotine-induced MMP-9, HIF-1alpha, and CD31 tumor tissue expression. Subsequently, BEL was observed to reduce nicotine-induced lung metastasis. Conclusion The present study indicates that nicotine-induced migration is mediated by MMP-9 production in an iPLA2β dependent manner. Our data suggests that BEL is a possible chemotherapeutic agent as it was found to reduce both nicotine-induced breast cancer tumor growth and lung metastasis. PMID:26588686

  11. Determination of macrocyclic lactone drug residues in animal muscle by liquid chromatography/tandem mass spectrometry.

    PubMed

    He, Limin; Zhao, Donghao; Su, Yijuan; Liu, Yahong; Nie, Jianrong; Lian, Jin

    2009-01-01

    A robust, credible, and practical multiresidue method based on liquid chromatography/tandem/mass spectrometry (LC/MS/MS) was developed for the simultaneous determination of 9 macrocyclic lactone drugs (abamectin B1a, doramectin, erythromycin, ivermectin B1a, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin A) in bovine, porcine, chicken, and sheep muscles. The drugs were extracted with acetonitrile, and the extracts were defatted with n-hexane and further cleaned up on a C18 solid-phase extraction cartridge. LC/MS/MS data acquisition was achieved by using the multiple-reaction monitoring (MRM) mode, i.e., 2 transitions, to provide a high degree of sensitivity and repeatability. Matrix-matched standard calibration curves were used to achieve the best accuracy of the method by compensating for the matrix effect. The calibration graphs were linear (r > 0.998) from 10 to 1000 ng/mL for erythromycin, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin, and from 5 to 250 ng/mL for abamectin, doramectin, and ivermectin. The average recoveries of the 9 drugs were between 64.5 and 105%, calculated by using matrix-matched calibration, with relative standard deviation values ranging from 1.6 to 14%. The limits of detection were 0.1 microg/kg for erythromycin, josamycin, roxithromycin, and tylosin; 0.2 microg/kg for tilmicosin and kitasamycin; and 0.5 microg/kg for abamectin, doramectin, and ivermectin. For confirmation, the MRM ratios for the 9 drug residues in the samples and the solvent were evaluated and found to be within the ratio criteria set by the guidelines of the European Union. PMID:19382593

  12. Concurrent supercritical fluid chromatographic analysis of terpene lactones and ginkgolic acids in Ginkgo biloba extracts and dietary supplements.

    PubMed

    Wang, Mei; Carrell, Emily J; Chittiboyina, Amar G; Avula, Bharathi; Wang, Yan-Hong; Zhao, Jianping; Parcher, Jon F; Khan, Ikhlas A

    2016-07-01

    Supercritical fluid chromatography was used to resolve and determine ginkgolic acids (GAs) and terpene lactones concurrently in ginkgo plant materials and commercial dietary supplements. Analysis of GAs (C13:0, C15:0, C15:1, and C17:1) was carried out by ESI (-) mass detection. The ESI (-) spectra of GAs simply displayed only the [M-H](-) pseudo-molecular ions, and selected ion monitoring (SIM) for those ions was used for the quantification. Analysis of terpene lactones (ginkgolides A, B, C, J and bilobalide) was complicated by in-source collision-induced dissociation (IS-CID) in the ESI source. Thus, MS analysis could be influenced by the fragmentation pattern produced by the IS-CID. However, it was established that the fragmentation pattern, measured by ion survival yield (ISY), was independent of analyte concentration or matrix at a fixed cone voltage in the ESI source. Therefore, MS with SIM mode was applicable for the analysis of these analytes. The reported method provided consistent and sensitive analysis for the analytes of interest. The LOQs and LODs were determined to be below 100 and 40 ng/mL for GAs and 1 μg/mL and 400 ng/mL for terpene lactones, respectively. Intra- and inter-day precisions were found to be satisfactory with RSDs being below 5.2 %. Analyte recoveries ranged from 87 to 109 %. The developed method was successfully applied to the analysis of 11 ginkgo plant samples and 8 dietary supplements with an analysis time of less than 12 min. PMID:27129974

  13. Salmonella Typhimurium invasion of HEp-2 epithelial cells in vitro is increased by N-acylhomoserine lactone quorum sensing signals

    PubMed Central

    2011-01-01

    Background In Gram-negative bacteria, the most commonly studied quorum sensing signals are the N-acylhomoserine lactones (AHLs). In Salmonella, AHLs are recognized by SdiA, which is believed to be a sensor of AHLs produced by other bacteria, since Salmonella does not produce AHLs itself. It has been speculated that AHLs produced by the gastrointestinal flora may influence the regulation of virulence traits in Salmonella. The aim of the present work was to study the effect of AHLs on epithelial cell invasion by Salmonella in vitro. Methods Invasion by Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) strain and its isogenc sdiA mutant was studied using a conventional gentamycin invasion assay with HEp-2 cells at 37°C. Gene expression was studied using a semi-quantitative PCR. Results The S. Typhimurium strain, but not its isogenic sdiA mutant, displayed increased in vitro invasion after addition of both N-hexanoyl-DL-homoserine lactone (C6-AHL) and N-octanoyl-DL-homoserine lactone (C8-AHL). Increased expression of two of the genes in the SdiA regulon (rck and srgE) was observed in the wild type strain, but not in the sdiA mutant. Conclusions The results from the present study show that S. Typhimurium can respond to two different AHL quorum sensing signals (C6-AHL and C8-AHL) with increased cell invasion at 37°C in vitro, and that this response most likely is sdiA mediated. These results indicate that if AHLs are present in the intestinal environment, they may increase the invasiveness of Salmonella. PMID:21711544

  14. Crystal Violet Lactone Salicylaldehyde Hydrazone Zn(II) Complex: a Reversible Photochromic Material both in Solution and in Solid Matrix

    PubMed Central

    Li, Kai; Li, Yuanyuan; Tao, Jing; Liu, Lu; Wang, Lili; Hou, Hongwei; Tong, Aijun

    2015-01-01

    Crystal violet lactone (CVL) is a classic halochromic dye which has been widely used as chromogenic reagent in thermochromic and piezochromic systems. In this work, a very first example of CVL-based reversible photochromic compound was developed, which showed distinct color change upon UV-visible light irradiation both in solution and in solid matrix. Moreover, metal complex of CVL salicylaldehyde hydrozone was facilely synthesized, exhibiting reversible photochromic properties with good fatigue resistance. It was served as promising solid material for photo-patterning. PMID:26412101

  15. Crystal Violet Lactone Salicylaldehyde Hydrazone Zn(II) Complex: a Reversible Photochromic Material both in Solution and in Solid Matrix.

    PubMed

    Li, Kai; Li, Yuanyuan; Tao, Jing; Liu, Lu; Wang, Lili; Hou, Hongwei; Tong, Aijun

    2015-01-01

    Crystal violet lactone (CVL) is a classic halochromic dye which has been widely used as chromogenic reagent in thermochromic and piezochromic systems. In this work, a very first example of CVL-based reversible photochromic compound was developed, which showed distinct color change upon UV-visible light irradiation both in solution and in solid matrix. Moreover, metal complex of CVL salicylaldehyde hydrozone was facilely synthesized, exhibiting reversible photochromic properties with good fatigue resistance. It was served as promising solid material for photo-patterning. PMID:26412101

  16. Crystal Violet Lactone Salicylaldehyde Hydrazone Zn(II) Complex: a Reversible Photochromic Material both in Solution and in Solid Matrix

    NASA Astrophysics Data System (ADS)

    Li, Kai; Li, Yuanyuan; Tao, Jing; Liu, Lu; Wang, Lili; Hou, Hongwei; Tong, Aijun

    2015-09-01

    Crystal violet lactone (CVL) is a classic halochromic dye which has been widely used as chromogenic reagent in thermochromic and piezochromic systems. In this work, a very first example of CVL-based reversible photochromic compound was developed, which showed distinct color change upon UV-visible light irradiation both in solution and in solid matrix. Moreover, metal complex of CVL salicylaldehyde hydrozone was facilely synthesized, exhibiting reversible photochromic properties with good fatigue resistance. It was served as promising solid material for photo-patterning.

  17. Polycyclic musks in the Ruhr catchment area--transport, discharges of waste water, and transformations of HHCB, AHTN and HHCB-lactone.

    PubMed

    Bester, Kai

    2005-01-01

    The polycyclic musk fragrance compounds HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran; trade name, e.g. galaxolide) and AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene, trade name, e.g. tonalide) and the transformation product of HHCB (HHCB-lactone) were analysed in surface water samples and sewage treatment plants (STP) effluents in the Ruhr megalopolis. The STPs were the dominant source for these pollutants. In the part of the river where the drinking water is extracted from the river, about 60 ng L(-1) HHCB, 10 ng L(-1) AHTN and 20-30 ng L(-1) HHCB-lactone were found as typical riverine concentrations, while none of the compounds were detected near the spring of the river. On the other hand sewage treatment plant effluents exhibited concentrations up to 600 ng L(-1). The STP's effluent resulted in elevated concentrations in some parts of the river and in the lakes into which they discharge. As some of the plants emit HHCB-lactone with a significantly changed enantiomeric pattern, biotransformation of HHCB to HHCB-lactone occurs in some waste water treatment plants operating with activated sludge. In those parts of the river where no relevant discharges of waste water or fresh water takes place neither the concentration nor the pattern changes significantly. This holds true especially for the HHCB versus HHCB-lactone ratios which indicates degradation less than 15% of the HHCB inventory in the river Ruhr itself. In other rivers, such as the Rhine, higher levels of HHCB-lactone in comparison to HHCB were detected (ratio 1 : 1). PMID:15614401

  18. Functional Annotation and Structural Characterization of a Novel Lactonase Hydrolyzing d-Xylono-1,4-lactone-5-phosphate and l-Arabino-1,4-lactone-5-phosphate

    PubMed Central

    2015-01-01

    A novel lactonase from Mycoplasma synoviae 53 (MS53_0025) and Mycoplasma agalactiae PG2 (MAG_6390) was characterized by protein structure determination, molecular docking, gene context analysis, and library screening. The crystal structure of MS53_0025 was determined to a resolution of 2.06 Å. This protein adopts a typical amidohydrolase (β/α)8-fold and contains a binuclear zinc center located at the C-terminal end of the β-barrel. A phosphate molecule was bound in the active site and hydrogen bonds to Lys217, Lys244, Tyr245, Arg275, and Tyr278. Both docking and gene context analysis were used to narrow the theoretical substrate profile of the enzyme, thus directing empirical screening to identify that MS53_0025 and MAG_6390 catalyze the hydrolysis of d-xylono-1,4-lactone-5-phosphate (2) with kcat/Km values of 4.7 × 104 and 5.7 × 104 M–1 s–1 and l-arabino-1,4-lactone-5-phosphate (7) with kcat/Km values of 1.3 × 104 and 2.2 × 104 M–1 s–1, respectively. The identification of the substrate profile of these two phospho-furanose lactonases emerged only when all methods were integrated and therefore provides a blueprint for future substrate identification of highly related amidohydrolase superfamily members. PMID:24955762

  19. Synthesis of functionalized γ-lactone via Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol ester with a tethered acetal.

    PubMed

    Yin, Zhiping; Liu, Zengjin; Huang, Zhenggang; Chu, Yang; Chu, Zhiwen; Hu, Jia; Gao, Lu; Song, Zhenlei

    2015-03-20

    An efficient synthesis of functionalized γ-lactones has been developed involving Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol esters with a tethered acetal. While the steric and electronic effects of geminal bis(silane) favor the desired Sakurai pathway, the methoxy species formed in the deprotection step also facilitates both cyclization and rearrangement. The synthetic value of this approach has been demonstrated by efficiently transforming the E-vinylsilane into enyne and the γ-lactone moiety into multisubstituted THF. PMID:25730288

  20. Interference of Quorum Sensing by Delftia sp. VM4 Depends on the Activity of a Novel N-Acylhomoserine Lactone-Acylase

    PubMed Central

    Maisuria, Vimal B.; Nerurkar, Anuradha S.

    2015-01-01

    Background Turf soil bacterial isolate Delftia sp. VM4 can degrade exogenous N-acyl homoserine lactone (AHL), hence it effectively attenuates the virulence of bacterial soft rot pathogen Pectobacterium carotovorum subsp. carotovorum strain BR1 (Pcc BR1) as a consequence of quorum sensing inhibition. Methodology/Principal Findings Isolated Delftia sp. VM4 can grow in minimal medium supplemented with AHL as a sole source of carbon and energy. It also possesses the ability to degrade various AHL molecules in a short time interval. Delftia sp. VM4 suppresses AHL accumulation and the production of virulence determinant enzymes by Pcc BR1 without interference of the growth during co-culture cultivation. The quorum quenching activity was lost after the treatment with trypsin and proteinase K. The protein with quorum quenching activity was purified by three step process. Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) and Mass spectrometry (MS/MS) analysis revealed that the AHL degrading enzyme (82 kDa) demonstrates homology with the NCBI database hypothetical protein (Daci_4366) of D. acidovorans SPH-1. The purified AHL acylase of Delftia sp. VM4 demonstrated optimum activity at 20–40°C and pH 6.2 as well as AHL acylase type mode of action. It possesses similarity with an α/β-hydrolase fold protein, which makes it unique among the known AHL acylases with domains of the N-terminal nucleophile (Ntn)-hydrolase superfamily. In addition, the kinetic and thermodynamic parameters for hydrolysis of the different AHL substrates by purified AHL-acylase were estimated. Here we present the studies that investigate the mode of action and kinetics of AHL-degradation by purified AHL acylase from Delftia sp. VM4. Significance We characterized an AHL-inactivating enzyme from Delftia sp. VM4, identified as AHL acylase showing distinctive similarity with α/β-hydrolase fold protein, described its biochemical and thermodynamic properties for the first time and

  1. Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator.

    PubMed

    Corral-Lugo, Andrés; Daddaoua, Abdelali; Ortega, Alvaro; Espinosa-Urgel, Manuel; Krell, Tino

    2016-01-01

    Quorum sensing is a bacterial communication mechanism that controls genes, enabling bacteria to live as communities, such as biofilms. Homoserine lactone (HSL) molecules function as quorum-sensing signals for Gram-negative bacteria. Plants also produce previously unidentified compounds that affect quorum sensing. We identified rosmarinic acid as a plant-derived compound that functioned as an HSL mimic. In vitro assays showed that rosmarinic acid bound to the quorum-sensing regulator RhlR of Pseudomonas aeruginosa PAO1 and competed with the bacterial ligand N-butanoyl-homoserine lactone (C4-HSL). Furthermore, rosmarinic acid stimulated a greater increase in RhlR-mediated transcription in vitro than that of C4-HSL. In P. aeruginosa, rosmarinic acid induced quorum sensing-dependent gene expression and increased biofilm formation and the production of the virulence factors pyocyanin and elastase. Because P. aeruginosa PAO1 infection induces rosmarinic acid secretion from plant roots, our results indicate that rosmarinic acid secretion is a plant defense mechanism to stimulate a premature quorum-sensing response. P. aeruginosa is a ubiquitous pathogen that infects plants and animals; therefore, identification of rosmarinic acid as an inducer of premature quorum-sensing responses may be useful in agriculture and inform human therapeutic strategies. PMID:26732761

  2. [LC/ESI-MS/MS method for the simultaneous determination of macrocyclic lactone parasiticides in livestock products and fish].

    PubMed

    Inoue, Koichi; Yoshimi, Yukiko; Hino, Tomoaki; Oka, Hisao

    2010-01-01

    An LC/ESI (positive-mode)-MS/MS method was developed for simultaneous quantification of 8 macrocyclic lactones (abamectin B1a, abamectin 8,9-Z isomer B1a, emamectin benzoate B1a, emamectin benzoate 8,9-Z isomer B1a, ivermectin, eprinomectin B1a, doramectin and moxidectin) in animal tissues, egg, milk and honey. The separation was achieved on a TSK-GEL ODS 100 V column (2.0 x 50 mm, 3 microm) with a mobile phase consisting of 0.1% formic acid in acetonitrile, and 0.1 mM ammonium formate-0.1% formic acid in water, at a flow rate of 0.2 mL/min with gradient elution. Linear calibration plots were obtained with high correlation coefficients (r=0.998-0.999). The LOQ and LOD ranged from 0.02-1.5 ng/mL and 0.1-5 ng/mL, respectively. Average recoveries were in the range of 70.8-117.1% with associated RSD values<15% (n=10) for repeatability and reproducibility. The spiking levels for recoveries and RSDs met the validation criteria for Japanese maximum residue limits (MRLs). Based on these results, the proposed analytical method has been proven to be highly efficient and suitable for routine determinations of macrocyclic lactones in animal food matrices. PMID:20208403

  3. Isothiourea-Mediated Organocatalytic Michael Addition-Lactonization on a Surface: Modification of SAMs on Silicon Oxide Substrates.

    PubMed

    Chisholm, Ross; Parkin, John D; Smith, Andrew D; Hähner, Georg

    2016-04-01

    Tailoring the functionality of self-assembled monolayers (SAMs) can be achieved either by depositing prefunctionalized molecules with the appropriate terminal groups or by chemical modification of an existing SAM in situ. The latter approach is particularly advantageous to allow for diversity of surface functionalization from a single SAM and if the incorporation of bulky groups is desired. In the present study an organocatalytic isothiourea-mediated Michael addition-lactonization process analogous to a previously reported study in solution is presented. An achiral isothiourea, 3,4-dihydro-2H-pyrimido[2,1-b]benzothiazole (DHPB), promotes the intermolecular Michael addition-lactonization of a trifluoromethylenone terminated SAM and a variety of arylacetic acids affording C(6)-trifluoromethyldihydropyranones tethered to the surface. X-ray photoelectron spectroscopy, atomic force microscopy, contact angle, and ellipsometry analysis were conducted to confirm the presence of the substituted dihydropyranone. A model study of this approach was also performed in solution to probe the reaction diastereoselectivity as it cannot be measured directly on the surface. PMID:27015037

  4. Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts - A comparative study

    SciTech Connect

    Meeuwen, J.A. van Nijmeijer, S.; Mutarapat, T.; Ruchirawat, S.; Jong, P.C. de; Piersma, A.H.; Berg, M. van den

    2008-05-01

    Interference of exogenous chemicals with the aromatase enzyme can be useful as a tool to identify chemicals that could act either chemopreventive for hormone-dependent cancer or adverse endocrine disruptive. Aromatase is the key enzyme in the biosynthesis of steroids, as it converts androgens to estrogens. Certain flavonoids, plant derived chemicals, are known catalytic aromatase inhibitors. Various systems are in use to test aromatase inhibitory properties of compounds. Commonly used are microsomes derived from ovary or placental tissue characterized by high aromatase activity. To a lesser extent whole cell systems are used and specifically cell systems that are potential target tissue in breast cancer development. In this study aromatase inhibitory properties of fadrozole, 8-prenylnaringenin and a synthetic lactone (TM-7) were determined in human placental microsomes and in human primary breast fibroblasts. In addition, apigenin, chrysin, naringenin and two synthetic lactones (TM-8 and TM-9) were tested in human microsomes only. Comparison of the aromatase inhibitory potencies of these compounds between the two test systems showed that the measurement of aromatase inhibition in human placental microsomes is a good predictor of aromatase inhibition in human breast fibroblasts.

  5. Modelled microgravity cultivation modulates N-acylhomoserine lactone production in Rhodospirillum rubrum S1H independently of cell density.

    PubMed

    Mastroleo, Felice; Van Houdt, Rob; Atkinson, Steve; Mergeay, Max; Hendrickx, Larissa; Wattiez, Ruddy; Leys, Natalie

    2013-12-01

    The photosynthetic alphaproteobacterium Rhodospirillum rubrum S1H is part of the Micro-Ecological Life Support System Alternative (MELiSSA) project that is aiming to develop a closed life support system for oxygen, water and food production to support human life in space in forthcoming long-term space exploration missions. In the present study, R. rubrum S1H was cultured in a rotating wall vessel (RWV), simulating partial microgravity conditions on Earth. The bacterium showed a significant response to cultivation in simulated microgravity at the transcriptomic, proteomic and metabolic levels. In simulated microgravity conditions three N-acyl-l-homoserine lactones (C10-HSL, C12-HSL and 3-OH-C14-HSL) were detected in concentrations that were twice those detected under normal gravity, while no differences in cell density was detected. In addition, R. rubrum cultivated in modelled microgravity showed higher pigmentation than the normal gravity control, without change in culture oxygenation. When compared to randomized microgravity cultivation using a random positioning machine, significant overlap for the top differentially expressed genes and proteins was observed. Cultivation in this new artificial environment of simulated microgravity showed new properties of this well-known bacterium, including its first, to our knowledge, complete quorum-sensing-related N-acylhomoserine lactone profile. PMID:24025602

  6. Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts--a comparative study.

    PubMed

    van Meeuwen, J A; Nijmeijer, S; Mutarapat, T; Ruchirawat, S; de Jong, P C; Piersma, A H; van den Berg, M

    2008-05-01

    Interference of exogenous chemicals with the aromatase enzyme can be useful as a tool to identify chemicals that could act either chemopreventive for hormone-dependent cancer or adverse endocrine disruptive. Aromatase is the key enzyme in the biosynthesis of steroids, as it converts androgens to estrogens. Certain flavonoids, plant derived chemicals, are known catalytic aromatase inhibitors. Various systems are in use to test aromatase inhibitory properties of compounds. Commonly used are microsomes derived from ovary or placental tissue characterized by high aromatase activity. To a lesser extent whole cell systems are used and specifically cell systems that are potential target tissue in breast cancer development. In this study aromatase inhibitory properties of fadrozole, 8-prenylnaringenin and a synthetic lactone (TM-7) were determined in human placental microsomes and in human primary breast fibroblasts. In addition, apigenin, chrysin, naringenin and two synthetic lactones (TM-8 and TM-9) were tested in human microsomes only. Comparison of the aromatase inhibitory potencies of these compounds between the two test systems showed that the measurement of aromatase inhibition in human placental microsomes is a good predictor of aromatase inhibition in human breast fibroblasts. PMID:18201740

  7. Natural product inspired design and synthesis of β-carboline and γ-lactone based molecular hybrids.

    PubMed

    Singh, Dharmender; Devi, Nisha; Kumar, Vipin; Malakar, Chandi C; Mehra, Saloni; Rattan, Sunita; Rawal, Ravindra K; Singh, Virender

    2016-09-14

    β-Carboline and γ-lactone moieties have been selected by nature as privileged scaffolds and display a wide range of pharmacological properties. Following nature, we envisaged the preparation of new β-carboline and γ-lactone based molecular hybrids incorporating both the pharmacophores. In this regard, a water-assisted In-mediated environmentally benign and easy to execute single-step tandem Barbier type allylation-lactonisation process has been devised in order to afford the targeted molecular architectures. It is anticipated that aqueous medium plays the key role in allylation as well as in the subsequent lactonisation process for the diastereo-selective synthesis of these conjugates. It is believed that water drives the reaction pathway through dual activation, it increases the electrophilic character of formyl and ester functionalities and simultaneously enhances the nucleophilic potential of the hydroxyl group to facilitate the in situ intramolecular condensation. Importantly, during this synthetic strategy no column chromatographic purification was required at any stage. PMID:27511703

  8. Rheological properties of milk gels formed by a combination of rennet and glucono-delta-lactone.

    PubMed

    Lucey, J A; Tamehana, M; Singh, H; Munro, P A

    2000-08-01

    The effects of heat treatment of milk, and a range of rennet and glucono-delta-lactone (GDL) concentrations on the rheological properties, at small and large deformation, of milk gels were investigated. Gels were made from reconstituted skim milk at 30 degrees C, with two levels each of rennet and GDL. Together with controls this gave a total of sixteen gelation conditions, eight for unheated and eight for heated milk. Acid gels made from unheated milks had low storage moduli (G') of < 20 Pa. Heating milks at 80 degrees C for 30 min resulted in a large increase in the G' value of acid gels. Rennet-induced gels made from unheated milk had G' values in the range approximately 80-190 Pa. However, heat treatment severely impaired rennet coagulation: no gel was formed at low rennet levels and only a very weak gel was formed at high levels. In gels made with a combination of rennet and GDL unusual rheological behaviour was observed. After gelation, G' initially increased rapidly but then remained steady or even decreased, and at long ageing times G' values increased moderately or remained low. The loss tangent (tan delta) of acid gels made from heated milk increased after gelation to attain a maximum at pH approximately 5.1 but no maximum was observed in gels made from unheated milk. Gels made by a combination of rennet and GDL also exhibited a maximum in tan delta, indicating increased relaxation behaviour of the protein-protein bonds. We suggest that this maximum in tan delta was caused by a loosening of the intermolecular forces in casein particles caused by solubilization of colloidal calcium phosphate. We also suggest that in combination gels made from unheated milk a low value for the fracture stress and a high tan delta during gelation indicated an increased susceptibility of the network to excessive large scale rearrangements. In contrast. combination gels made from heated milk formed firmer gels crosslinked by denatured whey proteins and underwent fewer large

  9. A new regulatory element modulates homoserine lactone-mediated autoinduction of Ti plasmid conjugal transfer.

    PubMed Central

    Hwang, I; Cook, D M; Farrand, S K

    1995-01-01

    Conjugal transfer of the Agrobacterium tumefaciens nopaline-type Ti plasmid pTiC58 is induced by agrocinopines A and B, opines secreted by crown gall tumors induced by the bacterium. This regulation functions through the transcriptional repressor, AccR. However, actual transcription of the tra genes is regulated by autoinduction through the activator TraR and the substituted homoserine lactone second messenger, Agrobacterium autoinducer (AAI). We have identified a new regulatory element that modulates the response of TraR to AAI. The gene, called traM, suppresses TraR-AAI activation of transcription of tra genes carried on recombinant clones. The suppression could be relieved by increasing the expression of TraR but not by increasing AAI levels. traM is located between traR and traAF on pTiC58 and is transcribed in the clockwise direction. The 306-bp gene encodes an 11.2-kDa protein showing no significant relatedness to other proteins in the databases. Mutations in traM in pTiC58 conferred a transfer-constitutive phenotype, and strains harboring the Ti plasmid produced easily detectable amounts of AAI. These same mutations engineered into the transfer-constitutive Ti plasmid pTiC58 delta accR conferred a hyperconjugal phenotype and very high levels of AAI production. Expression of traM required TraR, indicating that transcription of the gene is regulated by the autoinduction system. TraM had no effect on the expression of traR, demonstrating that the suppressive effect is not due to repression of the gene encoding the activator. These results suggest that TraM is not a direct transcriptional regulator. Since the suppressive effect is demonstrable only when traM is overexpressed with respect to traR, we suggest that TraM functions to sequester TraR from the very small amounts of AAI produced under conditions when the agrocinopines are not present. PMID:7814335

  10. Identification of Quorum-Sensing Signal Molecules and a Biosynthetic Gene in Alicycliphilus sp. Isolated from Activated Sludge.

    PubMed

    Morohoshi, Tomohiro; Okutsu, Noriya; Xie, Xiaonan; Ikeda, Tsukasa

    2016-01-01

    Activated sludge is a complicated mixture of various microorganisms that is used to treat sewage and industrial wastewater. Many bacteria produce N-acylhomoserine lactone (AHL) as a quorum-sensing signal molecule to regulate the expression of the exoenzymes used for wastewater treatment. Here, we isolated an AHL-producing bacteria from an activated sludge sample collected from an electronic component factory, which we named Alicycliphilus sp. B1. Clone library analysis revealed that Alicycliphilus was a subdominant genus in this sample. When we screened the activated sludge sample for AHL-producing strains, 12 of 14 the AHL-producing isolates were assigned to the genus Alicycliphilus. A putative AHL-synthase gene, ALISP_0667, was cloned from the genome of B1 and transformed into Escherichia coli DH5α. The AHLs were extracted from the culture supernatants of the B1 strain and E. coli DH5α cells harboring the ALISP_0667 gene and were identified by liquid chromatography-mass spectrometry as N-(3-hydroxydecanoyl)-l-homoserine lactone and N-(3-hydroxydodecanoyl)-l-homoserine lactone. The results of comparative genomic analysis suggested that the quorum-sensing genes in the B1 strain might have been acquired by horizontal gene transfer within activated sludge. PMID:27490553

  11. SYNTHESIS OF ALPHA-AMINO GAMMA-LACTONE VIA A NOVEL TANDEM THREE-COMPONENT REACTION OF ALKENES, GLYOXYLATES AND AMINES. (R822668)

    EPA Science Inventory

    Abstract

    small alpha, Greek-Amino small gamma, Greek-lactones were generated by an InCl3...

  12. A Solvent-Free Baeyer-Villiger Lactonization for the Undergraduate Organic Laboratory: Synthesis of Gamma-T-Butyl-Epsilon-Caprolactone

    ERIC Educational Resources Information Center

    Esteb, John J.; Hohman, Nathan J.; Schlamandinger, Diana E.; Wilson, Anne M.

    2005-01-01

    The solvent-free or solid-state reaction systems like the Baeyer-Villiger rearrangement have become popular in the synthetic organic community and viable option for undergraduate laboratory series to reduce waste and cost and simplify reaction process. The reaction is an efficient method to transform ketones to esters and lactones.

  13. Acyl-homoserine-lactone autoinducer (AHL) in the gastrointestinal tract of feedlot cattle and correlation to season, E. coli 0157:H7 prevalence and diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acyl-homoserine-lactone autoinducer (AHL) produced by non-enterohemorrhagic E. coli (EHEC) species in cattle appears to be required for EHEC colonization of the gastro¬intestinal tract (GIT). The objectives of the current research were to examine the effect of season, diet, EHEC shedding, and locat...

  14. Vibration isolation

    NASA Technical Reports Server (NTRS)

    Bastin, Paul

    1990-01-01

    Viewgraphs on vibration isolation are presented. Techniques to control and isolate centrifuge disturbances were identified. Topics covered include: disturbance sources in the microgravity environment; microgravity assessment criteria; life sciences centrifuge; flight support equipment for launch; active vibration isolation system; active balancing system; and fuzzy logic control.

  15. A Sinorhizobium meliloti-specific N-acyl homoserine lactone quorum-sensing signal increases nodule numbers in Medicago truncatula independent of autoregulation

    PubMed Central

    Veliz-Vallejos, Debora F.; van Noorden, Giel E.; Yuan, Mengqi; Mathesius, Ulrike

    2014-01-01

    N-acyl homoserine lactones (AHLs) act as quorum sensing signals that regulate cell-density dependent behaviors in many gram-negative bacteria, in particular those important for plant-microbe interactions. AHLs can also be recognized by plants, and this may influence their interactions with bacteria. Here we tested whether the exposure to AHLs affects the nodule-forming symbiosis between legume hosts and rhizobia. We treated roots of the model legume, Medicago truncatula, with a range of AHLs either from its specific symbiont, Sinorhizobium meliloti, or from the potential pathogens, Pseudomonas aeruginosa and Agrobacterium vitis. We found increased numbers of nodules formed on root systems treated with the S. meliloti-specific AHL, 3-oxo-C14-homoserine lactone, at a concentration of 1 μM, while the other AHLs did not result in significant changes to nodule numbers. We did not find any evidence for altered nodule invasion by the rhizobia. Quantification of flavonoids that could act as nod gene inducers in S. meliloti did not show any correlation with increased nodule numbers. The effects of AHLs were specific for an increase in nodule numbers, but not lateral root numbers or root length. Increased nodule numbers following 3-oxo-C14-homoserine lactone treatment were under control of autoregulation of nodulation and were still observed in the autoregulation mutant, sunn4 (super numeric nodules4). However, increases in nodule numbers by 3-oxo-C14-homoserine lactone were not found in the ethylene-insensitive sickle mutant. A comparison between M. truncatula with M. sativa (alfalfa) and Trifolium repens (white clover) showed that the observed effects of AHLs on nodule numbers were specific to M. truncatula, despite M. sativa nodulating with the same symbiont. We conclude that plant perception of the S. meliloti-specific 3-oxo-C14-homoserine lactone influences nodule numbers in M. truncatula via an ethylene-dependent, but autoregulation-independent mechanism. PMID

  16. The safety-net story about macrocyclic lactone heartworm preventives: a review, an update, and recommendations.

    PubMed

    McCall, John W

    2005-10-24

    A number of safe, effective, and convenient heartworm preventatives are currently available for virtually all canine and feline pets. Yet, a 2001 survey of over 18,000 veterinary clinics in the United States identified more than 240,000 dogs and 3000 cats infected with Dirofilaria immitis. This high level of owner compliance failure is alarming. Prolonged administration of some of the macrocyclic lactone (ML) preventatives kills young larvae, older larvae, "immatures," young adults, and/or old adults. Efficacy of 95% or more requires dosing for 9-30 months, with older worms being more difficult to kill. Of the various MLs, ivermectin (IVM) has the most potent safety-net and adulticidal activity, milbemycin oxime has the least, and selamectin and moxidectin injectable lie somewhere in between. The unique effects of IVM are related to the age of the heartworms at initiation of treatment. The earlier treatment is started, the more stunted and smaller the worms and the shorter their survival time. Conversely, the later treatment is started, the longer the worms live, and the more likely the dog will be antigen- and microfilariae-positive. Drug effects do not appear to be enhanced by increasing the dosage or administering at shorter intervals, and it appears that continuous monthly treatment is needed to produce the full effects of the drug. The American Heartworm Society (AHS) recognizes the safety-net (or reach-back effect) and adulticidal properties of some MLs, particularly IVM. The AHS 2003 (American Heartworm Society, 2004. 2003 Updated guidelines for the diagnosis, prevention, and management of heartworm (Dirofilaria immitis) infection in dogs. In: McCall, et al., (Eds.), Proceedings of the Symposium Session on Recent Advances in Heartworm Disease, The 19th International Conference of the World Association for the Advancement of Veterinary Parasitology, New Orleans, LA, 10-14 August, 2003. Vet. Parasitol. 125, 105-130) canine guidelines state that it is

  17. Drimane Sesquiterpene-Conjugated Amino Acids from a Marine Isolate of the Fungus Talaromyces minioluteus (Penicillium Minioluteum)

    PubMed Central

    Ngokpol, Suthatip; Suwakulsiri, Wittaya; Sureram, Sanya; Lirdprapamongkol, Kriengsak; Aree, Thammarat; Wiyakrutta, Suthep; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2015-01-01

    Four new sesquiterpene lactones (3, 4, 6 and 7) and three known compounds, purpuride (1), berkedrimane B (2) and purpuride B (5), were isolated from the marine fungus, Talaromyces minioluteus (Penicillium minioluteum). New compounds were drimane sesquiterpenes conjugated with N-acetyl-l-valine, and their structures were elucidated by analysis of spectroscopic data, as well as by single crystal X-ray analysis. The isolated compounds could not inhibit the apoptosis-regulating enzyme, caspase-3, while three of the compounds (2, 3 and 7) exhibited weak cytotoxic activity. PMID:26058010

  18. Method to convert biomass to 5-(hydroxymethyl)-furfural (HMF) and furfural using lactones, furans, and pyrans as solvents

    DOEpatents

    Dumesic, James A.; Ribeiro Gallo, Jean Marcel; Alonso, David

    2014-07-08

    Described is a process to produce hydroxymethyl furfural (HMF) from biomass-derived sugars. The process includes the steps of reacting a C5 and/or C6 sugar-containing reactant derived from biomass in a monophasic or biphasic reaction solution comprising water and a co-solvent. The co-solvent can be beta-, gamma-, and/or delta-lactones derived from biomass, tetrahydrofuran (THF) derived from biomass, and/or methyltetrahydrofuran (MTHF) derived from biomass. The reaction takes place in the presence of an acid catalyst and a dehydration catalyst for a time and under conditions such that at least a portion of glucose or fructose present in the reactant is converted to HMF.

  19. Theoretical studies for the formation of γ-valero-lactone from levulinic acid and formic acid by homogeneous catalysis

    NASA Astrophysics Data System (ADS)

    Assary, Rajeev S.; Curtiss, Larry A.

    2012-07-01

    The γ-valero-lactone (GVL), a potential 'green' candidate for the production of liquid alkanes for transportation fuels, can be obtained by the hydrogenation of levulinic acid, a primary decomposition product of hexoses. On the search for the application of a bifunctional catalyst, we have identified that the versatile Shvo catalyst can be used to transfer the hydrogen required for the reduction of levulinic acid to GVL through a 2-hydroxy-pentanoic acid (2HP) intermediate. Density functional studies (DFT) have been employed here to compute the energetics for the conversion of levulinic acid to GVL. Additionally, we have investigated the potential application of an iron-based congener to replace the conventional Shvo catalyst due to its natural abundance and cost effectiveness.

  20. Identification of sesquiterpene lactones in the Bryophyta (mosses) Takakia: Takakia species are closely related chemically to the Marchantiophyta (liverworts).

    PubMed

    Asakawa, Yoshinori; Nii, Kaeko; Higuchi, Masanobu

    2015-01-01

    Takakia lepidozioides has been considered to be the most primitive liverwort morphologically and classified initially in the Marchantiophyta (liverworts). However, the Takakia have been reclassified from liverworts to mosses on the basis of the similarity of the male sporophyte of T. ceratophylla to that of some mosses. Reinvestigation of secondary metabolites of fresh T. lepidozioides resulted in identification of eudesmane-type sesquiterpene lactones and hydrocarbon that are significant chemical markers of several liverworts. T. lepidozioides also produces a small amount of hop-22(29)-ene, together with coumarin, which produce the characteristic odor of T. lepidozioides, and 1,4-hydroquinone; these are the predominant volatile components, whereas dihydrocoumarin, 1,4-benzoquinone, dihydrobenzofuran, α-asarone and α-tocopherol are minor components. These chemical results indicated that T. lepidozioides is more closely related to the Marchantiophyta than the Bryophyta. T. lepidozioides is morphologically similar to the liverwort Haplomitrium species. However, both species are totally different chemically. PMID:25920208

  1. Fluorinated Amino-Derivatives of the Sesquiterpene Lactone, Parthenolide, as 19F NMR Probes in Deuterium-Free Environments

    PubMed Central

    Woods, James R.; Mo, Huaping; Bieberich, Andrew A.; Alavanja, Tanja; Colby, David A.

    2011-01-01

    The design, synthesis, and biological activity of fluorinated amino-derivatives of the sesquiterpene lactone, parthenolide, are described. A fluorinated aminoparthenolide analogue with biological activity similar to the parent natural product was discovered, and its X-ray structure was obtained. This lead compound was then studied using 19F NMR in the presence and absence of glutathione to obtain additional mechanism of action data, and it was found that the aminoparthenolide eliminates amine faster in the presence of glutathione than in the absence of glutathione. The exact changes in concentrations of fluorinated compound and amine were quantified by a concentration-reference method using 19F NMR; a major benefit of applying this strategy is that no deuterated solvents or internal standards are required to obtain accurate concentrations. These mechanistic data with glutathione may contribute to the conversion of the amino-derivative to parthenolide, the active pharmacological agent, in glutathione-rich cancer cells. PMID:22029741

  2. New antitumour agents with α,β-unsaturated δ-lactone scaffold: Synthesis and antiproliferative activity of (-)-cleistenolide and analogues.

    PubMed

    Benedeković, Goran; Kovačević, Ivana; Popsavin, Mirjana; Francuz, Jovana; Kojić, Vesna; Bogdanović, Gordana; Popsavin, Velimir

    2016-07-15

    A stereoselective total synthesis of (-)-cleistenolide (1) from d-glucose has been achieved. This new approach for the synthesis of (-)-cleistenolide and analogues involves a one-C-atom degradation of the chiral precursor, (Z)-selective Wittig olefination, followed by the final δ-lactonisation. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially 2,4,6-trichlorobenzoyl derivative 12, which in the culture of MDA-MB 231 cells displayed the highest activity (IC50 0.02μM) of all compounds under evaluation. A preliminary SAR study reveals the structural features that are beneficial for antiproliferative activity of synthesized δ-lactones, such as presence of either electron-withdrawing or electron-donating substituents in the aromatic ring, as well as the presence of cinnamoyl functionality instead of benzoyl group at the O-7 position. PMID:27231128

  3. Morphological changes in Proteus mirabilis O18 biofilm under the influence of a urease inhibitor and a homoserine lactone derivative.

    PubMed

    Czerwonka, Grzegorz; Arabski, Michał; Wąsik, Sławomir; Jabłońska-Wawrzycka, Agnieszka; Rogala, Patrycja; Kaca, Wiesław

    2014-03-01

    Proteus mirabilis is a pathogenic gram-negative bacterium that frequently causes kidney infections, typically established by ascending colonization of the urinary tract. The present study is focused on ureolytic activity and urease inhibition in biofilms generated by P. mirabilis O18 cells. Confocal microscopy revealed morphological alterations in biofilms treated with urea and a urease inhibitor (acetohydroxamic acid, AHA), as some swarmer cells were found to protrude from the biofilm. The presence of a quorum-sensing molecule (N-butanoyl homoserine lactone, BHL) increased biofilm thickness and its ureolytic activity. Laser interferometric determination of diffusion showed that urea easily diffuses through P. mirabilis biofilm, while AHA is blocked. This may suggest that the use of urease inhibitors in CAUTIs may by less effective than in other urease-associated infections. Spectroscopic studies revealed differences between biofilm and planktonic cells indicating that polysaccharides and nucleic acids are involved in extracellular matrix and biofilm formation. PMID:24481535

  4. Dehalogenation Activity of Selected Fungi Toward δ-Iodo-γ-Lactone Derived from trans,trans-Farnesol.

    PubMed

    Gliszczyńska, Anna; Gładkowski, Witold; Świtalska, Marta; Wietrzyk, Joanna; Szumny, Antoni; Gębarowska, Elżbieta; Wawrzeńczyk, Czesław

    2016-04-01

    Time-course of biotransformation of racemic trans-4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-5-iodomethyl-4-methyldihydrofuran-2-one (1) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-4-methyl-5-methylenedihydrofuran-2-one (2) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ-iodo-γ-lactone 1, product of its biotransformation 2, and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL-60 (human promyelocytic leukemia). PMID:26923572

  5. From racemic precursors to fully stereocontrolled products: one-pot synthesis of chiral α-amino lactones and lactams.

    PubMed

    You, Zhi-Hao; Chen, Ying-Han; Liu, Yan-Kai

    2016-07-14

    Substituted racemic lactols or cyclic hemiaminals were directly used as nucleophiles in enamine-based asymmetric amination reactions to access enantioenriched α-amino lactones or lactams via a one-pot sequence. The desired products, which are very important building blocks in organic synthesis but difficult to be prepared in the optically enriched form, could be afforded with two stereogenic centers in high yields with excellent enantioselectivities. Moreover, starting from the racemic precursors and catalyzed by the enantiomeric pair of the catalyst, all possible stereoisomeric products were discretely provided only after simple column chromatography. Additionally, this protocol provides facile access to several novel bicyclic carbamates, and such drug-like heterocyclic compounds should be potentially useful in medicinal chemistry. PMID:27270561

  6. Chemoenzymatic Synthesis of an Enantiomerically Pure Lactone: A Three-Step Synthesis for Undergraduate Organic Chemistry Laboratory

    NASA Astrophysics Data System (ADS)

    McClure, Cynthia K.; Chenault, H. Keith

    1996-05-01

    A three-step laboratory sequence for the undergraduate organic laboratory is described. This series of experiments requires a student to use the product from one reaction as the starting material for a subsequent reaction, and thus the affords the student a "real world" experience of multistep synthesis. Thermal extrusion of sulfur dioxide from sulfolene is used to generate 1,3-butadiene in situ for a Diels-Alder cyclization with maleic anhydride. The anhydride is then reduced to the diol with lithium aluminum hydride. Oxidation of the diol to the chiral lactone is catalyzed by horse-liver alcohol dehydrogenase. This enzymatic oxidation illustrates in situ cofactor regeneration and allows students to measure simple enzyme kinetics.

  7. Structural elucidation and biological activity of acyl-homoserine lactones from the phytopathogen Pantoea ananatis Serrano 1928.

    PubMed

    Pomini, Armando M; Araújo, Welington L; Marsaioli, Anita J

    2006-08-01

    In Gram-negative bacteria, the acyl-homoserine lactones (acyl-HSLs) are the main signaling substances employed in cell-to-cell communication systems. This paper describes the chemical characterization of acyl-HSLs produced by the worldwide-spread phytopathogen Pantoea ananatis (Serrano 1928) by using gas chromatography-electron impact mass spectrometry. The absolute configuration of the major identified substance, (S)-(--)-N-hexanoyl-HSL, was determined with gas chromatography-flame ionization detection with a chiral capillary column. Biological activities of extracts, fractions, and synthetic products were evaluated with the specific reporter Agrobacterium tumefaciensNTL4(pZLR4) in beta-galactosidase expression assays. PMID:16900431

  8. New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.

    PubMed

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Lee, Chang-Min; Choi, Yung Hyun; Lee, Hak-Ju; Choi, Il-Whan; Kim, Gi-Young

    2015-01-01

    Microglia are main immune cells to exacerbate neural disorders in persistent overactivating. Therefore, it is a good strategy to regulate microglia for the treatment of neural disorders. In the present study, we isolated and characterized a novel compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton (5-DRL) from Clematis mandshurica, and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-treated BV2 microglial cells. 5-DRL inhibited the expression of LPS-stimulated proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as their regulatory genes inducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2). 5-DRL also downregulated the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of the nuclear translocation of the NF-κB subunits, p65 and p50. Consistent with the inhibition of iNOS and COX-2 via NF-κB activity with 5-DRL, an inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), also led to the suppression of LPS-induced iNOS and COX-2 expression. Additionally, 5-DRL corresponding with antioxidants, N-acetylcysteine (NAC) and glutathione (GSH), remarkably inhibited reactive oxygen species (ROS) generation. Both NAC and GSH, thus attenuated the expression of iNOS and COX-2 by suppressing NF-κB activation, indicating that 5-DRL suppresses LPS-induced iNOS and COX-2 expression through downregulation of the ROS-dependent NF-κB signaling pathway. The present study also indicated that 5-DRL suppresses NO and PGE2 production by inducing heme oxygenase-1 (HO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, the present data indicate that 5-DRL attenuates the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting ROS-dependent NF-κB activation and stimulating the Nrf2/HO-1 signal pathway. These data may be implicated in the application of 5-DRL in LPS

  9. Capsular polysaccharide biosynthesis and pathogenicity in Erwinia stewartii require induction by an N-acylhomoserine lactone autoinducer.

    PubMed

    Beck von Bodman, S; Farrand, S K

    1995-09-01

    N-Acylhomoserine lactone (acyl-HSL)-mediated gene expression, also called autoinduction, is conserved among diverse gram-negative bacteria. In the paradigm Vibrio fischeri system, bioluminescence is autoinducible, and the lux operon requires the transcriptional activator LuxR and the acyl-HSL autoinducer for expression. The production of the acyl-HSL signal molecule is conferred by the luxI gene, and luxR encodes the transcriptional regulator. We show here that Erwinia stewartii, the etiological agent of Stewart's wilt of sweet corn, synthesizes an acyl-HSL. Mass spectral analysis identified the signal molecule as N-(-3-oxohexanoyl)-L-homoserine lactone, which is identical to the V. fischeri autoinducer. We have cloned and sequenced the gene that confers acyl-HSL biosynthesis, called esaI, and the linked gene, esaR, that encodes a gene regulator. The two genes are convergently transcribed and show an unusual overlap of 31 bp at their 3' ends. Sequence analysis indicates that EsaI and EsaR are homologs of LuxI and LuxR, respectively. EsaR can repress its own expression but seems not to regulate the expression of esaI. The untranslated 5' region of esaR contains an inverted repeat with similarity to the lux box-like elements located in the promoter regions of other gene systems regulated by autoinduction. However, unlike the other systems, in which the inverted repeats are located upstream of the -35 promoter elements, the esaR-associated repeat overlaps a putative -10 element. We mutagenized the esaI gene in E. stewartii by gene replacement. The mutant no longer produced detectable levels of the acyl-HSL signal, leading to a concomitant loss of extracellular polysaccharide capsule production and pathogenicity. Both phenotypes were restored by complementation with esal or by exogenous addition of the acyl-HSL. PMID:7665477

  10. A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

    PubMed Central

    Lumaret, Jean-Pierre; Errouissi, Faiek; Floate, Kevin; Römbke, Jörg; Wardhaugh, Keith

    2012-01-01

    The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin

  11. Enzymatic PEGylated Poly(lactone-co-β-amino ester) Nanoparticles as Biodegradable, Biocompatible and Stable Vectors for Gene Delivery.

    PubMed

    Chen, Ya; Li, Yingqin; Gao, Jinbiao; Cao, Zhong; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

    2016-01-13

    We have developed new, efficient gene delivery systems based on PEGylated poly(lactone-co-β-amino ester) block copolymers that are biodegradable, stable and low in toxicity. The PEG-poly[PDL-co-3-(4-(methylene)piperidin-1-yl)propanoate] (PEG-PPM) diblock and PPM-PEG-PPM triblock copolymers with various compositions were synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL) and ethyl 3-(4-(hydroxymethyl)piperidin-1-yl)propanoate (EHMPP) with an appropriate PEG (MeO-PEG-OH or HO-PEG-OH). The amphiphilic block copolymers are capable of condensing DNA in aqueous medium via a self-assembly process to form polyplex micelle nanoparticles with desirable particle sizes (70-140 nm). These micelles possess low CMC values and are stable in the medium containing serum protein molecules (FBS). Among the PEG-PPM and PPM-PEG-PPM micelles, the PEG-PPM-15% PDL micelle particles exhibited high DNA-binding ability, the fastest cellular uptake rate and highest gene transfection efficacy. Flow cytometry analysis shows that LucDNA/PEG-PPM-15% PDL polyplex micelles can effectively escape from endosomal degradation after cellular uptake likely due to the presence of the tertiary amine groups in the copolymer chains that act as proton sponges. In vitro cytotoxicity and hemolysis assay experiments indicate that all copolymer samples are nonhemolytic and have minimal toxicity toward COS-7 cells within the polymer concentration range (≤200 μg/mL) used for the gene transfection. These results demonstrate that the PEGylated poly(lactone-co-β-amino ester) block copolymers are promising new vectors for gene delivery applications. PMID:26673948

  12. Capsular polysaccharide biosynthesis and pathogenicity in Erwinia stewartii require induction by an N-acylhomoserine lactone autoinducer.

    PubMed Central

    Beck von Bodman, S; Farrand, S K

    1995-01-01

    N-Acylhomoserine lactone (acyl-HSL)-mediated gene expression, also called autoinduction, is conserved among diverse gram-negative bacteria. In the paradigm Vibrio fischeri system, bioluminescence is autoinducible, and the lux operon requires the transcriptional activator LuxR and the acyl-HSL autoinducer for expression. The production of the acyl-HSL signal molecule is conferred by the luxI gene, and luxR encodes the transcriptional regulator. We show here that Erwinia stewartii, the etiological agent of Stewart's wilt of sweet corn, synthesizes an acyl-HSL. Mass spectral analysis identified the signal molecule as N-(-3-oxohexanoyl)-L-homoserine lactone, which is identical to the V. fischeri autoinducer. We have cloned and sequenced the gene that confers acyl-HSL biosynthesis, called esaI, and the linked gene, esaR, that encodes a gene regulator. The two genes are convergently transcribed and show an unusual overlap of 31 bp at their 3' ends. Sequence analysis indicates that EsaI and EsaR are homologs of LuxI and LuxR, respectively. EsaR can repress its own expression but seems not to regulate the expression of esaI. The untranslated 5' region of esaR contains an inverted repeat with similarity to the lux box-like elements located in the promoter regions of other gene systems regulated by autoinduction. However, unlike the other systems, in which the inverted repeats are located upstream of the -35 promoter elements, the esaR-associated repeat overlaps a putative -10 element. We mutagenized the esaI gene in E. stewartii by gene replacement. The mutant no longer produced detectable levels of the acyl-HSL signal, leading to a concomitant loss of extracellular polysaccharide capsule production and pathogenicity. Both phenotypes were restored by complementation with esal or by exogenous addition of the acyl-HSL. PMID:7665477

  13. Acyl-ACP Substrate Recognition in Burkholderia mallei BmaI1 Acyl-Homoserine Lactone Synthase

    PubMed Central

    2015-01-01

    The acyl-homoserine lactone (AHL) autoinducer mediated quorum sensing regulates virulence in several pathogenic bacteria. The hallmark of an efficient quorum sensing system relies on the tight specificity in the signal generated by each bacterium. Since AHL signal specificity is derived from the acyl-chain of the acyl-ACP (ACP = acyl carrier protein) substrate, AHL synthase enzymes must recognize and react with the native acyl-ACP with high catalytic efficiency while keeping reaction rates with non-native acyl-ACPs low. The mechanism of acyl-ACP substrate recognition in these enzymes, however, remains elusive. In this study, we investigated differences in catalytic efficiencies for shorter and longer chain acyl-ACP substrates reacting with an octanoyl-homoserine lactone synthase Burkholderia mallei BmaI1. With the exception of two-carbon shorter hexanoyl-ACP, the catalytic efficiencies of butyryl-ACP, decanoyl-ACP, and octanoyl-CoA reacting with BmaI1 decreased by greater than 20-fold compared to the native octanoyl-ACP substrate. Furthermore, we also noticed kinetic cooperativity when BmaI1 reacted with non-native acyl-donor substrates. Our kinetic data suggest that non-native acyl-ACP substrates are unable to form a stable and productive BmaI1·acyl-ACP·SAM ternary complex and are thus effectively discriminated by the enzyme. These results offer insights into the molecular basis of substrate recognition for the BmaI1 enzyme. PMID:25215658

  14. Identification of extracellular N-acylhomoserine lactone acylase from a Streptomyces sp. and its application to quorum quenching.

    PubMed

    Park, Sun-Yang; Kang, Hye-Ok; Jang, Hak-Sun; Lee, Jung-Kee; Koo, Bon-Tag; Yum, Do-Young

    2005-05-01

    N-acylhomoserine lactones (AHLs) play an important role in regulating virulence factors in pathogenic bacteria. Recently, the enzymatic inactivation of AHLs, which can be used as antibacterial targets, has been identified in several soil bacteria. In this study, strain M664, identified as a Streptomyces sp., was found to secrete an AHL-degrading enzyme into a culture medium. The ahlM gene for AHL degradation from Streptomyces sp. strain M664 was cloned, expressed heterologously in Streptomyces lividans, and purified. The enzyme was found to be a heterodimeric protein with subunits of approximately 60 kDa and 23 kDa. A comparison of AhlM with known AHL-acylases, Ralstonia strain XJ12B AiiD and Pseudomonas aeruginosa PAO1 PvdQ, revealed 35% and 32% identities in the deduced amino acid sequences, respectively. However, AhlM was most similar to the cyclic lipopeptide acylase from Streptomyces sp. strain FERM BP-5809, exhibiting 93% identity. A mass spectrometry analysis demonstrated that AhlM hydrolyzed the amide bond of AHL, releasing homoserine lactone. AhlM exhibited a higher deacylation activity toward AHLs with long acyl chains rather than short acyl chains. Interestingly, AhlM was also found to be capable of degrading penicillin G by deacylation, showing that AhlM has a broad substrate specificity. The addition of AhlM to the growth medium reduced the accumulation of AHLs and decreased the production of virulence factors, including elastase, total protease, and LasA, in P. aeruginosa. Accordingly, these results suggest that AHL-acylase, AhlM could be effectively applied to the control of AHL-mediated pathogenicity. PMID:15870355

  15. Ytterbium(III) porpholactones: β-lactonization of porphyrin ligands enhances sensitization efficiency of lanthanide near-infrared luminescence.

    PubMed

    Ke, Xian-Sheng; Yang, Bo-Yan; Cheng, Xin; Chan, Sharon Lai-Fung; Zhang, Jun-Long

    2014-04-01

    The near-infrared (NIR) luminescence efficiency of lanthanide complexes is largely dependent on the electronic and photophysical properties of antenna ligands. Although porphyrin ligands are efficient sensitizers of lanthanide NIR luminescence, non-pyrrolic porphyrin analogues, which have unusual symmetry and electronic states, have been much less studied. In this work, we used porpholactones, a class of β-pyrrolic-modified porphyrins, as ligands and investigated the photophysical properties of lanthanide porpholactones Yb-1 a-5 a. Compared with Yb porphyrin complexes, the porpholactone complexes displayed remarkable enhancement of NIR emission (50-120 %). Estimating the triplet-state levels of porphyrin and porpholactone in Gd complexes revealed that β-lactonization of porphyrinic ligands lowers the ligand T1 state and results in a narrow energy gap between this state and the lowest excited state of Yb(3+) . Transient absorption spectra showed that Yb(III) porpholactone has a longer transient decay lifetime at the Soret band than the porphyrin analogue (30.8 versus 17.0 μs). Thus, the narrower energy gap and longer lifetime arising from β-lactonization are assumed to enhance NIR emission of Yb porpholactones. To demonstrate the potential applications of Yb porpholactone, a water-soluble Yb bioprobe was constructed by conjugating glucose to Yb-1 a. Interestingly, the NIR emission of this Yb porpholactone could be specifically switched on in the presence of glucose oxidase and then switched off by addition of glucose. This is the first demonstration that non-pyrrolic porphyrin ligands enhance the sensitization efficiency of lanthanide luminescence and also display switchable NIR emission in the region of biological analytes (800-1400 nm). PMID:24590671

  16. Involvement of calmodulin in regulation of primary root elongation by N-3-oxo-hexanoyl homoserine lactone in Arabidopsis thaliana

    PubMed Central

    Zhao, Qian; Zhang, Chao; Jia, Zhenhua; Huang, Yali; Li, Haili; Song, Shuishan

    2015-01-01

    Many bacteria use signal molecules of low molecular weight to monitor their local population density and to coordinate their collective behavior in a process called “quorum sensing” (QS). N-acyl-homoserine lactones (AHLs) are the primary QS signals among Gram-negative bacteria. AHL-mediated QS plays an essential role in diverse bacterial physiological processes. Recent evidence shows that plants are able to sense bacterial AHLs and respond to them appropriately. However, little is known about the mechanism by which plants perceive and transduce the bacterial AHLs within cells. In this study, we found that the stimulatory effect of N-3-oxo-hexanoyl homoserine lactone (3OC6-HSL) on primary root elongation of Arabidopsis was abolished by the calmodulin (CaM) antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine (TFP). Western-blot and ELISA analysis revealed that the concentration of CaM protein in Arabidopsis roots increased after treatment with 1 μM 3OC6-HSL. Results from quantitative RT-PCR demonstrated that the transcription of all nine CaM genes in Arabidopsis genome was up-regulated in the plants treated with 3OC6-HSL. The loss-of-function mutants of each AtCaM gene (AtCaM1-9) were insensitive to 3OC6-HSL-stimulation of primary root elongation. On the other hand, the genetic evidence showed that CaM may not participates the inhibition of primary root length caused by application of long-chained AHLs such as C10-HSL and C12-HSL. Nevertheless, our results suggest that CaM is involved in the bacterial 3OC6-HSL signaling in plant cells. These data offer new insight into the mechanism of plant response to bacterial QS signals. PMID:25628641

  17. The Quorum-Sensing Molecules Farnesol/Homoserine Lactone and Dodecanol Operate via Distinct Modes of Action in Candida albicans▿

    PubMed Central

    Hall, Rebecca A.; Turner, Kara J.; Chaloupka, James; Cottier, Fabien; De Sordi, Luisa; Sanglard, Dominique; Levin, Lonny R.; Buck, Jochen; Mühlschlegel, Fritz A.

    2011-01-01

    Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules. PMID:21666074

  18. Indole inhibition of N-acylated homoserine lactone-mediated quorum signalling is widespread in Gram-negative bacteria.

    PubMed

    Hidalgo-Romano, Benjamin; Gollihar, Jimmy; Brown, Stacie A; Whiteley, Marvin; Valenzuela, Ernesto; Kaplan, Heidi B; Wood, Thomas K; McLean, Robert J C

    2014-11-01

    The LuxI/R quorum-sensing system and its associated N-acylated homoserine lactone (AHL) signal is widespread among Gram-negative bacteria. Although inhibition by indole of AHL quorum signalling in Pseudomonas aeruginosa and Acinetobacter oleivorans has been reported previously, it has not been documented among other species. Here, we show that co-culture with wild-type Escherichia coli, but not with E. coli tnaA mutants that lack tryptophanase and as a result do not produce indole, inhibits AHL-regulated pigmentation in Chromobacterium violaceum (violacein), Pseudomonas chlororaphis (phenazine) and Serratia marcescens (prodigiosin). Loss of pigmentation also occurred during pure culture growth of Chro. violaceum, P. chlororaphis and S. marcescens in the presence of physiologically relevant indole concentrations (0.5-1.0 mM). Inhibition of violacein production by indole was counteracted by the addition of the Chro. violaceum cognate autoinducer, N-decanoyl homoserine lactone (C10-HSL), in a dose-dependent manner. The addition of exogenous indole or co-culture with E. coli also affected Chro. violaceum transcription of vioA (violacein pigment production) and chiA (chitinase production), but had no effect on pykF (pyruvate kinase), which is not quorum regulated. Chro. violaceum AHL-regulated elastase and chitinase activity were inhibited by indole, as was motility. Growth of Chro. violaceum was not affected by indole or C10-HSL supplementation. Using a nematode-feeding virulence assay, we observed that survival of Caenorhabditis elegans exposed to Chro. violaceum, P. chlororaphis and S. marcescens was enhanced during indole supplementation. Overall, these studies suggest that indole represents a general inhibitor of AHL-based quorum signalling in Gram-negative bacteria. PMID:25165125

  19. New Sesquiterpene Lactone Dimer, Uvedafolin, Extracted from Eight Yacon Leaf Varieties (Smallanthus sonchifolius): Cytotoxicity in HeLa, HL-60, and Murine B16-F10 Melanoma Cell Lines.

    PubMed

    Kitai, Yurika; Hayashi, Kana; Otsuka, Moe; Nishiwaki, Hisashi; Senoo, Tatsuya; Ishii, Tomohiko; Sakane, Genta; Sugiura, Makoto; Tamura, Hirotoshi

    2015-12-23

    Uvedafolin, 1, a new sesquiterpene lactone dimer, was isolated from the leaves of Smallanthus sonchifolius with five related compounds, 2-6, and their cytotoxicity was assessed against three tumor cell lines (HeLa, HL-60, B16-F10 melanoma). The stereostructure of 1 was newly elucidated by ESI-TOF-MS, 1D/2D NMR, and single-crystal X-ray diffraction. Dimers 1 and 2 had the most effective IC50 values, 0.2-1.9 μM, against the three tumor cell lines when compared with monomers 3-6 (IC50 values 0.7-9.9 μM) and etoposide (IC50 values 0.8-114 μM). The ester linkages of two sets of monomers, uvedalin, 5, and sonchifolin, 6, for 1, and enhydrin, 4, and sonchifolin, 6, for 2, as well as the acetyl group at the C-9 position, were essential for the high cytotoxicity. Dimers 1 and 2 would have potential as anticancer agents. PMID:26576855

  20. Okilactomycin, a novel antibiotic produced by a Streptomyces species. I. Taxonomy, fermentation, isolation and characterization.

    PubMed

    Imai, H; Suzuki, K; Morioka, M; Numasaki, Y; Kadota, S; Nagai, K; Sato, T; Iwanami, M; Saito, T

    1987-11-01

    Okilactomycin, a novel antibiotic, was isolated from the culture filtrate of a strain of actinomycetes. The producing organism, strain YP-02908L, was identified as Streptomyces griseoflavus subsp. zamamiensis subsp. nov. The antibiotic was extracted with ethyl acetate and purified by silica gel column chromatography. It was obtained as colorless prisms from a dichloromethane solution. It exhibited weak antimicrobial activity against Ehrlich ascites carcinoma in vivo. The apparent molecular formula of okilactomycin was determined as C24H32O6. It is a new member of the lactone group antibiotics. PMID:3693116

  1. A novel antibiotic, sohbumycin. Taxonomy, fermentation, isolation and physico-chemical and biological characteristics.

    PubMed

    Umezawa, I; Tronquet, C; Funayama, S; Okada, K; Komiyama, K

    1985-08-01

    A new antibiotic sohbumycin, was isolated from the culture broth of Streptomyces sp. No. 82-85. It appeared to belong to the peptide lactone type of antibiotics from physico-chemical studies and has an empirical formula of C31H47N8O10Cl. In in vitro studies, the antibiotic was found to possess potent cytocidal activity against HeLa S3 cells and antimicrobial activities against Gram-positive bacteria with MIC values about 0.3-0.6 microgram/ml, but showed no activity on the Gram-negative bacteria, yeast and fungi tested. PMID:3840156

  2. Characterization of Antifungal Natural Products Isolated from Endophytic Fungi of Finger Millet (Eleusine coracana).

    PubMed

    Mousa, Walaa Kamel; Schwan, Adrian L; Raizada, Manish N

    2016-01-01

    Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti-Fusarium activity. However, active compounds were isolated from only one strain. The objectives of this study were to confirm the endophytic lifestyle of the three remaining anti-Fusarium isolates, to identify the major underlying antifungal compounds, and to initially characterize the mode(s) of action of each compound. Results of confocal microscopy and a plant disease assay were consistent with the three fungal strains behaving as endophytes. Using bio-assay guided fractionation and spectroscopic structural elucidation, three anti-Fusarium secondary metabolites were purified and characterized. These molecules were not previously reported to derive from fungi nor have antifungal activity. The purified antifungal compounds were: 5-hydroxy 2(3H)-benzofuranone, dehydrocostus lactone (guaianolide sesquiterpene lactone), and harpagoside (an iridoide glycoside). Light microscopy and vitality staining were used to visualize the in vitro interactions between each compound and Fusarium; the results suggested a mixed fungicidal/fungistatic mode of action. We conclude that finger millet possesses fungal endophytes that can synthesize anti-fungal compounds not previously reported as bio-fungicides against F. graminearum. PMID:27598120

  3. Pharmacokinetics and tissue distribution of ginkgolide A, ginkgolide B, and ginkgolide K after intravenous infusion of ginkgo diterpene lactones in a rat model.

    PubMed

    Wang, Shuyao; Ouyang, Bingchen; Aa, Jiye; Geng, Jianliang; Fei, Fei; Wang, Pei; Wang, Jiankun; Peng, Ying; Geng, Ting; Li, Yanjing; Huang, Wenzhe; Wang, Zhenzhong; Xiao, Wei; Wang, Guangji

    2016-07-15

    Ginkgo diterpene lactones are compounds that are extracted from the Ginkgo biloba leaf and possess pharmacologic activities with neuroprotective effects. To address the poor bioavailability of ginkgo diterpene lactones, ginkgo diterpene lactone meglumine injection (GDLI) was formulated and is commercially available. In this study, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the total amount and the amount of the prototype forms of ginkgolides A (GA), B (GB) and K (GK) in rat plasma and tissues. This method was used to calculate the concentrations of the hydrolysed carboxylic forms and assess the pharmacokinetics of the ginkgolides after intravenous (i.v.) GDLI administration in rats. Generally, all three ginkgolide forms showed dose-dependent plasma concentrations, and no obvious differences in pharmacokinetic parameters, i.e., area under the curve (AUC) of plasma concentration versus time and half-life, were observed after GDLI administration on 7 consecutive days. These ginkgolides primarily existed in the carboxylic form in the plasma, and the systemic concentrations of the carboxylic forms of GA and GB were 11- to 17- and 3- to 4-fold higher than those of their prototype forms, respectively. In contrast, dramatically increased levels of the GA and GB prototype lactones were detected in the liver and heart. GA, GB, and GK were extensively distributed in various organs/tissues; the highest levels were found in the kidneys, liver, and intestine, and the lowest levels were found in the brain. These data suggest that ginkgolides have difficulty crossing the blood-brain barrier and that their targets for protecting against cerebral ischaemia are located outside the central system. PMID:27182682

  4. Detailed 1H and 13C NMR structural assignment and relative stereochemistry determination for three new and one known semi-synthetic sesquiterpene lactones

    NASA Astrophysics Data System (ADS)

    Sass, Daiane Cristina; Heleno, Vladimir Constantino Gomes; Soares, Ana Carolina Ferreira; Lopes, João Luis Callegari; Constantino, Mauricio Gomes

    2012-01-01

    In this work is described a complete 1H and 13C NMR analysis for a group of four sesquiterpene lactones, three previously unknown. The unequivocal assignments were achieved by 1H NMR, 13C{ 1H} NMR, J-resolved, gCOSY, gHMQC, gHMBC and NOESY experiments and no ambiguities were left behind. All hydrogen coupling constants were measured, clarifying all hydrogen signals multiplicities.

  5. Formal [4+2] cycloaddition of di-tert-butyl 2-ethoxycyclobutane-1,1-dicarboxylate with ketones or aldehydes and tandem lactonization.

    PubMed

    Okado, Ryohei; Nowaki, Aya; Matsuo, Jun-Ichi; Ishibashi, Hiroyuki

    2012-01-01

    A catalytic amount of tin(IV) chloride catalyzed formal [4+2] cycloaddition reaction of di-tert-butyl 2-ethoxycyclobutane-1,1-carboxylate with ketones or aldehydes to give diethyl 6-ethoxydihydro-2H-pyran-3,3(4H)-dicarboxylates, whereas two equivalents of trimethylsilyl triflate promoted tandem [4+2] cycloaddition and lactonization to afford 3-oxo-2,6-dioxabicyclo[2.2.2]octane-4-carboxylate esters. PMID:22223370

  6. Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine: a potential role for homoserine kinase in insect-stage Trypanosoma brucei.

    PubMed

    Ong, Han B; Lee, Wai S; Patterson, Stephen; Wyllie, Susan; Fairlamb, Alan H

    2015-01-01

    De novo synthesis of threonine from aspartate occurs via the β-aspartyl phosphate pathway in plants, bacteria and fungi. However, the Trypanosoma brucei genome encodes only the last two steps in this pathway: homoserine kinase (HSK) and threonine synthase. Here, we investigated the possible roles for this incomplete pathway through biochemical, genetic and nutritional studies. Purified recombinant TbHSK specifically phosphorylates L-homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype in vitro or loss of virulence in vivo. However, following transformation into procyclic forms, homoserine, homoserine lactone and certain acyl homoserine lactones (AHLs) were found to substitute for threonine in growth media for wild-type procyclics, but not HSK null mutants. The tsetse fly is considered to be an unlikely source of these nutrients as it feeds exclusively on mammalian blood. Bioinformatic studies predict that tsetse endosymbionts possess part (up to homoserine in Wigglesworthia glossinidia) or all of the β-aspartyl phosphate pathway (Sodalis glossinidius). In addition S. glossinidius is known to produce 3-oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that T. brucei has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting. PMID:25367138

  7. Unravelling the genome of long chain N-acylhomoserine lactone-producing Acinetobacter sp. strain GG2 and identification of its quorum sensing synthase gene

    PubMed Central

    How, Kah Yan; Hong, Kar-Wai; Sam, Choon-Kook; Koh, Chong-Lek; Yin, Wai-Fong; Chan, Kok-Gan

    2015-01-01

    Myriad proteobacteria use N-acyl homoserine lactone (AHL) molecules as quorum sensing (QS) signals to regulate different physiological functions, including virulence, antibiotic production, and biofilm formation. Many of these proteobacteria possess LuxI/LuxR system as the QS mechanism. Recently, we reported the 3.89 Mb genome of Acinetobacter sp. strain GG2. In this work, the genome of this long chain AHL-producing bacterium was unravelled which led to the molecular characterization of luxI homologue, designated as aciI. This 552 bp gene was cloned and overexpressed in Escherichia coli BL21(DE3). The purified protein was ∼20.5 kDa and is highly similar to several autoinducer proteins of LuxI family among Acinetobacter species. To verify the AHL synthesis activity of this protein, high-resolution liquid chromatography–mass spectrometry analysis revealed the production of 3-oxo-dodecanoyl-homoserine lactone and 3-hydroxy-dodecanoyl-homoserine lactone from induced E. coli harboring the recombinant AciI. Our data show for the first time, the cloning and characterization of the luxI homologue from Acinetobacter sp. strain GG2, and confirmation of its AHLs production. These data are of great significance as the annotated genome of strain GG2 has provided a valuable insight in the study of autoinducer molecules and its roles in QS mechanism of the bacterium. PMID:25926817

  8. Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine: a potential role for homoserine kinase in insect-stage Trypanosoma brucei

    PubMed Central

    Ong, Han B; Lee, Wai S; Patterson, Stephen; Wyllie, Susan; Fairlamb, Alan H

    2015-01-01

    De novo synthesis of threonine from aspartate occurs via the β-aspartyl phosphate pathway in plants, bacteria and fungi. However, the Trypanosoma brucei genome encodes only the last two steps in this pathway: homoserine kinase (HSK) and threonine synthase. Here, we investigated the possible roles for this incomplete pathway through biochemical, genetic and nutritional studies. Purified recombinant TbHSK specifically phosphorylates L-homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype in vitro or loss of virulence in vivo. However, following transformation into procyclic forms, homoserine, homoserine lactone and certain acyl homoserine lactones (AHLs) were found to substitute for threonine in growth media for wild-type procyclics, but not HSK null mutants. The tsetse fly is considered to be an unlikely source of these nutrients as it feeds exclusively on mammalian blood. Bioinformatic studies predict that tsetse endosymbionts possess part (up to homoserine in Wigglesworthia glossinidia) or all of the β-aspartyl phosphate pathway (Sodalis glossinidius). In addition S. glossinidius is known to produce 3-oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that T. brucei has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting. PMID:25367138

  9. A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line.

    PubMed Central

    Fenteany, G; Standaert, R F; Reichard, G A; Corey, E J; Schreiber, S L

    1994-01-01

    Lactacystin, a microbial natural product, induces neurite outgrowth in Neuro 2A mouse neuroblastoma cells and inhibits progression of synchronized Neuro 2A cells and MG-63 human osteosarcoma cells beyond the G1 phase of the cell cycle. A related beta-lactone, clasto-lactacystin beta-lactone, formally the product of elimination of N-acetylcysteine from lactacystin, is also active, whereas the corresponding clastolactacystin dihydroxy acid is completely inactive. Structural analogs of lactacystin altered only in the N-acetylcysteine moiety are active, while structural or stereochemical modifications of the gamma-lactam ring or the hydroxyisobutyl group lead to partial or complete loss of activity. The inactive compounds do not antagonize the effects of lactacystin in either neurite outgrowth or cell cycle progression assays. The response to lactacystin involves induction of a predominantly bipolar morphology that is maximal 16-32 h after treatment and is distinct from the response to several other treatments that result in morphological differentiation. Neurite outgrowth in response to lactacystin appears to be dependent upon microtubule assembly, actin polymerization, and de novo protein synthesis. The observed structure-activity relationships suggest that lactacystin and its related beta-lactone may act via acylation of one or more relevant target molecule(s) in the cell. Images PMID:8159752

  10. Vitamin B12[c-lactone], a biologically inactive corrinoid compound, occurs in cultured and dried lion's mane mushroom (Hericium erinaceus) fruiting bodies.

    PubMed

    Teng, Fei; Bito, Tomohiro; Takenaka, Shigeo; Yabuta, Yukinori; Watanabe, Fumio

    2014-02-19

    This study determined the vitamin B12 content of the edible medicinal mushroom Hericium erinaceus, lion's mane mushroom fruiting body, using a microbiological assay based on Lactobacillus delbrueckii ATCC 7830. Trace levels (0.04-0.36 μg/100 g dry weight) of vitamin B12 were found in most of the dried mushroom samples, and two samples contained slightly higher levels (0.56 and 1.04 μg/100 g dry weight, respectively) of vitamin B12. We purified the corrinoid compounds from the extracts of dried lion's mane mushroom fruiting bodies using an immunoaffinity column and identified them as vitamin B12 or vitamin B12[c-lactone] (or both) based on LC/ESI-MS/MS chromatograms. This is the first report on an unnatural corrinoid, vitamin B12[c-lactone], occurring in foods. Vitamin B12[c-lactone] was simple to produce during incubation of authentic vitamin B12 and chloramine-T, an antimicrobial agent, at varying pH values (3.0-7.0) and was completely inactive in the vitamin B12-dependent bacteria that are generally used in vitamin B12 bioassays. PMID:24506286

  11. Asymmetric Synthesis, Structure, and Reactivity of Unexpectedly Stable Spiroepoxy-β-Lactones Including Facile Conversion to Tetronic Acids: Application to (+)-Maculalactone A

    PubMed Central

    Duffy, Richard J.; Morris, Kay A.; Vallakati, Ravikrishna; Zhang, Wei; Romo, Daniel

    2009-01-01

    A novel class of small spirocyclic heterocycles, spiroepoxy-β-lactones (1,4-dioxaspiro[2.3]-hexan-5-ones), is described that exhibit a number of interesting reactivity patterns. These spiroheterocycles, including an optically active series, are readily synthesized by epoxidation of ketene dimers (4-alkylidene-2-oxetanones) available from homo- or heteroketene dimerization. An analysis of bond lengths in these systems by X-ray crystallography and comparison to data for known spirocycles and those determined computationally, suggest that anomeric effects in these systems may be more pronounced due to their rigidity and may contribute to their surprising stability. The synthetic utility of spiroepoxy-β-lactones was explored and one facile rearrangement identified under several conditions provides a 3-step route from acid chlorides to optically active tetronic acids, ubiquitous heterocycles in bioactive natural products. The addition of various nucleophiles to these spirocycles leads primarily to addition at C5 and C2. The utility of an optically active spiroepoxy-β-lactone was demonstrated in the concise, enantioselective synthesis of the anti-fouling agent, (+)-maculalactone A, which proceeds in 5 steps from hydrocinnamoyl chloride by way of a tetronic acid intermediate. PMID:19453152

  12. Asymmetric synthesis, structure, and reactivity of unexpectedly stable spiroepoxy-beta-lactones including facile conversion to tetronic acids: application to (+)-maculalactone A.

    PubMed

    Duffy, Richard J; Morris, Kay A; Vallakati, Ravikrishna; Zhang, Wei; Romo, Daniel

    2009-07-01

    A novel class of small spirocyclic heterocycles, spiroepoxy-beta-lactones (1,4-dioxaspiro[2.3]-hexan-5-ones), is described that exhibit a number of interesting reactivity patterns. These spiroheterocycles, including an optically active series, are readily synthesized by epoxidation of ketene dimers (4-alkylidene-2-oxetanones) available from homo- or heteroketene dimerization. An analysis of bond lengths in these systems by X-ray crystallography and comparison to data for known spirocycles and those determined computationally suggest that anomeric effects in these systems may be more pronounced due to their rigidity and may contribute to their surprising stability. The synthetic utility of spiroepoxy-beta-lactones was explored, and one facile rearrangement identified under several conditions provides a three-step route from acid chlorides to optically active tetronic acids, ubiquitous heterocycles in bioactive natural products. The addition of various nucleophiles to these spirocycles leads primarily to addition at C5 and C2. The utility of an optically active spiroepoxy-beta-lactone was demonstrated in the concise, enantioselective synthesis of the antifouling agent, (+)-maculalactone A, which proceeds in five steps from hydrocinnamoyl chloride by way of a tetronic acid intermediate. PMID:19453152

  13. Alkaloids from Pandanus amaryllifolius: Isolation and Their Plausible Biosynthetic Formation.

    PubMed

    Tsai, Yu-Chi; Yu, Meng-Lun; El-Shazly, Mohamed; Beerhues, Ludger; Cheng, Yuan-Bin; Chen, Lei-Chin; Hwang, Tsong-Long; Chen, Hui-Fen; Chung, Yu-Ming; Hou, Ming-Feng; Wu, Yang-Chang; Chang, Fang-Rong

    2015-10-23

    Pandanus amaryllifolius Roxb. (Pandanaceae) is used as a flavor and in folk medicine in Southeast Asia. The ethanolic crude extract of the aerial parts of P. amaryllifolius exhibited antioxidant, antibiofilm, and anti-inflammatory activities in previous studies. In the current investigation, the purification of the ethanolic extract yielded nine new compounds, including N-acetylnorpandamarilactonines A (1) and B (2); pandalizines A (3) and B (4); pandanmenyamine (5); pandamarilactones 2 (6) and 3 (7), and 5(E)-pandamarilactonine-32 (8); and pandalactonine (9). The isolated alkaloids, with either a γ-alkylidene-α,β-unsaturated-γ-lactone or γ-alkylidene-α,β-unsaturated-γ-lactam system, can be classified into five skeletons including norpandamarilactonine, indolizinone, pandanamine, pandamarilactone, and pandamarilactonine. A plausible biosynthetic route toward 1-5, 7, and 9 is proposed. PMID:26461164

  14. Simple Preparation of Rhodococcus erythropolis DSM 44534 as Biocatalyst to Oxidize Diols into the Optically Active Lactones.

    PubMed

    Martinez-Rojas, Enriqueta; Olejniczak, Teresa; Neumann, Konrad; Garbe, Leif-Alexander; Boratyñski, Filip

    2016-09-01

    In the current study, we present a green toolbox to produce ecological compounds like lactone moiety. Rhodococcus erythropolis DSM 44534 cells have been used to oxidize both decane-1,4-diol () and decane-1,5-diol () into the corresponding γ- () and δ-decalactones () with yield of 80% and enantiomeric excess (ee) = 75% and ee = 90%, respectively. Among oxidation of meso diols, (-)-(1S,5R)-cis-3-oxabicyclo[4.3.0]non-7-en-2-one (5a) with 56% yield and ee = 76% as well as (-)-(2R,3S)-cis-endo-3-oxabicyclo[2.2.1]dec-7-en-2-one (6a) with 100% yield and ee = 90% were formed. It is worth mentioning that R. erythropolis DSM 44534 grew in a mineral medium containing ethanol as the sole source of energy and carbon Chirality 28:623-627, 2016. © 2016 Wiley Periodicals, Inc. PMID:27496202

  15. Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target

    PubMed Central

    Chang, Chien-Yi; Krishnan, Thiba; Wang, Hao; Chen, Ye; Yin, Wai-Fong; Chong, Yee-Meng; Tan, Li Ying; Chong, Teik Min; Chan, Kok-Gan

    2014-01-01

    N-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography–mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach. PMID:25430794

  16. Effects of High-Pressure, Microbial Transglutaminase and Glucono-δ-Lactone on the Aggregation Properties of Skim Milk.

    PubMed

    Lee, Sang Yoon; Choi, Mi-Jung; Cho, Hyung-Yong; Davaatseren, Munkhtugs

    2016-01-01

    The object in this study is to investigate the effects of high pressure and freezing processes on the curdling of skim milk depending on the presence of transglutaminase (TGase) and glucono-δ-lactone (GdL). Skim milk was treated with atmospheric freezing (AF), high pressure (HP), pressure-shift freezing (PSF) and high pressure sub-zero temperature (HPST) processing conditions. After freezing and pressure processing, these processed milk samples were treated with curdling agents, such as TGase and GdL. Pressurized samples (HP, PSF and HPST) had lower lightness than that of the control. In particular, PSF had the lowest lightness (p<0.05). Likewise, the PSF proteins were the most insoluble regardless of whether they were activated by TGase and GdL, indicating the highest rate of protein aggregation (p<0.05). Furthermore, the TGase/GdL reaction resulted in thick bands corresponding to masses larger than 69 kDa, indicating curdling. Casein bands were the weakest in PSF-treated milk, revealing that casein was prone to protein aggregation. PSF also had the highest G' value among all treatments after activation by TGase, implying that PSF formed the hardest curd. However, adding GdL decreased the G' values of the samples except HPST-treated samples. Synthetically, the PSF process was advantageous for curdling of skim milk. PMID:27433104

  17. Genomic analysis reveals versatile organisms for quorum quenching enzymes: acyl-homoserine lactone-acylase and -lactonase.

    PubMed

    Kalia, Vipin Chandra; Raju, Sajan C; Purohit, Hemant J

    2011-01-01

    Microbial virulence and their resistance to multiple drugs have obliged researchers to look for novel drug targets. Virulence of pathogenic microbes is regulated by signal molecules such as acylated homoserine lactone (AHL) produced during a cell density dependent phenomenon of quorum sensing (QS). In contrast, certain microbes produce AHL-lactonases and -acylases to degrade QS signals, also termed as quorum quenching. Mining sequenced genome databases has revealed organisms possessing conserved domains for AHL-lactonases and -acylases: i) Streptomyces (Actinobacteria), ii) Deinococcus (Deinococcus-Thermus), iii) Hyphomonas (α-Proteobacteria), iv) Ralstonia (β-Proteobacteria), v) Photorhabdus (γ-Proteobacteria), and certain marine gamma proteobacterium. Presence of genes for both the enzymes within an organism was observed in the following: i) Deinococcus radiodurans R1, ii) Hyphomonas neptunium ATCC 15444 and iii) Photorhabdus luminescens subsp. laumondii TTO1. These observations are supported by the presence motifs for lactonase and acylase in these strains. Phylogenetic analysis and multiple sequence alignment of the gene sequences for AHL-lactonases and -acylases have revealed consensus sequences which can be used to design primers for amplifying these genes even among mixed cultures and metagenomes. Quorum quenching can be exploited to prevent food spoilage, bacterial infections and bioremediation. PMID:21660112

  18. Anthelmintic activity of chicory (Cichorium intybus): in vitro effects on swine nematodes and relationship to sesquiterpene lactone composition.

    PubMed

    Williams, Andrew R; Peña-Espinoza, Miguel A; Boas, Ulrik; Simonsen, Henrik T; Enemark, Heidi L; Thamsborg, Stig M

    2016-05-01

    Chicory is a perennial crop that has been investigated as a forage source for outdoor-reared ruminants and pigs, and has been reported to have anthelmintic properties. Here, we investigated in vitro anthelmintic effects of forage chicory-extracts against the highly prevalent swine parasites Ascaris suum and Oesophagostomum dentatum. Methanol extracts were prepared and purified from two different cultivars of chicory (Spadona and Puna II). Marked differences were observed between the anthelmintic activity of extracts from the two cultivars. Spadona extracts had potent activity against A. suum third (L3) and fourth (L4) - stage larvae, as well as O. dentatum L4 and adults, whereas Puna II extracts had less activity against A. suum and no activity towards O. dentatum L4. Transmission-electron microscopy of A. suum L4 exposed to Spadona extracts revealed only subtle changes, perhaps indicative of a specific anthelmintic effect rather than generalized toxicity. Ultra-high liquid chromatography-mass spectrometry analysis revealed that the purified extracts were rich in sesquiterpene lactones (SL), and that the SL profile differed significantly between cultivars. This is the first report of anthelmintic activity of forage chicory towards swine nematodes. Our results indicate a significant anthelmintic effect, which may possibly be related to SL composition. PMID:26935644

  19. Sodium houttuyfonate affects production of N-acyl homoserine lactone and quorum sensing-regulated genes expression in Pseudomonas aeruginosa

    PubMed Central

    Wu, Daqiang; Huang, Weifeng; Duan, Qiangjun; Li, Fang; Cheng, Huijuan

    2014-01-01

    Quorum sensing (QS) is a means of cell-to-cell communication that uses diffusible signaling molecules that are sensed by the population to determine population density, thus allowing co-ordinate gene regulation in response to population density. In Pseudomonas aeruginosa, production of the QS signaling molecule, N-acyl homoserine lactone (AHL), co-ordinates expression of key factors of pathogenesis, including biofilm formation and toxin secretion. It is predicted that the inhibition of AHL sensing would provide an effective clinical treatment to reduce the expression of virulence factors and increase the effectiveness of antimicrobial agents. We previously demonstrated that sodium houttuyfonate (SH), commonly used in traditional Chinese medicine to treat infectious diseases, can effectively inhibit QS-regulated processes, including biofilm formation. Here, using a model system, we demonstrate that SH causes the dose-dependent inhibition of AHL production, through down-regulation of the AHL biosynthesis gene, lasI. Addition of SH also resulted in down-regulation of expression of the AHL sensor and transcriptional regulator, LasR, and inhibited the production of the QS-regulated virulence factors, pyocyanin and LasA. These results suggest that the antimicrobial activity of SH may be due to its ability to disrupt QS in P. aeruginosa. PMID:25505457

  20. Effects of High-Pressure, Microbial Transglutaminase and Glucono-δ-Lactone on the Aggregation Properties of Skim Milk

    PubMed Central

    Lee, Sang Yoon; Choi, Mi-Jung; Cho, Hyung-Yong

    2016-01-01

    The object in this study is to investigate the effects of high pressure and freezing processes on the curdling of skim milk depending on the presence of transglutaminase (TGase) and glucono-δ-lactone (GdL). Skim milk was treated with atmospheric freezing (AF), high pressure (HP), pressure-shift freezing (PSF) and high pressure sub-zero temperature (HPST) processing conditions. After freezing and pressure processing, these processed milk samples were treated with curdling agents, such as TGase and GdL. Pressurized samples (HP, PSF and HPST) had lower lightness than that of the control. In particular, PSF had the lowest lightness (p<0.05). Likewise, the PSF proteins were the most insoluble regardless of whether they were activated by TGase and GdL, indicating the highest rate of protein aggregation (p<0.05). Furthermore, the TGase/GdL reaction resulted in thick bands corresponding to masses larger than 69 kDa, indicating curdling. Casein bands were the weakest in PSF-treated milk, revealing that casein was prone to protein aggregation. PSF also had the highest G' value among all treatments after activation by TGase, implying that PSF formed the hardest curd. However, adding GdL decreased the G' values of the samples except HPST-treated samples. Synthetically, the PSF process was advantageous for curdling of skim milk. PMID:27433104

  1. A Method for the Simultaneous Determination of Chlorogenic Acid and Sesquiterpene Lactone Content in Industrial Chicory Root Foodstuffs

    PubMed Central

    Hance, Philippe; Fertin, Anne; Voedts, Najia; Duhal, Nathalie; Goossens, Jean-François; Hilbert, Jean-Louis

    2014-01-01

    A method for the simultaneous determination of free chlorogenic acids (CGA) and sesquiterpene lactones (STL) in chicory root and its dried (flour) and roasted (grain) forms is described. The method uses one extraction and one analysis for all chicory root products. Various solvents with low to high polarity, such as methanol, chloroform, or n-hexane, were tested alone, in combination in different proportions or with acidified or neutral aqueous solvent. The water/chloroform/methanol (30/30/40, v/v/v) mixture generated the best extraction yield, 21% higher than alcohol mixtures. The profiling of CGA and STL content was performed through a conventional HPLC-DAD method using a PFP core shell column in a fast single run. Good retention time and area repeatability (RDD mean % 0.46 and 5.6, resp.) and linearity (R2 ≥ 0.96) were obtained. The STL and chlorogenic acids levels determined were 254.7 and 100.2 μg/g of dry matter in the root, 792.5 and 1,547 μg/g in flour, and 160.4 and 822.5 μg/g in the roasted grains, respectively. With an average recovery of 106% and precision of 90%, this method is rapid, reproducible, and straightforward way to quantify the chlorogenic acids and STL in chicory raw material and end products. PMID:25548785

  2. The Molting Biomarker Metabolite N-acetylglucosamino-1,5-lactone in Female Urine of the Helmet Crab Telmessus cheiragonus.

    PubMed

    Yano, Hirona; Kamio, Michiya; Nagai, Hiroshi

    2016-04-01

    N-acetylglucosamino-1,5-lactone (NAGL) is a molting biomarker in the blue crab Callinectes sapidus The concentration of this compound in urine is highest at the premolt stage. Since sexually mature premolt females release sex pheromone in their urine, NAGL is a candidate sex pheromone molecule in C. sapidus This compound has not been reported in other species. In the present study, we quantified the concentration of NAGL in the urine of the helmet crab Telmessus cheiragonus, using nuclear magnetic resonance spectroscopy, and found that the concentration increases toward the day of molting and decreases after molting. However, the total amount of NAGL collected from individual animals was greatest two to five days after molting, because the amount of urine collected was the lowest at the premolt stage, and it increased after molting. The highest median concentration of NAGL in T. cheiragonas was 29 μmol l(-1), which is 75% of the highest concentration reported in C. sapidus This is the first report of NAGL as a molting biomarker in a species other than C. sapidus We assume that NAGL is part of a pheromone bouquet in these two species. PMID:27132136

  3. Synthesis of Gold Mediated Biocompatible Nanocomposite of Lactone Enriched Fraction from Sahadevi (Vernonia cinerea Lees): An Assessment of Antimalarial Potential.

    PubMed

    Jyotshna; Shanker, Karuna; Khare, Puja; Tiwari, Nimisha; Mohanty, Shilpa; Bawankule, Dnyaneshwar U; Pal, Anirban

    2016-01-01

    Metals reduction into submicro/nano size through bhasma preparations for therapeutic use is well established in ancient traditional system of Indian medicines i.e. Ayurveda. Recently, nanotechnology has drawn the attention of researchers to develeope various size and shape nanoparicles / composite for number of applications.In this article, we report the enrichment of lactone enriched fraction (LEF) by liquid-liquid portioning of Vernonia cinerea metabolic extract and sysnthesis of mediated nano-gold composite (LEF-AuNPs) in single step process. The morphological characteristic based on transmission electron microscope (TEM) image analysis showed that LEF-AuNPs were predominantly nanopolygons and nanobots in shapes ranging from 50-200 nm in size. Abundance of phytochemicals in both LEF and LEF-AuNPs was dissimilar. In LEF, montanol- a diterpenoid, while in LEF-AuNPs, neophytadiene- a phytanes was the major compound. HPLC profile of relatively polar compounds also varied drastically. In-vitro biocompatibility, cytotoxicity [MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) based assay] and storage stabilitiy of LEF-AuNPs were evaluated. The moderate ability of LEF-AuNPs to restrict parasitaemia, extended mean survival time of mice infected with Plasmodium berghei and lack of any evident toxicity provides new opportunities for the safe delivery and applications of such nanocomposites in malaria therapy. PMID:26876516

  4. Genomic Analysis Reveals Versatile Organisms for Quorum Quenching Enzymes: Acyl-Homoserine Lactone-Acylase and -Lactonase

    PubMed Central

    Kalia, Vipin Chandra; Raju, Sajan C; Purohit, Hemant J

    2011-01-01

    Microbial virulence and their resistance to multiple drugs have obliged researchers to look for novel drug targets. Virulence of pathogenic microbes is regulated by signal molecules such as acylated homoserine lactone (AHL) produced during a cell density dependent phenomenon of quorum sensing (QS). In contrast, certain microbes produce AHL-lactonases and -acylases to degrade QS signals, also termed as quorum quenching. Mining sequenced genome databases has revealed organisms possessing conserved domains for AHL-lactonases and –acylases: i) Streptomyces (Actinobacteria), ii) Deinococcus (Deinococcus-Thermus), iii) Hyphomonas (α-Proteobacteria), iv) Ralstonia (β-Proteobacteria), v) Photorhabdus (γ-Proteobacteria), and certain marine gamma proteobacterium. Presence of genes for both the enzymes within an organism was observed in the following: i) Deinococcus radiodurans R1, ii) Hyphomonas neptunium ATCC 15444 and iii) Photorhabdus luminescens subsp. laumondii TTO1. These observations are supported by the presence motifs for lactonase and acylase in these strains. Phylogenetic analysis and multiple sequence alignment of the gene sequences for AHL-lactonases and –acylases have revealed consensus sequences which can be used to design primers for amplifying these genes even among mixed cultures and metagenomes. Quorum quenching can be exploited to prevent food spoilage, bacterial infections and bioremediation. PMID:21660112

  5. So different and still so similar: The plant compound rosmarinic acid mimics bacterial homoserine lactone quorum sensing signals

    PubMed Central

    Corral-Lugo, Andrés; Daddaoua, Abdelali; Ortega, Alvaro; Espinosa-Urgel, Manuel; Krell, Tino

    2016-01-01

    ABSTRACT Apart from inter-bacteria communication quorum sensing (QS) mechanisms also enable inter-domain interactions. To interfere with bacterial QS, plants were found to secrete compounds; most of which of unknown identity. We have identified the plant compound rosmarinic acid (RA) to modulate Pseudomonas aeruginosa QS by binding to the RhlR QS regulator. RA was found to be a homoserine-lactone (HSL) mimic that caused agonistic effects on transcription, resulting ultimately in a stimulation of several RhlR controlled phenotypes like virulence factor synthesis or biofilm formation. Our study was initiated by in silico screening of an RhlR model with compound libraries, demonstrating that this approach is suitable to tackle a major bottleneck in signal transduction research, which is the identification of sensor protein ligands. Previous work has shown that plant compounds interfere with the function of orphan QS regulators. Our study demonstrates that this has not necessarily to be the case since RhlR forms a functional pair with the RhlI synthase. A wide range of structurally dissimilar compounds have been found to mimic HSLs suggesting that this class of QS regulators is characterized by a significant plasticity in the recognition of effector molecules. Further research will show to what extent RA impacts on QS mechanisms of other bacteria. PMID:27195067

  6. Influences of "spasmolytic powder" on pgp expression of Coriaria Lactone-kindling drug-resistant epileptic rat model.

    PubMed

    Chen, Lei; Feng, Peimin; Li, Yaohua; Zhou, Dong

    2013-09-01

    The earliest records of traditional Chinese medicine (TCM) prevention and treatment of epilepsy dated back to famous "Huang Di Nei Jing." TCM "spasmolytic powder" (equal-ratio compatibility of scorpion and centipede) is a famous prescription which was recognized as a useful add-on drug for refractory epilepsy in clinical observations. Multidrug resistance gene (mdr1) product Pgp overexpression in blood-brain barrier and blood-cerebrospinal fluid barrier is well recognized as the drug resistance mechanism of refractory epilepsy. Here, we established the drug-resistant epilepsy Sprague-Dawley rat model induced by Coriaria Lactone and treated these rats with topiramate and verapamil and low dose, middle dose, and high dose of spasmolytic powder by intragastric administration for 1 week. Electroencephalogram, real-time PCR, and immunohistochemistry were respectively used to detect epileptic discharge frequencies and amplitudes and expression of mdrl mRNA and Pgp on hippocampus and temporal lobe of rats. The results showed that the seizure decreases significantly in the high- and middle-dose groups of spasmolytic powder and topiramate group; in addition, mdr1 mRNA and Pgp expressions on hippocampus and temporal lobe of these drug intervention groups were significantly less than the model group (P < 0.05). These findings indicate that inhibition of intracephalic Pgp expression is possibly one of mechanisms of spasmolytic powder treating refractory epilepsy. PMID:23263794

  7. 4-Hydroxy-7-oxo-5-heptenoic Acid (HOHA) Lactone is a Biologically Active Precursor for the Generation of 2-(ω-Carboxyethyl)pyrrole (CEP) Derivatives of Proteins and Ethanolamine Phospholipids.

    PubMed

    Wang, Hua; Linetsky, Mikhail; Guo, Junhong; Choi, Jaewoo; Hong, Li; Chamberlain, Amanda S; Howell, Scott J; Howes, Andrew M; Salomon, Robert G

    2015-05-18

    2-(ω-Carboxyethyl)pyrrole (CEP) derivatives of proteins were previously shown to have significant pathological and physiological relevance to age-related macular degeneration, cancer and wound healing. Previously, we showed that CEPs are generated in the reaction of ε-amino groups of protein lysyl residues with 1-palmityl-2-(4-hydroxy-7-oxo-5-heptenoyl)-sn-glycero-3-phosphatidylcholine (HOHA-PC), a lipid oxidation product uniquely generated by oxidative truncation of docosahexanenate-containing phosphatidylcholine. More recently, we found that HOHA-PC rapidly releases HOHA-lactone and 2-lyso-PC (t1/2 = 30 min at 37 °C) by nonenzymatic transesterification/deacylation. Now we report that HOHA-lactone reacts with Ac-Gly-Lys-OMe or human serum albumin to form CEP derivatives in vitro. Incubation of human red blood cell ghosts with HOHA-lactone generates CEP derivatives of membrane proteins and ethanolamine phospholipids. Quantitative analysis of the products generated in the reaction HOHA-PC with Ac-Gly-Lys-OMe showed that HOHA-PC mainly forms CEP-dipeptide that is not esterified to 2-lysophosphatidycholine. Thus, the HOHA-lactone pathway predominates over the direct reaction of HOHA-PC to produce the CEP-PC-dipeptide derivative. Myleoperoxidase/H2O2/NO2(-) promoted in vitro oxidation of either 1-palmityl-2-docosahexaneoyl-sn-glycero-3-phosphatidylcholine (DHA-PC) or docosahexaenoic acid (DHA) generates HOHA-lactone in yields of 0.45% and 0.78%, respectively. Lipid oxidation in human red blood cell ghosts also releases HOHA-lactone. Oxidative injury of ARPE-19 human retinal pigmented epithelial cells by exposure to H2O2 generated CEP derivatives. Treatment of ARPE-19 cells with HOHA-lactone generated CEP-modified proteins. Low (submicromolar), but not high, concentrations of HOHA-lactone promote increased vascular endothelial growth factor (VEGF) secretion by ARPE-19 cells. Therefore, HOHA-lactone not only serves as an intermediate for the generation of CEPs but

  8. Identification of N-acyl-l-homoserine lactones produced by non-pigmented Chromobacterium aquaticum CC-SEYA-1(T) and pigmented Chromobacterium subtsugae PRAA4-1(T).

    PubMed

    Rekha, P D; Young, Chiu-Chung; Arun, A B

    2011-12-01

    Many members of the genus Chromobacterium produce violacein, a characteristic purple pigment which is induced by small diffusible N-acyl homoserine lactones (AHL) quorum-sensing molecules. In this study, the production of AHL of the non-pigmented C. aquaticum CC-SEYA-1(T) and the pigmented C. subtsugae PRAA4-1(T) were determined by using a CV026 biosensor assay. The profile of AHL was identified from the extracts of stationary phase cultures using gas chromatography-mass spectroscopy (GC-MS) and thin layer chromatography (TLC). CV026 biosensor assay revealed that both the non-pigmented C. aquaticum CC-SEYA-1(T) and the pigmented C. subtsugae PRAA4-1(T) produced AHL molecules, which were identified, respectively, as N-octanoyl homoserine lactone (OHL) [also known as C-8 homoserine lactone (C8-HSL)] and N-hexanoyl homoserine lactone (HHL) [also known as C-6 homoserine lactone (C6-HSL)]. The pigment produced by C. subtsugae PRAA4-1(T) was similar to that of Chromobacterium violaceum ATCC12472(T) but no characteristic visible spectral peaks of the pigment were observed in the extracts of C. aquaticum CC-SEYA-1(T). In addition, C. aquaticum CC-SEYA-1(T) and C. subtsugae PRAA4-1(T) showed hemolytic activities. PMID:22558542

  9. Differential growth inhibitory effects of highly oxygenated guaianolides isolated from the Middle Eastern indigenous plant Achillea falcata in HCT-116 colorectal cancer cells.

    PubMed

    Tohme, Rita; Al Aaraj, Lamis; Ghaddar, Tarek; Gali-Muhtasib, Hala; Saliba, Najat A; Darwiche, Nadine

    2013-01-01

    Medicinal plants play a crucial role in traditional medicine and in the maintenance of human health worldwide. Sesquiterpene lactones represent an interesting group of plant-derived compounds that are currently being tested as lead drugs in cancer clinical trials. Achillea falcata is a medicinal plant indigenous to the Middle Eastern region and belongs to the Asteraceae family, which is known to be rich in sesquiterpene lactones. We subjected Achillea falcata extracts to bioassay-guided fractionation against the growth of HCT-116 colorectal cancer cells and identified four secotanapartholides, namely 3-β-methoxy-isosecotanapartholide (1), isosecotanapartholide (2), tanaphallin (3), and 8-hydroxy-3-methoxyisosecotanapartholide (4). Three highly oxygenated guaianolides were isolated for the first time from Achillea falcata, namely rupin A (5), chrysartemin B (6), and 1β, 2β-epoxy-3β,4α,10α-trihydroxyguaian-6α,12-olide (7). These sesquiterpene lactones showed no or minor cytotoxicity while exhibiting promising anticancer effects against HCT-116 cells. Further structure-activity relationship studies related the bioactivity of the tested compounds to their skeleton, their lipophilicity, and to the type of functional groups neighboring the main alkylating center of the molecule. PMID:23860275

  10. Inhibition of rabbit muscle glycogen phosphorylase by D-gluconohydroximo-1,5-lactone-N-phenylurethane.

    PubMed

    Papageorgiou, A C; Oikonomakos, N G; Leonidas, D D

    1989-08-01

    The effect of the beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone-N-phenylurethane (PUG) on the kinetic and ultracentrifugation properties of glycogen phosphorylase has been studied. Recent crystallographic work at 2.4 A resolution [D. Barford et al. (1988) Biochemistry 27, 6733-6741] has shown that PUG binds in the catalytic site of phosphorylase b crystals with its gluconohydroximolactone moiety occupying a position similar to that observed for other glucosyl compounds and the N-phenylurethane side chain fitting into an adjacent cavity with little conformational change in the enzyme. In solution, PUG was shown to be a potent inhibitor of phosphorylase b, directly competitive with alpha-D-glucopyranose 1-phosphate (glucose-1-P) (Ki = 0.40 mM) and noncompetitive with respect to glycogen and AMP. When PUG was tested for synergistic inhibition in the presence of caffeine, the Dixon plots of reciprocal velocity versus PUG concentration at different fixed caffeine concentrations provided intersecting lines with interaction constant (alpha) values of 0.95-1.38, indicating that the binding of one inhibitor is not significantly affected by the binding of the other. For glycogen phosphorolysis, PUG was noncompetitive with respect to phosphate, suggesting that it can bind to the central enzyme-AMP-glycogen-phosphate complex. PUG was shown to inhibit phosphorylase alpha (without AMP) activity (Ki = 0.43 mM) in a manner similar to that of the b form. However, in the presence of AMP, PUG exhibited complex kinetics, acting as a noncompetitive inhibitor with respect to glucose-1-P, while a twofold decrease of PUG binding to the enzyme-AMP-glycogen complex was observed. Ultracentrifugation experiments demonstrated that PUG does not cause any significant dissociation of phosphorylase alpha tetramer. Furthermore the dimerization of phosphorylase alpha by glucose is completely prevented in the presence of PUG. These observations are consistent with PUG binding to both the

  11. Dehydrocostuslactone, a medicinal plant-derived sesquiterpene lactone, induces apoptosis coupled to endoplasmic reticulum stress in liver cancer cells.

    PubMed

    Hsu, Ya-Ling; Wu, Ling-Yu; Kuo, Po-Lin

    2009-05-01

    This study is the first to investigate the anticancer effect of dehydrocostuslactone [DHE (3aS,6aR,9aR,9bS)-decahydro-3,6,9-tris(methylene) azuleno[4,5-b]furan-2(3H)-one)], a medicinal plant-derived sesquiterpene lactone, on hepatocellular carcinoma. Our results showed that DHE inhibits the proliferation of HepG2 and PLC/PRF/5 cells by inducing apoptosis. DHE induces up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, and nuclear relocation of the mitochondrial factors apoptosis-inducing factor (AIF) and endonuclease G (Endo G). DHE triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol-calcium levels, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase phosphorylation, inositol-requiring protein 1 (IRE1) and CHOP/GADD153 up-regulation, X-box transcription factor-1 mRNA splicing, and caspase-4 activation. Enhancement of ER stress by DHE is through p38 and extracellular signal-regulated kinase 1/2-dependent manners and subsequently causes c-Jun NH(2)-terminal kinase activation, resulting in AIF and Endo G nuclear relocation. Both of IRE1 small interfering RNA transfection and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester pretreatment inhibit DHE-mediated apoptosis, supporting the hypothesis that DHE induces cell death through ER stress. It is noteworthy that animal studies have revealed a dramatic 50% reduction in tumor volume after 45 days of treatment. This study demonstrates that DHE may be a novel anticancer agent for the treatment of liver cancer. PMID:19188481

  12. Plant Responses to Bacterial N-Acyl l-Homoserine Lactones are Dependent on Enzymatic Degradation to l-Homoserine

    PubMed Central

    2015-01-01

    Many bacteria use quorum sensing (QS) to regulate phenotypes that ultimately benefit the bacterial population at high cell densities. These QS-dependent phenotypes are diverse and can have significant impacts on the bacterial host, including virulence factor production, motility, biofilm formation, bioluminescence, and root nodulation. As bacteria and their eukaryotic hosts have coevolved over millions of years, it is not surprising that certain hosts appear to be able to sense QS signals, potentially allowing them to alter QS outcomes. Recent experiments have established that eukaryotes have marked responses to the N-acyl l-homoserine lactone (AHL) signals used by Gram-negative bacteria for QS, and the responses of plants to AHLs have received considerable scrutiny to date. However, the molecular mechanisms by which plants, and eukaryotes in general, sense bacterial AHLs remain unclear. Herein, we report a systematic analysis of the responses of the model plants Arabidopsis thaliana and Medicago truncatula to a series of native AHLs and byproducts thereof. Our results establish that AHLs can significantly alter seedling growth in an acyl-chain length dependent manner. Based upon A. thaliana knockout studies and in vitro biochemical assays, we conclude that the observed growth effects are dependent upon AHL amidolysis by a plant-derived fatty acid amide hydrolase (FAAH) to yield l-homoserine. The accumulation of l-homoserine appears to encourage plant growth at low concentrations by stimulating transpiration, while higher concentrations inhibit growth by stimulating ethylene production. These results offer new insights into the mechanisms by which plant hosts can respond to QS signals and the potential role of QS in interkingdom associations. PMID:24918118

  13. Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.

    PubMed

    Tao, Shiyu; Luo, Yanwen; Bin He; Liu, Jie; Qian, Xi; Ni, Yingdong; Zhao, Ruqian

    2016-01-01

    A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL's effect on intestinal mucus barrier function. PMID:27364593

  14. Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone

    PubMed Central

    Tao, Shiyu; Luo, Yanwen; Bin He; Liu, Jie; Qian, Xi; Ni, Yingdong; Zhao, Ruqian

    2016-01-01

    A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL’s effect on intestinal mucus barrier function. PMID:27364593

  15. Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats.

    PubMed

    Gardiner, S M; Chhabra, S R; Harty, C; Williams, P; Pritchard, D I; Bycroft, B W; Bennett, T

    2001-08-01

    N-acylhomoserine lactones (AHLs) are small, diffusible signalling molecules, employed by Gram-negative bacteria to coordinate gene expression with cell population density. Recent in vitro findings indicate that AHLs may function as virulence determinants per se, through modification of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels. In the present study, we assessed the influence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic effect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modification of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic effect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated. In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic effects of the LPS, 6 h after the onset of its infusion. Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an influence of bacterial quorum sensing signalling molecules on the host. PMID:11487515

  16. Two drimane lactones, valdiviolide and 11-epivaldiviolide, in the form of a 1:1 cocrystal obtained from Drimys winteri extracts.

    PubMed

    Paz Robles, Cristian; Mercado, Darío; Suarez, Sebastián; Baggio, Ricardo

    2014-12-01

    A cocrystal, C15H22O3·C15H22O3, (I), obtained from Drimys winteri, is composed of two isomeric drimane sesquiterpene lactones, namely valdiviolide, (Ia), and 11-epivaldiviolide, (Ib), neither of which has been reported in the crystal form. Both diastereoisomers present three chiral centres at sites 5, 10 and 11, with an SSR sequence in (Ia) and an SSS sequence in (Ib). O-H···O hydrogen bonds bind molecules into chains running along [120] and the chains are in turn linked by π-π stacking interactions to define planar weakly interacting arrays parallel to (001). PMID:25471409

  17. Cycloisomerization of acetylenic acids to γ-alkylidene lactones using a palladium(II) catalyst supported on amino-functionalized siliceous mesocellular foam.

    PubMed

    Nagendiran, Anuja; Verho, Oscar; Haller, Clémence; Johnston, Eric V; Bäckvall, Jan-E

    2014-02-01

    Cycloisomerization of various γ-acetylenic acids to their corresponding γ-alkylidene lactones by the use of a heterogeneous Pd(II) catalyst supported on amino-functionalized siliceous mesocellular foam is described. Substrates containing terminal as well as internal alkynes were cyclized in high to excellent yields within 2–24 h under mild reaction conditions. The protocol exhibited high regio- and stereoselectivity, favoring the exo-dig product with high Z selectivity. Moreover, the catalyst displayed excellent stability under the employed reaction conditions, as demonstrated by its good recyclability and low leaching. PMID:24467515

  18. Synthesis and biological evaluation of 4-methylideneisoxazolidin-5-ones--a new class of highly cytotoxic alpha-methylidene-gamma-lactones.

    PubMed

    Rózalski, Marek; Krajewska, Urszula; Panczyk, Mariusz; Mirowski, Marek; Rózalska, Barbara; Wasek, Tomasz; Janecki, Tomasz

    2007-02-01

    Two 4-methylideneisoxazolidin-5-ones (4a,b), which are alpha-methylidene-gamma-lactones containing a nitrogen atom in the lactone ring, were synthesized. Their cytotoxic properties were evaluated against promyelocytic leukemia HL-60 cells. Both 4a and 4b exhibited relatively high cytotoxic activity with an IC(50) of 4.1 and 5.4 microM, respectively. Caspase-3 activity assay revealed that both isoxazolidinones (4) were able to induce apoptosis process in time- and concentration-dependent manner. Using multiplex PCR analysis, it was observed that 4 caused distinct inhibition of BCL-2 gene expression. Expression of BAX, a pro-apoptotic gene remained unchanged. It was also found that 4a,b did not induce the expression of MDR1 and MRP1 genes, related to multidrug resistance. In addition, cytotoxicity data obtained for drug-sensitive and drug-resistant HL-60 ADR cells revealed that the investigated compounds were poor substrates for transport by MRP1 efflux pump, suggesting that they might be useful for treating drug-resistant tumors. Furthermore, antimicrobial properties of 4a,b were evaluated. They showed significant activity against fungi Candida albicans, but only a weak activity against all tested Gram-positive and Gram-negative bacterial strains. PMID:17069934

  19. Acylhomoserine lactone production and degradation by the fish pathogen Tenacibaculum maritimum, a member of the Cytophaga-Flavobacterium-Bacteroides (CFB) group.

    PubMed

    Romero, Manuel; Avendaño-Herrera, Rubén; Magariños, Beatriz; Cámara, Miguel; Otero, Ana

    2010-03-01

    Tenacibaculum maritimum (formerly Flexibacter maritimus) is a filamentous, biofilm-forming member of the Cytophaga-Flavobacterium-Bacteroides group (or Bacteroidetes), which causes the widely distributed marine fish disease tenacibaculosis. A search for N-acylhomoserine lactones (AHLs) quorum-sensing (QS) signals in the culture media of nine representative strains of this species using different biosensor strains revealed the presence of short-type AHL activity in all of them. N-butyryl-L-homoserine lactone (C4-HSL) was identified in T. maritimum NCIMB2154(T) by LC-MS. A degradation activity for long-acyl AHLs (C10-HSL) was subsequently demonstrated in T. maritimum NCIMB2154(T). The acidification of the culture medium after degradation did not allow the recovery of C10-HSL, which indicates a possible acylase-type degradation activity. Even though the physiological processes under the control of AHL-mediated QS in T. maritimum need to be further characterized, this discovery extends the paradigm of AHL-mediated QS signalling beyond the Proteobacteria and reinforces its ecological significance. PMID:20377642

  20. Complete genome sequencing of Pandoraea pnomenusa RB38 and Molecular Characterization of Its N-acyl homoserine lactone synthase gene ppnI

    PubMed Central

    Lim, Yan-Lue; Ee, Robson; How, Kah-Yan; Lee, Siew-Kim; Yong, Delicia; Tee, Kok Keng; Yin, Wai-Fong

    2015-01-01

    In this study, we sequenced the genome of Pandoraea pnomenusa RB38 using Pacific Biosciences RSII (PacBio) Single Molecule Real Time (SMRT) sequencing technology. A pair of cognate luxI/R homologs was identified where the luxI homolog, ppnI, was found adjacent to a luxR homolog, ppnR1. An additional orphan luxR homolog, ppnR2, was also discovered. Multiple sequence alignment and phylogenetic analysis revealed that ppnI is an N-acyl homoserine lactone (AHL) synthase gene that is distinct from those of the nearest phylogenetic neighbor viz. Burkholderia spp. High resolution tandem mass spectrometry (LC-MS/MS) analysis showed that Escherichia coli BL21 harboring ppnI produced a similar AHL profile (N-octanoylhomoserine lactone, C8-HSL) as P. pnomenusa RB38, the wild-type donor strain, confirming that PpnI directed the synthesis of AHL in P. pnomenusa RB38. To our knowledge, this is the first documentation of the luxI/R homologs of the genus Pandoraea. PMID:26336650

  1. Cobalt carbonyl catalyzed reactions of esters and lactones with hydrosilane and carbon monoxide. A novel synthetic method for the introduction of the siloxymethylidene group

    SciTech Connect

    Chatani, N.; Fujii, S.; Yamasaki, Y.; Murai, S.; Sonoda, N.

    1986-11-12

    The catalytic reactions of esters and lactones with hydrosilane and carbon monoxide in the presence of Co/sub 2/(CO)/sub 8/ have been studied in detail with the emphasis being focused on their utility in organic synthesis. The catalytic reaction of secondary alkyl acetates underwent clean incorporation of carbon monoxide to give (siloxymethylidene)alkanes (enol silyl ethers). Lactones of secondary alkyl ester type reacted similarly. The siloxymethylidenation products were converted to aldehydes. Primary alkyl acetates gave several products in a nonselective manner. In the case of tertiary alkyl esters, no incorporation of carbon monoxide took place except for bridgehead alkyl acetates. The mechanism of the catalytic reaction has been proposed, and the importance of the silycobalt carbonyl, R/sub 3/SiCO(CO)/sub 4/, as the key catalyst species has been suggested. The high affinity of the silicon in R/sub 3/SiCo(CO)/sub 4/ toward the oxygen atom in the ester is suggested to be the driving force for the formation of alkylcobalt carbonyls as the intermediates. This step illustrates a new methodology for the formation of a carbon-transition metal bond.

  2. N-acyl-homoserine lactone-mediated regulation of phenazine gene expression by Pseudomonas aureofaciens 30-84 in the wheat rhizosphere.

    PubMed Central

    Wood, D W; Gong, F; Daykin, M M; Williams, P; Pierson, L S

    1997-01-01

    Pseudomonas aureofaciens 30-84 is a soilborne bacterium that colonizes the wheat rhizosphere. This strain produces three phenazine antibiotics which suppress take-all disease of wheat by inhibition of the causative agent Gaeumannomyces graminis var. tritici. Phenazines also enhance survival of 30-84 within the wheat rhizosphere in competition with other organisms. Expression of the phenazine biosynthetic operon is controlled by the phzR/phzI N-acyl-homoserine lactone (AHL) response system (L. S. Pierson III et al., J. Bacterial 176:3966-3974, 1994; D. W. Wood and L. S. Pierson III, Gene 168:49-53, 1996). By using high-pressure liquid chromatography coupled with high-resolution mass spectrometry, the AHL produced by PhzI has now been identified as N-hexanoyl-homoserine lactone (HHL). In addition, the ability of HHL to serve as an interpopulation signal molecule in the wheat rhizosphere has been examined by using isogenic reporter strains. Disruption of phzI reduced expression of the phenazine biosynthetic operon 1,000-fold in the wheat rhizosphere. Coinoculation of an isogenic strain which produced the endogenous HHL signal restored phenazine gene expression in the phzI mutant to wild-type levels in situ. These results demonstrate that HHL is required for phenazine expression in situ and is an effective interpopulation signal molecule in the wheat rhizosphere. PMID:9401023

  3. Uptake, degradation and chiral discrimination of N-acyl-D/L-homoserine lactones by barley (Hordeum vulgare) and yam bean (Pachyrhizus erosus) plants.

    PubMed

    Götz, Christine; Fekete, Agnes; Gebefuegi, Istvan; Forczek, Sándor T; Fuksová, Kvetoslava; Li, Xiaojing; Englmann, Matthias; Gryndler, Milan; Hartmann, Anton; Matucha, Miroslav; Schmitt-Kopplin, Philippe; Schröder, Peter

    2007-11-01

    Bacterial intraspecies and interspecies communication in the rhizosphere is mediated by diffusible signal molecules. Many Gram-negative bacteria use N-acyl-homoserine lactones (AHLs) as autoinducers in the quorum sensing response. While bacterial signalling is well described, the fate of AHLs in contact with plants is much less known. Thus, adsorption, uptake and translocation of N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL) and N-decanoyl-homoserine lactone (C10-HSL) were studied in axenic systems with barley (Hordeum vulgare L.) and the legume yam bean (Pachyrhizus erosus (L.) Urban) as model plants using ultra-performance liquid chromatography (UPLC), Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tritium-labelled AHLs. Decreases in AHL concentration due to abiotic adsorption or degradation were tolerable under the experimental conditions. The presence of plants enhanced AHL decline in media depending on the compounds' lipophilicity, whereby the legume caused stronger AHL decrease than barley. All tested AHLs were traceable in root extracts of both plants. While all AHLs except C10-HSL were detectable in barley shoots, only C6-HSL was found in shoots of yam bean. Furthermore, tritium-labelled AHLs were used to determine short-term uptake kinetics. Chiral separation by GC-MS revealed that both plants discriminated D-AHL stereoisomers to different extents. These results indicate substantial differences in uptake and degradation of different AHLs in the plants tested. PMID:17899036

  4. Combined Experimental and Theoretical Study on Hydrogen-Bonded Complexes between Cyclic Ketones, Lactones, and Lactams with 3,4-Dinitrophenol

    NASA Astrophysics Data System (ADS)

    Esseffar, M.; Firdoussi, A. El; Bouab, W.; Abboud, J.-L. M.; Mó, O.; Yáñez, M.

    2009-10-01

    The interaction of 3,4 dinitrophenol (DNP) with cyclic ketones, lactones, and lactams was investigated by UV-visible spectroscopy and density functional theory (DFT) methods. Equilibrium constants KHB for 1:1 hydrogen bonded complexes were determined in solution in CCl4 and C6H12. For the entire range of studied bases, the pKHB scale, varying between 2.92 for β-propiolactone to 5.53 for 1-methyl-γ-caprolactam, indicates that the basicity increases with the ring size. Geometries, energies, and vibrational characteristics of complexes were obtained by means of DFT calculations. For lactones and lactams, the energy difference between the two most stable conformers, cis and trans, with respect to the ring oxygen (nitrogen) atom, is relatively small, suggesting that the complex observed in solution is probably an equilibrium mixture of both forms. The good correlation between Gibbs free energies in solution and in the gas phase, computed at the B3LYP/6-311++G(3df,2p) level of theory, confirms the reliability of our results. The electron density of the complexes has been analyzed by means of the atoms in molecules (AIM) theory and the natural bond orbital (NBO) method have been used to characterize the orbital interactions. Our theoretical survey shows that the 1:1 complexes are stabilized by a network of conventional and/or nonconventional intermolecular hydrogen bonds.

  5. Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant Stenotrophomonas maltophilia Clinical Isolates.

    PubMed

    Calvopiña, Karina; Umland, Klaus-Daniel; Rydzik, Anna M; Hinchliffe, Philip; Brem, Jürgen; Spencer, James; Schofield, Christopher J; Avison, Matthew B

    2016-07-01

    Acetamido derivatives of the naturally antibacterial non-β-lactam lactivicin (LTV) have improved activity against their penicillin binding protein targets and reduced hydrolysis by β-lactamases, but penetration into Gram-negative bacteria is still relatively poor. Here we report that modification of the LTV lactone with a catechol-type siderophore increases potency 1,000-fold against Stenotrophomonas maltophilia, a species renowned for its insusceptibility to antimicrobials. The MIC90 of modified lactone compound 17 (LTV17) against a global collection of extensively drug-resistant clinical S. maltophilia isolates was 0.063 μg · ml(-1) Sideromimic modification does not reduce the ability of LTVs to induce production of the L1 and L2 β-lactamases in S. maltophilia and does not reduce the rate at which LTVs are hydrolyzed by L1 or L2. We conclude, therefore, that lactivicin modification with a siderophore known to be preferentially used by S. maltophilia substantially increases penetration via siderophore uptake. LTV17 has the potential to be developed as a novel antimicrobial for treatment of infections by S. maltophilia More generally, our work shows that sideromimic modification in a species-targeted manner might prove useful for the development of narrow-spectrum antimicrobials that have reduced collateral effects. PMID:27139464

  6. An organocatalytic Michael-cyclization cascade of 4-oxa-α,β-unsaturated carboxylic acids with aldehydes: facile synthesis of chiral γ-lactols and trisubstituted γ-lactones.

    PubMed

    Lin, Jun-Bing; Xu, Shi-Ming; Xie, Ji-Kang; Li, Hong-Yu; Xu, Peng-Fei

    2015-02-28

    An organocatalytic Michael-cyclization cascade of aldehydes with 4-oxa-α,β-unsaturated carboxylic acids has been developed, giving functionalized γ-lactols with high yields and enantioselectivities. The products could be easily transformed into complex trisubstituted γ-lactones and γ-lactams. PMID:25633800

  7. Chemical compounds isolated from Talinum triangulare (Portulacaceae).

    PubMed

    de Oliveira Amorim, Ana Paula; de Carvalho, Almir Ribeiro; Lopes, Norberto Peporine; Castro, Rosane Nora; de Oliveira, Marcia Cristina Campos; de Carvalho, Mário Geraldo

    2014-10-01

    This first phytochemical study of Talinum triangulare Leach (Portulacaceae), also known as 'cariru', which is a commonly consumed food in Northern Brazil, allowed the isolation and structural determination of four new compounds: one acrylamide, 3-N-(acryloyl, N-pentadecanoyl) propanoic acid (5), and three new phaeophytins named (15(1)S, 17R, 18R)-Ficuschlorin D acid (3(1),3(2)-didehydro-7-oxo-17(3)-O-phytyl-rhodochlorin-15-acetic acid), (13), Talichorin A (17R, 18R)-phaeophytin b-15(1)-hidroxy, 15(2),15(3)-acetyl-13(1)-carboxilic acid (14), and (15(1)S, 17R, 18R)-phaeophytin b peroxylactone or (15(1)S, 17R, 18R)-hydroperoxy-ficuschlorin D (16), together with twelve known compounds, including four phaeophytins (11,12, 15 and 17). The structures of the compounds were established on the basis of 1D and 2D NMR, IR, HRESI-MS spectra, including GC-MS, and HPLC-UV analysis, as well as comparisons with the literature data. The CD spectra data analysis were used to define the absolute configuration of phaeophytins 12 (13(2)R, 17R, 18R)-13(2)-hydroxyphaeophytin a, 13 and 16, 15 (15(1)S, 17R, 18R)-3(1),3(2)-didehydro-15(1)-hydroxyrhodochlorin-15-acetic acid δ-lactone-15(2)-methyl-17(3)-phytyl ester and 17 (17R, 18R)-purpurin 18-phytyl ester. PMID:24799228

  8. [Activation of the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones in the presence of nitrofurans and NO generators].

    PubMed

    Zaĭtseva, Iu V; Granik, V G; Belik, A S; Koksharova, O A; Khmel', I A

    2010-01-01

    Nitrofurans (nitrofurazone, nitrofurantoin, furazidin, nifuroxazide), and nitric oxide generators (sodium nitroprusside and isosorbide mononitrate) in subinhibitory concentrations were shown to significantly increase the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones, signaling molecules of Quorum Sensing (QS) regulatory systems. The highest activation of bioluminescence (up to 250-400 fold) was observed in the presence of nitrofurazone on E. coli DH5alpha biosensors containing lux-reporter plasmids pSB401 or pSB536. However, this activation was not specifically associated with the functioning of QS systems. We suggest that the effect observed results from a direct action of nitrofurans and NO donors on the process of bioluminescence. The data indicate the necessity of using the biosensors that make it possible to detect specific effects of substances tested on QS regulation. PMID:20540359

  9. An experimental study of the structural and vibrational properties of sesquiterpene lactone cnicin using FT-IR, FT-Raman, UV-visible and NMR spectroscopies

    NASA Astrophysics Data System (ADS)

    Chain, Fernando; Romano, Elida; Leyton, Patricio; Paipa, Carolina; Catalán, César Atilio Nazareno; Fortuna, Mario Antonio; Brandán, Silvia Antonia

    2014-05-01

    An experimental and theoretical investigation of cnicin is presented, combining the use of infrared, Raman, NMR and UV-visible spectroscopies with density functional theory (DFT) that employs hybrid B3LYP exchange correlation functional and a 6-31G∗ basis set. The molecular electrostatic potentials, atomic charges, bond orders, stabilization energies, topological properties and energy gap are presented by performing NBO, AIM and HOMO-LUMO calculations at the same level of theory as cnicin. A complete vibrational compound assignment was performed by employing internal coordinate analysis and a scaled quantum mechanical force field (SQMFF) methodology. Comparisons between the theoretical and experimental vibrational and ultraviolet-visible spectra show a strong concordance. The geometrical parameters and NBO studies suggest a probable negative Cotton effect for cnicin, which can be attributed to the π → π∗ transition for an α,β-unsaturated γ-lactone, as reported in the literature.

  10. Enzymatic kinetic resolution and chemoenzymatic dynamic kinetic resolution of delta-hydroxy esters. An efficient route to chiral delta-lactones.

    PubMed

    Pàmies, Oscar; Bäckvall, Jan-E

    2002-02-22

    A successful kinetic resolution of a racemic mixture of delta-hydroxy esters 1 was obtained via lipase-catalyzed transesterification (E value up to 360). The combination of the enzymatic kinetic resolution with a ruthenium-catalyzed alcohol racemization led to an efficient dynamic kinetic resolution (ee up to 99% and conversion up to 92%). The synthetic utility of this procedure was illustrated by the practical syntheses of delta-lactones (R)-6-methyl- and (R)-6-ethyl-tetrahydropyran-2-one and (S)-5-(tert-butyldimethylsiloxy)heptanal. The former are important building blocks in the synthesis of natural products and biologically active compounds, and the latter is a key intermediate in the synthesis of widely used commercial insecticide Spinosyn A. PMID:11846671

  11. Acyl-homoserine lactone-based quorum sensing in the Roseobacter clade: complex cell-to-cell communication controls multiple physiologies

    PubMed Central

    Cude, W. Nathan; Buchan, Alison

    2013-01-01

    Bacteria have been widely reported to use quorum sensing (QS) systems, which employ small diffusible metabolites to coordinate gene expression in a population density dependent manner. In Proteobacteria, the most commonly described QS signaling molecules are N-acyl-homoserine lactones (AHLs). Recent studies suggest that members of the abundant marine Roseobacter lineage possess AHL-based QS systems and are environmentally relevant models for relating QS to ecological success. As reviewed here, these studies suggest that the roles of QS in roseobacters are varied and complex. An analysis of the 43 publically available Roseobacter genomes shows conservation of QS protein sequences and overall gene topologies, providing support for the hypothesis that QS is a conserved and widespread trait in the clade. PMID:24273537

  12. Biomimetic composites by surface-initiated polymerization of cyclic lactones at anorganic bone: preparation and in vitro evaluation of osteoblast and osteoclast competence.

    PubMed

    Wiegand, Troy; Hiebner, Kris; Gauza, Lukasz; Schwartz, Chris; Song, Zheng; Miller, Steve; Zacharias, Nora; Wooley, Paul H; Redepenning, Jody

    2014-06-01

    Biomimetic composites were constructed using anorganic bone to initiate the polymerization of cyclic lactones. The resulting anorganic bone/polylactone composites preserve the inorganic structure and the mechanical properties of the original bone. Thermal conditions used to prepare the anorganic bone were shown to control the surface functionalities, surface area, and crystallinity, all of which influence the rates of subsequent polymerizations. Thermal pretreatment of anorganic bone was examined as a function of time and temperature, ranging from 400°C to 800°C. Polymerization rates of different monomers were also compared. Additionally, in vitro evaluations of anorganic bone/poly-L-lactide and anorganic bone/polyglycolide composites for osteoblast and osteoclast competence suggest that these composites are good candidates for potential in vivo use, since both composites promoted osteoblast differentiation. The anorganic bone/poly-L-lactide composite also promoted osteoclast differentiation. PMID:23776188

  13. Effect of N-acy-l-homoserine lactones-like molecules from aerobic granules on biofilm formation by Escherichia coli K12.

    PubMed

    Ren, Ting-ting; Li, Xiao-yan; Yu, Han-qing

    2013-02-01

    A laboratory study was conducted to investigate the production of quorum sensing (QS) molecules by aerobic granules in membrane-partitioned bioreactor. Flow-chamber (FC) tests with Escherichia coli K12 demonstrated that granules induced more attached growth of E. coli cells than activated sludge flocs, leading to more cell adhesion and biofilm formation on the FC cover slide. Using the thin-layer chromatography, N-acy-l-homoserine lactones (AHLs) with acyl chains shorter than 10 carbons were detected in the liquid phase of granular sludge. Organic substances extracted with acidified ethyl acetate from the supernatant of granular sludge promoted the adhesion and growth of E. coli cells on the glass surface. AHL-like signal molecules were apparently produced by granules and might be involved in the formation of granules and the maintenance of granular structures during wastewater treatment. PMID:23305896

  14. Synthesis of 1-O-methylchlorogenic acid: reassignment of structure for MCGA3 isolated from bamboo (Phyllostachys edulis) leaves.

    PubMed

    Zeller, Wayne E

    2014-02-26

    The first synthesis of 1-O-methylchlorogenic acid is described. The short and efficient synthesis of this compound provides laboratory-scale quantities of the material to investigate its biological properties. The synthesis involves C-1 alkylation of the known (-)-4,5-cyclohexylidenequinic acid lactone followed by methoxide opening to the hydroxyl ester. Acylation of the C-5 hydroxyl group followed by sequential removal of protecting groups afforded 1-O-methylchlorogenic acid. The NMR spectroscopic characteristics of this compound do not coincide with those reported for the original isolation from bamboo (Phyllostachys edulis) leaves of the compound designated MCGA3. Comparison of the published spectroscopic data reported for MCGA3, with both reported literature values and spectroscopic data obtained from an authentic sample, leads to the conclusion that the compound isolated from bamboo (Phyllostachys edulis) leaves is instead methyl chlorogenate. PMID:24460043

  15. 3β-Angeloyloxy-8β,10β-dihydroxyeremophila-7(11)-en-12,8α-lactone Inhibits Lipopolysaccharide-Induced Nitric Oxide Production in RAW264.7 Cells.

    PubMed

    Sun, Xiao; Jiang, Changyou; Ma, Lisha; Zhao, Xinxin; Chang, Juanjuan; Zheng, Beibei; Li, Lin; Xie, Weidong; Li, Xia

    2015-01-01

    Farfugium japonicum (L.) KITAM, named "Lian-Peng-Cao" in China, has been traditionally used in Chinese folk medicine to treat sore throat, cold and cough due to its anti-inflammatory properties. In this study, the anti-inflammatory action of 3β-angeloyloxy-8β,10β-dihydroxyeremophila-7(11)-en-12,8α-lactone (FJ1) isolated from Farfugium japonicum and its molecular mechanism in RAW264.7 cells were investigated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that FJ1 with or without 3 µg/mL lipopolysaccharide (LPS) had no significant cytotoxicity in RAW264.7 cells. The production of nitric oxide (NO) was identified with a Griess reagent kit. The mRNA expression of inducible nitric oxide synthase (iNOS) and cytokines, including tumor necrosis factor α (TNF-α) and cyclooxygenase-2 (COX-2), was measured by real-time polymerase chain reaction (PCR). Reactive oxygen species (ROS) production was detected by flow cytometry analysis. Western blot was used to examine the protein expression of nuclear factor-kappa B (NF-κB)/p65, inhibitor of kappa B (IκB)-α, phosphorylated IκB-α (p-IκB-α), mitogen-activated protein kinase (MAPK) molecules, iNOS, and TNF-α. We discovered that FJ1 possesses anti-inflammatory effects that inhibit the release of LPS-stimulated pro-inflammatory cytokines, including NO and ROS. The molecular mechanism of FJ1-mediated anti-inflammation is associated with decreasing phosphorylation of MAPK molecules, including extracellular signal-related kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH2-terminal kinase (JNK), FJ1 also reverses IκB degradation and attenuates the mRNA and protein expression of NF-κB-related downstream inducible enzymes and cytokines, such as iNOS, TNF-α in RAW264.7 cells. The results suggest that FJ1 has anti-inflammatory properties, which indicates that F. japonicum can be utilized to treat inflammatory diseases. The potential mechanism is associated with the NF-κB and MAPK activation

  16. Modulation of violacein production and phenotypes associated with biofilm by exogenous quorum sensing N-acylhomoserine lactones in the marine bacterium Pseudoalteromonas ulvae TC14.

    PubMed

    Mireille Ayé, Armande; Bonnin-Jusserand, Maryse; Brian-Jaisson, Florence; Ortalo-Magné, Annick; Culioli, Gérald; Koffi Nevry, Rose; Rabah, Nadia; Blache, Yves; Molmeret, Maëlle

    2015-10-01

    Various phenotypes ranging from biofilm formation to pigment production have been shown to be regulated by quorum sensing (QS) in many bacteria. However, studies of the regulation of pigments produced by marine bacteria in saline conditions and of biofilm-associated phenotypes are scarcer. This study focuses on the demonstration of the existence of a QS communication system involving N-acylhomoserine lactones (AHLs) in the Mediterranean Sea strain Pseudoalteromonas ulvae TC14. We have investigated whether TC14 produces the violacein pigment, and whether intrinsic or exogenous AHLs could influence its production and modulate biofilm-associated phenotypes. Here, we demonstrate that the purple pigment produced by TC14 is violacein. The study shows that in planktonic conditions, TC14 produces more pigment in the medium in which it grows less. Using different approaches, the results also show that TC14 does not produce intrinsic AHLs in our conditions. When exogenous AHLs are added in planktonic conditions, the production of violacein is upregulated by C6-, C12-, 3-oxo-C8 and 3-oxo-C12-HSLs (homoserine lactones), and downregulated by 3-oxo-C6-HSL. In sessile conditions, 3-oxo-C8-HSL upregulates the production of violacein. The study of the biofilm-associated phenotypes shows that oxo-derived-HSLs decrease adhesion, swimming and biofilm formation. While 3-oxo-C8 and 3-oxo-C12-HSLs decrease both swimming and adhesion, 3-oxo-C6-HSLs decrease not only violacein production in planktonic conditions but also swimming, adhesion and more subtly biofilm formation. Therefore, TC14 may possess a functional LuxR-type QS receptor capable of sensing extrinsic AHLs, which controls violacein production, motility, adhesion and biofilm formation. PMID:26318530

  17. A LuxR-type Repressor of Burkholderia cenocepacia Inhibits Transcription via Antiactivation and is Inactivated by its Cognate Acylhomoserine Lactone

    PubMed Central

    Ryan, Gina T.; Wei, Yuping; Winans, Stephen C.

    2012-01-01

    Burkholderia cenocepacia is an opportunistic human pathogen that encodes two LuxI-type acylhomoserine lactone (AHL) synthases and three LuxR-type AHL receptors. Of these, cepI and cepR form a cognate synthase/receptor pair, as do cciI and cciR, while cepR2 lacks a genetically linked AHL synthase gene. Another group showed that a cepR2 mutant overexpressed a cluster of linked genes that appear to direct the production of a secondary metabolite (Malott et al., 2009). We found that these same genes were upregulated by octanoylhomoserine lactone (OHL), which is synthesized by CepI. These data suggest that several cepR2-linked promoters are repressed by CepR2 and that CepR2 is antagonized by OHL. Fusions of two divergent promoters to lacZ were used to confirm these hypotheses, and promoter resections and DNase I footprinting assays revealed a single CepR2 binding site between the two promoters. This binding site lies well upstream of both promoters, suggesting an unusual mode of repression. Adjacent to the cepR2 gene is a gene that we designate cepS, which encodes an AraC-type transcription factor. CepS is essential for expression of both promoters, regardless of the CepR2 status or OHL concentration. CepS therefore acts downstream of CepR2, and CepR2 appears to function as a CepS antiactivator. PMID:23136852

  18. Mechanism of chemical degradation and determination of solubility by kinetic modeling of the highly unstable sesquiterpene lactone nobilin in different media.

    PubMed

    Thormann, Ursula; De Mieri, Maria; Neuburger, Markus; Verjee, Sheela; Altmann, Peter; Hamburger, Matthias; Imanidis, Georgios

    2014-10-01

    The objective of this work was first to investigate the chemical degradation of the sesquiterpene lactone nobilin and determine its solubility under conditions of concurrent degradation for partially amorphous starting material; second, to determine the effect of biorelevant media used in the in vitro measurement of intestinal absorption on degradation and solubility of nobilin. Purely aqueous medium (aq-TMCaco ), fasted and fed state simulated intestinal fluid (FaSSIF-TMCaco and FeSSIF-TMCaco ), and two liposomal formulations (LiposomesFaSSIF and LiposomesFeSSIF ) with the same lipid concentration as FaSSIF-TMCaco and FeSSIF-TMCaco were used. Degradation products were identified by nuclear magnetic resonance and X-ray crystallography and the order of reaction kinetics was determined. Solubility was deduced with a mathematical model encompassing dissolution, degradation, and reprecipitation kinetics that took into account particle size distribution of the solid material. Degradation mechanism of nobilin involved water-catalyzed opening of the lactone ring and transannular cyclization resulting in five degradation products. Degradation followed first-order kinetics in aq-TMCaco and FaSSIF-TMCaco , and higher-order kinetics in FeSSIF-TMCaco and the two liposomal formulations, whereas degradation in the latter media was diminished. Solubility of nobilin increased in the order: aq-TMCaco < FaSSIF-TMCaco , < LiposomesFaSSIF < FeSSIF-TMCaco < LiposomesFeSSIF . Improvement of stability and solubility was consistent with the incorporation of the nobilin molecule into colloidal lipid particles. The developed kinetic model is proposed to be a useful tool for deducing solubility under dynamic conditions. PMID:25176605

  19. LplR, a Repressor Belonging to the TetR Family, Regulates Expression of the l-Pantoyl Lactone Dehydrogenase Gene in Rhodococcus erythropolis

    PubMed Central

    Si, Dayong; Urano, Nobuyuki; Shimizu, Sakayu

    2012-01-01

    The l-pantoyl lactone (l-PL) dehydrogenase (LPLDH) gene (lpldh) has been cloned from Rhodococcus erythropolis AKU2103, and addition of 1,2-propanediol (1,2-PD) was shown to be required for lpldh expression in this strain. In this study, based on an exploration of the nucleotide sequence around lpldh, a TetR-like regulator gene, which we designated lplR, was found upstream of lpldh, and three putative open reading frames existed between the two genes. Disruption of lplR led to 22.8 times higher lpldh expression, even without 1,2-PD induction, than that in wild-type R. erythropolis AKU2103 without 1,2-PD addition. Introduction of a multicopy vector carrying lplR (multi-lplR) into the wild-type and ΔlplR strains led to no detectable LPLDH activity even in the presence of 1,2-PD. The results of an electrophoretic mobility shift assay revealed that purified LplR bound to a 6-bp inverted-repeat sequence located in the promoter/operator region of the operon containing lpldh. These results indicated that LplR is a negative regulator in lpldh expression. Based on the clarification of the expression mechanism of lpldh, recombinant cells showing high LPLDH activity were constructed and used as a catalyst for the conversion of l-PL to ketopantoyl lactone. Finally, a promising production process of d-PL from dl-PL was constructed. PMID:22941082

  20. A proteomic analysis of Arabidopsis thaliana seedling responses to 3-oxo-octanoyl-homoserine lactone, a bacterial quorum-sensing signal

    SciTech Connect

    Miao, Chunjuan; Liu, Fang; Zhao, Qian; Jia, Zhenhua; Song, Shuishan

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer 3OC8-HSL can change the expression of diverse proteins in Arabidopsis. Black-Right-Pointing-Pointer 3OC8-HSL responsive proteins were identified using MALDI-TOF-MS. Black-Right-Pointing-Pointer Plant could have an extensive range of functional responses to bacterial AHL. -- Abstract: N-acyl-homoserine lactones (AHLs) are a class of bacterial quorum-sensing (QS) signals that are commonly used by Gram-negative bacteria for cell-to-cell communication. Recently, it has become evident that AHLs can regulate plant root growth and trigger plant defense responses; however, little is known about the plant response mechanisms to bacterial QS signals. In this study, we used a proteomic approach to investigate the responses of Arabidopsis thaliana seedlings to N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL), a bacterial QS signal. The results revealed that the abundance of 53 protein spots was significantly altered; two thirds of these proteins were found to be up-regulated after 3OC8-HSL treatment. Thirty-four proteins were identified using MALDI-TOF-MS. These 3OC8-HSL-responsive proteins, in addition to one protein of unknown function, are implicated in a variety of physiological processes, including metabolism of carbohydrate and energy, protein biosynthesis and quality control systems, defense response and signal transduction and cytoskeleton remodeling. Our bioinformatic analysis indicated that the chloroplasts are the intracellular organelles most influenced by the exposure to 3OC8-HSL. Our data indicate that plants have an extensive range of functional responses to bacterial AHLs that may play important roles in the interaction between plants and bacteria.