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Sample records for agonist allyl isothiocyanate

  1. Allyl isothiocyanate induces stomatal closure in Vicia faba.

    PubMed

    Sobahan, Muhammad Abdus; Akter, Nasima; Okuma, Eiji; Uraji, Misugi; Ye, Wenxiu; Mori, Izumi C; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Isothiocyanates are enzymatically produced from glucosinolates in plants, and allyl isothiocyanate (AITC) induces stomatal closure in Arabidopsis thaliana. In this study, we investigated stomatal responses to AITC in Vicia faba. AITC-induced stomatal closure accompanied by reactive oxygen species (ROS) and NO production, cytosolic alkalization and glutathione (GSH) depletion in V. faba. GSH monoethyl ester induced stomatal reopening and suppressed AITC-induced GSH depletion in guard cells. Exogenous catalase and a peroxidase inhibitor, salicylhydroxamic acid, inhibited AITC-induced stomatal closure, unlike an NAD(P)H oxidase inhibitor, diphenylene iodonium chloride. The peroxidase inhibitor also abolished the AITC-induced ROS production, NO production, and cytosolic alkalization. AITC-induced stomatal closure was suppressed by an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and an agent to acidify cytosol, butyrate. These results indicate that AITC-induced stomatal closure in V. faba as well as in A. thaliana and suggest that AITC signaling in guard cells is conserved in both plants. PMID:26027691

  2. Effect of Allyl Isothiocyanate on developmental toxicity in exposed Xenopus laevis embryos

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pungent natural compound allyl isothiocyanate isolated from the seeds of Cruciferous (Brassica) plants such as mustard is reported to exhibit numerous beneficial health-promoting antimicrobial, antifungal, anticarcinogenic, cardioprotective, and neuroprotective properties. Because it is also re...

  3. Release of allyl isothiocyanate from mustard seed meal powder.

    PubMed

    Dai, Ruyan; Lim, Loong-Tak

    2014-01-01

    Allyl isothiocyanate (AITC) is a wide-spectrum antimicrobial compound found in mustard seeds, produced when their tissues are disrupted. The formation of AITC in mustard seed is mediated by the myrosinase enzyme which catalyzes the release of volatile AITC from a glucosinolate-sinigrin. Since water is a substrate in the reaction, humidity from the air can be used to activate the release of AITC from mustard seed. In this study, defatted and partially defatted mustard seed meals were ground into powders with particle size ranging from 5 to 300 μm. The mustard seed meal powder (MSMP) samples were enclosed within hermetically sealed glass jars wherein the headspace air was adjusted to 85% or 100% relative humidity at 5, 20, or 35 °C. Data from gas chromatography analysis showed that AITC release rate and amount increased with increasing relative humidity and temperature. Moreover, the release rate can be manipulated by particle size and lipid content of the MSMP samples. The amount of AITC released ranged from 2 to 17 mg/g MSMP within 24 h under the experimental conditions tested. In view of the antimicrobial properties of AITC, the mustard meal powder may be used as a natural antimicrobial material for extending the shelf life of food products. PMID:24313968

  4. Allyl isothiocyanate affects the cell cycle of Arabidopsis thaliana

    PubMed Central

    Åsberg, Signe E.; Bones, Atle M.; Øverby, Anders

    2015-01-01

    Isothiocyanates (ITCs) are degradation products of glucosinolates present in members of the Brassicaceae family acting as herbivore repellents and antimicrobial compounds. Recent results indicate that allyl ITC (AITC) has a role in defense responses such as glutathione depletion, ROS generation and stomatal closure. In this study we show that exposure to non-lethal concentrations of AITC causes a shift in the cell cycle distribution of Arabidopsis thaliana leading to accumulation of cells in S-phases and a reduced number of cells in non-replicating phases. Furthermore, transcriptional analysis revealed an AITC-induced up-regulation of the gene encoding cyclin-dependent kinase A while several genes encoding mitotic proteins were down-regulated, suggesting an inhibition of mitotic processes. Interestingly, visualization of DNA synthesis indicated that exposure to AITC reduced the rate of DNA replication. Taken together, these results indicate that non-lethal concentrations of AITC induce cells of A. thaliana to enter the cell cycle and accumulate in S-phases, presumably as a part of a defensive response. Thus, this study suggests that AITC has several roles in plant defense and add evidence to the growing data supporting a multifunctional role of glucosinolates and their degradation products in plants. PMID:26042144

  5. Allyl isothiocyanate enhances shelf life of minimally processed shredded cabbage.

    PubMed

    Banerjee, Aparajita; Penna, Suprasanna; Variyar, Prasad S

    2015-09-15

    The effect of allyl isothiocyanate (AITC), in combination with low temperature (10°C) storage on post harvest quality of minimally processed shredded cabbage was investigated. An optimum concentration of 0.05μL/mL AITC was found to be effective in maintaining the microbial and sensory quality of the product for a period of 12days. Inhibition of browning was shown to result from a down-regulation (1.4-fold) of phenylalanine ammonia lyase (PAL) gene expression and a consequent decrease in PAL enzyme activity and o-quinone content. In the untreated control samples, PAL activity increased following up-regulation in PAL gene expression that could be linearly correlated with enhanced o-quinone formation and browning. The efficacy of AITC in extending the shelf life of minimally processed shredded cabbage and its role in down-regulation of PAL gene expression resulting in browning inhibition in the product is reported here for the first time. PMID:25863635

  6. Allyl isothiocyanates and cinnamaldehyde potentiate miniature excitatory postsynaptic inputs in the supraoptic nucleus in rats.

    PubMed

    Yokoyama, Toru; Ohbuchi, Toyoaki; Saito, Takeshi; Sudo, Yuka; Fujihara, Hiroaki; Minami, Kouichiro; Nagatomo, Toshihisa; Uezono, Yasuhito; Ueta, Yoichi

    2011-03-25

    Allyl isothiocyanates (AITC) and cinnamaldehyde are pungent compounds present in mustard oil and cinnamon oil, respectively. These compounds are well known as transient receptor potential ankyrin 1 (TRPA1) agonists. TRPA1 is activated by low temperature stimuli, mechanosensation and pungent irritants such as AITC and cinnamaldehyde. TRPA1 is often co-expressed in TRPV1. Recent study showed that hypertonic solution activated TRPA1 as well as TRPV1. TRPV1 is involved in excitatory synaptic inputs to the magnocellular neurosecretory cells (MNCs) that produce vasopressin in the supraoptic nucleus (SON). However, it remains unclear whether TRPA1 may be involved in this activation. In the present study, we examined the role of TRPA1 on the synaptic inputs to the MNCs in in vitro rat brain slice preparations, using whole-cell patch-clamp recordings. In the presence of tetrodotoxin, AITC (50μM) and cinnamaldehyde (30μM) increased the frequency of miniature excitatory postsynaptic currents without affecting the amplitude. This effect was significantly attenuated by previous exposure to ruthenium red (10μM), non-specific TRP channels blocker, high concentration of menthol (300μM) and HC-030031 (10μM), which are known to antagonize the effects of TRPA1 agonists. These results suggest that TRPA1 may exist at presynaptic terminals to the MNCs and enhance glutamate release in the SON. PMID:21266172

  7. Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Allyl isothiocyanate (AITC) is a dietary component with potentially important anti-cancer effects, though much of the information about AITC and cancer processes has been obtained from cell studies. To investigate the effect of AITC on DNA integrity and repair in vivo, a human feeding study was con...

  8. Effect of allyl isothiocyanate on antioxidants and fruit decay of blueberries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of allyl isothiocyanate (AITC) on flavonoids, radical scavenging capacity, fruit decay and quality of blueberries (Vaccinium corymbosum L. cv. Duke) was evaluated. Results from this study showed that AITC was effective in retarding blueberry decay during storage at 10 'C. AITC treatment r...

  9. Effect of allyl isothiocyanate on antioxidant enzyme activities, flavonoids and fruit quality of blueberry (Vaccinium corymbosum L., cv. Duke)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of allyl isothiocyanate (AITC) on antioxidant enzyme activities, flavonoid content, and fruit quality of blueberries var. Duke (Vaccinium corymbosum L.) was evaluated. Results from this study showed that AITC was effective in maintaining higher amounts of sugars and lower organic acids co...

  10. Antimicrobial effect of allyl isothiocyanate and modified atmosphere on Pseudomonas aeruginosa in fresh catfish fillet under abuse temperatures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomonas aeruginosa, a common spoilage microorganism on fresh catfish products, can grow rapidly at temperatures above 4 degree C during storage and transportation. Allyl isothiocyanate (AIT), an extract of horseradish oil, and modified atmosphere (MA) can be used to inhibit the growth of P. aeru...

  11. Effect of allyl isothiocyanate in headspace and modified atmosphere on Pseduomonas Aeruginosa growth in fresh catfish fillets under abuse temperatures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomonas aeruginosa, a common spoilage microorganism on fresh catfish products, can grow rapidly at temperatures above 4 deg C during storage and transportation. Allyl isothiocyanate (AIT), an extract of horseradish oil, and modified atmosphere (MA) can be used to inhibit the growth of P. aerugin...

  12. Growth behavior prediction of fresh catfish fillet with Pseudomonas aeruginosa under stresses of allyl isothiocyanate, temperature and modified atmosphere

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomonas aeruginosa, a common spoilage microorganism in fish, grows rapidly when temperature rises above 4 degree C. The combination of allyl isothiocyanate (AIT) and modified atmosphere (MA) was applied and proved to be effective to retard the growth of P. aeruginosa. The objective of this resea...

  13. Antimicrobial activity of allyl isothiocyanate used to coat biodegradable composite films as affected by storage and handling conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We evaluated the effects of storage and handling conditions on the antimicrobial activity of biodegradable composite films (polylactic acid and sugar beet pulp) coated with allyl isothiocyanate (AIT). Polylactic acid (PLA) and chitosan were incorporated with AIT and coated on one side of the film. T...

  14. Multidirectional Time-Dependent Effect of Sinigrin and Allyl Isothiocyanate on Metabolic Parameters in Rats

    PubMed Central

    2010-01-01

    Sinigrin (SIN) and allyl isothiocyanate (AITC) are compounds found in high concentrations in Brassica family vegetables, especially in Brussels sprouts. Recently, they have been used as a nutrition supplement for their preventive and medicinal effect on some types of cancer and other diseases. In this research, nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day was studied by the evaluation of their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration. Additionally, the aim of this trial was to evaluate the direct action of AITC on basal and epinephrine-induced lipolysis in isolated rat adipocytes at concentration 1 μM, 10 μM and 100 μM in vitro. Sole AITC after 4 h of its ingestion caused liver triacylglycerols increment at both doses and glycaemia only at the higher dose. Multiple SIN treatment showed its putative bioconversion into AITC. It was found that SIN and AITC multiple administration in the same way strongly disturbed lipid and carbohydrate homeostasis, increasing esterified and total cholesterol, free fatty acids and lowering tracylglycerols in the blood serum. Additionally, AITC at both doses elevated insulinaemia and liver glycogen enhancement. The in vitro experiment revealed that AITC potentiated basal lipolysis process at 10 μM, and had stimulatory effect on epinephrine action at 1 μM and 10 μM. The results of this study demonstrated that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered “normal” seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead

  15. Allyl Isothiocyanate Inhibits Actin-Dependent Intracellular Transport in Arabidopsis thaliana.

    PubMed

    Sporsheim, Bjørnar; Øverby, Anders; Bones, Atle Magnar

    2015-01-01

    Volatile allyl isothiocyanate (AITC) derives from the biodegradation of the glucosinolate sinigrin and has been associated with growth inhibition in several plants, including the model plant Arabidopsis thaliana. However, the underlying cellular mechanisms of this feature remain scarcely investigated in plants. In this study, we present evidence of an AITC-induced inhibition of actin-dependent intracellular transport in A. thaliana. A transgenic line of A. thaliana expressing yellow fluorescent protein (YFP)-tagged actin filaments was used to show attenuation of actin filament movement by AITC. This appeared gradually in a time- and dose-dependent manner and resulted in actin filaments appearing close to static. Further, we employed four transgenic lines with YFP-fusion proteins labeling the Golgi apparatus, endoplasmic reticulum (ER), vacuoles and peroxisomes to demonstrate an AITC-induced inhibition of actin-dependent intracellular transport of or, in these structures, consistent with the decline in actin filament movement. Furthermore, the morphologies of actin filaments, ER and vacuoles appeared aberrant following AITC-exposure. However, AITC-treated seedlings of all transgenic lines tested displayed morphologies and intracellular movements similar to that of the corresponding untreated and control-treated plants, following overnight incubation in an AITC-absent environment, indicating that AITC-induced decline in actin-related movements is a reversible process. These findings provide novel insights into the cellular events in plant cells following exposure to AITC, which may further expose clues to the physiological significance of the glucosinolate-myrosinase system. PMID:26690132

  16. Allyl isothiocyanate depletes glutathione and upregulates expression of glutathione S-transferases in Arabidopsis thaliana

    PubMed Central

    Øverby, Anders; Stokland, Ragni A.; Åsberg, Signe E.; Sporsheim, Bjørnar; Bones, Atle M.

    2015-01-01

    Allyl isothiocyanate (AITC) is a phytochemical associated with plant defense in plants from the Brassicaceae family. AITC has long been recognized as a countermeasure against external threats, but recent reports suggest that AITC is also involved in the onset of defense-related mechanisms such as the regulation of stomatal aperture. However, the underlying cellular modes of action in plants remain scarcely investigated. Here we report evidence of an AITC-induced depletion of glutathione (GSH) and the effect on gene expression of the detoxification enzyme family glutathione S-transferases (GSTs) in Arabidopsis thaliana. Treatment of A. thaliana wild-type with AITC resulted in a time- and dose-dependent depletion of cellular GSH. AITC-exposure of mutant lines vtc1 and pad2-1 with elevated and reduced GSH-levels, displayed enhanced and decreased AITC-tolerance, respectively. AITC-exposure also led to increased ROS-levels in the roots and loss of chlorophyll which are symptoms of oxidative stress. Following exposure to AITC, we found that GSH rapidly recovered to the same level as in the control plant, suggesting an effective route for replenishment of GSH or a rapid detoxification of AITC. Transcriptional analysis of genes encoding GSTs showed an upregulation in response to AITC. These findings demonstrate cellular effects by AITC involving a reversible depletion of the GSH-pool, induced oxidative stress, and elevated expression of GST-encoding genes. PMID:25954298

  17. Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites

    PubMed Central

    Ahn, Jiyun; Chung, Woo-Jae; Jang, Young Jin; Seong, Ki-Seung; Moon, Jae-Hak; Ha, Tae Youl; Jung, Chang Hwa

    2015-01-01

    Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis. PMID:26317351

  18. Allyl Isothiocyanate Inhibits Actin-Dependent Intracellular Transport in Arabidopsis thaliana

    PubMed Central

    Sporsheim, Bjørnar; Øverby, Anders; Bones, Atle Magnar

    2015-01-01

    Volatile allyl isothiocyanate (AITC) derives from the biodegradation of the glucosinolate sinigrin and has been associated with growth inhibition in several plants, including the model plant Arabidopsis thaliana. However, the underlying cellular mechanisms of this feature remain scarcely investigated in plants. In this study, we present evidence of an AITC-induced inhibition of actin-dependent intracellular transport in A. thaliana. A transgenic line of A. thaliana expressing yellow fluorescent protein (YFP)-tagged actin filaments was used to show attenuation of actin filament movement by AITC. This appeared gradually in a time- and dose-dependent manner and resulted in actin filaments appearing close to static. Further, we employed four transgenic lines with YFP-fusion proteins labeling the Golgi apparatus, endoplasmic reticulum (ER), vacuoles and peroxisomes to demonstrate an AITC-induced inhibition of actin-dependent intracellular transport of or, in these structures, consistent with the decline in actin filament movement. Furthermore, the morphologies of actin filaments, ER and vacuoles appeared aberrant following AITC-exposure. However, AITC-treated seedlings of all transgenic lines tested displayed morphologies and intracellular movements similar to that of the corresponding untreated and control-treated plants, following overnight incubation in an AITC-absent environment, indicating that AITC-induced decline in actin-related movements is a reversible process. These findings provide novel insights into the cellular events in plant cells following exposure to AITC, which may further expose clues to the physiological significance of the glucosinolate-myrosinase system. PMID:26690132

  19. Hepatoprotective effects of allyl isothiocyanate against carbon tetrachloride-induced hepatotoxicity in rat.

    PubMed

    Ahn, Meejung; Kim, Jeongtae; Bang, Hyojin; Moon, Jihwan; Kim, Gi Ok; Shin, Taekyun

    2016-07-25

    We evaluated the hepatoprotective activity of allyl isothiocyanate (AITC) against carbon tetrachloride (CCl4)-induced liver injury in rats. Sprague Dawley rats were orally administered AITC at doses of 5 (AITC 5) and 50 (AITC 50) mg/kg body weight once daily for 3 days, with or without intraperitoneal injection of CCl4. Serum chemistry was assessed for changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The enzyme activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were examined in liver tissues, while pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) mRNA expression were analyzed using real-time polymerase chain reaction. And heme oxygenase-1 (HO-1) and ionized calcium binding protein-1 (Iba-1) immunoreactivities were evaluated by Western blot analysis and immunohistochemistry, respectively. In serum chemistry, the oral administration of AITC itself did not affect the serum levels of ALT or AST, furthermore pretreatment with AITC 5 and AITC 50 significantly reduced the ALT and AST activity levels that were elevated in CCl4-intoxicated rats. In addition, AITC significantly suppressed the reduction of SOD and CAT, and the elevation of MDA, TNF-α mRNA expression, on the other hands, induced the expression of HO-1 compared with those of the vehicle-treated CCl4 group. The histopathological evaluation and Iba-1 immunoreactivity also supported the hepatoprotective effects of AITC against CCl4-induced liver injury. These results suggest that AITC ameliorates oxidative liver injury, possibly through reducing lipid peroxidation, enhancing antioxidant enzymes, and suppressing Kupffer cells and macrophages. PMID:27241356

  20. Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil).

    PubMed

    Sávio, André Luiz Ventura; da Silva, Glenda Nicioli; Salvadori, Daisy Maria Fávero

    2015-01-01

    Natural compounds hold great promise for combating antibiotic resistance, the failure to control some diseases, the emergence of new diseases and the toxicity of some contemporary medical products. Allyl isothiocyanate (AITC), which is abundant in cruciferous vegetables and mustard seeds and is commonly referred to as mustard essential oil, exhibits promising antineoplastic activity against bladder cancer, although its mechanism of action is not fully understood. Therefore, the aim of this study was to investigate the effects of AITC activity on bladder cancer cell lines carrying a wild type (wt; RT4) or mutated (T24) TP53 gene. Morphological changes, cell cycle kinetics and CDK1, SMAD4, BAX, BCL2, ANLN and S100P gene expression were evaluated. In both cell lines, treatment with AITC inhibited cell proliferation (at 62.5, 72.5, 82.5 and 92.5μM AITC) and induced morphological changes, including scattered and elongated cells and cellular debris. Gene expression profiles revealed increased S100P and BAX and decreased BCL2 expression in RT4 cells following AITC treatment. T24 cells displayed increased BCL2, BAX and ANLN and decreased S100P expression. No changes in SMAD4 and CDK1 expression were observed in either cell line. In conclusion, AITC inhibits cell proliferation independent of TP53 status. However, the mechanism of action of AITC differed in the two cell lines; in RT4 cells, it mainly acted via the classical BAX/BCL2 pathway, while in T24 cells, AITC modulated the activities of ANLN (related to cytokinesis) and S100P. These data confirm the role of AITC as a potential antiproliferative compound that modulates gene expression according to the tumor cell TP53 genotype. PMID:25771977

  1. Active packaging of cheese with allyl isothiocyanate, an alternative to modified atmosphere packaging.

    PubMed

    Winther, Mette; Nielsen, Per Vaeggemose

    2006-10-01

    The natural antimicrobial compound allyl isothiocyanate (AITC), found in mustard oil, is effective against cheese-related fungi both on laboratory media and cheese. Penicillium commune, Penicillium roqueforti, and Aspergillus flavus were more sensitive to AITC when it was added just after the spores had completed 100% germination and branching had started on Czapek yeast extract agar than were spores in the dormant phase. The use of 1 AITC label (Wasaouro interior labels, LD30D, 20 by 20 mm) in combination with atmospheric air in the packaging extended the shelf life of Danish Danbo cheese from 4 1/2 to 13 weeks. Two AITC labels extended the shelf life from 4 1/2 to 28 weeks. Both 1 and 2 labels in combination with modified atmosphere packaging extended the shelf life of the cheese from 18 to 28 weeks. This study showed that AITC was absorbed in the cheese, but it was not possible to detect any volatile breakdown products from AITC in the cheese. Cheese stored for up to 12 weeks with an AITC label had an unacceptable mustard flavor. The mustard flavor decreased to an acceptable level between weeks 12 and 28. Cheese stored in atmospheric air had a fresher taste without a CO2 off-flavor than did cheese stored in modified atmosphere packaging. AITC may be a good alternative to modified atmosphere packaging for cheese. The extended shelf life of cheese in the package is very desirable: the cheese can be transported longer distances, and the packaging can be used for the final maturing of the cheese. Furthermore, AITC can address problems such as pinholes and leaking seals in cheese packaging. PMID:17066923

  2. Allyl isothiocyanate from mustard seed is effective in reducing the levels of volatile sulfur compounds responsible for intrinsic oral malodor.

    PubMed

    Tian, Minmin; Hanley, A Bryan; Dodds, Michael W J

    2013-06-01

    Oral malodor is a major social and psychological issue that affects general populations. Volatile sulfur compounds (VSCs), particularly hydrogen sulfide (H₂S) and methyl mercaptan (CH₃SH), are responsible for most oral malodor. The objectives for this study were to determine whether allyl isothiocyanate (AITC) at an organoleptically acceptable level can eliminate VSCs containing a free thiol moiety and further to elucidate the mechanism of action and reaction kinetics. The study revealed that gas chromatograph with a sulfur detector demonstrated a good linearity, high accuracy and sensitivity on analysis of VSCs. Zinc salts eliminate the headspace level of H₂S but not CH₃SH. AITC eliminates both H₂S and CH₃SH via a nucleophilic addition reaction. In addition, a chemical structure-activity relationship study revealed that the presence of unsaturated group on the side chain of the isothiocyanate accelerates the elimination of VSCs. PMID:23470258

  3. Modulation of Histone Deacetylase Activity by Dietary Isothiocyanates and Allyl Sulfides: Studies with Sulforaphane and Garlic Organosulfur Compounds

    PubMed Central

    Nian, Hui; Delage, Barbara; Ho, Emily; Dashwood, Roderick H.

    2009-01-01

    Histone deacetylase (HDAC) inhibitors reactivate epigenetically-silenced genes in cancer cells, triggering cell cycle arrest and apoptosis. Recent evidence suggests that dietary constituents can act as HDAC inhibitors, such as the isothiocyanates found in cruciferous vegetables and the allyl compounds present in garlic. Broccoli sprouts are a rich source of sulforaphane (SFN), an isothiocyanate that is metabolized via the mercapturic acid pathway and inhibits HDAC activity in human colon, prostate, and breast cancer cells. In mouse preclinical models, SFN inhibited HDAC activity and induced histone hyperacetylation coincident with tumor suppression. Inhibition of HDAC activity also was observed in circulating peripheral blood mononuclear cells obtained from people who consumed a single serving of broccoli sprouts. Garlic organosulfur compounds can be metabolized to allyl mercaptan (AM), a competitive HDAC inhibitor that induced rapid and sustained histone hyperacetylation in human colon cancer cells. Inhibition of HDAC activity by AM was associated with increased histone acetylation and Sp3 transcription factor binding to the promoter region of the P21WAF1 gene, resulting in elevated p21 protein expression and cell cycle arrest. Collectively, the results from these studies, and others reviewed herein, provide new insights into the relationships between reversible histone modifications, diet, and cancer chemoprevention. PMID:19197985

  4. Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation

    PubMed Central

    Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P.; Owen, Laurie B.; Piazza, Gary A.

    2015-01-01

    Allyl isothiocyanate (AITC), a constituent of many cruciferous vegetables exhibits significant anticancer activities in many cancer models. Our studies provide novel insights into AITC-induced anticancer mechanisms in human A549 and H1299 non-small cell lung cancer (NSCLC) cells. AITC exposure induced replication stress in NSCLC cells as evidenced by γH2AX and FANCD2 foci, ATM/ATR-mediated checkpoint responses and S and G2/M cell cycle arrest. Furthermore, AITC-induced FANCD2 foci displayed co-localization with BrdU foci, indicating stalled or collapsed replication forks in these cells. Although PITC (phenyl isothiocyanate) exhibited concentration-dependent cytotoxic effects, treatment was less effective compared to AITC. Previously, agents that induce cell cycle arrest in S and G2/M phases were shown to sensitize tumor cells to radiation. Similar to these observations, combination therapy involving AITC followed by radiation treatment exhibited increased DDR and cell killing in NSCLC cells compared to single agent treatment. Combination index (CI) analysis revealed synergistic effects at multiple doses of AITC and radiation, resulting in CI values of less than 0.7 at Fa of 0.5 (50% reduction in survival). Collectively, these studies identify an important anticancer mechanism displayed by AITC, and suggest that the combination of AITC and radiation could be an effective therapy for NSCLC. PMID:25742788

  5. Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination.

    PubMed

    Bhattacharya, Arup; Li, Yun; Shi, Yi; Zhang, Yuesheng

    2013-11-01

    Allyl isothiocyanate (AITC) occurs in cruciferous vegetables that are commonly consumed by humans and has been shown to inhibit urinary bladder cancer growth and progression in previous preclinical studies. However, AITC does not significantly modulate cyclooxygenase-2 (Cox-2), whose oncogenic activity has been well documented in bladder cancer and other cancers. Celecoxib is a selective Cox-2 inhibitor and has been widely used for treatment of several diseases. Celecoxib has also been evaluated in bladder cancer patients, but its efficacy against bladder cancer as a single agent remains unclear. In a syngeneic rat model of orthotopic bladder cancer, treatment of the animals with the combination of AITC and celecoxib at low dose levels (AITC at 1 mg/kg and celecoxib at 10 mg/kg) led to increased or perhaps synergistic inhibition of bladder cancer growth and muscle invasion, compared with each agent used alone. The combination regime was also more effective than each single agent in inhibiting microvessel formation and stimulating microvessel maturation in the tumor tissues. The anticancer efficacy of the combination regime was associated with depletion of prostaglandin E2, a key downstream signaling molecule of Cox-2, caspase activation and downregulation of vascular endothelial growth factor in the tumor tissues. These data show that AITC and celecoxib complement each other for inhibition of bladder cancer and provide a novel combination approach for potential use for prevention or treatment of human bladder cancer. PMID:23946495

  6. Transcriptional responses to exposure to the brassicaceous defence metabolites camalexin and allyl-isothiocyanate in the necrotrophic fungus Alternaria brassicicola.

    PubMed

    Sellam, Adnane; Dongo, Anita; Guillemette, Thomas; Hudhomme, Piétrick; Simoneau, Philippe

    2007-03-01

    SUMMARY Alternaria brassicicola is the causative agent of black spot disease of Brassicaceae belonging to the genera Brassica and Raphanus. During host infection, A. brassicicola is exposed to high levels of antimicrobial defence compounds such as indolic phytoalexins and glucosinolate breakdown products. To investigate the transcriptomic response of A. brassicicola when challenged with brassicaceous defence metabolites, suppression subtractive hybridization (SSH) was performed to generate two cDNA libraries from germinated conidia treated either with allyl isothiocyanate (Al-ITC) or with camalexin. Following exposure to Al-ITC, A. brassicicola displayed a response similar to that experienced during oxidative stress. Indeed, a substantial subset of differentially expressed genes was related to cell protection against oxidative damage. Treatment of A. brassicicola conidia with the phytoalexin camalexin appeared to activate a compensatory mechanism to preserve cell membrane integrity and, among the camalexin-elicited genes, several were involved in sterol and sphingolipid biosynthesis. The transcriptomic analysis suggested that protection against the two tested compounds also involved mechanisms aimed at limiting their intracellular accumulation, such as melanin biosynthesis (in the case of camalexin exposure only) and drug efflux. From the Al-ITC and the camalexin differentially expressed genes identified here, 25 were selected to perform time-course studies during interactions with brassicaceous hosts. In planta, up-regulation of all the selected genes was observed during infection of Raphanus sativus whereas only a subset were over-expressed during the incompatible interaction with Arabidopsis thaliana ecotype Columbia. PMID:20507491

  7. Factors affecting the dissolution and degradation of oriental mustard-derived sinigrin and allyl isothiocyanate in aqueous media.

    PubMed

    Tsao, R; Yu, Q; Friesen, I; Potter, J; Chiba, M

    2000-05-01

    Sinigrin, the predominant glucosinolate in the oriental mustard Brassica juncea, is mainly degraded upon the enzymatic action of myrosinase under normal conditions to give allyl isothiocyanate (AITC) in an aqueous media. Because AITC is considered to be the principal nematicidal ingredient in B. juncea, its stability in aqueous media is an important issue in achieving efficient nematode control. Pure sinigrin and AITC were found to be relatively stable in buffered water in the pH range of 5.00-7.00 but less stable at pH 9.00. Both sinigrin and AITC were more stable in soil water (supernatant of a 1:1 water/air-dried soil mixture) than in buffered water at the same pH range of 5.00-9.00. Sinigrin dissolved from the mustard bran or ground seed into water very quickly and was degraded by codissolved myrosinase to AITC. The AITC that formed from the degradation of sinigrin was found to be more stable in the soil water than in the buffered water. Buffer capacity was considered to be one of the factors that contributed to the stabilization of AITC in the soil water, but other unknown factors from both bran or seed and soil may also have contributed to the stabilization. PMID:10820112

  8. Influence of the antimicrobial compound allyl isothiocyanate against the Aspergillus parasiticus growth and its aflatoxins production in pizza crust.

    PubMed

    Quiles, Juan M; Manyes, Lara; Luciano, Fernando; Mañes, Jordi; Meca, Giuseppe

    2015-09-01

    Aflatoxins (AFs) are secondary metabolites produced by different species of Aspergillus, such as Aspergillus flavus and Aspergillus parasiticus, which possess mutagenic, teratogenic and carcinogenic activities in humans. In this study, active packaging devices containing allyl isothiocyanate (AITC) or oriental mustard flour (OMF) + water were tested to inhibit the growth of A. parasiticus and AFs production in fresh pizza crust after 30 d. The antimicrobial and anti-aflatoxin activities were compared to a control group (no antimicrobial treatment) and to a group added with commercial preservatives (sorbic acid + sodium propionate). A. parasiticus growth was only inhibited after 30 d by AITC in filter paper at 5 μL/L and 10 μL/L, AITC sachet at 5 μL/L and 10 μL/L and OMF sachet at 850 mg + 850 μL of water. However, AFs production was inhibited by all antimicrobial treatments in a dose-dependent manner. More importantly, AITC in a filter paper at 10 μL/L, AITC sachet at 10 μL/L, OMF sachet at 850 mg + 850 μL of water and sorbic acid + sodium propionate at 0.5-2.0 g/Kg completely inhibited AFs formation. The use of AITC in active packaging devices could be a natural alternative to avoid the growth of mycotoxinogenic fungi in refrigerated bakery products in substitution of common commercial preservatives. PMID:26146190

  9. Inhibition of Listeria monocytogenes on cooked cured chicken breasts by acidified coating containing allyl isothiocyanate or deodorized Oriental mustard extract.

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2016-08-01

    Ready-to-eat meats are considered foods at high risk to cause life-threatening Listeria monocytogenes infections. This study screened 5 L. monocytogenes strains for their ability to hydrolyze sinigrin (a glucosinolate in Oriental mustard), which formed allyl isothiocyanate (AITC) and reduced L. monocytogenes viability on inoculated vacuum-packed, cooked, cured roast chicken slices at 4 °C. Tests involved incorporation of 25-50 μl/g AITC directly or 100-250 mg/g Oriental mustard extract in 0.5% (w/v) κ-carrageenan/2% (w/v) chitosan-based coatings prepared using 1.5% malic or acetic acid. L. monocytogenes strains hydrolyzed 33.6%-48.4% pure sinigrin in MH broth by 21 d at 25 °C. Acidified κ-carrageenan/chitosan coatings containing 25-50 μl/g AITC or 100-250 mg/g mustard reduced the viability of L. monocytogenes and aerobic bacteria on cooked, cured roast chicken slices by 4.1 to >7.0 log10 CFU/g compared to uncoated chicken stored at 4 °C for 70 d. Coatings containing malic acid were significantly more antimicrobial than those with acetic acid. During storage for 70 d, acidified κ-carrageenan/chitosan coatings containing 25-50 μl/g AITC or 250 mg/g mustard extract reduced lactic acid bacteria (LAB) numbers 3.8 to 5.4 log10 CFU/g on chicken slices compared to uncoated samples. Acidified κ-carrageenan/chitosan-based coatings containing either AITC or Oriental mustard extract at the concentrations tested had the ability to control L. monocytogenes viability and delay growth of potential spoilage bacteria on refrigerated, vacuum-packed cured roast chicken. PMID:27052706

  10. Allyl isothiocyanate suppresses the proteolytic activation of sterol regulatory element-binding proteins and de novo fatty acid and cholesterol synthesis.

    PubMed

    Miyata, Shingo; Inoue, Jun; Shimizu, Makoto; Sato, Ryuichiro

    2016-05-01

    Sterol regulatory element-binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of genes involved in fatty acid and cholesterol synthesis. In this study, we used a stable cell line that expresses a luciferase reporter gene driven by an SRE-containing fatty acid synthase promoter to identify allyl isothiocyanate (AITC), one of the major isothiocyanates in cruciferous vegetables, as a novel SREBP inactivator. We found that AITC downregulated the proteolytic processing of SREBPs and the expression of their target genes in human hepatoma Huh-7 cells. Furthermore, AITC reduced the de novo synthesis of both fatty acids and cholesterol. Our results indicate a novel physiological function of AITC in lipid metabolism regulation. PMID:26822063

  11. Toxicity of allyl isothiocyanate and cinnamic aldehyde assessed using cultured human KB cells and yeast, Saccharomyces cervisiae

    SciTech Connect

    Mochida, K.; Gomyoda, M.; Fujita, T.; Yamagata, K.

    1988-03-01

    The main components of mustard and cinnamon oils are allyl isothiocyante (AIT) and cinnamic aldehyde (CA), substances used as food additives. The acute toxicity of these substances has been noted in rats (Jenner et al. 1964) and it is desirable to obtain information on the toxic effects of these compounds in vitro systems. The authors report the toxicity of AIT and CA on human KB cells and Saccharomyces cervisiae cultivated in culture systems.

  12. Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway

    PubMed Central

    Wang, Shujun; Wang, Shanshan; Wang, Chenyin; Chen, Yajun; Li, Jie; Wang, Xueqi; Wang, Dianlei; Li, Zegeng; Peng, Zhaoliang; Fan, Ling

    2015-01-01

    Multidrug resistance-associated protein 1 (MRP1) plays a protective role in the etiology and progression of chronic obstructive pulmonary disease (COPD) which results from oxidative stress and inflammation of lung injury. The lower functional MRP1 activity is related to COPD development. Our previous study showed that Allyl isothiocyanate (AITC) induced the expression and activity of MRP1 in a dose-dependent manner. However, which signaling pathway contributes to the upregulation of MRP1 by AITC is unclear. In this study, signaling pathway specific inhibitors were used to examine the mechanism of AITC. We found that JNK inhibitor SP600125 treatment decreased MRP1 mRNA expression in 16HBE14o- cells. But the ERK inhibitor U0126 or PI3K/Akt inhibitor LY294002 produced no obvious effect. The AITC-induced increase of MRP1 mRNA expression was abolished by cotreatment of SP600125, while it was not obviously affected by U0126 or LY294002. Furthermore, AITC acivates the JNK signaling pathway in 16HBE14o- cells. Finally, we found that JNK pathway mediated the upregulation of AITC-induced expression and function of MRP1. Taken together, our results indicated that AITC increased the expression and the activity of MRP1 via a JNK-dependent pathway. ERK and PI3K signaling pathway were not involved in the expression of MRP1 mRNA. PMID:26273426

  13. Degradation of Biofumigant Isothiocyanates and Allyl Glucosinolate in Soil and Their Effects on the Microbial Community Composition

    PubMed Central

    Hanschen, Franziska S.; Yim, Bunlong; Winkelmann, Traud; Smalla, Kornelia; Schreiner, Monika

    2015-01-01

    Brassicales species rich in glucosinolates are used for biofumigation, a process based on releasing enzymatically toxic isothiocyanates into the soil. These hydrolysis products are volatile and often reactive compounds. Moreover, glucosinolates can be degraded also without the presence of the hydrolytic enzyme myrosinase which might contribute to bioactive effects. Thus, in the present study the stability of Brassicaceae plant-derived and pure glucosinolates hydrolysis products was studied using three different soils (model biofumigation). In addition, the degradation of pure 2-propenyl glucosinolate was investigated with special regard to the formation of volatile breakdown products. Finally, the influence of pure glucosinolate degradation on the bacterial community composition was evaluated using denaturing gradient gel electrophoresis of 16S rRNA gene amplified from total community DNA. The model biofumigation study revealed that the structure of the hydrolysis products had a significant impact on their stability in the soil but not the soil type. Following the degradation of pure 2-propenyl glucosinolate in the soils, the nitrile as well as the isothiocyanate can be the main degradation products, depending on the soil type. Furthermore, the degradation was shown to be both chemically as well as biologically mediated as autoclaving reduced degradation. The nitrile was the major product of the chemical degradation and its formation increased with iron content of the soil. Additionally, the bacterial community composition was significantly affected by adding pure 2-propenyl glucosinolate, the effect being more pronounced than in treatments with myrosinase added to the glucosinolate. Therefore, glucosinolates can have a greater effect on soil bacterial community composition than their hydrolysis products. PMID:26186695

  14. Control of Salmonella on fresh chicken breasts by κ-carrageenan/chitosan-based coatings containing allyl isothiocyanate or deodorized Oriental mustard extract plus EDTA.

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2015-06-01

    Control of Salmonella in poultry is a public health concern as salmonellosis is one of the most common foodborne diseases worldwide. This study aimed to screen the ability of 5 Salmonella serovars to degrade the mustard glucosinolate, sinigrin (by bacterial myrosinase) in Mueller-Hinton broth at 25 °C for 21 d and to reduce Salmonella on fresh chicken breasts by developing an edible 0.2% (w/v) κ-carrageenan/2% (w/v) chitosan-based coating containing Oriental mustard extract, allyl isothiocyanate (AITC), EDTA or their combinations. Individual Salmonella serovars degraded 50.2%-55.9% of the sinigrin present in 21 d. κ-Carrageenan/chitosan-based coatings containing 250 mg Oriental mustard extract/g or 50 μl AITC/g reduced the numbers of Salmonella on chicken breasts 2.3 log10 CFU/g at 21 d at 4 °C. However, when either mustard extract or AITC was combined with 15 mg/g EDTA in κ-carrageenan/chitosan-based coatings, Salmonella numbers were reduced 2.3 log10 CFU/g at 5 d and 3.0 log10 CFU/g at 21 d. Moreover, these treatments reduced numbers of lactic acid bacteria and aerobic bacteria by 2.5-3.3 log10 CFU/g at 21 d. κ-Carrageenan/chitosan coatings containing either 50 μl AITC/g or 250 mg Oriental mustard extract/g plus 15 mg EDTA/g have the potential to reduce Salmonella on raw chicken. PMID:25790995

  15. Anti-inflammatory potential of allyl-isothiocyanate--role of Nrf2, NF-(κ) B and microRNA-155.

    PubMed

    Wagner, Anika Eva; Boesch-Saadatmandi, Christine; Dose, Janina; Schultheiss, Gerhard; Rimbach, Gerald

    2012-04-01

    In this study, the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) were analysed in vitro and in vivo. Murine RAW264.7 macrophages stimulated with lipopolysaccharide (LPS) were supplemented with increasing concentrations of AITC. In addition, C57BL/6 mice (n= 10 per group) were fed a pro-inflammatory high-fat diet and AITC was administered orally via gavage for 7 days. Biomarkers of inflammation were determined both in cultured cells and in mice. AITC significantly decreased tumour necrosis factor α mRNA levels and its secretion in LPS stimulated RAW264.7 macrophages. Furthermore, gene expression of other pro-inflammatory markers including interleukin-1β and inducible nitric oxide synthase were down-regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NF-κB. Importantly, our data indicate that AITC significantly attenuated microRNA-155 levels in LPS-stimulated RAW264.7 macrophages in a dose-dependent manner. The anti-inflammatory effects of AITC were accompanied by an increase in Nrf2 nuclear translocation and consequently by an increase of mRNA and protein levels of the Nrf2 target gene heme-oxygenase 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down-regulating inflammation in LPS-stimulated macrophages. A significant increase in nuclear Nrf2 and heme-oxygenase 1 gene expression and only a moderate down-regulation of interleukin-1β and microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti-inflammatory activity in cultured macrophages in vitro but has only little anti-inflammatory activity in mice in vivo. PMID:21692985

  16. Inhibition of Campylobacter jejuni on fresh chicken breasts by κ-carrageenan/chitosan-based coatings containing allyl isothiocyanate or deodorized oriental mustard extract.

    PubMed

    Olaimat, Amin N; Fang, Yuan; Holley, Richard A

    2014-09-18

    Campylobacter species are common bacterial pathogens associated with human gastroenteritis worldwide. The objectives of this study were to determine the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations of allyl isothiocyanate (AITC) against 4 Campylobacter jejuni strains in Mueller-Hinton (MH) broth at 4, 21, 37 and 42°C and to screen the C. jejuni strains for their ability to degrade sinigrin (which forms AITC) in pH7.0 MH broth at 35°C for 21d. Also evaluated was the antimicrobial activity of an edible 0.2% κ-carrageenan/2% chitosan-based coating containing AITC or deodorized oriental mustard extract against a 4 strain C. jejuni cocktail (6.2log10CFU/g) on vacuum-packaged fresh chicken breasts during 4°C storage. MIC values of AITC were 0.63 to 1.25ppm and 2.5 to 5ppm against tested strains at 37 and 42°C, respectively. However, the MBC was 2.5 and 5ppm at 37 and 42°C, respectively, and increased to a range of 40 to 160ppm at 4°C. κ-Carrageenan/chitosan-based coatings containing 50 or 100μl/g AITC reduced viable C. jejuni to undetectable levels on chicken breast after 5d at 4°C, while 25μl/g AITC or 200 to 300mg/g mustard extract in coatings reduced C. jejuni numbers by 1.75 to 2.78log10CFU/g more than control coatings without antimicrobial. Both oriental mustard extract (50 to 300mg/g) and AITC (≥25μl/g) reduced aerobic bacteria by 1.72 to 2.75log10CFU/g and lactic acid bacteria (LAB) by 0.94 to 3.36log10CFU/g by 21d compared to the control coating. κ-Carrageenan/chitosan coatings containing ≥50μl/g AITC or ≥300mg/g oriental mustard showed excellent potential to control C. jejuni viability on raw chicken. PMID:25058687

  17. Active packaging of fresh chicken breast, with allyl isothiocyanate (AITC) in combination with modified atmosphere packaging (MAP) to control the growth of pathogens.

    PubMed

    Shin, Joongmin; Harte, Bruce; Ryser, Elliot; Selke, Susan

    2010-03-01

    Listeria monocytogenes and Salmonella typhimurium are major bacterial pathogens associated with poultry products. Ally isothiocyanate (AITC), a natural antimicrobial compound, is reportedly effective against these pathogenic organisms. A device was designed for the controlled release of AITC with modified atmosphere packaging (MAP), and then evaluated for its ability to control the growth of L. monocytogenes and S. typhimurium on raw chicken breast during refrigerated storage. In order to obtain controlled release during the test period, a glass vial was filled with AITC and triglyceride. It was then sealed using high-density polyethylene film. The release of AITC was controlled by the concentration (mole fraction) of AITC in the triglyceride and by the AITC vapor permeability through the film. The fresh chicken samples were inoculated with one or the other of the pathogens at 10(4) CFU/g, and the packages (with and without AITC-controlled release device) were flushed with ambient air or 30% CO(2)/70% N(2) before sealing, and then stored at 4 degrees C for up to 21 d. The maximum reduction in MAP plus AITC (compared to MAP alone) was 0.77 log CFU/g for L. monocytogenes and 1.3 log CFU/g for S. typhimurium. The color of the chicken breast meat was affected by the concentration of AITC. Overall, a release rate of 0.6 microg/h of AITC was found to not affect the color, whereas at 1.2 microg/h of AITC the surface of the chicken was discolored. PMID:20492243

  18. Allyl astatide

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Syuch, Z.

    1988-11-01

    Allyl astatide was prepared by the interhalogen exchange method, by replacement of the bromine in allyl bromide with astatide ion. The most favorable conditions for the synthesis were found by variations of the method that uses hydrazine hydrate and sodium formaldehyde sulfoxylate as reductants. A by-product is formed by the reaction of allyl bromide with excited astatine-211 which forms by disintegration of radon-211. Allyl astatide was identified by radio gas-liquid chromatography. Its retention indexes on nonpolar and weakly polar liquid phases were found. The stability of this newly prepared astatine compound was studied. The extrapolated boiling point of allyl astatide is 129 +/- 2/sup 0/C.

  19. Allyl alcohol

    Integrated Risk Information System (IRIS)

    Allyl alcohol ; CASRN 107 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  20. Allyl chloride

    Integrated Risk Information System (IRIS)

    Allyl chloride ; CASRN 107 - 05 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  1. A Potent and Site-Selective Agonist of TRPA1.

    PubMed

    Takaya, Junichiro; Mio, Kazuhiro; Shiraishi, Takuya; Kurokawa, Tatsuki; Otsuka, Shinya; Mori, Yasuo; Uesugi, Motonari

    2015-12-23

    TRPA1 is a member of the transient receptor potential (TRP) cation channel family that is expressed primarily on sensory neurons. This chemosensor is activated through covalent modification of multiple cysteine residues with a wide range of reactive compounds including allyl isothiocyanate (AITC), a spicy component of wasabi. The present study reports on potent and selective agonists of TRPA1, discovered through screening 1657 electrophilic molecules. In an effort to validate the mode of action of hit molecules, we noted a new TRPA1-selective agonist, JT010 (molecule 1), which opens the TRPA1 channel by covalently and site-selectively binding to Cys621 (EC50 = 0.65 nM). The results suggest that a single modification of Cys621 is sufficient to open the TRPA1 channel. The TRPA1-selective probe described herein might be useful for further mechanistic studies of TRPA1 activation. PMID:26630251

  2. Definition of two agonist types at the mammalian cold-activated channel TRPM8.

    PubMed

    Janssens, Annelies; Gees, Maarten; Toth, Balazs Istvan; Ghosh, Debapriya; Mulier, Marie; Vennekens, Rudi; Vriens, Joris; Talavera, Karel; Voets, Thomas

    2016-01-01

    Various TRP channels act as polymodal sensors of thermal and chemical stimuli, but the mechanisms whereby chemical ligands impact on TRP channel gating are poorly understood. Here we show that AITC (allyl isothiocyanate; mustard oil) and menthol represent two distinct types of ligands at the mammalian cold sensor TRPM8. Kinetic analysis of channel gating revealed that AITC acts by destabilizing the closed channel, whereas menthol stabilizes the open channel, relative to the transition state. Based on these differences, we classify agonists as either type I (menthol-like) or type II (AITC-like), and provide a kinetic model that faithfully reproduces their differential effects. We further demonstrate that type I and type II agonists have a distinct impact on TRPM8 currents and TRPM8-mediated calcium signals in excitable cells. These findings provide a theoretical framework for understanding the differential actions of TRP channel ligands, with important ramifications for TRP channel structure-function analysis and pharmacology. PMID:27449282

  3. Tetraalkylammonium uranyl isothiocyanates.

    PubMed

    Rowland, Clare E; Kanatzidis, Mercouri G; Soderholm, L

    2012-11-01

    Three tetraalkylammonium uranyl isothiocyanates, [(CH(3))(4)N](3)UO(2)(NCS)(5) (1), [(C(2)H(5))(4)N](3)UO(2)(NCS)(5) (2), and [(C(3)H(7))(4)N](3)UO(2)(NCS)(5) (3), have been synthesized from aqueous solution and their structures determined by single-crystal X-ray diffraction. All of the compounds consist of the uranyl cation equatorially coordinated to five N-bound thiocyanate ligands, UO(2)(NCS)(5)(3-), and charge-balanced by three tetraalkylammonium cations. Raman spectroscopy data have been collected on compounds 1-3, as well as on solutions of uranyl nitrate with increasing levels of sodium thiocyanate. By tracking the Raman signatures of thiocyanate, the presence of both free and bound thiocyanate is confirmed in solution. The shift in the Raman signal of the uranyl symmetric stretching mode suggests the formation of higher-order uranyl thiocyanate complexes in solution, while the solid-state Raman data support homoleptic isothiocyanate coordination about the uranyl cation. Presented here are the syntheses and crystal structures of 1-3, pertinent Raman spectra, and a discussion regarding the relationship of these isothiocyanates to previously described uranyl halide phases, UO(2)X(4)(2-). PMID:23072277

  4. Antimicrobial Activity of Isothiocyanates from Cruciferous Plants against Methicillin-Resistant Staphylococcus aureus (MRSA)

    PubMed Central

    Dias, Carla; Aires, Alfredo; Saavedra, Maria José

    2014-01-01

    Purified isothiocyanates from cruciferous plants (Brassicacea, Syn. Cruciferae) plants were evaluated against 15 isolates of methicillin-resistant S. aureus isolated from diabetic foot-ulcer patients aiming the study of the potential usage of allyl-isothiocyanate, benzyl-isothiocyanate and 2-phenylethyl-isothiocyanate against this important bacteria. Disc diffusion and minimum inhibitory concentration methods were used to access the antimicrobial activity. The index (Ia) and rate (Ra) of the antibacterial activity for each compound were calculated. The results showed a highly dose-dependent compound and chemical structure antibacterial effectiveness. The results showed a strong relation between the chemical structure of isothiocyanates and its antibacterial effectiveness. The benzyl-isothiocyanate was the most effective with a minimum inhibitory concentration varying between 2.9 and 110 µg· mL−1 with an antibacterial activity rate up to 87%. Moreover, their antibacterial activity was mainly bactericidal. This study provides scientific evidence that isothiocyanates have an interesting biological value and must be considered as an important tool to be used against MRSA. PMID:25353177

  5. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    SciTech Connect

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  6. Assessing Natural Isothiocyanate Air Emissions after Field Incorporation of Mustard Cover Crop

    SciTech Connect

    Trott, Donna M.; LePage, Jane; Hebert, Vincent

    2012-01-01

    A regional air assessment was performed to characterize volatile natural isothiocyanate (NITC) compounds in air during soil incorporation of mustard cover crops in Washington State. Field air sampling and analytical methods were developed specific to three NITCs known to be present in air at appreciable concentrations during/after field incorporation. The maximum observed concentrations in air for the allyl, benzyl, and phenethyl isothiocyanates were respectively 188, 6.1, and 0.7 lg m-3 during mustard incorporation. Based on limited inhalation toxicity information, airborne NITC concentrations did not appear to pose an acute human inhalation exposure concern to field operators and bystanders.

  7. Antimicrobial Activities of Isothiocyanates Against Campylobacter jejuni Isolates

    PubMed Central

    Dufour, Virginie; Alazzam, Bachar; Ermel, Gwennola; Thepaut, Marion; Rossero, Albert; Tresse, Odile; Baysse, Christine

    2012-01-01

    Food-borne human infection with Campylobacter jejuni is a medical concern in both industrialized and developing countries. Efficient eradication of C. jejuni reservoirs within live animals and processed foods is limited by the development of antimicrobial resistances and by practical problems related to the use of conventional antibiotics in food processes. We have investigated the bacteriostatic and bactericidal activities of two phytochemicals, allyl-isothiocyanate (AITC), and benzyl isothiocyanate (BITC), against 24 C. jejuni isolates from chicken feces, human infections, and contaminated foods, as well as two reference strains NCTC11168 and 81-176. AITC and BITC displayed a potent antibacterial activity against C. jejuni. BITC showed a higher overall antibacterial effect (MIC of 1.25–5 μg mL−1) compared to AITC (MIC of 50–200 μg mL−1). Both compounds are bactericidal rather than bacteriostatic. The sensitivity levels of C. jejuni isolates against isothiocyanates were neither correlated with the presence of a GGT (γ-Glutamyl Transpeptidase) encoding gene in the genome, with antibiotic resistance nor with the origin of the biological sample. However the ggt mutant of C. jejuni 81-176 displayed a decreased survival rate compared to wild-type when exposed to ITC. This work determined the MIC of two ITC against a panel of C. jejuni isolates, showed that both compounds are bactericidal rather than bacteriostatic, and highlighted the role of GGT enzyme in the survival rate of C. jejuni exposed to ITC. PMID:22919644

  8. Regioselective synthesis of novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole and 2,2‧-(1,3-phenylene)bis(3-substituted-2-imino-4-phenyl-3H-thiazole) derivatives as antibacterial agents

    NASA Astrophysics Data System (ADS)

    Abbasi Shiran, Jafar; Yahyazadeh, Asieh; Mamaghani, Manouchehr; Rassa, Mehdi

    2013-05-01

    Several novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole derivatives were synthesized by the reaction of allyl-thioureas and 2-bromoacetophenone. We also report the synthesis of bis-allyl-3H thiazoles using the reaction of various isothiocyanates and 1,3-phenylenediamine. The structures of all compounds were characterized by spectral and elemental analysis. Most of the synthesized compounds exhibited efficient antibacterial activities against Salmonella enterica, Micrococcus luteus, Bacillus subtilis and Pseudomonas aeruginosa.

  9. Pd-Catalyzed Synthesis of Allylic Silanes from Allylic Ethers

    PubMed Central

    Moser, Ralph; Nishikata, Takashi; Lipshutz, Bruce H.

    2009-01-01

    Allylic phenyl ethers serve as electrophiles towards Pd(0) en route to a variety of allylic silanes. The reactions can be run at room temperature in water as the only medium using micellar catalysis. PMID:19950911

  10. PHOTOOXIDATION OF ALLYL CHLORIDE

    EPA Science Inventory

    The photooxidation of allyl chloride was studied by irradiation either in 100-L Teflon bags or in a 22.7-cu m Teflon smog chamber in the presence of added NOx. In the absence of added hydrocarbons, the reaction involves a Cl atom chain, which leads to a highly reactive system. A ...

  11. Definition of two agonist types at the mammalian cold-activated channel TRPM8

    PubMed Central

    Janssens, Annelies; Gees, Maarten; Toth, Balazs Istvan; Ghosh, Debapriya; Mulier, Marie; Vennekens, Rudi; Vriens, Joris; Talavera, Karel; Voets, Thomas

    2016-01-01

    Various TRP channels act as polymodal sensors of thermal and chemical stimuli, but the mechanisms whereby chemical ligands impact on TRP channel gating are poorly understood. Here we show that AITC (allyl isothiocyanate; mustard oil) and menthol represent two distinct types of ligands at the mammalian cold sensor TRPM8. Kinetic analysis of channel gating revealed that AITC acts by destabilizing the closed channel, whereas menthol stabilizes the open channel, relative to the transition state. Based on these differences, we classify agonists as either type I (menthol-like) or type II (AITC-like), and provide a kinetic model that faithfully reproduces their differential effects. We further demonstrate that type I and type II agonists have a distinct impact on TRPM8 currents and TRPM8-mediated calcium signals in excitable cells. These findings provide a theoretical framework for understanding the differential actions of TRP channel ligands, with important ramifications for TRP channel structure-function analysis and pharmacology. DOI: http://dx.doi.org/10.7554/eLife.17240.001 PMID:27449282

  12. Isothiocyanates as effective agents against enterohemorrhagic Escherichia coli: insight to the mode of action

    PubMed Central

    Nowicki, Dariusz; Rodzik, Olga; Herman-Antosiewicz, Anna; Szalewska-Pałasz, Agnieszka

    2016-01-01

    Production of Shiga toxins by enterohemorrhagic Escherichia coli (EHEC) which is responsible for the pathogenicity of these strains, is strictly correlated with induction of lambdoid bacteriophages present in the host’s genome, replication of phage DNA and expression of stx genes. Antibiotic treatment of EHEC infection may lead to induction of prophage into a lytic development, thus increasing the risk of severe complications. This, together with the spread of multi-drug resistance, increases the need for novel antimicrobial agents. We report here that isothiocyanates (ITC), plant secondary metabolites, such as sulforaphane (SFN), allyl isothiocyanate (AITC), benzyl isothiocynanate (BITC), phenyl isothiocyanate (PITC) and isopropyl isothiocyanate (IPRITC), inhibit bacterial growth and lytic development of stx-harboring prophages. The mechanism underlying the antimicrobial effect of ITCs involves the induction of global bacterial stress regulatory system, the stringent response. Its alarmone, guanosine penta/tetraphosphate ((p)ppGpp) affects major cellular processes, including nucleic acids synthesis, which leads to the efficient inhibition of both, prophage induction and toxin synthesis, abolishing in this way EHEC virulence for human and simian cells. Thus, ITCs could be considered as potential therapeutic agents in EHEC infections. PMID:26922906

  13. Soil bacterial and fungal communities respond differently to various isothiocyanates added for biofumigation

    PubMed Central

    Hu, Ping; Hollister, Emily B.; Somenahally, Anilkumar C.; Hons, Frank M.; Gentry, Terry J.

    2015-01-01

    The meals from many oilseed crops have potential for biofumigation due to their release of biocidal compounds such as isothiocyanates (ITCs). Various ITCs are known to inhibit numerous pathogens; however, much less is known about how the soil microbial community responds to the different types of ITCs released from oilseed meals (SMs). To simulate applying ITC-releasing SMs to soil, we amended soil with 1% flax SM (contains no biocidal chemicals) along with four types of ITCs (allyl, butyl, phenyl, and benzyl ITC) in order to determine their effects on soil fungal and bacterial communities in a replicated microcosm study. Microbial communities were analyzed based on the ITS region for fungi and 16S rRNA gene for bacteria using qPCR and tag-pyrosequencing with 454 GS FLX titanium technology. A dramatic decrease in fungal populations (~85% reduction) was observed after allyl ITC addition. Fungal community compositions also shifted following ITC amendments (e.g., Humicola increased in allyl and Mortierella in butyl ITC amendments). Bacterial populations were less impacted by ITCs, although there was a transient increase in the proportion of Firmicutes, related to bacteria know to be antagonistic to plant pathogens, following amendment with allyl ITC. Our results indicate that the type of ITC released from SMs can result in differential impacts on soil microorganisms. This information will aid selection and breeding of plants for biofumigation-based control of soil-borne pathogens while minimizing the impacts on non-target microorganisms. PMID:25709600

  14. Soil bacterial and fungal communities respond differently to various isothiocyanates added for biofumigation.

    PubMed

    Hu, Ping; Hollister, Emily B; Somenahally, Anilkumar C; Hons, Frank M; Gentry, Terry J

    2014-01-01

    The meals from many oilseed crops have potential for biofumigation due to their release of biocidal compounds such as isothiocyanates (ITCs). Various ITCs are known to inhibit numerous pathogens; however, much less is known about how the soil microbial community responds to the different types of ITCs released from oilseed meals (SMs). To simulate applying ITC-releasing SMs to soil, we amended soil with 1% flax SM (contains no biocidal chemicals) along with four types of ITCs (allyl, butyl, phenyl, and benzyl ITC) in order to determine their effects on soil fungal and bacterial communities in a replicated microcosm study. Microbial communities were analyzed based on the ITS region for fungi and 16S rRNA gene for bacteria using qPCR and tag-pyrosequencing with 454 GS FLX titanium technology. A dramatic decrease in fungal populations (~85% reduction) was observed after allyl ITC addition. Fungal community compositions also shifted following ITC amendments (e.g., Humicola increased in allyl and Mortierella in butyl ITC amendments). Bacterial populations were less impacted by ITCs, although there was a transient increase in the proportion of Firmicutes, related to bacteria know to be antagonistic to plant pathogens, following amendment with allyl ITC. Our results indicate that the type of ITC released from SMs can result in differential impacts on soil microorganisms. This information will aid selection and breeding of plants for biofumigation-based control of soil-borne pathogens while minimizing the impacts on non-target microorganisms. PMID:25709600

  15. Mild and Site-Selective Allylation of Enol Carbamates with Allylic Carbonates under Rhodium Catalysis.

    PubMed

    Sharma, Satyasheel; Han, Sang Hoon; Oh, Yongguk; Mishra, Neeraj Kumar; Han, Sangil; Kwak, Jong Hwan; Lee, Seok-Yong; Jung, Young Hoon; Kim, In Su

    2016-03-18

    The rhodium(III)-catalyzed mild and site-selective C-H allylation of enol carbamates with 4-vinyl-1,3-dioxolan-2-one and allylic carbonates affords allylic alcohols and terminal allylated products, respectively. The assistance of the carbamoyl directing group provides a straightforward preparation of biologically and synthetically important allylated enol carbamates. PMID:26906724

  16. Induction of unscheduled DNA synthesis in HeLa cells by allylic compounds.

    PubMed

    Schiffmann, D; Eder, E; Neudecker, T; Henschler, D

    1983-10-01

    Thirteen allylic compounds, mostly with close structural relationship, were tested for their ability to induce unscheduled DNA synthesis (UDS) in HeLa cells and mutations in the Ames test; 11 induced UDS in dose dependence. Allyl isothiocyanate was negative in UDS (borderline in the Ames test) and acrolein (positive in the Ames test) proved toxic to HeLa cells, therefore UDS measurement was excluded. In general, positive qualitative and quantitative correlation between UDS, Ames test and alkylating properties (as measured in the 4-nitrobenzyl-pyridine test, NBP) were found. Among structural analogs and typical allylic compounds with various leaving groups, the amount of induced DNA repair at equimolar concentrations decreased in the same order as the mutagenic and alkylating activities in the other 2 test systems: 1,3-dichloropropene (cis) greater than 1,3-dichloropropene (trans) greater than 2,3-dichloro-1-propene; 1-chloro-2-butene greater than 3-chloro-1-butene greater than 3-chloro-2-methyl-1-propene greater than allyl chloride; allyl-methane-sulfonate greater than -iodide greater than -bromide greater than -chloride. PMID:6627227

  17. Tsuji-Trost N-allylation with allylic acetates using cellulose-Pd catalyst

    EPA Science Inventory

    Allylic amines are synthesized using heterogeneous cellulose-Pd catalyst via N-allylation of amines; aliphatic and benzyl amines undergo facile reaction with substituted and unsubstituted allyl acetates in high yields.

  18. Regioselective Transition-Metal-Free Allyl-Allyl Cross-Couplings.

    PubMed

    Ellwart, Mario; Makarov, Ilya S; Achrainer, Florian; Zipse, Hendrik; Knochel, Paul

    2016-08-22

    Readily prepared allylic zinc halides undergo SN 2-type substitutions with allylic bromides in a 1:1 mixture of THF and DMPU providing 1,5-dienes regioselectively. The allylic zinc species reacts at the most branched end (γ-position) of the allylic system furnishing exclusively γ,α'-allyl-allyl cross-coupling products. Remarkably, the double bond stereochemistry of the allylic halide is maintained during the cross-coupling process. Also several functional groups (ester, nitrile) are tolerated. This cross-coupling of allylic zinc reagents can be extended to propargylic and benzylic halides. DFT calculations show the importance of lithium chloride in this substitution. PMID:27430745

  19. Overexpression of Glutathione Transferase E7 in Drosophila Differentially Impacts Toxicity of Organic Isothiocyanates in Males and Females

    PubMed Central

    Mannervik, Bengt; Mannervik, Mattias

    2014-01-01

    Organic isothiocyanates (ITCs) are allelochemicals produced by plants in order to combat insects and other herbivores. The compounds are toxic electrophiles that can be inactivated and conjugated with intracellular glutathione in reactions catalyzed by glutathione transferases (GSTs). The Drosophila melanogaster GSTE7 was heterologously expressed in Escherichia coli and purified for functional studies. The enzyme showed high catalytic activity with various isothiocyanates including phenethyl isothiocyanate (PEITC) and allyl isothiocyanate (AITC), which in millimolar dietary concentrations conferred toxicity to adult D. melanogaster leading to death or a shortened life-span of the flies. In situ hybridization revealed a maternal contribution of GSTE7 transcripts to embryos, and strongest zygotic expression in the digestive tract. Transgenesis involving the GSTE7 gene controlled by an actin promoter produced viable flies expressing the GSTE7 transcript ubiquitously. Transgenic females show a significantly increased survival when subjected to the same PEITC treatment as the wild-type flies. By contrast, transgenic male flies show a significantly lower survival rate. Oviposition activity was enhanced in transgenic flies. The effect was significant in transgenic females reared in the absence of ITCs as well as in the presence of 0.15 mM PEITC or 1 mM AITC. Thus the GSTE7 transgene elicits responses to exposure to ITC allelochemicals which differentially affect life-span and fecundity of male and female flies. PMID:25329882

  20. Allyl-isatin suppresses cell viability, induces cell cycle arrest, and promotes cell apoptosis in hepatocellular carcinoma HepG2 cells.

    PubMed

    Bian, Weihua; An, Yukuan; Qu, Huiqing; Yang, Yue; Yang, Junhou; Xu, Yanyan

    2016-06-01

    The anticancer effect of the newly synthesized isatin derivative, N-allyl-isatin (Allyl-I), was evaluated in vitro with human hepatocellular carcinoma HepG2 cells. Cell viability was detected by cell counting kit-8 (CCK8) assay. Acridine orange (AO)/ethidium bromide (EB) double staining was used to observe the cell morphology. Flow cytometry was used to assess the effects of Allyl-I on the cell cycle, apoptosis rate, and mitochondrial membrane potential (MMP). Western blot analysis was performed to detect the influence of Ally1-I on the expression of cytochrome c (cyt c), Bax, Bcl-2, and cleaved caspase-3. Allyl-I significantly inhibited HepG2 cell viability in a time- and dose-dependent manner. Allyl-I can induce cell cycle arrest in HepG2 cells at the G2/M phase. Apoptotic nuclear morphological changes were observed after AO/EB double staining. Fluorescein isothiocyanate-conjugated Annexin V (Annexin V-FITC) and propidium iodide (PI) double staining showed that the apoptotic rates significantly increased in the presence of Allyl-I. Rhodamine 123 staining indicated that Allyl-I can decrease the MMP. Allyl-I also altered the expression of mitochondrial apoptosis-related proteins. Protein levels of cyt c and cleaved caspase-3 were upregulated following Allyl-I treatment. By contrast, the Bcl-2/Bax ratio decreased. Results suggest that Allyl-I suppresses cell viability, induces cell cycle arrest, and promotes cell apoptosis in HepG2 cells. Furthermore, the induction of apoptosis might be correlated with the mitochondrial pathway. PMID:26945926

  1. Iridium-Catalyzed Allylic Substitution

    NASA Astrophysics Data System (ADS)

    Hartwig, John F.; Pouy, Mark J.

    Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced cyclometalation at the methyl group of this substituent to generate an iridium metalacycle bound by the COD ligand of the [Ir(COD)Cl]2 precursor and one additional labile dative ligand. Such complexes catalyze the reactions of linear allylic esters with alkylamines, arylamines, phenols, alcohols, imides, carbamates, ammonia, enolates and enolate equivalents, as well as typical stabilized carbon nucleophiles generated from malonates and cyanoesters. Iridium catalysts for enantioselective allylic substitution have also been generated from phosphorus ligands with substituents bound by heteroatoms, and an account of the studies of such systems, along with a description of the development of iridium catalysts is included.

  2. Effects of transient receptor potential (TRP) channel agonists and antagonists on slowly adapting type II mechanoreceptors in the rat sinus hair follicle.

    PubMed

    Cahusac, Peter M B

    2009-12-01

    The possible functional role of transient receptor potential (TRP) channels was investigated by testing various TRP agonists and antagonists in an isolated rat sinus hair follicle preparation. Extracellular recordings from slowly adapting type II mechanoreceptor units were made. The antagonist capsazepine depressed spontaneous and mechanically evoked activity, with an IC(50) of 82 microM. In one-third of units, capsazepine caused a selective depression of mechanically evoked firing, such that the existing spontaneous firing was interrupted by an absence of activity during the mechanical stimulus. The broad spectrum TRP blocker ruthenium red (30 microM) had inconsistent effects, although in some units a delayed onset (following wash) bursting and paroxysmal firing ensued. The agonist icilin (50-100 microM) had an excitatory effect on spontaneous firing, and (-)-menthol (200 microM) had inconsistent effects. Cinnamaldehyde (1-2 mM) depressed all types of activity equally, mechanically evoked and spontaneous. Camphor (0.5-2 mM) also depressed all types of activity, although it had a preferential effect on spontaneous activity. Capsaicin (1-10 microM) and allyl isothiocyanate (50-100 microM) had no clear effects. These results rule out any role for TRPA1 and TRPV1 channels in mechanotransduction processes of slowly adapting type II mechanoreceptors. PMID:20021572

  3. The TRPA1 Activator Allyl Isothiocyanate (AITC) Contracts Human Jejunal Muscle: Pharmacological Analysis.

    PubMed

    Sandor, Zsolt; Dekany, Andras; Kelemen, Dezsö; Bencsik, Timea; Papp, Robert; Bartho, Lorand

    2016-09-01

    The contractile effect of AITC (300 μM) on human jejunal longitudinal strips was inhibited by the TRPA1 antagonist HC 030031 and atropine or scopolamine, but was insensitive to tetrodotoxin, purinoceptor antagonists or capsaicin desensitization. It is concluded that TRPA1 activation stimulates a cholinergic mechanism in a tetrodotoxin-resistant manner. PMID:26928772

  4. Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa.

    PubMed

    Moon, Hana; Kim, Min Jung; Son, Hee Jin; Kweon, Hae-Jin; Kim, Jung Tae; Kim, Yiseul; Shim, Jaewon; Suh, Byung-Chang; Rhyu, Mee-Ra

    2015-01-01

    Transient receptor potential ankyrin1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer) O. Kuntze (A.rugosa), commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae) selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid) on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM), our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1. PMID:25978436

  5. Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa

    PubMed Central

    Son, Hee Jin; Kweon, Hae-Jin; Kim, Jung Tae; Kim, Yiseul; Shim, Jaewon; Suh, Byung-Chang; Rhyu, Mee-Ra

    2015-01-01

    Transient receptor potential ankyrin1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer) O. Kuntze (A.rugosa), commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae) selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid) on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM), our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1. PMID:25978436

  6. Regioselective hydroformylation of allylic alcohols.

    PubMed

    Lightburn, Thomas E; De Paolis, Omar A; Cheng, Ka H; Tan, Kian L

    2011-05-20

    A highly regioselective hydroformylation of allylic alcohols is reported toward the synthesis of β-hydroxy-acid and aldehyde products. The selectivity is achieved through the use of a ligand that reversibly binds to alcohols in situ, allowing for a directed hydroformylation to occur. The application to trisubstituted olefins was also demonstrated, which yields a single diastereomer product consistent with a stereospecific addition of CO and hydrogen. PMID:21504208

  7. Regioselective Hydroformylation of Allylic Alcohols

    PubMed Central

    Lightburn, Thomas E.; De Paolis, Omar A.; Cheng, Ka H.; Tan, Kian L.

    2011-01-01

    A highly regioselective hydroformylation of allylic alcohols is reported towards the synthesis of β-hydroxy-acid and aldehyde products. The selectivity is achieved through the use of a ligand that reversibly binds to alcohols in situ, allowing for a directed hydroformylation to occur. The application to trisubstituted olefins was also demonstrated, which yields a single diastereomer product consistent with a stereospecific addition of CO and hydrogen. PMID:21504208

  8. Interplay of metal-allyl and metal-metal bonding in dimolybdenum allyl complexes

    SciTech Connect

    John, Kevin D; Martin, Richard L; Obrey, Steven J; Scott, Brian L

    2008-01-01

    Addition of PMe{sub 3} to Mo{sub 2}(allyl){sub 4} afforded Mo{sub 2}(allyl){sub 4}(PMe{sub 3}){sub 2}, in which two of the allyl groups adopt an unprecedented {mu}{sub 2{sup -}}{eta}{sup 1}, {eta}{sup 3} bonding mode; theoretical studies elucidate the role sof the {sigma}- and {pi}-donor ligands in the interplay of metal-allyl and metal-metal bonding.

  9. 1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1

    PubMed Central

    2012-01-01

    Background Essential oils are often used in alternative medicine as analgesic and anti-inflammatory remedies. However, the specific compounds that confer the effects of essential oils and the molecular mechanisms are largely unknown. TRPM8 is a thermosensitive receptor that detects cool temperatures and menthol whereas TRPA1 is a sensor of noxious cold. Ideally, an effective analgesic compound would activate TRPM8 and inhibit TRPA1. Results We screened essential oils and fragrance chemicals showing a high ratio of human TRPM8-activating ability versus human TRPA1-activating ability using a Ca2+-imaging method, and identified 1,8-cineole in eucalyptus oil as particularly effective. Patch-clamp experiments confirmed that 1,8-cineole evoked inward currents in HEK293T cells expressing human TRPM8, but not human TRPA1. In addition, 1,8-cineole inhibited human TRPA1 currents activated by allyl isothiocyanate, menthol, fulfenamic acid or octanol in a dose-dependent manner. Furthermore, in vivo sensory irritation tests showed that 1,8-cineole conferred an analgesic effect on sensory irritation produced by TRPA1 agonists octanol and menthol. Surprisingly, 1,4-cineole, which is structurally similar and also present in eucalyptus oil, activated both human TRPM8 and human TRPA1. Conclusions 1,8-cineole is a rare natural antagonist of human TRPA1 that has analgesic and anti-inflammatory effects possibly due to its inhibition of TRPA1. PMID:23192000

  10. Naturally Occurring Isothiocyanates Exert Anticancer Effects by Inhibiting Deubiquitinating Enzymes.

    PubMed

    Lawson, Ann P; Long, Marcus J C; Coffey, Rory T; Qian, Yu; Weerapana, Eranthie; El Oualid, Farid; Hedstrom, Lizbeth

    2015-12-01

    The anticancer properties of cruciferous vegetables are well known and attributed to an abundance of isothiocyanates such as benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). While many potential targets of isothiocyanates have been proposed, a full understanding of the mechanisms underlying their anticancer activity has remained elusive. Here we report that BITC and PEITC effectively inhibit deubiquitinating enzymes (DUB), including the enzymes USP9x and UCH37, which are associated with tumorigenesis, at physiologically relevant concentrations and time scales. USP9x protects the antiapoptotic protein Mcl-1 from degradation, and cells dependent on Mcl-1 were especially sensitive to BITC and PEITC. These isothiocyanates increased Mcl-1 ubiquitination and either isothiocyanate treatment, or RNAi-mediated silencing of USP9x decreased Mcl-1 levels, consistent with the notion that USP9x is a primary target of isothiocyanate activity. These isothiocyanates also increased ubiquitination of the oncogenic fusion protein Bcr-Abl, resulting in degradation under low isothiocyanate concentrations and aggregation under high isothiocyanate concentrations. USP9x inhibition paralleled the decrease in Bcr-Abl levels induced by isothiocyanate treatment, and USP9x silencing was sufficient to decrease Bcr-Abl levels, further suggesting that Bcr-Abl is a USP9x substrate. Overall, our findings suggest that USP9x targeting is critical to the mechanism underpinning the well-established anticancer activity of isothiocyanate. We propose that the isothiocyanate-induced inhibition of DUBs may also explain how isothiocyanates affect inflammatory and DNA repair processes, thus offering a unifying theme in understanding the function and useful application of isothiocyanates to treat cancer as well as a variety of other pathologic conditions. PMID:26542215

  11. O-Allylation of phenols with allylic acetates in aqueous media using a magnetically separable catalytic system

    EPA Science Inventory

    Allylic ethers were synthesized in water using magnetically recoverable heterogeneous Pd catalyst via O-allylation of phenols with allylic acetates under ambient conditions. Aqueous reaction medium, easy recovery of the catalyst using an external magnet, efficient recycling, and ...

  12. Blockade of ATP binding site of P2 purinoceptors in rat parotid acinar cells by isothiocyanate compounds.

    PubMed

    Soltoff, S P; McMillian, M K; Talamo, B R; Cantley, L C

    1993-05-01

    Extracellular ATP activates a P2Z-type purinergic receptor (purinoceptor) in rat parotid acinar cells that increases the intracellular free Ca2+ concentration via the entry of extracellular Ca2+ through an ATP-sensitive cation channel (Soltoff et al., Am J Physiol 262: C934-C940, 1992). To learn more about the ATP binding site of the purinoceptor, we examined the effects of several stilbene isothiocyanate analogs of DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), which block the binding of [32P]ATP to intact parotid cells (McMillian et al., Biochem J 255:291-300, 1988) and blocked the activation of the P2Z purinoceptor. The ATP-stimulated 45Ca2+ uptake was blocked by DIDS, H2DIDS (dihydro-DIDS; 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid), and SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid), but not by DNDS (4,4'-dinitrostilbene-2,2'-disulfonic acid), a stilbene disulfonate compound lacking isothiocyanate (SCN-) groups, or by KSCN. The potency of the stilbene disulfonates was related to the number of isothiocyanate groups on each compound. Under the experimental conditions, the IC50 value of DIDS (approximately 35 microM), which has two SCN-groups, was much lower than that of SITS (approximately 125 microM), which has only one SCN-group. The inhibitory effects of DIDS appeared to be much more potent than those of SITS due to the kinetics of their binding to the purinoceptors. Eosin-5-isothiocyanate (EITC) and fluorescein-5-isothiocyanate (FITC), non-stilbene isothiocyanate compounds with single SCN-groups, also blocked the response to ATP and were less potent than DIDS. Trinitrophenyl-ATP (TNP-ATP), an ATP derivative that is not an effective agonist of the parotid P2Z receptor, blocked the covalent binding of DIDS to the plasma membrane, suggesting that ATP and DIDS bind to the same site. Reactive Blue 2 (Cibacron Blue 3GA), an anthraquinone-sulfonic acid derivative that is a noncovalent purinergic antagonist, also blocked

  13. Broad spectrum antibacterial activity of a mixture of isothiocyanates from nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix).

    PubMed

    Conrad, A; Biehler, D; Nobis, T; Richter, H; Engels, I; Biehler, K; Frank, U

    2013-02-01

    Isothiocyanates have been reported to exert antimicrobial activity. These compounds are found in a licensed native preparation of nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix) which is used for treatment of upper respiratory and urinary tract infections. The aim of our investigation was to assess the antimicrobial activity of a mixture of the contained benzyl-, allyl-, and phenylethyl- isothiocyanates against clinically important bacterial and fungal pathogens including antimicrobial resistant isolates. Susceptibility testing was performed by agar-dilution technique. Isothiocyanates were mixed in proportions identical to the licensed drug. Minimum inhibitory- and minimum bactericidal concentrations were assessed. The Minimum inhibitory concentration90 was defined as the concentration which inhibited 90% of the microbial species tested. H. influenzae, M. catarrhalis, S. marcescens, P. vulgaris, and Candida spp. were found to be highly susceptible, with minimum inhibitory concentration90 -values ranging between ≤0.0005% and 0.004% (v/v) of total ITC. Intermediate susceptibilities were observed for S. aureus, S. pyogenes, S. pneumoniae, K. pneumoniae, E. coli and P. aeruginosa, with Minimum inhibitory concentration90 -values ranging between 0.004% and 0.125% (v/v), but with elevated Minimum bactericidal concentrations90-values (2-7 dilution steps above Minimum inhibitory concentration90). Low susceptibilities were determined for viridans streptococci and enterococci. Interestingly, both resistant and non-resistant bacteria were similarly susceptible to the test preparation. PMID:23447075

  14. Regiodivergent Addition of Phenols to Allylic Oxides

    PubMed Central

    Vaccarello, David N.; Moschitto, Matthew J.; Lewis, Chad A.

    2015-01-01

    The regiodivergent addition of substituted phenols to allylic-oxides has been demonstrated using C2-symmetric palladium complexes. Complex phenol donors tyrosine, estradiol, and griseofulvin follow the predictive model. The Tsuji-Trost reaction is a powerful method to append both O- and C-donors to η3-allyl systems.1 The η3-allyl progenitor structures include allylic esters, carbonates, halides, and oxides. Internal allylic oxides2 remain one of the few systems that retain a marker of stereochemical induction with the newly liberated carbinol. The origin of the products can be traced to the diastereomeric η3-allyl intermediate and stereoisomer of oxide employed. We have recently identified3 a system capable of the conversion of racemic allylic oxides to distinct enantioenriched regioisomers using achiral phenol donors (Scheme 1). The allylic oxide regio-resolution (AORR) allowed the preparation of enantioenriched carbasugar natural products. We have now expanded this study to include a diverse array of achiral and chiral phenol donors. PMID:25933102

  15. Peculiar Reactivity of Isothiocyanates with Pentaphenylborole.

    PubMed

    Huang, Kexuan; Martin, Caleb D

    2016-01-01

    The reactions of isothiocyanates with the antiaromatic pentaphenylborole were investigated, revealing significantly different outcomes than the analogous reactions with isocyanates. The 1:1 stoichiometric reaction products isolated include a seven-membered BNC5 heterocycle and a fused bicyclic 4/5-ring system. Studies suggest that the seven-membered ring undergoes an intramolecular [2 + 2] electrocyclic ring closure to produce the bicyclic system. The only derivative for which stoichiometry influenced the reaction outcome was 4-methoxyphenylisothiocyanate. The reaction of borole with an excess of 4-methoxyphenylisothiocyanate resulted in the formation of a fused tetracyclic species with two equivalents of isothiocyanate incorporated into the product. Rational pathways for these unusual transformations are presented. PMID:26682496

  16. Derivatization of isothiocyanates and their reactive adducts for chromatographic analysis.

    PubMed

    Agerbirk, Niels; De Nicola, Gina Rosalinda; Olsen, Carl Erik; Müller, Caroline; Iori, Renato

    2015-10-01

    Isothiocyanates form adducts with a multitude of biomolecules, and these adducts need analytical methods. Likewise, analytical methods for hydrophilic isothiocyanates are needed. We considered reaction with ammonia to form thiourea derivatives. The hydrophilic, glycosylated isothiocyanate moringin, 4-(α-L-rhamnopyranosyloxy)benzyl isothiocyanate, was efficiently derivatized to the thiourea derivative by incubation with ammonia. The hydrophobic benzyl isothiocyanate was also efficiently derivatized to the thiourea derivative. The thiourea group provided a UV absorbing chromophore, and the derivatives showed expectable sodium and hydrogen adducts in ion trap mass spectrometry and were suitable for liquid chromatography analysis. Reactive dithiocarbamate adducts constitute the major type of reactive ITC adduct expected in biological matrices. Incubation of a model dithiocarbamate with ammonia likewise resulted in conversion to the corresponding thiourea derivative, suggesting that a variety of matrix-bound reactive isothiocyanate adducts can be determined using this strategy. As an example of the application of the method, recovery of moringin and benzyl isothiocyanate applied to cabbage leaf discs was studied in simulated insect feeding assays. The majority of moringin was recovered as native isothiocyanate, but a major part of benzyl isothiocyanate was converted to reactive adducts. PMID:26342619

  17. Monitoring of isothiocyanates emanating from Arabidopsis thaliana upon paraquat spraying.

    PubMed

    Vercammen, J; Pham-Tuan, H; Arickx, I; Van der Straeten, D; Sandra, P

    2001-03-30

    Arabidopsis thaliana plants were sprayed with the superoxide-generating herbicide paraquat. The headspace of sprayed plants was characterized by a number of compounds, which were absent in the headspace of untreated plants. They were identified as isothiocyanates (ITCs) with 4-methylthiobutyl isothiocyanate as main compound. After identification, a GC-system, based on PDMS sorption, was used to continuously monitor the ITC emissions. The specificity of isothiocyanate emission was also determined by subjecting the Arabidopsis thaliana plants to in vitro mechanical wounding. Again, 4-methylthiobutyl isothiocyanate was the main component, but the emission profile was completely different since the compound was emitted immediately, i.e., during wounding itself. PMID:11307975

  18. Catalytic deallylation of allyl- and diallylmalonates.

    PubMed

    Necas, David; Turský, Matyás; Kotora, Martin

    2004-08-25

    Substituted allylmalonates undergo the selective C-C bond cleavage in the presence of triethylaluminum and a catalytic amount of nickel and ruthenium phosphine complexes, resulting in the loss of the allyl moiety and formation of monosubstituted malonates. Comparison of reactivity of the nickel and ruthenium complexes showed that the use of the former is general with respect to the structure of the substituted allylmalonates, and the activity of the latter depended on the substitution pattern of the double bond of the allylic moiety. The smooth deallylation may encourage the use of the allyl group as a protective group for the acidic hydrogen in malonates. PMID:15315416

  19. Asymmetric Allylic Alkylation of β-Ketoesters with Allylic Alcohols by a Nickel/Diphosphine Catalyst.

    PubMed

    Kita, Yusuke; Kavthe, Rahul D; Oda, Hiroaki; Mashima, Kazushi

    2016-01-18

    Asymmetric allylic alkylation of β-ketoesters with allylic alcohols catalyzed by [Ni(cod)2]/(S)-H8-BINAP was found to be a superior synthetic protocol for constructing quaternary chiral centers at the α-position of β-ketoesters. The reaction proceeded in high yield and with high enantioselectivity using various β-ketoesters and allylic alcohols, without any additional activators. The versatility of this methodology for accessing useful and enantioenriched products was demonstrated. PMID:26637131

  20. Palladium(0)-Catalyzed Allylation of Highly Acidic and Nonnucleophilic Anilines. The Origin of Stereochemical Scrambling When Using Allylic Carbonates.

    PubMed

    Moreno-Mañas, Marcial; Morral, Lurdes; Pleixats, Roser

    1998-09-01

    Acidic anilines such as diphenylamine, phenothiazine, and nitroanilines are efficiently allylated under palladium catalysis using allyl carbonates as allylating reagents. A stereochemical study of the reactions of ethyl cis-5-methyl-2-cyclohexenylcarbonate with 4-nitro- and 2,4-dinitroaniline was performed. Bidentate phosphines as stabilizing ligands gave clean retention of configuration whereas triphenylphosphine permitted cis-trans isomerization of the allylic carbonate, the allylation reactions occurring under Curtin-Hammet preequilibrium conditions. PMID:11672246

  1. SaxA-Mediated Isothiocyanate Metabolism in Phytopathogenic Pectobacteria.

    PubMed

    Welte, Cornelia U; Rosengarten, Jamila F; de Graaf, Rob M; Jetten, Mike S M

    2016-04-01

    Pectobacteria are devastating plant pathogens that infect a large variety of crops, including members of the family Brassicaceae. To infect cabbage crops, these plant pathogens need to overcome the plant's antibacterial defense mechanisms, where isothiocyanates are liberated by hydrolysis of glucosinolates. Here, we found that a Pectobacterium isolate from the gut of cabbage root fly larvae was particularly resistant to isothiocyanate and even seemed to benefit from the abundant Brassica root metabolite 2-phenylethyl isothiocyanate as a nitrogen source in an ecosystem where nitrogen is scarce. The Pectobacterium isolate harbored a naturally occurring mobile plasmid that contained a sax operon. We hypothesized that SaxA was the enzyme responsible for the breakdown of 2-phenylethyl isothiocyanate. Subsequently, we heterologously produced and purified the SaxA protein and characterized the recombinant enzyme. It hydrolyzed 2-phenylethyl isothiocyanate to yield the products carbonyl sulfide and phenylethylamine. It was also active toward another aromatic isothiocyanate but hardly toward aliphatic isothiocyanates. It belongs to the class B metal-dependent beta-lactamase fold protein family but was not, however, able to hydrolyze beta-lactam antibiotics. We discovered that several copies of the saxA gene are widespread in full and draft Pectobacterium genomes and therefore hypothesize that SaxA might be a new pathogenicity factor of the genus Pectobacterium, possibly compromising food preservation strategies using isothiocyanates. PMID:26873319

  2. The first naturally occurring aromatic isothiocyanates, rapalexins A and B, are cruciferous phytoalexins.

    PubMed

    Pedras, M Soledade C; Zheng, Qing-An; Gadagi, Ravi S

    2007-01-28

    The discovery of the first naturally occurring aromatic isothiocyanates, indole-3-isothiocyanates, their first synthesis, antimicrobial activity and proposed biogenetic origin in canola plants are reported. PMID:17220973

  3. N-Allylation of amines with allyl acetates using chitosan-immobilized palladium

    EPA Science Inventory

    A simple procedure for N-Allylation of allyl Acetates has been developed using a biodegradable and easily recyclable heterogeneous chitosan-supported palladium catalyst. The general methodology, applicable to wide range of substrates, has sustainable features that include a ligan...

  4. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

    PubMed Central

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  5. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines.

    PubMed

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  6. Mechanisms of the Anticancer Effects of Isothiocyanates.

    PubMed

    Fofaria, Neel M; Ranjan, Alok; Kim, Sung-Hoon; Srivastava, Sanjay K

    2015-01-01

    Cancer results from aberrant signaling pathways that result in uncontrolled cellular proliferation. The epidemiological studies have shown a strong inverse correlation between dietary consumption of cruciferous vegetables and incidences of cancer. Isothiocyanates (ITCs) are present in cruciferous vegetables like broccoli, cabbage, watercress, etc. and are identified as the major active constituents. Several mechanistic studies have demonstrated chemopreventive and chemotherapeutic activity of ITCs against various tumor types. ITCs exert anticancer activity by suppressing various critical hallmarks of cancer like cellular proliferation, angiogenesis, apoptosis, metastasis, etc., in vitro as well as in preclinical animal model. ITCs also generate reactive oxygen species to induce apoptosis in cancer cells. Due to promising preclinical results, few ITCs have also advanced to clinical trials. This chapter provides a candid review on the chemopreventive and chemotherapeutic activity of various major ITCs. PMID:26298458

  7. The stability of allyl radicals following the photodissociation of allyl iodide at 193 nm.

    SciTech Connect

    Fan, H.; Pratt, S. T.; Chemistry

    2006-01-01

    The photodissociation of allyl iodide (C{sub 3}H{sub 5}I) at 193 nm was investigated by using a combination of vacuum-ultraviolet photoionization of the allyl radical, resonant multiphoton ionization of the iodine atoms, and velocity map imaging. The data provide insight into the primary C-I bond fission process and into the dissociative ionization of the allyl radical to produce C{sub 3}H{sup 3+}. The experimental results are consistent with the earlier results of Szpunar et al. [J. Chem. Phys. 119, 5078 (2003)], in that some allyl radicals with internal energies higher than the secondary dissociation barrier are found to be stable. This stability results from the partitioning of available energy between the rotational and vibrational degrees of freedom of the radical, the effects of a centrifugal barrier along the reaction coordinate, and the effects of the kinetic shift in the secondary dissociation of the allyl radical. The present results suggest that the primary dissociation of allyl iodide to allyl radicals plus I*({sup 2}P{sub 1/2}) is more important than previously suspected.

  8. The stability of allyl radicals following the photodissociation of allyl iodide at 193 nm.

    PubMed

    Fan, H; Pratt, S T

    2006-10-14

    The photodissociation of allyl iodide (C3H5I) at 193 nm was investigated by using a combination of vacuum-ultraviolet photoionization of the allyl radical, resonant multiphoton ionization of the iodine atoms, and velocity map imaging. The data provide insight into the primary C-I bond fission process and into the dissociative ionization of the allyl radical to produce C3H3+. The experimental results are consistent with the earlier results of Szpunar et al. [J. Chem. Phys. 119, 5078 (2003)], in that some allyl radicals with internal energies higher than the secondary dissociation barrier are found to be stable. This stability results from the partitioning of available energy between the rotational and vibrational degrees of freedom of the radical, the effects of a centrifugal barrier along the reaction coordinate, and the effects of the kinetic shift in the secondary dissociation of the allyl radical. The present results suggest that the primary dissociation of allyl iodide to allyl radicals plus I*(2P(1/2)) is more important than previously suspected. PMID:17042585

  9. Transition‐Metal‐Free Borylation of Allylic and Propargylic Alcohols

    PubMed Central

    Miralles, Núria; Alam, Rauful

    2016-01-01

    Abstract The base‐catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1‐disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid–base adduct, [Hbase]+[MeO‐B2pin2]− favored the formation of 1,2,3‐triborylated species from the tertiary allylic alcohols and 1‐propargylic cyclohexanol at 90 °C. PMID:26934578

  10. Transition-Metal-Free Borylation of Allylic and Propargylic Alcohols.

    PubMed

    Miralles, Núria; Alam, Rauful; Szabó, Kálmán J; Fernández, Elena

    2016-03-18

    The base-catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1-disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid-base adduct, [Hbase](+) [MeO-B2 pin2 ](-) favored the formation of 1,2,3-triborylated species from the tertiary allylic alcohols and 1-propargylic cyclohexanol at 90 °C. PMID:26934578

  11. Enantioselective synthesis of fluorinated branched allylic compounds via Ir-catalyzed allylations of functionalized fluorinated methylene derivatives.

    PubMed

    Zhang, Hongbo; Chen, Jiteng; Zhao, Xiao-Ming

    2016-08-14

    Enantioselective introduction of the functionalized monofluorinated methylenes into the allylic fragment under Ir catalysis has been realized, which gave the fluorinated branched allyl products in good to high yields with excellent regio- and enantioselectivities. PMID:27383920

  12. Catalytic Asymmetric Synthesis of Chiral Allylic Esters

    PubMed Central

    Cannon, Jeffrey S.; Kirsch, Stefan F.; Overman, Larry E.

    2010-01-01

    A broadly useful catalytic enantioselective synthesis of branched allylic esters from prochiral (Z)-2-alkene-1-ols has been developed. The starting allylic alcohol is converted to its trichloroacetimidate intermediate by reaction with trichloroacetonitrile, either in situ or in a separate step, and this intermediate undergoes clean enantioselective SN2′ substitution with a variety of carboxylic acids in the presence of the palladium(II) catalyst (Rp,S)-di-μ -acetatobis[(η5-2-(2'-(4'-methylethyl)oxazolinyl)cyclopentadienyl,1-C,3'-N)(η4-tetraphenylcyclobutadiene)cobalt]dipalladium, (Rp,S)-[COP-OAc]2 or its enantiomer. The scope and limitations of this useful catalytic asymmetric allylic esterification are defined. PMID:15740118

  13. Kinetic Resolution of Racemic and Branched Monosubstituted Allylic Acetates by a Ruthenium-Catalyzed Regioselective Allylic Etherification.

    PubMed

    Shinozawa, Toru; Terasaki, Shou; Mizuno, Shota; Kawatsura, Motoi

    2016-07-01

    We demonstrated the kinetic resolution of racemic and branched monosubstituted allylic acetates by a ruthenium-catalyzed regioselective allylic etherification. The reaction was effectively catalyzed by the chiral ruthenium catalyst, which was generated by [RuCl2(p-cymene)]2 and (S,S)-iPr-pybox and a catalytic amount of TFA, and both the allylic etherification product and recovered allylic acetate were obtained as an enantiomerically enriched form with up to a 103 s value. PMID:27276556

  14. Peptide Reactivity of Isothiocyanates - Implications for Skin Allergy.

    PubMed

    Karlsson, Isabella; Samuelsson, Kristin; Ponting, David J; Törnqvist, Margareta; Ilag, Leopold L; Nilsson, Ulrika

    2016-01-01

    Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6-isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins. PMID:26883070

  15. Peptide Reactivity of Isothiocyanates – Implications for Skin Allergy

    PubMed Central

    Karlsson, Isabella; Samuelsson, Kristin; Ponting, David J.; Törnqvist, Margareta; Ilag, Leopold L.; Nilsson, Ulrika

    2016-01-01

    Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6-isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins. PMID:26883070

  16. Effects of Brassicaceae Isothiocyanates on Prostate Cancer.

    PubMed

    Novío, Silvia; Cartea, María Elena; Soengas, Pilar; Freire-Garabal, Manuel; Núñez-Iglesias, María Jesús

    2016-01-01

    Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models. PMID:27187332

  17. Palladium-Catalyzed Aminocarbonylation of Allylic Alcohols.

    PubMed

    Li, Haoquan; Neumann, Helfried; Beller, Matthias

    2016-07-11

    A benign and efficient palladium-catalyzed aminocarbonylation reaction of allylic alcohols is presented. The generality of this novel process is demonstrated by the synthesis of β,γ-unsaturated amides including aliphatic, cinnamyl, and terpene derivatives. The choice of ligand is crucial for optimal carbonylation processes: Whereas in most cases the combination of PdCl2 with Xantphos (L6) gave best results, sterically hindered substrates performed better in the presence of simple triphenylphosphine (L10), and primary anilines gave the best results using cataCXium® PCy (L8). The reactivity of the respective catalyst system is significantly enhanced by addition of small amounts of water. Mechanistic studies and control experiments revealed a tandem allylic alcohol amination/C-N bond carbonylation reaction sequence. PMID:27283958

  18. Asymmetric synthesis of α-chiral allylic silanes by enantioconvergent γ-selective copper(I)-catalyzed allylic silylation.

    PubMed

    Delvos, Lukas B; Vyas, Devendra J; Oestreich, Martin

    2013-04-22

    Gamma way: Regio- and enantioselective allylic substitution with a silicon nucleophile generated by copper(I)-catalyzed Si-B bond activation provides direct access to α-chiral allylic silanes from linear acceptors. The enantioconvergent catalysis employing McQuade's six-membered N-heterocyclic-carbene-copper(I) catalyst is applicable to aryl- and alkyl-substituted allylic phosphates (see scheme). PMID:23512610

  19. Enantioselective domino reaction of CO2, amines and allyl chlorides under iridium catalysis: formation of allyl carbamates.

    PubMed

    Zhang, Min; Zhao, Xiaoming; Zheng, Shengcai

    2014-05-01

    The enantioselective domino reaction between CO2 (1 atm), amines and linear allyl chlorides in the presence of an iridium complex, DABCO and toluene at 15 °C was realized, which gave branched allyl carbamates in acceptable to high yields with up to excellent regioselectivity (99/1) and 94% ee. This is the first example of the synthesis of chiral allyl carbamates through catalytic domino reactions using CO2. PMID:24652315

  20. Temperature-controlled redox-neutral ruthenium(ii)-catalyzed regioselective allylation of benzamides with allylic acetates.

    PubMed

    Manikandan, Rajendran; Jeganmohan, Masilamani

    2016-08-10

    Substituted aromatic amides reacted efficiently with allylic acetates in the presence of a cationic ruthenium complex in ClCH2CH2Cl at room temperature providing ortho allylated benzamides in a highly regioselective manner without any oxidant and base. The whole catalytic reaction occurred in a Ru(ii) oxidation state and thus the oxidation step is avoided. By tuning the reaction temperature, ortho allyl and vinyl benzamides were prepared exclusively. Later, ortho allyl and vinylated benzamides were converted into biologically useful six- and five-membered benzolactones in the presence of HCl. PMID:27456467

  1. Behavioral Response of Meloidogyne incognita to Benzyl Isothiocyanate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One reported mechanism of plant-parasitic nematode suppression by brassicaceous cover crops is the production of isothiocyanates (ITC) in soil after biomass incorporation. While plant-parasitic nematode mortality is the objective when using these cover crops for biofumigation, very little is known ...

  2. Isothiocyanates of Phosphorus Acids, N-Phosphorylated Thiocarbamates and Thioureas

    NASA Astrophysics Data System (ADS)

    Kamalov, R. M.; Zimin, M. G.; Pudovik, A. N.

    1985-12-01

    Current data on the synthesis, structures, the activities, and practical applications of the isothiocyanates of tricoordinate, tetracoordinate, pentacoordinate, and hexacoordinate phosphorus acids and N-phosphorylated and N-thiophosphorylated thiocarbamates, dithiocarbamates, and thioureas are examined and surveyed. The bibliography includes 223 references.

  3. Water and methyl isothiocyanate distribution in soil after drip fumigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methyl isothiocyanate (MITC) generators, such as metam sodium (Met-Na), are used for soil fumigation of agricultural land. The ban on the fumigant methyl bromide (MBr) has resulted in greater use of MITC generators. In order to understand the efficacy of MITC, it is necessary to assess its generat...

  4. Novel Route to Transition Metal Isothiocyanate Complexes Using Metal Powders and Thiourea

    NASA Technical Reports Server (NTRS)

    Harris, Jerry D.; Eckles, William E.; Hepp, Aloysius F.; Duraj, Stan A.; Hehemann, David G.; Fanwick, Phillip E.; Richardson, John

    2003-01-01

    A new synthetic route to isothiocyanate-containing materials is presented. Eight isothiocyanate- 4-methylpyridine (y-picoline) compounds were prepared by refluxing metal powders (Mn, Fe, Co, Ni, and Cu) with thiourea in y-picoline. With the exception of compound 5,prepared with Co, the isothiocyanate ligand was generated in situ by the isomerization of thiourea to NH4+SCN- at reflux temperatures. The complexes were characterized by x-ray crystallography. Compounds 1,2, and 8 are the first isothiocyanate- 4-methylpyridine anionic compounds ever prepared and structurally characterized. Compounds 1 and 2 are isostructural with four equatorially bound isothiocyanate ligands and two axially bound y-picoline molecules. Compound 8 is a five-coordinate copper(II) molecule with a distorted square-pyramidal geometry. Coordinated picoline and two isothiocyanates form the basal plane and the remaining isothiocyanate is bound at the apex. Structural data are presented for all compounds.

  5. Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells.

    PubMed

    Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2016-04-01

    Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF-STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress-mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells. PMID:26882972

  6. Decarboxylative Allylation of Amino Alkanoic Acids and Esters via Dual Catalysis

    PubMed Central

    2015-01-01

    A combination of photoredox and palladium catalysis has been employed to facilitate the room temperature decarboxylative allylation of recalcitrant α-amino and phenylacetic allyl esters. This operationally simple process produces CO2 as the only byproduct and provides direct access to allylated alkanes. After photochemical oxidation, the carboxylate undergoes radical decarboxylation to site-specifically generate radical intermediates which undergo allylation. A radical dual catalysis mechanism is proposed. Free phenylacetic acids were also allylated utilizing similar reactions conditions. PMID:25228064

  7. Copper(I)-Catalyzed Allylic Substitutions with a Hydride Nucleophile.

    PubMed

    Nguyen, T N Thanh; Thiel, Niklas O; Pape, Felix; Teichert, Johannes F

    2016-05-20

    An easily accessible copper(I)/N-heterocyclic carbene (NHC) complex enables a regioselective hydride transfer to allylic bromides, an allylic reduction. The resulting aryl- and alkyl-substituted branched α-olefins, which are valuable building blocks for synthesis, are obtained in good yields and regioselectivity. A commercially available silane, (TMSO)2Si(Me)H, is employed as hydride source. This protocol offers a unified alternative to the established metal-catalyzed allylic substitutions with carbon nucleophiles, as no adaption of the catalyst to the nature of the nucleophile is required. PMID:27151495

  8. Allyl­ammonium hydrogen oxalate hemihydrate

    PubMed Central

    Dziuk, Błażej; Zarychta, Bartosz; Ejsmont, Krzysztof

    2014-01-01

    In the title hydrated mol­ecular salt, C3H8N+·C2HO4 −·0.5H2O, the water O atom lies on a crystallographic twofold axis. The C=C—C—N torsion angle in the cation is 2.8 (3)° and the dihedral angle between the CO2 and CO2H planes in the anion is 1.0 (4)°. In the crystal, the hydrogen oxalate ions are linked by O—H⋯O hydrogen bonds, generating [010] chains. The allyl­ammonium cations bond to the chains through N—H⋯O and N—H⋯(O,O) hydrogen bonds. The water mol­ecule accepts two N—H⋯O hydrogen bonds and makes two O—H⋯O hydrogen bonds. Together, the hydrogen bonds generate (100) sheets. PMID:25249903

  9. Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides.

    PubMed

    Li, Yuanyuan; Qiu, Dachuan; Gu, Rongrong; Wang, Junli; Shi, Jiarong; Li, Yang

    2016-08-31

    An aryne 1,2,3-trisubstitution with aryl allyl sulfoxides is accomplished, featuring an incorporation of C-S, C-O, and C-C bonds on the consecutive positions of a benzene ring. The reaction condition is mild with broad substrate scope. Preliminary mechanistic study suggests a cascade formal [2 + 2] reaction of aryne with S═O bond, an allyl S → O migration, and a Claisen rearrangement. PMID:27527334

  10. Synthesis of a Series of γ-Keto Allyl Phosphonates.

    PubMed

    Elleuch, Haitham; Ayadi, Marwa; Bouajila, Jalloul; Rezgui, Farhat

    2016-03-01

    Under solvent-free conditions and at 80 °C, a DMAP- or imidazole-mediated clean and rapid conversion of cyclic Morita-Baylis-Hillman (MBH) acetates into the corresponding γ-keto allyl phosphonates in 70-93% yields is described herein. This allylic nucleophilic substitution works well with primary and secondary acetates bearing, at the β'-position, linear or branched alkyl groups and aryl groups. PMID:26872500

  11. A one-pot approach to pyridyl isothiocyanates from amines.

    PubMed

    Zhang, Hao; Liu, Rui-Quan; Liu, Ke-Chang; Li, Qi-Bo; Li, Qing-Yang; Liu, Shang-Zhong

    2014-01-01

    A one-pot preparation of pyridyl isothiocyanates (ITCs) from their corresponding amines has been developed. This method involves aqueous iron(III) chloride-mediated desulfurization of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide in the present of DABCO or sodium hydride. The choice of base is of decisive importance for the formation of the dithiocarbamate salts. This one-pot process works well for a wide range of pyridyl ITCs. Utilizing this protocol, some highly electron-deficient pyridyl and aryl ITCs are obtained in moderate to good yields. PMID:25185069

  12. The anti-oxidant properties of isothiocyanates: a review.

    PubMed

    de Figueiredo, Sônia M; Filho, Sidney A V; Nogueira-Machado, José A; Caligiorne, Rachel B

    2013-09-01

    Cruciferous vegetables, such as broccoli and watercress, have been studied extensively aiming to evaluate their chemopreventive properties. Some of them have already been established using animal models. The ITCs induce Phase II enzymes related to detoxification processes of chemical carcinogens to prevent the start of carcinogenesis. They also exhibit antitumor activity at post-initiation phase, suggesting their additional role(s) in cancer prevention. Sulforaphane is the most extensively studied isothiocyanate, focused in its anti-tumoral activity and it is mainly found in great amounts in broccoli and other cruciferous. In a dose dependent manner, ITCs inhibit the cell viability of human cervical cancer cells, human pancreatic cancer cells, human hepatocellular carcinoma cells, human ovarian cancer cells, and have antiinflammatory properties in the treatment of human T-cell leukemia cells. This protective effect may be due to improved antioxidant status. Although the health effects of diet in humans are generally considered promising, there are definite challenges and limitations of the current data in better understanding of the molecular mechanisms responsible for this effect, together with the possible interactions between different dietary constituents. The survey of relevant patents on the use of isothiocyanates such as sulforaphane for cancer and cardiovascular diseases treatments is also included in this review. PMID:23978168

  13. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    PubMed Central

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A.; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E.

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  14. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster.

    PubMed

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  15. Phenethyl Isothiocyanate: A comprehensive review of anti-cancer mechanisms

    PubMed Central

    Gupta, Parul; Wright, Stephen E.; Kim, Sung-Hoon; Srivastava, Sanjay K.

    2014-01-01

    The epidemiological evidence suggests a strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer. Among other constituents of cruciferous vegetables, isothiocyanates (ITC) are the main bioactive chemicals present. Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects. PEITC is known to not only prevent the initiation phase of carcinogenesis process but also to inhibit the progression of tumorigenesis. PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis. Pre-clinical evidence suggests that combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy. Based on accumulating evidence, PEITC appears to be a promising agent for cancer therapy and is already under clinical trials for leukemia and lung cancer. This is the first review which provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of PEITC as a future anti-cancer agent. PMID:25152445

  16. Myrosinase-dependent and –independent formation and control of isothiocyanate products of glucosinolate hydrolysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brassicales contain a myrosinase enzyme that hydrolyzes glucosinolates to form toxic isothiocyanates, as a defense against bacteria, fungi, insects and herbivores including man. Low levels of isothiocyanates trigger a host defense system in mammals that protects them against chronic diseases. Becaus...

  17. Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer risk1234

    PubMed Central

    Gao, Yu-Tang; Shu, Xiao-Ou; Cai, Qiuyin; Li, Guo-Liang; Li, Hong-Lan; Ji, Bu-Tian; Rothman, Nathaniel; Dyba, Marcin; Xiang, Yong-Bing; Chung, Fung-Lung; Chow, Wong-Ho; Zheng, Wei

    2010-01-01

    Background: Isothiocyanates, compounds found primarily in cruciferous vegetables, have been shown in laboratory studies to possess anticarcinogenic activity. Glutathione S-transferases (GSTs) are involved in the metabolism and elimination of isothiocyanates; thus, genetic variations in these enzymes may affect in vivo bioavailability and the activity of isothiocyanates. Objective: The objective was to prospectively evaluate the association between urinary isothiocyanate concentrations and colorectal cancer risk as well as the potential modifying effect of GST genotypes on the association. Design: A nested case-control study of 322 cases and 1251 controls identified from the Shanghai Women's Health Study was conducted. Results: Urinary isothiocyanate concentrations were inversely associated with colorectal cancer risk; the inverse association was statistically significant or nearly significant in the GSTM1-null (P for trend = 0.04) and the GSTT1-null (P for trend = 0.07) genotype groups. The strongest inverse association was found among individuals with both the GSTM1-null and the GSTT1-null genotypes, with an adjusted odds ratio of 0.51 (95% CI: 0.27, 0.95), in a comparison of the highest with the lowest tertile of urinary isothiocyanates. No apparent associations between isothiocyanate concentration and colorectal cancer risk were found among individuals who carried either the GSTM1 or GSTT1 gene (P for interaction < 0.05). Conclusion: This study suggests that isothiocyanate exposure may reduce the risk of colorectal cancer, and this protective effect may be modified by the GSTM1 and GSTT1 genes. PMID:20042523

  18. Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

    PubMed Central

    Dufour, Virginie; Stahl, Martin; Rosenfeld, Eric; Stintzi, Alain

    2013-01-01

    Campylobacter jejuni is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anticancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood. We investigated the early cellular response of C. jejuni to benzyl isothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of C. jejuni to benzyl isothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. Oxygen consumption was progressively impaired by benzyl isothiocyanate treatment, as revealed by high-resolution respirometry, while the ATP content increased soon after benzyl isothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzyl isothiocyanate induced intracellular protein aggregation. These results indicate that benzyl isothiocyanate affects C. jejuni by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death. PMID:24014524

  19. Allyl-silica Hybrid Monoliths For Chromatographic Application

    NASA Astrophysics Data System (ADS)

    Guo, Wenjuan

    Column technology continues to be the most investigated topics in the separation world, since the column is the place where the chromatographic separation happens, making it the heart of the separation system. Allyl-silica hybrid monolithic material has been exploited as support material and potential stationary phases for liquid chromatography; the stationary phase anchored to the silica surface by Si-C bond, which is more pH stable than traditional stationary phase. First, nuclear magnetic resonance spectroscopy has been used to study the sol in the synthesis of allyl-silica hybrid monoliths. Allyl-trimethoxysilane (allyl-TrMOS), dimethyldimethoxysilane (DMDMOS) and tetramethoxysilane (TMOS) have been served as co-precursors in the sol-gel synthesis of organo-silica hybrid monolithic columns for liquid chromatography (LC). 29Si nuclear magnetic resonance (NMR) and 1H NMR spectroscopy were employed to monitor reaction profiles for the acid-catalyzed hydrolysis and initial condensation reactions of the individual precursor and the hybrid system. 29Si-NMR has also been used to identify different silane species formed during the reactions. The overall hydrolysis rate has been found to follow the trend DMDMOS > allyl-TrMOS > TMOS, if each precursor is reacted individually (homo-polymerization). Precursors show different hydrolysis rate when reacted together in the hybrid system than they are reacted individually. Cross-condensation products of TMOS and DMDMOS (QD) arise about 10 minutes of initiation of the reaction. The allyl-silica monolithic columns for capillary liquid chromatography can only be prepared in capillaries with 50 im internal diameter with acceptable performance. One of the most prominent problems related to the synthesis of silica monolithic structures is the volume shrinkage. The synthesis of allylfunctionalized silica hybrid monolithic structures has been studied in an attempt to reduce the volume shrinkage during aging, drying and heat treatment

  20. Scalable and sustainable electrochemical allylic C-H oxidation.

    PubMed

    Horn, Evan J; Rosen, Brandon R; Chen, Yong; Tang, Jiaze; Chen, Ke; Eastgate, Martin D; Baran, Phil S

    2016-05-01

    New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics". Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact. PMID:27096371

  1. Catalytic Asymmetric Generation of (Z)-Disubstituted Allylic Alcohols

    PubMed Central

    Salvi, Luca; Jeon, Sang-Jin; Fisher, Ethan L.; Carroll, Patrick J.; Walsh, Patrick J.

    2008-01-01

    A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetallation with dialkylzinc reagents generates (Z)-disubstituted vinylzinc intermediates. In situ reaction of these reagents with aldehydes in the presence of a catalyst derived from (−)-MIB generates (Z)-disubstituted allylic alcohols. It was found that the resulting allylic alcohols were racemic, most likely due to a rapid addition reaction promoted by LiX (X = Br and Cl). To suppress the LiX promoted reaction, a series of inhibitors was screened. It was found that 20–30 mol % tetraethylethylene diamine (TEEDA) inhibited LiCl without inhibiting the chiral zinc-based Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem diastereoselective epoxidation reactions to provide epoxy alcohols and allylic epoxy alcohols with up to three contiguous stereogenic centers, enabling the rapid construction of complex building blocks with high levels of enantio- and diastereoselectivity. PMID:18052173

  2. The Reaction of Carbon Dioxide with Palladium Allyl Bonds

    PubMed Central

    Wu, Jianguo; Green, Jennifer C.; Hruszkewycz, Damian P.; Incarvito, Christopher D.; Schmeier, Timothy J.

    2010-01-01

    A family of palladium allyl complexes of the type bis(2-methylallyl)Pd(L) (L = PMe3 (1), PEt3 (2), PPh3 (3) or NHC (4); NHC = 1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) have been prepared through the reaction of bis(2-methylallyl)Pd with the appropriate free ligand. Compounds 1–4 contain one η1 and one η3-2-methylallyl ligand and 3 was characterized by X-ray crystallography. These complexes react rapidly with CO2 at low temperature to form well defined unidentate palladium carboxylates of the type (η3-2-methylallyl)Pd(OC(O)C4H7)(L) (L = PMe3 (6), PEt3 (7), PPh3 (8) or NHC (9). The structure of 9 was elucidated using X-ray crystallography. The mechanism of the reaction of 1–4 with CO2 was probed using a combination of experimental and theoretical (density functional theory) studies. The coordination mode of the allyl ligand is crucial and whereas nucleophilic η1-allyls react rapidly with CO2, η3-allyls do not react. We propose that the reaction of η1-palladium allyls with CO2 does not proceed via direct insertion of CO2 into the Pd-C bond but through nucleophilic attack of the terminal olefin on electrophilic CO2, followed by an associative substitution at palladium. PMID:21218132

  3. Scalable and sustainable electrochemical allylic C–H oxidation

    NASA Astrophysics Data System (ADS)

    Horn, Evan J.; Rosen, Brandon R.; Chen, Yong; Tang, Jiaze; Chen, Ke; Eastgate, Martin D.; Baran, Phil S.

    2016-05-01

    New methods and strategies for the direct functionalization of C–H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C–H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as “classics”. Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C–H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C–H oxidation (demonstrated on 100 grams), enabling the adoption of this C–H oxidation strategy in large-scale industrial settings without substantial environmental impact.

  4. Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Temporal growth of tumor xenografts in mice on a control diet was compared to mice supplemented daily with 3 µmol/g of the cancer preventive compound phenethyl isothiocyanate. Phenethyl isothiocyanate decreased the rate of tumor growth. The effects of phenethyl isothiocyanate on tumor growth were ex...

  5. Copper-catalyzed divergent kinetic resolution of racemic allylic substrates.

    PubMed

    Pineschi, Mauro; Di Bussolo, Valeria; Crotti, Paolo

    2011-10-01

    When a racemic mixture is fully consumed the products may still be enantiomerically enriched. In particular, the regiodivergent kinetic resolution is a process in which a single chiral catalyst or reagent reacts with a racemic substrate to form regioisomers possessing an opposite configuration on the newly-formed stereogenic centers. This review reports the major advances in the field of the copper-catalyzed regiodivergent and stereodivergent kinetic resolution of allylic substrates with organometallic reagents. The chiral recognition matching phenomena found with particular allylic substrates with the absolute configuration of the chiral catalyst allows in some cases an excellent control of the regio- and stereoselectivity, sheding some light on the so-called "black-box" mechanism of a copper-catalyzed asymmetric allylic alkylation. PMID:21837639

  6. Pyridine-NHC: effective ligand in Pd-catalyzed cyclopropanation of esters with substituted allyl carbonates.

    PubMed

    Huang, Jian-Qiang; Ding, Chang-Hua; Hou, Xue-Long

    2014-12-19

    By consideration of the mechanism of Pd-catalyzed cyclopropanation and allylation, NHC-pyridine compounds were adopted as the ligand in Pd-catalyzed cyclopropanation of esters and monosubstituted allylic reagents. The corresponding cyclopropanes were afforded as major products in moderate to good yields with high cyclopropane/allylation selectivity. PMID:25284365

  7. 40 CFR 721.9952 - Alkoxylated aliphatic diisocyanate allyl ether (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... allyl ether (generic). 721.9952 Section 721.9952 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.9952 Alkoxylated aliphatic diisocyanate allyl ether... identified generically as alkoxylated aliphatic diisocyanate allyl ether (PMN P-00-0353) is subject...

  8. 40 CFR 721.9952 - Alkoxylated aliphatic diisocyanate allyl ether (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... allyl ether (generic). 721.9952 Section 721.9952 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.9952 Alkoxylated aliphatic diisocyanate allyl ether... identified generically as alkoxylated aliphatic diisocyanate allyl ether (PMN P-00-0353) is subject...

  9. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  10. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  11. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  12. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  13. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  14. Genetic Incorporation of a Reactive Isothiocyanate Group into Proteins.

    PubMed

    Xuan, Weimin; Li, Jack; Luo, Xiaozhou; Schultz, Peter G

    2016-08-16

    Methods for the site-specific modification of proteins are useful for introducing biological probes into proteins and engineering proteins with novel activities. Herein, we genetically encode a novel noncanonical amino acid (ncAA) that contains an aryl isothiocyanate group which can form stable thiourea crosslinks with amines under mild conditions. We show that this ncAA (pNCSF) allows the selective conjugation of proteins to amine-containing molecular probes through formation of a thiourea bridge. pNCSF was also used to replace a native salt bridge in myoglobin with an intramolecular crosslink to a proximal Lys residue, leading to increased thermal stability. Finally, we show that pNCSF can form stable intermolecular crosslinks between two interacting proteins. PMID:27418387

  15. Cruciferous vegetables, isothiocyanates, and prevention of bladder cancer

    PubMed Central

    Veeranki, Omkara L.; Bhattacharya, Arup; Tang, Li; Marshall, James R.; Zhang, Yuesheng

    2015-01-01

    Approximately 80% of human bladder cancers (BC) are non-muscle invasive when first diagnosed and are usually treated by transurethral tumor resection. But 50–80% of patients experience cancer recurrence. Agents for prevention of primary BC have yet to be identified. Existing prophylactics against BC recurrence, e.g., Bacillus Calmette-Guerin (BCG), have limited efficacy and utility; they engender significant side effects and require urethral catheterization. Many cruciferous vegetables, rich sources of isothiocyanates (ITCs), are commonly consumed by humans. Many ITCs possess promising chemopreventive activities against BC and its recurrence. Moreover, orally ingested ITCs are selectively delivered to bladder via urinary excretion. This review is focused on urinary delivery of ITCs to the bladder, their cellular uptake, their chemopreventive activities in preclinical and epidemiological studies that are particularly relevant to prevention of BC recurrence and progression, and their chemopreventive mechanisms in BC cells and tissues. PMID:26273545

  16. Isothiocyanates: a class of bioactive metabolites with chemopreventive potential.

    PubMed

    Kumar, Gaurav; Tuli, Hardeep Singh; Mittal, Sonam; Shandilya, Jitendra Kumar; Tiwari, Anil; Sandhu, Sardul Singh

    2015-06-01

    In recent years, growing interest has been focused on the field of chemoprevention using natural therapies. The reason to turn toward "natural" remedies is associated with diverse beneficial pharmacological properties of natural compounds. Isothiocyanates (ITCs), the major pharmacological active constituents of cruciferous vegetables, are derived from the enzymatic hydrolysis of glucosinolates (GSLs). ITCs govern many intracellular targets including cytochrome P 450 (CYP) enzymes, proteins involved in antioxidant response, tumorigenesis, apoptosis, cell cycle, and metastasis. Investigation of the mechanisms of anti-cancer drugs has given important information regarding the use of natural chemopreventive compounds. This extensive review covers various molecular aspects of the interactions of ITCs with their recognized cellular targets involved in cancer treatment in order to enhance anti-tumor outcome with decreased toxicity to patients. PMID:25835976

  17. Antimicrobial activities of phenethyl isothiocyanate isolated from horseradish.

    PubMed

    Chen, Hongxia; Wang, Chengzhang; Ye, Jianzhong; Zhou, Hao; Chen, Xijuan

    2012-01-01

    Phenethyl isothiocyanate (PEITC) was obtained from horseradish. The preparation procedure was as follows: the horseradish powder was hydrolysed in the water first, and then, after filtration, the residue was extracted by petroleum ether; finally, PEITC was isolated by silica gel column. The structure of PEITC was identified by IR, MS, ¹H-NMR and ¹³C-NMR chromatography methods. The inhibitory activities of PEITC against Gibberella zeae, Xanthomonas axonopodis pv . citri, Cytospora sp . and Phytophthora capsisi showed that PEITC had good inhibition effects. The EC₅₀ values of G. zeae, X. axonopodis pv . citri, Cytospora sp . and P. capsisi were 13.92, 1.20, 0.73 and 3.69 µg mL⁻¹, respectively. PMID:21815843

  18. Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.

    PubMed

    Prier, Christopher K; Hyster, Todd K; Farwell, Christopher C; Huang, Audrey; Arnold, Frances H

    2016-04-01

    Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A "P411" serine-ligated variant of cytochrome P450BM3 has been engineered to initiate a sulfimidation/[2,3]-sigmatropic rearrangement sequence in whole E. coli cells, a non-natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non-allylic sulfides. PMID:26970325

  19. Iridium-Catalyzed Selective Isomerization of Primary Allylic Alcohols.

    PubMed

    Li, Houhua; Mazet, Clément

    2016-06-21

    This Account presents the development of the iridium-catalyzed isomerization of primary allylic alcohols in our laboratory over the past 8 years. Our initial interest was driven by the long-standing challenge associated with the development of a general catalyst even for the nonasymmetric version of this seemingly simple chemical transformation. The added value of the aldehyde products and the possibility to rapidly generate molecular complexity from readily accessible allylic alcohols upon a redox-economical isomerization reaction were additional sources of motivation. Certainly influenced by the success story of the related isomerization of allylic amines, most catalysts developed for the selective isomerization of allylic alcohols were focused on rhodium as a transition metal of choice. Our approach has been based on the commonly accepted precept that hydrogenation and isomerization are often competing processes, with the latter being usually suppressed in favor of the former. The cationic iridium complexes [(Cy3P)(pyridine)Ir(cod)]X developed by Crabtree (X = PF6) and Pfaltz (X = BArF) are usually considered as the most versatile catalysts for the hydrogenation of allylic alcohols. Using molecular hydrogen to generate controlled amounts of the active form of these complexes but performing the reaction in the absence of molecular hydrogen enabled deviation from the typical hydrogenation manifold and favored exclusively the isomerization of allylic alcohols into aldehydes. Isotopic labeling and crossover experiments revealed the intermolecular nature of the process. Systematic variation of the ligand on the iridium center allowed us to identify the structural features beneficial for catalytic activity. Subsequently, three generations of chiral catalysts have been investigated and enabled us to reach excellent levels of enantioselectivity for a wide range of 3,3-disubstituted aryl/alkyl and alkyl/alkyl primary allylic alcohols leading to β-chiral aldehydes. The

  20. Association between consumption of cruciferous vegetables and condiments and excretion in urine of isothiocyanate mercapturic acids.

    PubMed

    Vermeulen, Martijn; van den Berg, Robin; Freidig, Andreas P; van Bladeren, Peter J; Vaes, Wouter H J

    2006-07-26

    A high intake of cruciferous vegetables is associated with a reduced risk of cancer and cardiovascular diseases. This protective effect has been linked to isothiocyanates, enzymatic hydrolysis products of glucosinolates. In this study, the metabolic fate of glucosinolates and isothiocyanates after ingestion of 19 different cruciferous vegetables was studied in three male subjects. After the consumption of 13 cruciferous vegetables (glucosinolate content, 0.01-0.94 mmol/kg) and six condiments (isothiocyanate content, 0.06-49.3 mmol/kg), eight different isothiocyanate mercapturic acids were determined in urine samples. Excretion levels after the consumption of raw vegetables and condiments were higher (bioavailability, 8.2-113%) as compared to cooked vegetables (bioavailability, 1.8-43%), but the excretion rate was similar (t1/2=2.1-3.9 h). Isothiocyanates in urine remain longer at a nonzero level after the consumption of glucosinolates from cooked vegetables, as compared to raw vegetables and condiments, and maximal levels in urine were reached about 4 h later. Isothiocyanate mercapturic acids can be used as a biomarker to reflect the active dose of isothiocyanates absorbed. PMID:16848516

  1. Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro.

    PubMed

    Waterman, Carrie; Cheng, Diana M; Rojas-Silva, Patricio; Poulev, Alexander; Dreifus, Julia; Lila, Mary Ann; Raskin, Ilya

    2014-07-01

    Moringa (Moringa oleifera Lam.) is an edible plant used as both a food and medicine throughout the tropics. A moringa concentrate (MC), made by extracting fresh leaves with water, utilized naturally occurring myrosinase to convert four moringa glucosinolates into moringa isothiocyanates. Optimum conditions maximizing MC yield, 4-[(α-L-rhamnosyloxy)benzyl]isothiocyanate, and 4-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate content were established (1:5 fresh leaf weight to water ratio at room temperature). The optimized MC contained 1.66% isothiocyanates and 3.82% total polyphenols. 4-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate exhibited 80% stability at 37°C for 30 days. MC, and both of the isothiocyanates described above significantly decreased gene expression and production of inflammatory markers in RAW macrophages. Specifically, both attenuated expression of iNOS and IL-1β and production of nitric oxide and TNFα at 1 and 5 μM. These results suggest a potential for stable and concentrated moringa isothiocyanates, delivered in MC as a food-grade product, to alleviate low-grade inflammation associated with chronic diseases. PMID:24731259

  2. Total isothiocyanate yield from raw cruciferous vegetables commonly consumed in the United States

    PubMed Central

    Tang, Li; Paonessa, Joseph D.; Zhang, Yuesheng; Ambrosone, Christine B.; McCann, Susan E.

    2013-01-01

    Dietary isothiocyanates are a group of promising chemopreventive agents obtained primarily from cruciferous vegetables. Due to their potent chemopreventive and/or anti-cancer activities, there is a growing interest in assessing dietary isothiocyanate exposure and its impact on human health. Using the HPLC-based cyclocondensation assay, the current study measured total isothiocyanate yield from raw cruciferous vegetables. A total of 73 samples comprising nine types of cruciferous vegetables were analyzed. We observed a wide range of isothiocyanate content across the individual vegetables with an average level of 16.2 μmol/100g wet weight, ranging from 1.5 μmol in raw cauliflower to 61.3 μmol in raw mustard greens. The data represent the maximum amount of isothiocyanates released from the intake of raw cruciferous vegetables. Given that the vegetables assayed in this study include the most commonly consumed cruciferous vegetables in western diets, the data may be particularly useful in estimation of dietary isothiocyanate exposure in these populations. However, due to the variation observed within each vegetable, biomarkers such as urinary isothiocyanate level may be necessary for accurate estimation of individual exposure. PMID:24443655

  3. Highly Enantioselective Formation of α-Allyl-α-Arylcyclopentanones via Pd-Catalysed Decarboxylative Asymmetric Allylic Alkylation.

    PubMed

    Akula, Ramulu; Doran, Robert; Guiry, Patrick J

    2016-07-11

    A highly enantioselective Pd-catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived α-aryl-β-keto esters employing the (R,R)-ANDEN-phenyl Trost ligand has been developed. The product (S)-α-allyl-α-arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all-carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+)-tanikolide. PMID:27191198

  4. [Cu(NHC)]-Catalyzed C-H Allylation and Alkenylation of both Electron-Deficient and Electron-Rich (Hetero)arenes with Allyl Halides.

    PubMed

    Xie, Weilong; Chang, Sukbok

    2016-01-26

    New reactivity of a [Cu(NHC)] (NHC=N-heterocyclic carbene) catalyst is disclosed for the efficient C-H allylation of polyfluoroarenes using allyl halides in benzene at room temperature. The same catalyst system also promotes an isomerization-induced alkenylation of initially the generated allyl arenes when the reaction is run in tetrahydrofuran. Significantly, not only electron-deficient but also electron-rich (hetero)arenes undergo this double-bond migration process, thus leading to alkenylated products. The present system features mild reaction conditions, broad scope with respect to the arene substrates and allyl halide reactants, good functional-group tolerance, and high stereoselectivity. PMID:26695120

  5. Health and environmental effects profile for allyl chloride

    SciTech Connect

    Not Available

    1986-07-01

    The Health and Environmental Effects Profile for allyl chloride was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life, and environmental effects of hazardous-waste constituents. Quantitative estimates are presented provided sufficient data are available. Allyl chloride has been evaluated as a carcinogen. The human carcinogen potency factor (q1*) for allyl chloride is 0.0206 for oral exposure. The Reportable Quantity (RQ) value of 1, 10, 100, 1000 or 5000 pounds is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified by CERCLA based on chronic toxicity. The RQ value for allyl chloride is 100.

  6. Sulfonium-based Ionic Liquids Incorporating the Allyl Functionality

    PubMed Central

    Zhao, Dongbin; Fei, Zhaofu; Ang, Wee Han; Dyson, Paul J.

    2007-01-01

    A series of sulfonium halides bearing allyl groups have been prepared and characterized. Anion metathesis with Li[Tf2N] and Ag[N(CN)2] resulted in sulfonium-based ionic liquids which exhibit low viscosities at room temperature. The solid state structure of one of the halide salts was determined by single crystal X-ray diffraction.

  7. Mechanistically Driven Development of Iridium Catalysts for Asymmetric Allylic Substitution

    PubMed Central

    Hartwig, John F.; Stanley, Levi M.

    2010-01-01

    Conspectus Enantioselective allylic substitution reactions comprise some of the most versatile methods for preparing enantiomerically enriched materials. These reactions form products that contain multiple functionalities by creating carbon–nitrogen, carbon–oxygen, carbon–carbon, and carbon–sulfur bonds. For many years, the development of catalysts for allylic substitution focused on palladium complexes. However, studies of complexes of other metals have revealed selectivities that often complement those of palladium systems. Most striking is the observation that reactions with unsymmetrical allylic electrophiles that typically occur with palladium catalysts at the less hindered site of an allylic electrophile occur at the more hindered site with catalysts based on other metals. In this Account, we describe an iridium precursor and a phosphoramidite ligand that catalyze reactions with a particularly broad scope of nucleophiles. The active form of this iridium catalyst is not generated by the simple binding of the phosphoramidite ligand to the metal precursor. Instead, the initial phosphoramidite and iridium precursor react in the presence of base to form a metallacyclic species that is the active catalyst. This species is generated either in situ or separately in isolated form by reactions with added base. The identification of the structure of the active catalyst led to the development of simplified catalysts as well as the most active form of the catalyst now available, which is stabilized by a loosely bound ethylene. Most recently, this structure was used to prepare intermediates containing allyl ligands, the structures of which provide a model for the enantioselectivities discussed here. Initial studies from our laboratory on the scope of iridium-catalyzed allylic substitution showed that reactions of primary and secondary amines, including alkylamines, benzylamines, and allylamines, and reactions of phenoxides and alkoxides occurred in high yields

  8. Proteins as binding targets of isothiocyanates in cancer prevention

    PubMed Central

    Mi, Lixin; Di Pasqua, Anthony J.

    2011-01-01

    Isothiocyanates are versatile cancer-preventive compounds. Evidence from animal studies indicates that the anticarcinogenic activities of ITCs involve all the major stages of tumor growth: initiation, promotion and progression. Epidemiological studies have also shown that dietary intake of ITCs is associated with reduced risk of certain human cancers. A number of mechanisms have been proposed for the chemopreventive activities of ITCs. To identify the molecular targets of ITCs is a first step to understand the molecular mechanisms of ITCs. Studies in recent years have shown that the covalent binding to certain protein targets by ITCs seems to play an important role in ITC-induced apoptosis and cell growth inhibition and other cellular effects. The knowledge gained from these studies may be used to guide future design and screen of better and more efficacious compounds. In this review, we intend to cover all potential protein targets of ITCs so far studied and summarize what are known about their binding sites and the potential biological consequences. In the end, we also offer discussions to shed light onto the relationship between protein binding and reactive oxygen species generation by ITCs. PMID:21665889

  9. Oxidative conversion of isothiocyanates to isocyanates by rat liver.

    PubMed Central

    Lee, M S

    1994-01-01

    This report describes the oxidative metabolism of isothiocyanates to isocyanates catalyzed by rat liver microsomes. Incubation of 2-naphthylisothiocyanate, microsomes, and NADPH yielded either N,N'-di-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ureas were formed by the production of the known genotoxicant, 2-naphthylisocyanate, which reacted with its hydrolysis product, 2-aminonaphthalene, to yield the symmetrical urea, or with 2-aminofluorene to form the mixed urea. Formation of N,N'-di-2-naphthylthiourea was also observed because 2-aminonaphthalene reacted with the substrate. Urea formation was dependent on the microsomes, NADPH, and oxygen. Use of microsomes from rats previously treated with Aroclor 1254 increased urea formation greater than 10-fold. The enzyme activity was inhibited by alpha-napthoflavone, flavone, or CO, and slightly inhibited by metyrapone, 7-ethoxycoumarin, or SKF-525A. It was not inhibited by methimazole or paraoxon, suggesting that neither flavin-containing monooxygenase nor hydrolytic enzyme was involved. These data are consistent with a cytochrome P450-dependent, oxidative desulfuration of 2-naphthylisothiocyanate to yield 2-naphthylisocyanate. Further studies with the isomeric 1-naphthylisothiocyanate and the dietary benzylisothiocyanate showed that they can also be metabolized to their isocyanates, as evidenced by the trapping of isocyanates with 2-aminofluorene to form the mixed ureas. PMID:7889832

  10. Molecular Targets of Isothiocyanates in Cancer: Recent Advances

    PubMed Central

    Gupta, Parul; Kim, Bonglee; Kim, Sung-Hoon; Srivastava, Sanjay K.

    2014-01-01

    Cancer is a multistep process resulting in uncontrolled cell division. It results from aberrant signaling pathways that lead to uninhibited cell division and growth. Various recent epidemiological studies have indicated that consumption of cruciferous vegetables such as garden cress, broccoli, etc., reduces the risk of cancer. Isothiocyanates (ITC) have been identified as major active constituents of cruciferous vegetables. ITCs occur in plants as glucosinolate and can readily be derived by hydrolysis. Numerous mechanistic studies have demonstrated the anti-cancer effects of ITCs in various cancer types. ITCs suppress tumor growth by generating reactive oxygen species or by inducing cycle arrest leading to apoptosis. Based on the exciting outcomes of pre-clinical studies, few ITCs have advanced to the clinical phase. Available data from pre-clinical as well as available clinical studies suggests ITCs to be one of the promising anti-cancer agents available from natural sources. This is an up-to-date exhaustive review on the preventive and therapeutic effects of ITCs in cancer. PMID:24510468

  11. Branching Out: Rhodium-Catalyzed Allylation with Alkynes and Allenes.

    PubMed

    Koschker, Philipp; Breit, Bernhard

    2016-08-16

    We present a new and efficient strategy for the atom-economic transformation of both alkynes and allenes to allylic functionalized structures via a Rh-catalyzed isomerization/addition reaction which has been developed in our working group. Our methodology thus grants access to an important structural class valued in modern organic chemistry for both its versatility for further functionalization and the potential for asymmetric synthesis with the construction of a new stereogenic center. This new methodology, inspired by mechanistic investigations by Werner in the late 1980s and based on preliminary work by Yamamoto and Trost, offers an attractive alternative to other established methods for allylic functionalization such as allylic substitution or allylic oxidation. The main advantage of our methodology consists of the inherent atom economy in comparison to allylic oxidation or substitution, which both produce stoichiometric amounts of waste and, in case of the substitution reaction, require prefunctionalization of the starting material. Starting out with the discovery of a highly branched-selective coupling reaction of carboxylic acids with terminal alkynes using a Rh(I)/DPEphos complex as the catalyst system, over the past 5 years we were able to continuously expand upon this chemistry, introducing various (pro)nucleophiles for the selective C-O, C-S, C-N, and C-C functionalization of both alkynes and the double-bond isomeric allenes by choosing the appropriate rhodium/bidentate phosphine catalyst. Thus, valuable compounds such as branched allylic ethers, sulfones, amines, or γ,δ-unsaturated ketones were successfully synthesized in high yields and with a broad substrate scope. Beyond the branched selectivity inherent to rhodium, many of the presented methodologies display additional degrees of selectivity in regard to regio-, diastereo-, and enantioselective transformations, with one example even proceeding via a dynamic kinetic resolution. Many advances

  12. Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

    SciTech Connect

    Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.; Stewart, Deirdre S.; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E.; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S.

    2012-12-10

    We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

  13. Preservation of acidified cucumbers with a natural preservative combination of fumaric acid and allyl isothiocyanate that target lactic acid bacteria and yeasts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Without the addition of preservative compounds cucumbers acidified with 150 mM acetic acid with pH adjusted to 3.5 typically undergo fermentation by lactic acid bacteria. Fumaric acid (20 mM) inhibited growth of Lactobacillus plantarum and the lactic acid bacteria present on fresh cucumbers, but sp...

  14. Competing sigmatropic shift rearrangements in excited allyl radicals

    SciTech Connect

    Stranges, D.; O'Keeffe, P.; Scotti, G.; Di Santo, R.; Houston, P. L.

    2008-04-21

    The competition between rearrangement of the excited allyl radical via a 1,3 sigmatropic shift versus sequential 1,2 shifts has been observed and characterized using isotopic substitution, laser excitation, and molecular beam techniques. Both rearrangements produce a 1-propenyl radical that subsequently dissociates to methyl plus acetylene. The 1,3 shift and 1,2 shift mechanisms are equally probable for CH{sub 2}CHCH{sub 2}, whereas the 1,3 shift is favored by a factor of 1.6 in CH{sub 2}CDCH{sub 2}. The translational energy distributions for the methyl and acetylene products of these two mechanisms are substantially different. Both of these allyl dissociation channels are minor pathways compared to hydrogen atom loss.

  15. ION EXCHANGE SUBSTANCES BY SAPONIFICATION OF ALLYL PHOSPHATE POLYMERS

    DOEpatents

    Kennedy, J.

    1959-04-14

    An ion exchange resin having a relatively high adsorption capacity tor uranyl ion as compared with many common cations is reported. The resin comprises an alphyl-allyl hydrogen phosphate polymer, the alphyl group being either allyl or a lower alkyl group having up to 5 carbon atoins. The resin is prepared by polymerizing compounds such as alkyl-diallyl phosphate and triallyl phosphate in the presence of a free radical generating substance and then partially hydrolyzing the resulting polymer to cause partial replacement of organic radicals by cations. A preferred free radical gencrating agent is dibenzoyl peroxide. The partial hydrolysis is brought about by refluxing the polymer with concentrated aqueous NaOH for three or four hours.

  16. Copper-catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols.

    PubMed

    Lei, Jian; Liu, Xiaowu; Zhang, Shaolin; Jiang, Shuang; Huang, Minhao; Wu, Xiaoxing; Zhu, Qiang

    2015-04-27

    An efficient copper-catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols with Togni's reagent has been developed. This strategy, accompanied by a double-bond migration, leads to various branched CF3-substituted alcohols by using readily available trisubstituted cyclic/acyclic alcohols as substrates. Moreover, for alcohols in which β-H elimination is prohibited, CF3-containing oxetanes are isolated as the sole product. PMID:25810003

  17. Rotational Spectroscopy of Isocyanic Molecules: Allyl Isocyanide and Diisocyanomethane

    NASA Astrophysics Data System (ADS)

    Motiyenko, R. A.; Margules, L.; Haykal, I.; Huet, T. R.; Cocinero, E. J.; Ecija, P.; Fernandez, J. A.; Castano, F.; Lesarri, A.; Guillemin, J.-C.

    2012-06-01

    Isocyanides are less stable isomers of nitriles and some of them have already been observed in the interstellar medium (HNC, CH_3NC, HCCNC). But still there exists a lack of experimental spectroscopic data on simple isocyanic molecules that can represent potential astrophysical interest. In this view we have performed high resolution studies of rotational spectra of allyl isocyanide (CH_2=CH--CH_2--NC) and diisocyanomethane (CN--CH_2--NC). The rotational spectra of allyl isocyanide have been measured in the frequency range 6 -- 18 GHz by means of FTMW spectrometer in Bilbao and in the frequency range 150 -- 945 GHz by means of classic absorption spectroscopy in Lille. Two stable confomers of allyl isocyanide have been observed in both series of measurements. In addition, all 13C-monosubstituted isotopologues and 15N isotopologues were detected in natural abundance. Due to much lower kinetic stability the rotational spectrum of diisocyanomethane has been measured only in absorption using the Lille spectrometer. The spectral assignments have been supported by high-level quantum chemical calculations. For both molecules accurate sets of rotational and centrifugal distortion constants (up to the octics) have been produced. As a result, reliable predictions of transitions frequencies suitable for astrophysical detection have been obtained for both molecules. Finally, the effective and substitution structures were determined for the two conformers of allyl isocyanide, comparing the result with ab initio data. This work is supported by Centre Nationale d'Etudes Spatiales (CNES), Action sur Projet Physico-Chimie du Milieu Interstellaire (PCMI-CNRS) and by the contract ANR-08-BLAN-0054. Spanish part acknowledges funding from the MICINN and the MINECO.

  18. Silver-Catalyzed Decarboxylative Allylation of Aliphatic Carboxylic Acids in Aqueous Solution.

    PubMed

    Cui, Lei; Chen, He; Liu, Chao; Li, Chaozhong

    2016-05-01

    Direct decarboxylative radical allylation of aliphatic carboxylic acids is described. With K2S2O8 as the oxidant and AgNO3 as the catalyst, the reactions of aliphatic carboxylic acids with allyl sulfones in aqueous CH3CN solution gave the corresponding alkenes in satisfactory yields under mild conditions. This site-specific allylation method is applicable to all primary, secondary, and tertiary alkyl acids and exhibits wide functional group compatibility. PMID:27065060

  19. Kinetic Resolution of Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted Hydrazines.

    PubMed

    Yan, Liang; Xu, Jing-Kun; Huang, Chao-Fan; He, Zeng-Yang; Xu, Ya-Nan; Tian, Shi-Kai

    2016-09-01

    A new strategy has been established for the kinetic resolution of racemic allylic alcohols through a palladium/sulfonyl-hydrazide-catalyzed asymmetric OH-substitution under mild conditions. In the presence of 1 mol % [Pd(allyl)Cl]2 , 4 mol % (S)-SegPhos, and 10 mol % 2,5-dichlorobenzenesulfonyl hydrazide, a range of racemic allylic alcohols were smoothly resolved with selectivity factors of more than 400 through an asymmetric allylic alkylation of monosubstituted hydrazines under air at room temperature. Importantly, this kinetic resolution process provided various allylic alcohols and allylic hydrazine derivatives with high enantiopurity. PMID:27339655

  20. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    SciTech Connect

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  1. Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates.

    PubMed

    Fahey, Jed W; Stephenson, Katherine K; Wade, Kristina L; Talalay, Paul

    2013-05-24

    Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 260-320 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

  2. Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro

    PubMed Central

    Waterman, Carrie; Cheng, Diana M.; Rojas-Silva, Patricio; Poulev, Alexander; Dreifus, Julia; Ann Lila, Mary; Raskin, Ilya

    2014-01-01

    Moringa (Moringa oleifera Lam.) is an edible plant used as food and medicine throughout the tropics. A moringa concentrate (MC) made by extracting fresh leaves with water utilized naturally occurring myrosinase to convert four moringa glucosinolates (1–4) into moringa isothiocyanates (5–8). Optimum conditions maximizing MC yield, compound 5 (4-[(α-L-rhamnosyloxy)benzyl]isothiocyanate), and compound 8 (4-[(4’-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate) content were established (1:5 fresh leaf weight to water ratio at room temperature). The optimized MC contained 1.66% isothiocyanates and 3.82% total polyphenols. Compound 8 exhibited 80% stability at 37 °C for 30 days. MC, 5, and 8 significantly decreased gene expression and production of inflammatory markers in RAW macrophages. Specifically, 5 and 8 attenuated expression of iNOS and IL-1β and production of nitric oxide and TNFβ at 1 and 5 µM. Our results suggest a potential for stable and concentrated moringa isothiocyanates (5–8), delivered in MC as a food-grade product, to alleviate low-grade inflammation associated with chronic diseases. PMID:24731259

  3. Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates

    PubMed Central

    Fahey, Jed W.; Stephenson, Katherine K.; Wade, Kristina L.; Talalay, Paul

    2013-01-01

    Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

  4. Trajectory study of energy transfer and unimolecular dissociation of highly excited allyl with argon.

    PubMed

    Conte, Riccardo; Houston, Paul L; Bowman, Joel M

    2014-09-11

    The influence of rotational excitation on energy transfer in single collisions of allyl with argon and on allyl dissociation is investigated. About 90,000 classical scattering simulations are performed in order to determine collision-induced changes in internal energy and in allyl rotational angular momentum. Dissociation is studied by means of about 50,000 additional trajectories evolved for the isolated allyl under three different conditions: allyl with no angular momentum (J = 0); allyl with the same microcanonically sampled initial conditions used for the collisions (J*); allyl evolving from the corresponding exit conditions after the collision. The potential energy surface is the sum of an intramolecular potential and an interaction one, and it has already been used in a previous work on allyl-argon scattering (Conte, R.; Houston, P. L.; Bowman, J. M. J. Phys. Chem. A 2013, 117, 14028-14041). Energy transfer data show that increased initial rotation favors, on average, increased relaxation of the excited molecule. The availability of a high-level intramolecular potential energy surface permits us to study the dependence of energy transfer on the type of starting allyl isomer. A turning point analysis is presented, and highly efficient collisions are detected. Collision-induced variations in the allyl rotational angular momentum may be quite large and are found to be distributed according to three regimes. The roles of rotational angular momentum, collision, and type of isomer on allyl unimolecular dissociation are considered by looking at dissociations times, kinetic energies of the fragments, and branching ratios. Generally, rotational angular momentum has a strong influence on the dissociation dynamics, while the single collision and the type of starting isomer are less influential. PMID:25116695

  5. In vitro studies of phenethyl isothiocyanate against the growth of LN229 human glioma cells.

    PubMed

    Su, Ji-Chun; Lin, Kai; Wang, Yan; Sui, Shao-Hua; Gao, Zhi-Yu; Wang, Zhi-Gang

    2015-01-01

    Phenethyl isothiocyanate (PEITC) is one of the best studied members of isothiocyanates (ITC), a variety of edible cruciferous vegetables including broccoli, watercress, and cabbage, and have generated particular interest because of its remarkable chemopreventive activity. Many literature reports proved that phenethyl isothiocyanate exhibited significant anti-cancer chemopreventive effects including lung, glioma and leukemia cancer. In this study, we explored the inhibitory effects as well as mechanisms of PEITC on human glioma LN229 cells. Results demonstrated that PEITC possesses the potential ability to inhibit proliferation, induce apoptosis and arrest cell cycling against LN229 human glioma cells. Moreover, investigated results showed that PEITC inhibited the expression of superoxide dismutase (SOD) and glutathione (GSH), and caused oxidative stress to tumor cells. Collective results suggested us to believe that PEITC can inhibit the growth of LN229 cells and its mechanism can be related to the fact that PEITC can cause oxidative stress to tumor cells. PMID:26097624

  6. In vitro studies of phenethyl isothiocyanate against the growth of LN229 human glioma cells

    PubMed Central

    Su, Ji-Chun; Lin, Kai; Wang, Yan; Sui, Shao-Hua; Gao, Zhi-Yu; Wang, Zhi-Gang

    2015-01-01

    Phenethyl isothiocyanate (PEITC) is one of the best studied members of isothiocyanates (ITC), a variety of edible cruciferous vegetables including broccoli, watercress, and cabbage, and have generated particular interest because of its remarkable chemopreventive activity. Many literature reports proved that phenethyl isothiocyanate exhibited significant anti-cancer chemopreventive effects including lung, glioma and leukemia cancer. In this study, we explored the inhibitory effects as well as mechanisms of PEITC on human glioma LN229 cells. Results demonstrated that PEITC possesses the potential ability to inhibit proliferation, induce apoptosis and arrest cell cycling against LN229 human glioma cells. Moreover, investigated results showed that PEITC inhibited the expression of superoxide dismutase (SOD) and glutathione (GSH), and caused oxidative stress to tumor cells. Collective results suggested us to believe that PEITC can inhibit the growth of LN229 cells and its mechanism can be related to the fact that PEITC can cause oxidative stress to tumor cells. PMID:26097624

  7. Isocyanates and isothiocyanates as versatile platforms for accessing (thio)amide-type compounds.

    PubMed

    Pace, Vittorio; Monticelli, Serena; de la Vega-Hernández, Karen; Castoldi, Laura

    2016-08-16

    The addition of carbon (Grignard and organolithium reagents) and hydride nucleophiles (Schwartz reagent) to isocyanates and isothiocyanates constitutes a versatile, direct and high yielding approach to the synthesis of functionalized (thio)amide derivatives including haloamides and formamides. The chemoselective delivery of a nucleophilic (eventually configurationally stable) organometallic species to a given iso(thio)cyanate is the crucial parameter for the success of the strategy. Thus, the influence of the factors governing classical methodologies (e.g. dehydrative condensation) such as steric hindrance and electronic properties of the reactants become practically negligible. PMID:27461156

  8. Evaluation of antibacterial activity of 3-butenyl, 4-pentenyl, 2-phenylethyl, and benzyl isothiocyanate in Brassica vegetables.

    PubMed

    Jang, Miran; Hong, Eunyoung; Kim, Gun-Hee

    2010-09-01

    This study investigated antibacterial activities of 4 isothiocyanates (3-butenyl, 4-phentenyl, 2-phenylethyl, and benzyl isothiocyanate) against 4 Gram-positive bacteria (Bacillus cereus, Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus) and 7 Gram-negative bacteria (Aeromonas hydrophila, Pseudomonas aeruginosa, Salmonella choleaesuis, Salmonella enterica, Serratia marcescens, Shigella sonnei, and Vibrio parahaemolyticus) by an agar disc diffusion assay. Benzyl isothiocyanate (> 90.00 mm inhibition zone diameter at 0.1 μL/mL) and 2-phenylethyl isothiocyanate (58.33 mm at 0.2 μL/mL) showed large inhibition zones especially against B. cereus. Also, 3-butenyl isothiocyanate (21.67 mm at 1.0 μL/mL) and 4-pentenyl isothiocyanate (19.67 mm at 1.0 μL/mL) displayed potent antibacterial activity against A. hydrophila. Benzyl and 2-phenylethyl isothiocyanate indicated higher activity against most of the pathogenic bacteria than 3-butenyl and 4-pentenyl isothiocyanate, and were more effective against Gram-positive bacteria than Gram-negative bacteria. PMID:21535549

  9. Palladium(0)-Catalyzed Intermolecular Allylic Dearomatization of Indoles by a Formal [4+2] Cycloaddition Reaction.

    PubMed

    Gao, Run-Duo; Xu, Qing-Long; Zhang, Bo; Gu, Yiting; Dai, Li-Xin; You, Shu-Li

    2016-08-01

    Bridged indoline derivatives were synthesized by an intermolecular Pd-catalyzed allylic dearomatization reaction of substituted indoles. The reaction between indoles and allyl carbonates bearing a nucleophilic alcohol side-chain proceeds in a cascade fashion, providing bridged indolines in excellent enantioselectivity. PMID:27321285

  10. Magnetic silica supported palladium catalyst: synthesis of allyl aryl ethers in water

    EPA Science Inventory

    A simple and benign procedure for the synthesis of aryl allyl ethers has been developed using phenols, allyl acetates and magnetically recyclable silica supported palladium catalyst in water; performance of reaction in air and easy separation of the catalyst using an external mag...

  11. Trifluoromethylallylation of Heterocyclic C-H Bonds with Allylic Carbonates under Rhodium Catalysis.

    PubMed

    Choi, Miji; Park, Jihye; Sharma, Satyasheel; Jo, Hyeim; Han, Sangil; Jeon, Mijin; Mishra, Neeraj Kumar; Han, Sang Hoon; Lee, Jong Suk; Kim, In Su

    2016-06-01

    The rhodium(III)-catalyzed γ-trifluoromethylallylation of various heterocyclic C-H bonds with CF3-substituted allylic carbonates is described. These reactions provide direct access to linear CF3-containing allyl frameworks with complete trans-selectivity via C-H bond activation followed by a formal SN-type reaction pathway. PMID:27187625

  12. Catalyst-controlled switch of regioselectivity in the asymmetric allylic alkylation of oxazolones with MBHCs.

    PubMed

    Zhu, Gongming; Yang, Junxian; Bao, Guangjun; Zhang, Ming; Li, Jing; Li, Yiping; Sun, Wangsheng; Hong, Liang; Wang, Rui

    2016-06-14

    A catalyst-controlled switch of regioselectivity in asymmetric allylic alkylation of oxazolones with MBHCs was described. The SN2'-SN2' reaction catalysed by a quinine-derived base produced γ-selective secondary allylic oxazolone derivatives, whereas the addition-elimination reaction catalysed by an amino acid-derived bifunctional urea catalyst provided β-selective primary adducts. PMID:27250517

  13. Beta-Adrenergic Agonists

    PubMed Central

    Barisione, Giovanni; Baroffio, Michele; Crimi, Emanuele; Brusasco, Vito

    2010-01-01

    Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β2-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β2-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β2-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised.

  14. 1-Allyl-3-chloro-5-nitro-1H-indazole

    PubMed Central

    Chicha, Hakima; Rakib, El Mostapha; Spinelli, Domenico; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    In the title compound, C10H8ClN3O2, the indazole ring system makes a dihedral angle of 7.9 (3)° with the plane through the nitro group. The allyl group is rotated out of the plane of the indazole ring system [N—N—C—C torsion angle = 104.28 (19)°]. In the crystal, mol­ecules are linked by C—H⋯O hydrogen bonds, forming zigzag chains propagating along the b-axis direction. PMID:24427047

  15. Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates.

    PubMed

    Bauer, Johannes Moritz; Frey, Wolfgang; Peters, René

    2016-04-11

    The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral β- and γ-aminoalcohols as well as α- and β-aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N-tosylisocyanate in a single step into highly enantioenriched N-tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation-induced [3,3]-rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl-protected allylic amines, which can be deprotected under non-reductive conditions. PMID:26990446

  16. Palladium-Catalyzed Allylic C-H Bond Functionalization of Olefins

    NASA Astrophysics Data System (ADS)

    Liu, Guosheng; Wu, Yichen

    Transition metal-mediated carbon-hydrogen bond cleavage and functionalization is a mechanistically interesting and synthetically attractive process. One of the important cases is the removal of a allylic hydrogen from an olefin by a PdII salt to yield a π-allylpalladium complex, followed by nucleophilic attack to efficient produce allylic derivatives. In contrast to the well-known allylic acetoxylation of cyclohexene, the reaction of open-chain olefins is fairly poor until recent several years. Some palladium catalytic systems have been reported to achieve allylic C-H functionalization, including acetoxylation, amination and alkylation of terminal alkenes. In the most of cases, ligand is crucial to the success of the transformation. This review surveys the recent development of palladium-catalyzed allylic C-H functionalziation of alkenes. These results promise a significant increase in the scope of olefin transformation.

  17. Practical Stannylation of Allyl Acetates Catalyzed by Nickel with Bu3 SnOMe.

    PubMed

    Komeyama, Kimihiro; Itai, Yuuhei; Takaki, Ken

    2016-06-27

    A practical and scalable nickel-catalyzed allylic stannylation of allyl acetates with Bu3 SnOMe is described. A variety of acyclic and cyclic allyl acetates, even with base-sensitive moieties, undergoes the stannylation by using NiBr2 /4,4'-di-tert-butylbipyridine (dtbpy)/Mn catalyst system to afford highly functionalized allyl stannanes with excellent regioselectivity and yields. Furthermore, the scope of protocol is also extended by the reaction of propargyl acetates, giving rise to propargyl or allenyl stannanes. Additionally, a unique diastereoselectivity using the nickel catalyst different from the palladium was demonstrated for the stannylation of cyclic allyl acetates. In the reaction, inexpensive and stable nickel complexes, abundant reductant (Mn), and atom-economical stannyl source were used. PMID:27124370

  18. Allyl alcohol activation of protein kinase C delta leads to cytotoxicity of rat hepatocytes.

    PubMed

    Maddox, Jane F; Roth, Robert A; Ganey, Patricia E

    2003-05-01

    Hepatotoxicity of allyl alcohol involves its bioactivation to acrolein and subsequent protein sulfhydryl loss and lipid peroxidation. However, the links between these events and hepatocellular death are not known. The purpose of these studies was to examine whether specific signal transduction pathways are associated with allyl alcohol toxicity in hepatocytes. Inhibition or augmentation of cyclic AMP and/or protein kinase A (PKA) by Rp-Ado-3N,5N-cyclic monophosphorothioate triethylamine salt or 3-isobutyl-1-methylxanthine had no effect on allyl alcohol-induced cell death. H-7, an inhibitor of PKA, PKC, and PKG, partially inhibited cell killing by allyl alcohol, whereas chelerythrine chloride, a nonselective PKC inhibitor, almost completely abolished allyl alcohol cytotoxicity. Neither 2,2N,3,3N,4,4N-hexahydroxy-1,1N,-biphenyl-6,6N-dimethanol-dimethyl ether, a selective PKC alpha and beta inhibitor, nor bisindolylmaleimide I, an inhibitor of PKC alpha, beta, and epsilon, had any effect on allyl alcohol cytotoxicity. In contrast, rottlerin, a selective PKCdelta inhibitor, blocked hepatocellular killing by allyl alcohol. Cytoprotection by chelerythrine chloride and rottlerin was not the result of inhibition of bioactivation of allyl alcohol because each inhibitor also prevented cell death from acrolein. Western blotting and immunohistochemical techniques revealed that allyl alcohol stimulated phosphorylation and translocation of PKCdelta to hepatocyte membranes (i.e., activation), and this activity was inhibited by rottlerin. Cell death appeared to occur via oncotic necrosis rather than apoptosis based on single-stranded DNA ELISA and propidium iodide staining. Together, these results indicate that activation of PKCdelta is a critical, early event in initiating hepatocyte injury and death from allyl alcohol. PMID:12755590

  19. Oxidative addition of allylic halides to ruthenium(II) compounds. Preparation, reactions, and X-ray crystallographic structure of ruthenium(IV)-allyl complexes

    SciTech Connect

    Nagashima, Hideo; Mukai, Katsunori; Shiota, Yusuke; Yamaguchi, Keitaro; Ara, Kenichi; Fukahori, Takahiko; Itoh, Kenji ); Suzuki, Hiroharu; Akita, Munetaka; Moro-oka, Yoshihiko )

    1990-03-01

    The oxidative addition of allylic halides to (C{sub 5}R{sub 5})RuL{sub 2}X (R = H, Me; L = CO, PPh{sub 3}) gave new Ru(IV)-{eta}{sup 3}-allyl complexes, (C{sub 5}R{sub 5})RuX{sub 2}({eta}{sup 3}-allyl). An X-ray structure determination was carried out on (C{sub 5}Me{sub 5})RuBr{sub 2}({eta}{sup 3}-C{sub 3}H{sub 5}), indicating a pseudo-piano-stool structure having two Br atoms and two terminal carbons of the endo-{eta}{sup 3}-allyl ligand located at the basal positions. There is a crystal mirror plane bisecting the pentamethylcyclopentadienyl and the {pi}-allyl ligands. Crystal data: orthorhombic, space group P2{sub 1}2{sub 1}2{sub 1}, a = 22.738 (1) {angstrom}, b = 13.367 (7) {angstrom}, c = 9.383 (1) {angstrom}, Z = 4., data refined to R = 0.0695. Its {sup 1}H and {sup 13}C NMR spectra showed symmetric allyl signals, supporting that the above-described piano-stool structure is maintained even in solution.

  20. Effects of benzyl isothiocyanate on the reproduction of Meloidogyne incognita on Glycine max and Capsicum annuum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reproduction of Meloidogyne incognita on Capsicum annuum or Glycine max was suppressed when infective juveniles (J2) were exposed to 0.03 millimolar benzyl isothiocyanate (BITC) for 2hr prior to inoculation of the host. Infectivity assessed by gall index was significantly reduced on both G. max (co...

  1. DIETARY ISOTHIOCYANATE IBERIN INHIBITS GROWTH AND INDUCES APOPTOSIS IN HUMAN GLIOBLASTOMA CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we evaluated the antiproliferative and proapoptotic effects of the isothiocyanate iberin, a bioactive agent in Brassicaceae species, in human glioblastoma cells. The human glioblastoma cell cultures were treated with different concentrations of iberin and tested for growth inhibition...

  2. Spectroscopic and structural investigations of iron(III) isothiocyanates. A comparative theoretical and experimental study.

    PubMed

    Elijošiutė, Erika; Eicher-Lorka, Olegas; Griškonis, Egidijus; Kuodis, Zenonas; Jankūnaitė, Dalia; Denafas, Gintaras

    2014-08-14

    A combined experimental and theoretical study on the molecular structure and vibrational spectra of [Fe(NCS)](2+) complex in the aqueous solution at the pH∼2 ± 0.1 have been performed. Experimental Raman spectra of the iron(III) isothiocyanate with higher coordination number in the acidic aqueous solution have been analyzed. Molecular modeling of the iron(III) monoisothiocyanate complex was accomplished by the density functional theory (DFT) method using B3LYP and PBE1PBE functionals. Theoretical vibrational spectra of the iron(III) monoisothiocyanate were interpreted by means of the potential energy distributions (PEDs). The influence of different solvation models and position of SO4(2)(-) ligand vs. NCS(-) ligand upon its geometry and vibrational frequencies have been evaluated. The effect of H2O/D2O isotopic substitution on the experimental and calculated Raman spectra of iron(III) isothiocyanates has been examined. Procedures of Raman spectra subtraction have been applied for the extractions of weak and/or obscured Raman signals. As a result, the presence of bound SO4(2)(-) ion and water molecules in the first coordination sphere in the acidic aqueous iron(III) isothiocyanate solution was confirmed. The vibrational assignments for the investigated iron(III) isothiocyanates were proposed here for the first time. PMID:24721282

  3. Water and Methyl-Isothiocyanate Distribution in Soil Following Drip Fumigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methyl isothiocyanate (MITC) generators, such as metam sodium (Met-Na), are used for soil fumigation of agricultural land. The ban on the fumigant methyl bromide (MBr) has resulted in greater use of MITC generators. In order to understand the efficacy of MITC, it is necessary to assess its generat...

  4. Benzyl isothiocyanate affects development, hatching and reproduction of the soybean cyst nematode Heterodera glycines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Benzyl isothiocyanate (BITC) applied at micromolar doses decreased Heterodera glycines J2 movement, H. glycines hatching, and reproduction of H. glycines on soybean, Glycine max. Direct exposure of J2 to 30 microM BITC caused an immediate decrease (17%; P < 0.05) in J2 movement relative to 1% methan...

  5. Evaluating surface seals in soil columns to mitigate methy isothiocyanate volatilization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The banning of methyl bromide (MeBr) as a pre-plant soil fumigant due to its implication as an ozone depleting substance, has led to increased interest in finding alternative soil fumigants to replace MeBr. One of the promising alternatives for certain crops is methyl isothiocyanate (MITC) generati...

  6. A Quick and Simple Conversion of Carboxylic Acids into Their Anilides of Heating with Phenyl Isothiocyanate.

    ERIC Educational Resources Information Center

    Ram, Ram N.; And Others

    1983-01-01

    Converting carboxylic acids into their anilides, which usually involves preparation of acid chloride or mixed anhydride followed by treatment with aniline, is tedious and/or time-consuming. A quick and easier procedure, using phenyl isothiocyanate, is provided. Reactions involved and a summary table of results are included. (JN)

  7. Cross-Coupling of Aromatic Bromides with Allylic Silanolate Salts

    PubMed Central

    Denmark, Scott E; Werner, Nathan S.

    2009-01-01

    The sodium salts of allyldimethylsilanol and 2-butenyldimethylsilanol undergo palladium-catalyzed cross-coupling with a wide variety of aryl bromides to afford allylated and crotylated arenes. The coupling of both silanolates required extensive optimization to deliver the expected products in high yields. The reaction of the allyldimethylsilanolate takes place at 85 °C in DME with allylpalladium chloride dimer (2.5 mol %) to afford 7–95% yields of the allylation products. Both electron-rich and sterically-hindered bromides reacted smoothly, whereas electron-poor bromides cross-coupled in poor yield because of a secondary isomerization to the 1-propenyl isomer (and subsequent polymerization). The 2-butenyldimethylsilanolate (E/Z, 80:20) required additional optimization to maximize the formation of the branched (γ-substitution product). A remarkable influence of added alkenes (dibenzylideneacetone and norbornadiene) led to good selectivities for electron-rich and electron-poor bromides in 4–83% yields. However, bromides containing coordinating groups (particularly in the ortho position) gave lower, and in one case even reversed, selectivity. Configurationally homogeneous E-silanolates gave slightly higher γ-selectivity than the pure Z-silanolates. A unified mechanistic picture involving initial γ-transmetalation followed by direct reductive elimination or σ–π isomerization can rationalize all of the observed trends. PMID:18998687

  8. Crystal structure of bis­(allyl­ammonium) oxalate

    PubMed Central

    Dziuk, Błażej; Zarychta, Bartosz; Ejsmont, Krzysztof

    2014-01-01

    The title salt, 2C3H8N+·C2O4 2−, crystallized with six independent allyl­ammonium cations and three independent oxalate dianions in the asymmetric unit. One of the oxalate dianions is nearly planar [dihedral angle between CO2 planes = 1.91 (19)°], while the other two are twisted with angles of 11.3 (3) and 26.09 (13)°. One cation has a synperiplanar (cis) conformation with an N—C—C—C torsion angle of 0.9 (3)°, whereas the five remaining cations are characterized by gauche arrangements, with the N—C—C—C torsion angles ranging from 115.9 (12) to 128.8 (3)°. One of the allyl­ammonium cations is positionally disordered (fixed occupancy ratio = 0.45:0.55). In the crystal, the cations and anions are connected by a number of strong N—H⋯O and N—H⋯(O,O) hydrogen bonds, forming layers parallel to (001), with the vinyl groups protruding into the space between the layers. PMID:25553015

  9. A principal mechanism for the cancer chemopreventive activity of phenethyl isothiocyanate is modulation of carcinogen metabolism.

    PubMed

    Ioannides, Costas; Konsue, Nattaya

    2015-08-01

    Isothiocyanates are small molecules characterized by high chemical reactivity that allows them to interact readily with cellular constituents eliciting a plethora of biological activities. They are present exclusively in cruciferous vegetables, as glucosinolates, the intake of which has been associated with cancer chemoprevention. When the physical structure of these vegetables is disturbed, e.g. during mastication, the enzyme myrosinase is released and converts the glucosinolates to isothiocyanates (R-N=C=S), where R can be aliphatic or aromatic. Although sulforaphane, an aliphatic isothiocyanate, has received most attention worldwide, the most extensively studied aromatic isothiocyanate is phenethyl isothiocyanate (PEITC), and there are substantial differences in biological activity between the two sub-classes. In animal cancer models, PEITC effectively antagonized the carcinogenicity of chemicals, especially nitrosocompounds. A principal mechanism of their action is to protect the integrity of DNA by decreasing the levels of the genotoxic metabolites of chemical carcinogens. Extensive studies established that PEITC modulates the metabolism of the tobacco-specific carcinogenic nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by inhibiting its cytochrome P450-mediated bioactivation. Moreover, PEITC is a potent inducer of detoxification enzymes such as quinone reductase, glutathione S-transferase and glucuronosyl transferase. PEITC is rapidly absorbed and is characterized by a large bioavailability; Cmax concentrations achieved in plasma after dietary intake are sufficient to modulate carcinogen metabolism. PEITC is primarily metabolized by glutathione conjugation and is excreted in the urine and bile as the mercapturate. The ability of PEITC to perturb carcinogen metabolism through modulation of cytochrome P450 and phase II detoxification enzymes is comprehensively and critically reviewed. PMID:26119477

  10. Enantioselective Functionalization of Allylic C-H Bonds Following a Strategy of Functionalization and Diversification

    PubMed Central

    Sharma, Ankit; Hartwig, John F.

    2013-01-01

    We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S or C-C bond at the allylic position in good yield with high branched-to-linear selectivity and excellent enantioselectivity (ee ≤ 97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated. PMID:24156776

  11. Conformations of allylic fluorides and stereoselectivities of their diels-alder cycloadditions.

    PubMed

    Grée, D; Vallerie, L; Grée, R; Toupet, L; Washington, I; Pelicier, J P; Villacampa, M; Pérez, J M; Houk, K N

    2001-04-01

    The preparations of new allylic fluorides from the corresponding alcohols are reported. Conformational analysis is achieved by comparison of experimental NMR measurements with theoretical (B3LYP) calculations of relative energies of conformers and J(H,H) and J(H,F) coupling constants. The Diels-Alder reactions of allylic fluorides are investigated experimentally and theoretically. The stereoselectivities of the reactions were determined by NMR analysis and, in one case, by X-ray crystallography. Theoretical predictions of stereoselectivity based upon transition state modeling provided good agreement with experiment. Theoretical models for allylic fluorides and transition state conformations are reported. PMID:11281778

  12. Sequence-defined polymers via orthogonal allyl acrylamide building blocks.

    PubMed

    Porel, Mintu; Alabi, Christopher A

    2014-09-24

    Biological systems have long recognized the importance of macromolecular diversity and have evolved efficient processes for the rapid synthesis of sequence-defined biopolymers. However, achieving sequence control via synthetic methods has proven to be a difficult challenge. Herein we describe efforts to circumvent this difficulty via the use of orthogonal allyl acrylamide building blocks and a liquid-phase fluorous support for the de novo design and synthesis of sequence-specific polymers. We demonstrate proof-of-concept via synthesis and characterization of two sequence-isomeric 10-mer polymers. (1)H NMR and LCMS were used to confirm their chemical structure while tandem MS was used to confirm sequence identity. Further validation of this methodology was provided via the successful synthesis of a sequence-specific 16-mer polymer incorporating nine different monomers. This strategy thus shows promise as an efficient approach for the assembly of sequence-specific functional polymers. PMID:25204618

  13. Aerobic Linear Allylic C-H Amination: Overcoming Benzoquinone Inhibition.

    PubMed

    Pattillo, Christopher C; Strambeanu, Iulia I; Calleja, Pilar; Vermeulen, Nicolaas A; Mizuno, Tomokazu; White, M Christina

    2016-02-01

    An efficient aerobic linear allylic C-H amination reaction is reported under palladium(II)/bis-sulfoxide/Brønsted base catalysis. The reaction operates under preparative, operationally simple conditions (1 equiv of olefin, 1 atm O2 or air) with reduced Pd(II)/bis-sulfoxide catalyst loadings while providing higher turnovers and product yields than systems employing stoichiometric benzoquinone (BQ) as the terminal oxidant. Pd(II)/BQ π-acidic interactions have been invoked in various catalytic processes and are often considered beneficial in promoting reductive functionalizations. When such electrophilic activation for functionalization is not needed, however, BQ at high concentrations may compete with crucial ligand (bis-sulfoxide) binding and inhibit catalysis. Kinetic studies reveal an inverse relationship between the reaction rate and the concentration of BQ, suggesting that BQ is acting as a ligand for Pd(II) which results in an inhibitory effect on catalysis. PMID:26730458

  14. Rhodium-Catalyzed Regiodivergent Hydrothiolation of Allyl Amines and Imines.

    PubMed

    Kennemur, Jennifer L; Kortman, Gregory D; Hull, Kami L

    2016-09-14

    The regiodivergent Rh-catalyzed hydrothiolation of allyl amines and imines is presented. Bidentate phosphine ligands with larger natural bite angles (βn ≥ 99°), for example, DPEphos, dpph, or L1, promote a Markovnikov-selective hydrothiolation in up to 88% yield and >20:1 regioselectivity. Conversely, when smaller bite angle ligands (βn ≤ 86°), for example, dppbz or dppp, are employed, the anti-Markovnikov product is formed in up to 74% yield and >20:1 regioselectivity. Initial mechanistic investigations are performed and are consistent with an oxidative addition/olefin insertion/reductive elimination mechanism for each regioisomeric pathway. We hypothesize that the change in regioselectivity is an effect of diverging coordination spheres to favor either Rh-S or Rh-H insertion to form the branched or linear isomer, respectively. PMID:27547858

  15. DETERMINATION OF ALIPHATIC AMINES IN WATER USING DERIVATIZATION WITH FLUORESCEIN ISOTHIOCYANATE AND CAPILLARY ELECTROPHORESIS/LASER-INDUCED FLUORESCENCE DETECTION.

    EPA Science Inventory

    Detection-oriented derivatization of aliphatic amines and amine functional groups in coumpounds of environmental interest was studied using fluorescein isothiocyanate (FITC) with separation/determination by capillary electrophoresis/laser-induced fluorescence. Determinative level...

  16. Cross coupling of dialkylmagnesium derivatives with allylic compounds catalyzed by copper salts

    SciTech Connect

    Ibragimov, A.G.; Dzhemilev, U.M.; Saraev, R.A.

    1985-07-20

    The reaction of allylic compounds with Grignard reagents catalyzed by salts of copper, nickel, iron and cobalt, titanium and palladium is a simple and efficient method for the preparation of unsaturated hydrocarbons. However, information concerning the use of dialkylmagnesium derivatives, which are more reactive than Grignard reagents, is extremely limited in these reactions. To continue a study of the cross-coupling of allylic compounds with dialkylmagnesium derivatives in an effort to expand the scope of this reaction and to elucidate the effect of the R/sub 2/Mg reagent structure on its reactivity, the authors investigated the reaction of dialkylmagnesium and diarlmagnesium reagents with allylic ethers and esters, thioethers, and amines, by the action of transition metal salts. This work demonstrates the feasibility of the preparation of unsaturated hydrocarbons of given structure by the cross-coupling of dialkylmagnesium derivatives with functional allylic compounds by the action of catalytic amounts of copper complexes.

  17. Expanding the scope of Metal-Free enantioselective allylic substitutions: Anthrones

    PubMed Central

    Ceban, Victor; Tauchman, Jiří; Meazza, Marta; Gallagher, Greg; Light, Mark E.; Gergelitsová, Ivana; Veselý, Jan; Rios, Ramon

    2015-01-01

    The highly enantioselective asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with anthrones is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and excellent enantioselectivities. PMID:26592555

  18. Total Synthesis of Enantiopure (+)-γ -Lycorane Using Highly Efficient Pd-Catalyzed Asymmetric Allylic Alkylation

    PubMed Central

    Chapsal, Bruno D.; Ojima, Iwao

    2008-01-01

    Highly efficient short total synthesis of γ -lycorane (>99% ee, 41% overall yield) was achieved by using the asymmetric allylic alkylation in the key step catalyzed by palladium complexes with novel chiral biphenol-based monodentate phosphoramidite ligands. PMID:16562900

  19. Theoretical study on the mechanism of iron carbonyls mediated isomerization of allylic alcohols to saturated carbonyls.

    PubMed

    Branchadell, Vicenç; Crévisy, Christophe; Grée, René

    2003-05-01

    The conversion of allylic alcohols to enols mediated by Fe(CO)(3) has been studied through density functional theoretical calculations. From the results obtained a complete catalytic cycle has been proposed in which the first intermediate is the [(allyl alcohol)Fe(CO)(3)] complex. This intermediate evolves to the [(enol)Fe(CO)(3)] complex through two consecutive 1,3-hydrogen shifts involving a pi-allyl hydride intermediate. The highest Gibbs energy transition state corresponds to the partial decoordination ot the enol ligand prior to the coordination of a new allyl alcohol molecule that regenerates the first intermediate. Alternative processes for the [(enol)Fe(CO)(3)] complex such as [Fe(CO)(3)]-mediated enol-aldehyde transformation and enol isomerization have also been considered. The results obtained show that the former process is unfavourable, whereas the enol isomerization may compete with the enol decoordination step of the catalytic cycle. PMID:12740854

  20. Total Synthesis of Clavosolide A via Tandem Allylic Oxidation/Oxa-Conjugate Addition Reaction

    PubMed Central

    Baker, Joseph B.; Kim, Hyoungsu; Hong, Jiyong

    2015-01-01

    The tandem allylic oxidation/oxa-conjugate addition reaction promoted by the gem-disubstituent effect in conjunction with the NHC-mediated oxidative esterification was explored for the facile synthesis of clavosolide A. PMID:26236051

  1. Asymmetric Catalysis with CO2 : The Direct α-Allylation of Ketones.

    PubMed

    Pupo, Gabriele; Properzi, Roberta; List, Benjamin

    2016-05-10

    Quaternary stereocenters are found in numerous bioactive molecules. The Tsuji-Trost reaction has proven to be a powerful C-C bond forming process, and, at least in principle, should be well suited to access quaternary stereocenters via the α-allylation of ketones. However, while indirect approaches are known, the direct, catalytic asymmetric α-allylation of branched ketones has been elusive until today. By combining "enol catalysis" with the use of CO2 as a formal catalyst for asymmetric catalysis, we have now developed a solution to this problem: we report a direct, highly enantioselective and highly atom-economic Tsuji-Trost allylation of branched ketones with allylic alcohol. Our reaction delivers products bearing quaternary stereocenters with high enantioselectivity and water as the sole by-product. We expect our methodology to be of utility in asymmetric catalysis and inspire the design of other highly atom-economic transformations. PMID:27071633

  2. Nickel-Catalyzed Allylic Alkylation with Diarylmethane Pronucleophiles: Reaction Development and Mechanistic Insights.

    PubMed

    Sha, Sheng-Chun; Jiang, Hui; Mao, Jianyou; Bellomo, Ana; Jeong, Soo A; Walsh, Patrick J

    2016-01-18

    Palladium-catalyzed allylic substitution reactions are among the most efficient methods to construct C-C bonds between sp(3)-hybridized carbon atoms. In contrast, much less work has been done with nickel catalysts, perhaps because of the different mechanisms of the allylic substitution reactions. Palladium catalysts generally undergo substitution by a "soft"-nucleophile pathway, wherein the nucleophile attacks the allyl group externally. Nickel catalysts are usually paired with "hard" nucleophiles, which attack the metal before C-C bond formation. Introduced herein is a rare nickel-based catalyst which promotes substitution with diarylmethane pronucleophiles by the soft-nucleophile pathway. Preliminary studies on the asymmetric allylic alkylation are promising. PMID:26756444

  3. Immobilized catalysts for iridium-catalyzed allylic amination: rate enhancement by immobilization.

    PubMed

    Malakar, Chandi C; Helmchen, Günter

    2015-05-01

    The first immobilized catalyst for Ir-catalyzed asymmetric allylic aminations is described. The catalyst is a cationic (π-allyl)Ir complex bound by cation exchange to an anionic silica gel support. Preparation of the catalyst is facile, and the supported catalyst displayed considerably enhanced activity compared with the parent homogeneous catalyst. Up to 43 consecutive amination runs were possible in recycling experiments. PMID:25787122

  4. Mutagenic properties of allylic and alpha, beta-unsaturated compounds: consideration of alkylating mechanisms.

    PubMed

    Eder, E; Henschler, D; Neudecker, T

    1982-12-01

    1. Allyl and allylic compounds may exert alkylating activities by SN1, SN2 and SN2' mechanisms. This direct alkylating potential can be determined quantitatively by a modified 4-NBP (4-nitrobenzyl pyridine) test. 2. The alkylating activities in a systematically selected series of allyl and allylic compounds correlate well with the direct mutagenic potential as determined in the Ames test using Salmonella typhimurium TA 100 as tester strain. 3. The allylic structure is a prerequisite for these types of activities since structurally related molecules lacking the allylic moiety are inactive in this respect. 4. The potency of both the alkylating and mutagenic activity is determined by the strength of the leaving group: --OSO2CH3 greater than I greater than Br greater than Cl greater than--NCS. 5. Indirect mutagenicity, through metabolic activation of the olefinic bond (by addition of S9 mix to the tester medium), can be ruled out for practically all compounds, the only exception found being 2,3-dichloro-1-propene where an increase of mutagenicity is encountered after addition of S9 mix; mechanistic explanations for this exception are provided. 6. Analogous activation is demonstrated for benzyl halides, the alkylating potency of which is even higher than that of genuine allylic compounds. 7. A variety of methyl- and chlorine-substituted allyl compounds has been included in the study: both groups increase activity, either by +I (CH3) or by +M effects (Cl). 8. alpha, beta-Unsaturated carbonyl compounds, e.g. acrolein and crotonaldehyde, also display direct mutagenic activity which is due to a completely different mechanism: covalent binding to nucleophilic sites of DNA bases by Michael addition. Methyl and other alkyl substitutions decrease the mutagenic potential in this type of compound. The corresponding alcohols, also displaying mutagenic activity but to a lesser degree, are metabolically activated by ADH (alcohol dehydrogenase) of the tester strain microbes to the

  5. Control of Diastereoselectivity for Iridium-catalyzed Allylation of a Prochiral Nucleophile with a Phosphate Counterion

    PubMed Central

    Chen, Wenyong; Hartwig, John F.

    2013-01-01

    We report a highly diastereo- and enantioselective allylation of azlactones catalyzed by the combination of a metallayclic iridium complex and an optically inactive phosphate anion. The process demonstrates an approach to conduct diastereoselective reactions with prochiral nucleophiles in the presence of metallacyclic allyliridium complexes. The reaction provides access to an array of enantioenriched allylated azlactones containing adjacent tertiary and quaternary carbon centers. Preliminary mechanistic studies suggest that the phosphate and methyl carbonate anions together induce the unusually high diastereoselectivity. PMID:23286279

  6. A Concomitant Allylic Azide Rearrangement/Intramolecular Azide–Alkyne Cycloaddition Sequence

    PubMed Central

    2015-01-01

    An intramolecular Huisgen cycloaddition of an interconverting set of isomeric allylic azides with alkynes affords substituted triazoles in high yield. The stereoisomeric vinyl-substituted triazoloxazines formed depend on the rate of cycloaddition of the different allylic azide precursors when the reaction is carried out under thermal conditions. In contrast, dimerized macrocyclic products were obtained when the reaction was done using copper(I)-catalyzed conditions, demonstrating the ability to control the reaction products through changing conditions. PMID:24635056

  7. Enantiomerization of Allylic Trifluoromethyl Sulfoxides Studied by HPLC Analysis and DFT Calculations.

    PubMed

    Bailly, Laetitia; Petit, Emilie; Maeno, Mayaka; Shibata, Norio; Trapp, Oliver; Cardinael, Pascal; Chataigner, Isabelle; Cahard, Dominique

    2016-02-01

    Enantiomerization of allylic trifluoromethyl sulfoxides occurs spontaneously at room temperature through the corresponding allylic trifluoromethanesulfenates via a [2,3]-sigmatropic rearrangement. Dynamic enantioselective high-performance liquid chromatography (HPLC) analysis revealed the stereodynamics of these sulfoxides ranging from chromatographic resolution to peak coalescence at temperatures between 5 and 53 °C. The rate constant of enantiomerization and activation parameters were determined and compared with Density Functional Theory (DFT) calculations. PMID:26689286

  8. Reaction of /alpha/,/beta/-unsaturated acyl isothiocyanates with salts of dithiocarbamic acids

    SciTech Connect

    Krus, K.; Masias, A.; Beletskaya, I.P.

    1989-01-10

    The reaction of unsaturated isothiocyanates with the sodium and calcium salts of N-alkyl- and N,N-dialkyldithiocarbamic acids was studied. Depending on the structure of the dithiocarbamate, the reaction products are thiazines or acyl dithiocarbamates. For the salts of methyldithiocarbamic acid the effect of the concentration and the nature of the metal on the relative yields of 6-phenyl-3-methylpropiorhodanine and 6-phenylpropiorhodanine was studied. A method is proposed for the synthesis of 3-substituted propiorhodanines.

  9. Toward Self-Adjuvanting Subunit Vaccines: Model Peptide and Protein Antigens Incorporating Covalently Bound Toll-Like Receptor-7 Agonistic Imidazoquinolines

    PubMed Central

    Shukla, Nikunj M.; Lewis, Tyler C.; Day, Timothy P.; Mutz, Cole A.; Ukani, Rehman; Hamilton, Chase D.; Balakrishna, Rajalakshmi

    2011-01-01

    Toll-like receptor (TLR)-7 agonists show prominent Th1-biased immunostimulatory activities. A TLR7-active N1-(4-aminomethyl)benzyl substituted imidazoquinoline 1 served as a convenient precursor for the syntheses of isothiocyanate and maleimide derivatives for covalent attachment to free amine and thiol groups of peptides and proteins. 1 was also amenable to direct reductive amination with maltoheptaose without significant loss of activity. Covalent conjugation of the isothiocyanate derivative 2 to α-lactalbumin could be achieved under mild, non-denaturing conditions, in a controlled manner and with full preservation of antigenicity. The self-adjuvanting α-lactalbumin construct induced robust, high-affinity immunoglobulin titers in murine models. The premise of covalently decorating protein antigens with adjuvants offers the possibility of drastically reducing systemic exposure of the adjuvant, and yet eliciting strong, Th1-biased immune responses. PMID:21549593

  10. Inhibition of Bladder Cancer by Broccoli Isothiocyanates Sulforaphane and Erucin: Characterization, Metabolism and Interconversion

    PubMed Central

    Abbaoui, Besma; Riedl, Kenneth M; Ralston, Robin A; Thomas-Ahner, Jennifer M; Schwartz, Steven J; Clinton, Steven K; Mortazavi, Amir

    2013-01-01

    Epidemiologic evidence suggests diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Our objectives are to investigate these observations and determine the role of isothiocyanates in primary or secondary bladder cancer prevention. We initially investigate the mechanisms whereby broccoli and broccoli sprout extracts and pure isothiocyanates inhibit normal, non-invasive (RT4) and invasive (J82, UMUC3) human urothelial cell viability. Sulforaphane (IC50= 5.66±1.2μM) and erucin (IC50= 8.79±1.3μM) are found to be the most potent inhibitors and normal cells are least sensitive. This observation is associated with downregulation of survivin, EGFR and HER2/neu, G2/M cell cycle accumulation and apoptosis. In a murine UMUC3 xenograft model, we fed semipurified diets containing 4% broccoli sprouts, or 2% broccoli sprout isothiocyanate extract; or gavaged pure sulforaphane or erucin (each at 295 μmol/kg, similar to dietary exposure); and report tumor weight reduction of 42% (p=0.02), 42% (p=0.04), 33% (p=0.04) and 58% (p<0.0001), respectively. Sulforaphane and erucin metabolites are present in mouse plasma (micromolar range) and tumor tissue, with N-acetyl cysteine conjugates as the most abundant. Interconversion of sulforaphane and erucin metabolites was observed. This work supports development of fully characterized, novel food products for phase I/II human studies targeting bladder cancer prevention. PMID:23038615

  11. Direct and Indirect Antioxidant Activity of Polyphenol- and Isothiocyanate-Enriched Fractions from Moringa oleifera

    PubMed Central

    Boyunegmez Tumer, Tugba; Rojas-Silva, Patricio; Poulev, Alexander; Raskin, Ilya; Waterman, Carrie

    2016-01-01

    Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts used as nutritious food and traditional medicine. This study describes an efficient preparatory strategy to extract and fractionate moringa leaves by fast centrifugal partition chromatography (FCPC) to produce polyphenol and isothiocyanate (ITC) rich fractions. Characterization and further purification of these fractions showed that moringa polyphenols were potent direct antioxidants assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were effective indirect antioxidants assayed by induction of NAD(P)H quinone oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4-[(α-l-rhamnosyloxy)benzyl]-isothiocyanate and 4-[(4′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1 inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as SF in inducing NQO1 activity. These findings suggest that moringa leaves contain a potent mixture of direct and indirect antioxidants that can explain its various health-promoting effects. PMID:25605589

  12. Direct and indirect antioxidant activity of polyphenol- and isothiocyanate-enriched fractions from Moringa oleifera.

    PubMed

    Tumer, Tugba Boyunegmez; Rojas-Silva, Patricio; Poulev, Alexander; Raskin, Ilya; Waterman, Carrie

    2015-02-11

    Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts used as nutritious food and traditional medicine. This study describes an efficient preparatory strategy to extract and fractionate moringa leaves by fast centrifugal partition chromatography (FCPC) to produce polyphenol and isothiocyanate (ITC) rich fractions. Characterization and further purification of these fractions showed that moringa polyphenols were potent direct antioxidants assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were effective indirect antioxidants assayed by induction of NAD(P)H quinone oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4-[(α-l-rhamnosyloxy)benzyl]isothiocyanate and 4-[(4'-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1 inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as SF in inducing NQO1 activity. These findings suggest that moringa leaves contain a potent mixture of direct and indirect antioxidants that can explain its various health-promoting effects. PMID:25605589

  13. Induction of epoxide hydrolase, glucuronosyl transferase, and sulfotransferase by phenethyl isothiocyanate in male Wistar albino rats.

    PubMed

    Abdull Razis, Ahmad Faizal; Mohd Noor, Noramaliza; Konsue, Nattaya

    2014-01-01

    Phenethyl isothiocyanate (PEITC) is an isothiocyanate found in watercress as the glucosinolate (gluconasturtiin). The isothiocyanate is converted from the glucosinolate by intestinal microflora or when contacted with myrosinase during the chopping and mastication of the vegetable. PEITC manifested protection against chemically-induced cancers in various tissues. A potential mechanism of chemoprevention is by modulating the metabolism of carcinogens so as to promote deactivation. The principal objective of this study was to investigate in rats the effect of PEITC on carcinogen-metabolising enzyme systems such as sulfotransferase (SULT), N-acetyltransferase (NAT), glucuronosyl transferase (UDP), and epoxide hydrolase (EH) following exposure to low doses that simulate human dietary intake. Rats were fed for 2 weeks diets supplemented with PEITC at 0.06 µmol/g (low dose, i.e., dietary intake), 0.6 µmol/g (medium dose), and 6.0 µmol/g (high dose), and the enzymes were monitored in rat liver. At the Low dose, no induction of the SULT, NAT, and EH was noted, whereas UDP level was elevated. At the Medium dose, only SULT level was increased, whereas at the High dose marked increase in EH level was observed. It is concluded that PEITC modulates carcinogen-metabolising enzyme systems at doses reflecting human intake thus elucidating the mechanism of its chemoprevention. PMID:24592387

  14. Induction of Epoxide Hydrolase, Glucuronosyl Transferase, and Sulfotransferase by Phenethyl Isothiocyanate in Male Wistar Albino Rats

    PubMed Central

    Mohd Noor, Noramaliza; Konsue, Nattaya

    2014-01-01

    Phenethyl isothiocyanate (PEITC) is an isothiocyanate found in watercress as the glucosinolate (gluconasturtiin). The isothiocyanate is converted from the glucosinolate by intestinal microflora or when contacted with myrosinase during the chopping and mastication of the vegetable. PEITC manifested protection against chemically-induced cancers in various tissues. A potential mechanism of chemoprevention is by modulating the metabolism of carcinogens so as to promote deactivation. The principal objective of this study was to investigate in rats the effect of PEITC on carcinogen-metabolising enzyme systems such as sulfotransferase (SULT), N-acetyltransferase (NAT), glucuronosyl transferase (UDP), and epoxide hydrolase (EH) following exposure to low doses that simulate human dietary intake. Rats were fed for 2 weeks diets supplemented with PEITC at 0.06 µmol/g (low dose, i.e., dietary intake), 0.6 µmol/g (medium dose), and 6.0 µmol/g (high dose), and the enzymes were monitored in rat liver. At the Low dose, no induction of the SULT, NAT, and EH was noted, whereas UDP level was elevated. At the Medium dose, only SULT level was increased, whereas at the High dose marked increase in EH level was observed. It is concluded that PEITC modulates carcinogen-metabolising enzyme systems at doses reflecting human intake thus elucidating the mechanism of its chemoprevention. PMID:24592387

  15. Allyl-Assisted, Cu(I)-Catalyzed Azide-Alkyne Cycloaddition/Allylation Reaction: Assembly of the [1,2,3]Triazolo-4,5,6,7-tetrahydropyridine Core Structure.

    PubMed

    Deng, Xiaohu; Liang, Jimmy; Allison, Brett B; Dvorak, Curt; McAllister, Heather; Savall, Brad M; Mani, Neelakandha S

    2015-11-01

    We report a Cu(I)-catalyzed azide-alkyne-allyl halide three-component reaction for a one-pot synthesis of 1,4-disubstituted 5-allyl-1,2,3-triazoles. The allyl moiety provides not only the electrophile but also a coordinating ligand to Cu, which is essential for the reaction to occur under mild conditions. A concise synthesis of a potential drug candidate 1 is realized based on this key reaction. PMID:26458051

  16. Palladium-Catalyzed Dearomative Allylic Alkylation of Indoles with Alkynes To Synthesize Indolenines with C3-Quarternary Centers.

    PubMed

    Gao, Shang; Wu, Zijun; Fang, Xinxin; Lin, Aijun; Yao, Hequan

    2016-08-01

    A palladium-catalyzed dearomative allylic alkylation of indoles with alkynes to construct indolenines with C3-quarternary centers was reported. The in situ formed arylallene intermediate omitted the need to install leaving groups on the allylic compounds and employ extra oxidants to oxidize the allylic C-H bonds. The reaction exhibited good functional group tolerance and high atom economy. Moreover, the reaction was further expanded to synthesize pyrroloindolines and furanoindolines. PMID:27442021

  17. α-Sulfonyl succinimides: versatile sulfinate donors in Fe-catalyzed, salt-free, neutral allylic substitution.

    PubMed

    Jegelka, Markus; Plietker, Bernd

    2011-09-01

    Allyl sulfones are versatile intermediates in organic chemistry. The presence of two distinct functional groups sets the stage for a plethora of subsequent transformations. However, despite these advantages the preparation of regioisomerically enriched sulfones is not easy. The use of sulfinate salts as nucleophiles in substitutions is frequently accompanied by side reactions such as π-bond migration, β-elimination, and so on. Herein we present a preparatively simple way to synthesize a variety of different aryl or alkyl allyl sulfones starting from readily accessible allylic carbonates. By employing aryl or alkyl α-sulfonyl succinimides as sulfinate synthons, mild and regioselective ipso substitution of diverse allylic carbonates was realized. PMID:21818793

  18. Allylic and Allenic Halide Synthesis via NbCl5- and NbBr5-Mediated Alkoxide Rearrangements

    PubMed Central

    Ravikumar, P. C.; Yao, Lihua; Fleming, Fraser F.

    2009-01-01

    Addition of NbCl5, or NbBr5, to a series of magnesium, lithium, or potassium allylic or propargylic alkoxides directly provides allylic or allenic halides. Halogenation formally occurs through a metalla-halo-[3,3] rearrangement although concerted, ionic, and direct displacement mechanisms appear to operate competitively. Transposition of the olefin is equally effective for allylic alkoxides prepared by nucleophilic addition, deprotonation, or reduction. Experimentally, the niobium pentahalide halogenations are rapid, afford essentially pure E-allylic or allenic halides after extraction, and are applicable to a range of aliphatic and aromatic alcohols, aldehydes, and ketones. PMID:19739606

  19. Allylic and allenic halide synthesis via NbCl(5)- and NbBr(5)-mediated alkoxide rearrangements.

    PubMed

    Ravikumar, P C; Yao, Lihua; Fleming, Fraser F

    2009-10-01

    Addition of NbCl(5) or NbBr(5) to a series of magnesium, lithium, or potassium allylic or propargylic alkoxides directly provides allylic or allenic halides. Halogenation formally occurs through a metalla-halo-[3,3] rearrangement, although concerted, ionic, and direct displacement mechanisms appear to operate competitively. Transposition of the olefin is equally effective for allylic alkoxides prepared by nucleophilic addition, deprotonation, or reduction. Experimentally, the niobium pentahalide halogenations are rapid, afford essentially pure (E)-allylic or -allenic halides after extraction, and are applicable to a range of aliphatic and aromatic alcohols, aldehydes, and ketones. PMID:19739606

  20. Expression of the platelet-activating factor receptor enhances benzyl isothiocyanate-induced apoptosis in murine and human melanoma cells.

    PubMed

    Sahu, Ravi Prakash

    2015-07-01

    Melanoma cells often express platelet-activating factor receptor (PAF-R), which has been demonstrated to increase metastatic behavior. However, the effect of PAF-R on the responsiveness of melanoma to naturally occurring cytotoxic agents remains to be elucidated. The present study aimed to determine the relative cytotoxicity and mechanism of benzyl isothiocyanate (BITC), a component of cruciferous vegetables, in melanoma cells expressing PAF-R. To evaluate the importance of PAF-R signaling in melanoma cell growth, PAF-R-negative murine B16F10 cells were transduced with a retrovirus containing the cDNA for PAF-R to generate cells stably expressing PAF-R (B16-PAF-R) or an empty vector (MSCV) to generate PAF-R-deficient B16-MSCV control cells. Activation of PAF-R, using the PAF-R agonist, 1-hexadecyl-2-N-methylcarbamoyl-3-glycerophosphocholine, induced an increase in the proliferation of B16-PAF-R cells compared with the B16-MSCV cells. Reverse transcription quantitative polymerase chain reaction revealed the presence of functional PAF-R in human melanoma SK23MEL cells, but not in SK5MEL cells. The present study investigated the effect of BITC treatments on the survival of murine and human melanoma cells, in the presence or absence of functional PAF-R. The results revealed that treatment with BITC decreased the survival rate of the PAF-R-positive and negative murine and human melanoma cells. However, the expression of PAF-R substantially augmented BITC-mediated cytotoxicity in the PAF-R-positive cells at lower concentrations compared with the PAF-R-negative cells. In order to determine the underlying mechanism, flow cytometric analysis was used, which demonstrated a significant increase in the generation of reactive oxygen species (ROS) in the B16-PAF-R cells compared with the B16-MSCV cells, which enhanced apoptosis by BITC, as measured by increased caspase-3/7 luminescence. Notably, the BITC-mediated decreased cell survival rate, increased ROS and increased

  1. 2-Allyl-7-nitro-2H-indazole

    PubMed Central

    Kouakou, Assoman; Rakib, El Mostapha; Spinelli, Domenico; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    The asymmetric unit of the title compound, C10H9N3O2, contains two independent mol­ecules linked by a C—H⋯N hydrogen bond. Each mol­ecule has a similar conformation, being built up from fused five- and six-membered rings, each linked to an ally and nitro group, respectively. The indazole ring system makes dihedral angles of 2.7 (2) and 2.2 (2)°, respectively, with the plane through the nitro group. The allyl group is nearly perpendicular to the indazole system, as indicated by the N—N—C—C torsion angles of −75.3 (2) and −82.2 (2)°, this being the most important difference between the conformations of the two mol­ecules. In the crystal, mol­ecules are linked by C—H⋯O and π–π [inter-centroid distance = 3.6225 (8) Å] inter­actions to form a three-dimensional network. PMID:24454056

  2. Spectroscopic characterization of alumina-supported bis(allyl)iridium complexes : site-isolation, reactivity, and decomposition studies.

    SciTech Connect

    Trovitch, R. J.; Guo, N.; Janicke, M. T.; Li, H.; Marshall, C. L.; Miller, J. T.; Sattelberger, A. P.; John, K. D.; Baker, R. T.; LANL; Univ. of Ottawa

    2010-01-01

    The covalent attachment of tris(allyl)iridium to partially dehydroxylated ?-alumina is found to proceed via surface hydroxyl group protonation of one allyl ligand to form an immobilized bis(allyl)iridium moiety, (?AlO)Ir(allyl)2, as characterized by CP-MAS 13C NMR, inductively coupled plasma-mass spectrometry, and Ir L3 edge X-ray absorption spectroscopy. Extended X-ray absorption fine-structure (EXAFS) measurements taken on unsupported Ir(allyl)3 and several associated tertiary phosphine addition complexes suggest that the ?3-allyl ligands generally account for an Ir-C coordination number of 2 rather than 3, with an average Ir-C distance of 2.16 A. Using this knowledge, combined EXAFS and X-ray absorption near-edge structure studies reveal that a small amount of Ir0 is also formed upon reaction of Ir(allyl)3 with the surface. It was found that the addition of either 2,6-dimethylphenyl isocyanide or carbon monoxide to the supported complex allows spectroscopic identification of the supported bis(allyl)iridium complexes, (?AlO)Ir(allyl)2(CNAr) [Ar = 2,6-(CH3)2C6H4] and (?AlO)Ir(allyl)2(CO)2, respectively. Although samples of the supported bis(allyl)iridium complex are active for the dehydrogenation of cyclohexane to benzene at temperatures between 180 and 220C, in situ temperature-programmed reaction XAFS and continuous-flow reactor studies suggest that Ir0 nanoparticles, rather than a well-defined Ir3+ complex, are responsible for the observed activity.

  3. Resonance interactions in acyclic systems. 1. Energies and charge distributions in allyl anions and related compounds

    SciTech Connect

    Wiberg, K.B.; Breneman, C.M.; LePage, T.J. )

    1990-01-03

    The energies of dissociation of propane to 1-propyl cation and anion and of propene to allyl cation and anion may be satisfactorily reproduced via ab initio calculations at the MP4/6-311++G**//6-31G* level. The reaction of 1-propyl cation with propene to give the unconjugated allyl cation was found to be endothermic, whereas the corresponding reaction of the anion was exothermic. The rotational barrier for allyl cation was 36 kcal/mol, whereas that for the anion was 19 kcal/mol. These data were analyzed in terms of electron delocalization and the electrostatic energies of the ions, and it was concluded that whereas the cation had significant resonance stabilization, the anion had little stabilization. A series of allyl type anions were examined making use of 6-311++G** wave functions calculated at the 6-31G* geometries. Correction for electron correlation at the MP3 level led to calculated proton affinities which agreed well with the experimental values. Electronegative atoms at the central position had little affect on the proton affinities, but when they were at the terminal positions, there was a large change. The changes in electron population among the amions were studied via numerical integration of the charge densities within boundaries which may be assigned to the atoms in the ions. The more stable anions are characterized by a -+- charge distribution for the three atoms in the allylic system, leading to internal coulombic stabilization.

  4. The direct arylation of allylic sp3 C–H bonds via organocatalysis and photoredox catalysis

    PubMed Central

    Cuthbertson, James D.; MacMillan, David W. C.

    2015-01-01

    The direct functionalization of unactivated sp3 C–H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts,1 the establishment of general and mild strategies for the engagement of sp3 C–H bonds in carbon–carbon bond forming reactions has proven difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene, and methine carbons in a catalytic manner is a priority. While protocols for direct allylic C–H oxidation and amination have become widely established,2,3 the engagement of allylic substrates in carbon–carbon bond-forming reactions has thus far required the use of pre-functionalized coupling partners.4 In particular, the direct arylation of non-functionalized allylic systems would enable chemists to rapidly access a series of known pharmacophores, though a general solution to this longstanding challenge remains elusive. We describe herein the use of both photoredox and organic catalysis to accomplish the first mild, broadly effective direct allylic C–H arylation. This new C–C bond-forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants and has been used in the direct arylation of benzylic C–H bonds. PMID:25739630

  5. CXCR4 is a novel target of cancer chemopreventative isothiocyanates in prostate cancer cells.

    PubMed

    Sakao, Kozue; Vyas, Avani R; Chinni, Sreenivasa R; Amjad, Ali I; Parikh, Rahul; Singh, Shivendra V

    2015-05-01

    Isothiocyanates (ITCs) derived from cruciferous vegetables, including phenethyl isothiocyanate (PEITC) and sulforaphane (SFN), exhibit in vivo activity against prostate cancer in a xenograft and transgenic mouse model, and thus are appealing for chemoprevention of this disease. Watercress constituent PEITC and SFN-rich broccoli sprout extract are under clinical investigations but the molecular mechanisms underlying their cancer chemopreventive effects are not fully understood. The present study demonstrates that chemokine receptor CXCR4 is a novel target of ITCs in prostate cancer cells. Exposure of prostate cancer cells (LNCaP, 22Rv1, C4-2, and PC-3) to pharmacologically applicable concentrations of PEITC, benzyl isothiocyanate (BITC), and SFN (2.5 and 5 μmol/L) resulted in downregulation of CXCR4 expression. None of the ITCs affected secretion of CXCR4 ligand (stromal-derived factor-1). In vivo inhibition of PC-3 xenograft growth upon PEITC treatment was associated with a significant decrease in CXCR4 protein level. A similar trend was discernible in the tumors from SFN-treated TRAMP mice compared with those of control mice, but the difference was not significant. Stable overexpression of CXCR4 in PC-3 cells conferred significant protection against wound healing, cell migration, and cell viability inhibition by ITCs. Inhibition of cell migration resulting from PEITC and BITC exposure was significantly augmented by RNAi of CXCR4. This study demonstrates, for the first time, that cancer chemopreventive ITCs suppress CXCR4 expression in prostate cancer cells in vitro as well as in vivo. These results suggest that CXCR4 downregulation may be an important pharmacodynamic biomarker of cancer chemopreventative ITCs in prostate adenocarcinoma. PMID:25712054

  6. Metal-mediated reaction modeled on nature: the activation of isothiocyanates initiated by zinc thiolate complexes.

    PubMed

    Eger, Wilhelm A; Presselt, Martin; Jahn, Burkhard O; Schmitt, Michael; Popp, Jürgen; Anders, Ernst

    2011-04-18

    On the basis of detailed theoretical studies of the mode of action of carbonic anhydrase (CA) and models resembling only its reactive core, a complete computational pathway analysis of the reaction between several isothiocyanates and methyl mercaptan activated by a thiolate-bearing model complex [Zn(NH(3))(3)SMe](+) was performed at a high level of density functional theory (DFT). Furthermore, model reactions have been studied in the experiment using relatively stable zinc complexes and have been investigated by gas chromatography/mass spectrometry and Raman spectroscopy. The model complexes used in the experiment are based upon the well-known azamacrocyclic ligand family ([12]aneN(4), [14]aneN(4), i-[14]aneN(4), and [15]aneN(4)) and are commonly formulated as ([Zn([X]aneN(4))(SBn)]ClO(4). As predicted by our DFT calculations, all of these complexes are capable of insertion into the heterocumulene system. Raman spectroscopic investigations indicate that aryl-substituted isothiocyanates predominantly add to the C═N bond and that the size of the ring-shaped ligands of the zinc complex also has a very significant influence on the selectivity and on the reactivity as well. Unfortunately, the activated isothiocyanate is not able to add to the thiolate-corresponding mercaptan to invoke a CA analogous catalytic cycle. However, more reactive compounds such as methyl iodide can be incorporated. This work gives new insight into the mode of action and reaction path variants derived from the CA principles. Further, aspects of the reliability of DFT calculations concerning the prediction of the selectivity and reactivity are discussed. In addition, the presented synthetic pathways can offer a completely new access to a variety of dithiocarbamates. PMID:21405064

  7. Isothiocyanate synthetic analogs: biological activities, structure-activity relationships and synthetic strategies.

    PubMed

    Milelli, Andrea; Fimognari, Carmela; Ticchi, Nicole; Neviani, Paolo; Minarini, Anna; Tumiatti, Vincenzo

    2014-01-01

    Sulforaphane is a natural product that is constantly under biological investigation for its unique biological properties. This naturally occurring isothiocyanate (ITC) and its analogs are the main components of cruciferous vegetables, such as cauliflower, watercress, broccoli, cabbage, Brussels sprouts, widely used as chemopreventive agents. Due to their interesting biological profiles, natural ITCs have been exploited as starting point to develop new synthetic analogs. The present mini-review briefly highlights the most important biological actions of selected new synthetic ITCs focusing on their structure-activity relationships and related synthetic strategies. PMID:25373847

  8. Synthesis of Cyclic Azomethine Imines by Cycloaddition Reactions of N-Isocyanates and N-Isothiocyanates.

    PubMed

    Bongers, Amanda; Ranasinghe, Indee; Lemire, Philippe; Perozzo, Alyssa; Vincent-Rocan, Jean-François; Beauchemin, André M

    2016-08-01

    Various nitrogen-substituted iso(thio)cyanates engage in [3 + 2]-cycloaddition reactions to form azomethine imines containing triazolone, triazole-thione, and pyrazole-thione cores. First, iminoisothiocyanates are shown to undergo aminothiocarbonylation reactions with strained alkenes, and a comparison with recently reported reactions of iminoisocyanates highlights their reduced reactivity. In contrast, amino(thio)carbonylation reactions of imines with iminoisocyanates and iminoisothiocyanates proved more efficient, providing access to triazolone and triazole-thione cores. The dipole products can be converted to valuable heterocyclic cores through simple derivatization reactions. PMID:27458786

  9. Studies on the interaction of fluorescein isothiocyanate and its sugar analogues with cetyltrimethylammonium bromide

    NASA Astrophysics Data System (ADS)

    Ghosh, Sujit Kumar; Ali, Mohammed; Chatterjee, Hirak

    2013-03-01

    The interaction of fluorescein isothiocyanate (FITC) and its two sugar analogues (viz., FITC-Dextran 40S and FITC-Dextran 2000S) with cetyltrimethylammonium bromide has been elucidated by absorption, fluorescence, Fourier transform infrared spectroscopy and fluorescence microscopic studies. It is seen that the emission of the probe molecules is uniquely sensitive to the changes in surfactant concentrations at a particular regime due to the formation of dye-surfactant supramolecular assembly. The formation of supramolecular assembly becomes effective at a lower surfactant concentration with increasing dextran size as a consequence of definite dye-surfactant interaction and could pave a facile strategy for designing hierarchical superstructures.

  10. Agonist-trafficking and hallucinogens.

    PubMed

    González-Maeso, Javier; Sealfon, Stuart C

    2009-01-01

    Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT(2A) receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs. PMID:19275609

  11. The Natural Product Magnolol as a Lead Structure for the Development of Potent Cannabinoid Receptor Agonists

    PubMed Central

    Müller, Christa E.

    2013-01-01

    Magnolol (4-allyl-2-(5-allyl-2-hydroxyphenyl)phenol), the main bioactive constituent of the medicinal plant Magnolia officinalis, and its main metabolite tetrahydromagnolol were recently found to activate cannabinoid (CB) receptors. We now investigated the structure-activity relationships of (tetrahydro)magnolol analogs with variations of the alkyl chains and the phenolic groups and could considerably improve potency. Among the most potent compounds were the dual CB1/CB2 full agonist 2-(2-methoxy-5-propyl-phenyl)-4-hexylphenol (61a, Ki CB1∶0.00957 µM; Ki CB2∶0.0238 µM), and the CB2-selective partial agonist 2-(2-hydroxy-5-propylphenyl)-4-pentylphenol (60, Ki CB1∶0.362 µM; Ki CB2∶0.0371 µM), which showed high selectivity versus GPR18 and GPR55. Compound 61b, an isomer of 61a, was the most potent GPR55 antagonist with an IC50 value of 3.25 µM but was non-selective. The relatively simple structures, which possess no stereocenters, are easily accessible in a four- to five-step synthetic procedure from common starting materials. The central reaction step is the well-elaborated Suzuki-Miyaura cross-coupling reaction, which is suitable for a combinatorial chemistry approach. The scaffold is versatile and may be fine-tuned to obtain a broad range of receptor affinities, selectivities and efficacies. PMID:24204944

  12. Regio- and Enantioselective N-Allylations of Imidazole, Benzimidazole, and Purine Heterocycles Catalyzed by Single-Component Metallacyclic Iridium Complexes

    PubMed Central

    Stanley, Levi M.

    2010-01-01

    Highly regio- and enantioselective iridium-catalyzed N-allylations of benzimidazoles, imidazoles, and purines have been developed. N-Allylated benzimidazoles and imidazoles were isolated in high yields (up to 97%) with high branched-to-linear selectivity (up to 99:1) and enantioselectivity (up to 98% ee) from the reactions of benzimidazole and imidazole nucleophiles with unsymmetrical allylic carbonates in the presence of single component, ethylene-bound, metallacyclic iridium catalysts. N-Allylated purines were also obtained in high yields (up to 91%) with high N9:N7 selectivity (up to 96:4), high branched-to-linear selectivity (98:2), and high enantioselectivity (up to 98% ee) under similar conditions. The reactions encompass a range of benzimidazole, imidazole, and purine nucleophiles, as well as a variety of unsymmetrical aryl, heteroaryl, and aliphatic allylic carbonates. Competition experiments between common amine nucleophiles and the heterocyclic nitrogen nucleophiles studied in this work illustrate the effect of nucleophile pKa on the rate of iridium-catalyzed N-allylation reactions. Kinetic studies on the allylation of benzimidazole catalyzed by metallacyclic iridium-phosphoramidite complexes, in combination with studies on the deactivation of these catalysts in the presence of heterocyclic nucleophiles, provide insight into the effects of the structure of the phosphoramidite ligands on the stability of the metallacyclic catalysts. The data obtained from these studies has led to the development of N-allylations of benzimidazoles and imidazoles in the absence of an exogenous base. PMID:19480431

  13. Silver-Catalyzed Allylation of Ketones and Intramolecular Cyclization through Carbene Intermediates from Cyclopropenes Under Ambient Conditions.

    PubMed

    Nakano, Takeo; Endo, Kohei; Ukaji, Yutaka

    2016-03-01

    Tandem C-C bond formation was achieved through silver-catalyzed ring-opening of cyclopropenes via carbene intermediates. The reaction of cyclopropenes in the presence of a silver catalyst gave indene derivatives under ambient conditions. In contrast, the insertion of organozinc reagents to silver carbene or allylic cation intermediates afforded allylmetal intermediates for the tandem allylation of carbonyl compounds. PMID:26611195

  14. Regiodivergent Addition of Phenols to Allylic Oxides: Control of 1,2 and 1,4-Additions for Cyclitol Synthesis**

    PubMed Central

    Moschitto, Matthew J.; Vaccarello, David N.; Lewis, Chad A.

    2015-01-01

    Control of 1,2- and 1,4-addition of substituted phenols to allylic oxides is achieved by intercepting palladium π-allyl complexes. The interconversion of palladium complexes results in the total synthesis of MK7607, cyathiformine B type, streptol, and a new cyclitol. PMID:25533617

  15. A New Entry to Azomethine Ylides from Allylic Amines and Glyoxals: Shifting the Reliance on Amino Ester Precursors

    PubMed Central

    2015-01-01

    The first examples of azomethine ylides derived from allylic amine and glyoxal precursors are reported. The condensation of primary allylic and α-aryl amines with glyoxylates or α-aryl glyoxals affords conjugated azomethine ylides that undergo facile [3 + 2] cycloaddition, providing 5-alkenyl pyrrolidine cycloadducts that cannot be accessed through the classical use of amino esters as ylide precursors. PMID:25247255

  16. Rhodium-Catalyzed Enantioselective Intermolecular Hydroalkoxylation of Allenes and Alkynes with Alcohols: Synthesis of Branched Allylic Ethers.

    PubMed

    Liu, Zi; Breit, Bernhard

    2016-07-11

    Regio- and enantioselective additions of alcohols to either terminal allenes or internal alkynes provides access to allylic ethers by using a Rh(I) /diphenyl phosphate catalytic system. This method provides an atom-economic way to obtain chiral aliphatic and aryl allylic ethers in moderate to good yield with good to excellent enantioselectivities. PMID:27244349

  17. Iridium-catalyzed anti-diastereo- and enantioselective carbonyl (trimethylsilyl)allylation from the alcohol or aldehyde oxidation level.

    PubMed

    Han, Soo Bong; Gao, Xin; Krische, Michael J

    2010-07-01

    Using the ortho-cyclometalated pi-allyl iridium precatalyst (R)-I derived from [Ir(cod)Cl](2), 4-cyano-3-nitrobenzoic acid, (R)-SEGPHOS, and allyl acetate, enantioselective transfer hydrogenation of alpha-(trimethylsilyl)allyl acetate in the presence of aldehydes 2a-i mediated by 2-propanol delivers products of (trimethylsilyl)allylation 4a-i in good isolated yields and with exceptional levels of anti-diastereoselectivity and enantioselectivity (90-99% ee). In the absence of 2-propanol, but under otherwise identical reaction conditions, carbonyl (trimethylsilyl)allylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts 4a-i with roughly equivalent isolated yields and stereoselectivities. To evaluate the synthetic utility of the reaction products 4a-i, adduct 4g was converted to the 1,4-ene-diol 5g via dioxirane-mediated oxidative desilylation with allylic transposition, the allylic alcohol 6g via protodesilylation with allylic transposition, and the gamma-lactam 7g via chlorosulfonyl isocyanate-mediated cycloaddition. PMID:20540509

  18. Stereochemistry of C7-allyl yohimbine explored by X-ray crystallography

    NASA Astrophysics Data System (ADS)

    Kagawa, Natsuko; Masuda, Yoshitake; Morimoto, Tsumoru; Kakiuchi, Kiyomi

    2013-03-01

    X-ray crystallographic analysis revealed that the palladium-catalyzed β-allylation of yohimbine proceeded in a (7S)-selective manner. The crystal structure had an indolenine unit that was generally unstable in air. A stereoselective outcome was obtained when the palladium π-allyl complex approached yohimbine from the less-hindered pro-S side. However, during reserpine allylation—because the structure of reserpine is that of a transoid-3, 15-ring junction—the palladium π-allyl complex approached from both sides: pro-S and pro-R. A computational method was developed to discuss this selectivity. Experimental details and considerations of the reaction are provided.

  19. Targeted allylation and propargylation of galactose-containing polysaccharides in water.

    PubMed

    Leppänen, Ann-Sofie; Xu, Chunlin; Parikka, Kirsti; Eklund, Patrik; Sjöholm, Rainer; Brumer, Harry; Tenkanen, Maija; Willför, Stefan

    2014-01-16

    Galactose units of spruce galactoglucomannan (GGM), guar galactomannan (GM), and tamarind (galacto)xyloglucan (XG) were selectively allylated. Firstly aldehyde functionalities were formed at the C-6 position via enzymatic oxidation by galactose oxidase. The formed aldehydes were further derivatized by an indium mediated Barbier-Grignard type reaction, resulting in the formation of homoallylic alcohols. In addition to allylic halides, the same reaction procedure was also applicable for GGM, when using propargyl bromide as halide. All reaction steps were done in water, thus the polysaccharides were modified in a one-pot reaction. The formation of the allylated, or propargylated, product was identified by MALDI-TOF-MS. All polysaccharide products were isolated and further characterized by GC-MS or NMR spectroscopy. By this chemo-enzymatic process, we have demonstrated a novel method for derivatization of GGM and other galactose-containing polysaccharides. The derivatized polysaccharides are potential platforms for further functionalizations. PMID:24188837

  20. The effects of γ-irradiation on garlic oil content in garlic bulbs and on the radiolysis of allyl trisulfide

    NASA Astrophysics Data System (ADS)

    Genshuan, Wei; Guanghui, Wang; Ruipu, Yang; Jilan, Wu

    1996-02-01

    A study of the effects of γ-radiation on garlic oil content in garlic bulbs and on the radiolysis of allyl trisulfide and disulfide was carried out. The content of garlic oil in fresh garlic bulbs treated by gamma ray keeps nearly constant when stored for 10 months. The main components of garlic oil are allyl trisulfide (about 60%) and allyl disulfide (about 30%). The G values of radiolysis products of allyl disulfide and trisulfide in ethanol system were determined. The results show that allyl trisulfide is a very effective solvated electron scavenger and can oxidize CH 3CHOH radical into acetaldehyde, which means that the formation of 2,3-butanediol is extensively inhibited.

  1. Comparative study between extraction techniques and column separation for the quantification of sinigrin and total isothiocyanates in mustard seed.

    PubMed

    Cools, Katherine; Terry, Leon A

    2012-07-15

    Glucosinolates are β-thioglycosides which are found naturally in Cruciferae including the genus Brassica. When enzymatically hydrolysed, glucosinolates yield isothiocyanates and give a pungent taste. Both glucosinolates and isothiocyanates have been linked with anticancer activity as well as antifungal and antibacterial properties and therefore the quantification of these compounds is scientifically important. A wide range of literature exists on glucosinolates, however the extraction and quantification procedures differ greatly resulting in discrepancies between studies. The aim of this study was therefore to compare the most popular extraction procedures to identify the most efficacious method and whether each extraction can also be used for the quantification of total isothiocyanates. Four extraction techniques were compared for the quantification of sinigrin from mustard cv. Centennial (Brassica juncea L.) seed; boiling water, boiling 50% (v/v) aqueous acetonitrile, boiling 100% methanol and 70% (v/v) aqueous methanol at 70 °C. Prior to injection into the HPLC, the extractions which involved solvents (acetonitrile or methanol) were freeze-dried and resuspended in water. To identify whether the same extract could be used to measure total isothiocyanates, a dichloromethane extraction was carried out on the sinigrin extracts. For the quantification of sinigrin alone, boiling 50% (v/v) acetonitrile was found to be the most efficacious extraction solvent of the four tested yielding 15% more sinigrin than the water extraction. However, the removal of the acetonitrile by freeze-drying had a negative impact on the isothiocyanate content. Quantification of both sinigrin and total isothiocyanates was possible when the sinigrin was extracted using boiling water. Two columns were compared for the quantification of sinigrin revealing the Zorbax Eclipse to be the best column using this particular method. PMID:22743340

  2. Effect of Indole Ethyl Isothiocyanates on Proliferation, Apoptosis and MAPK Signaling in Neuroblastoma Cell Lines

    PubMed Central

    Singh, Rakesh K.; Lange, Thilo S.; Kim, Kyu Kwang; Zou, Yongping; Lieb, Casey; Sholler, Giselle L.; Brard, Laurent

    2007-01-01

    Several indole ethyl isothiocyanate (IEITC) analogs were designed, synthesized and screened to evaluate their cytotoxicity against neuroblastoma (NB) cells in-vitro. In NB, predominantly a tumor of early childhood, survival remains low despite aggressive treatments. Therefore, novel treatment strategies are greatly needed. The objective of the present study was to study the therapeutic potential of IEITC by analyzing the cytotoxic, anti-proliferative and apoptotic effects on NB cell lines. 7-methyl-indole-3-ethyl isothiocyanate (7Me-IEITC) proved to be cytotoxic to various NB cell lines (SMS-KCNR, SK-N-SH, SH-SY5Y, IMR-32) with an IC50 at 2.5-5.0 μM, while primary control cells (lung fibroblasts) were not affected. 7Me-IEITC led to the activation of apoptotic markers caspase-3, - 8 and -9, caused activation of pro-apoptotic p38 MAPK and SAP/JNK, and down-regulated pro-survival factor AKT in SMS-KCNR cells. Moreover, 7Me-IEITC displayed anti-proliferative effects (IC50 at 600 nM) and caused an arrest in cell cycle progression. This wide effect of 7Me-IEITC on NB cell signaling and survival suggests that it could be developed as a therapeutic agent against neuroblastoma. PMID:17855093

  3. Asymmetric epoxidation of allylic alcohols catalyzed by vanadium-binaphthylbishydroxamic Acid complex.

    PubMed

    Noji, Masahiro; Kobayashi, Toshihiro; Uechi, Yuria; Kikuchi, Asami; Kondo, Hisako; Sugiyama, Shigeo; Ishii, Keitaro

    2015-03-20

    A vanadium-binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric epoxidation of allylic alcohols is described. The optically active binaphthyl-based ligands BBHA 2a and 2b were synthesized from (S)-1,1'-binaphthyl-2,2'-dicarboxylic acid and N-substituted-O-trimethylsilyl (TMS)-protected hydroxylamines via a one-pot, three-step procedure. The epoxidations of 2,3,3-trisubstituted allylic alcohols using the vanadium complex of 2a were easily performed in toluene with a TBHP water solution to afford (2R)-epoxy alcohols in good to excellent enantioselectivities. PMID:25714329

  4. Allylic Amines as Key Building Blocks in the Synthesis of (E)-Alkene Peptide Isosteres

    PubMed Central

    Skoda, Erin M.; Davis, Gary C.

    2012-01-01

    Nucleophilic imine additions with vinyl organometallics have developed into efficient, high yielding, and robust methodologies to generate structurally diverse allylic amines. We have used the hydrozirconation-transmetalation-imine addition protocol in the synthesis of allylic amine intermediates for peptide bond isosteres, phosphatase inhibitors, and mitochondria-targeted peptide mimetics. The gramicidin S-derived XJB-5-131 and JP4-039 and their analogs have been prepared on up to 160 g scale for preclinical studies. These (E)-alkene peptide isosteres adopt type II′ β-turn secondary structures and display impressive biological properties, including selective reactions with reactive oxygen species (ROS) and prevention of apoptosis. PMID:22323894

  5. Chemoselective and stereoselective lithium carbenoid mediated cyclopropanation of acyclic allylic alcohols.

    PubMed

    Durán-Peña, M J; Flores-Giubi, M E; Botubol-Ares, J M; Harwood, L M; Collado, I G; Macías-Sánchez, A J; Hernández-Galán, R

    2016-03-01

    The reaction of geraniol with different lithium carbenoids generated from n-BuLi and the corresponding dihaloalkane has been evaluated. The reaction occurs in a chemo and stereoselective manner, which is consistent with a directing effect from the oxygen of the allylic moiety. Furthermore, a set of polyenes containing allylic hydroxyl or ether groups were chemoselectively and stereoselectively converted into the corresponding gem-dimethylcyclopropanes in one single step in moderate to good yields mediated by a lithium carbenoid generated in situ by the reaction of n-BuLi and 2,2-dibromopropane. PMID:26846582

  6. Visible-Light-Mediated Alkenylation, Allylation, and Cyanation of Potassium Alkyltrifluoroborates with Organic Photoredox Catalysts.

    PubMed

    Heitz, Drew R; Rizwan, Komal; Molander, Gary A

    2016-08-19

    Iridium- and ruthenium-free approaches to protected allylic amines and alkyl nitriles under photoredox conditions are reported. An inexpensive organic dye, eosin Y, catalyzes coupling of Boc-protected potassium α-aminomethyltrifluoroborates with a variety of substituted alkenyl sulfones through an α-aminomethyl radical addition-elimination pathway. Allylic and homoallylic amines were formed in moderate yields with high E/Z selectivity. The mechanistic approach was extended using tosyl cyanide as a radical trap, enabling the conversion of alkyltrifluoroborates to nitriles via a Fukuzumi acridinium-catalyzed process. PMID:27336284

  7. Transient Overexpression of adh8a Increases Allyl Alcohol Toxicity in Zebrafish Embryos

    PubMed Central

    Klüver, Nils; Ortmann, Julia; Paschke, Heidrun; Renner, Patrick; Ritter, Axel P.; Scholz, Stefan

    2014-01-01

    Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L). Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh) to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1) during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos). Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L). Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes involved in

  8. Transient overexpression of adh8a increases allyl alcohol toxicity in zebrafish embryos.

    PubMed

    Klüver, Nils; Ortmann, Julia; Paschke, Heidrun; Renner, Patrick; Ritter, Axel P; Scholz, Stefan

    2014-01-01

    Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L). Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh) to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1) during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos). Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L). Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes involved in

  9. Synthesis of (-)-Piperitylmagnolol Featuring ortho-Selective Deiodination and Pd-Catalyzed Allylation.

    PubMed

    Ikoma, Atsushi; Ogawa, Narihito; Kondo, Daiki; Kawada, Hiroki; Kobayashi, Yuichi

    2016-05-01

    A 1,4-addition strategy using an enone and a copper reagent was studied for the synthesis of (-)-piperitylmagnolol. A MOM-protected biphenol copper reagent was added to BF3·OEt2-activated 4-isopropylcyclohexenone, whereas 1,4-addition of protected monophenol reagents possessing an allyl group was found to be unsuccessful. The allyl group was later attached to the p-,p'-diiodo-biphenol ring by Pd-catalyzed coupling with allylborate. The aforementioned iodide was synthesized using a new method for ortho-selective deiodination of o-,p-diiodophenols. PMID:27109890

  10. Synthesis of substituted quinolines via allylic amination and intramolecular Heck-coupling.

    PubMed

    Murru, Siva; McGough, Brandon; Srivastava, Radhey S

    2014-12-01

    A new catalytic approach for the synthesis of substituted quinolines via C-N and C-C bond formation using 2-haloaryl hydroxylamines and allylic C-H substrates is described. Fe-catalyzed allylic C-H amination followed by Pd-catalyzed intramolecular Heck-coupling and aerobic dehydrogenation deliver the valuable quinoline and naphthyridine heterocycles in good to excellent overall yields. In this process, Pd(OAc)2 plays a dual role in catalyzing Heck coupling as well as aerobic dehydrogenation of dihydroquinolines. PMID:25247637

  11. Iridium-Catalyzed Diastereoselective and Enantioselective Allylic Substitutions with Acyclic α-Alkoxy Ketones.

    PubMed

    Jiang, Xingyu; Chen, Wenyong; Hartwig, John F

    2016-05-01

    The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. Reported herein are diastereoselective and enantioselective allylic substitutions with acyclic α-alkoxy ketones catalyzed by a metallacyclic iridium complex to form products with contiguous stereogenic centers derived from the nucleophile and electrophile. These reactions occur between allyl methyl carbonates and unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones. The resulting products can be readily converted into enantioenriched tertiary alcohols and tetrahydrofuran derivatives without erosion of enantiomeric purity. PMID:27038004

  12. Kinetic Studies that Evaluate the Solvolytic Mechanisms of Allyl and Vinyl Chloroformate Esters

    PubMed Central

    D’Souza, Malcolm J.; Givens, Aaron F.; Lorchak, Peter A.; Greenwood, Abigail E.; Gottschall, Stacey L.; Carter, Shannon E.; Kevill, Dennis N.

    2013-01-01

    At 25.0 °C the specific rates of solvolysis for allyl and vinyl chloroformates have been determined in a wide mix of pure and aqueous organic mixtures. In all the solvents studied, vinyl chloroformate was found to react significantly faster than allyl chloroformate. Multiple correlation analyses of these rates are completed using the extended (two-term) Grunwald-Winstein equation with incorporation of literature values for solvent nucleophilicity (NT) and solvent ionizing power (YCl). Both substrates were found to solvolyze by similar dual bimolecular carbonyl-addition and unimolecular ionization channels, each heavily dependent upon the solvents nucleophilicity and ionizing ability. PMID:23549265

  13. Solvent-Controlled, Tunable β-OAc and β-H Elimination in Rh(III)-Catalyzed Allyl Acetate and Aryl Amide Coupling via C-H Activation.

    PubMed

    Dai, Huimin; Yu, Chao; Wang, Zihao; Yan, Hong; Lu, Changsheng

    2016-07-15

    The Heck reaction between arenes and allyl acetate has led to cinnamyl derivatives and allyl products depending on the regioselectivity of β-elimination. The regioselectivity can be controlled by the solvent in the Rh(III)-catalyzed arene-allyl acetate coupling via C-H activation: (1) in THF, cinnamyl derivatives via β-H elimination were generated; (2) in MeOH, allyl products via β-OAc elimination were produced. Both routes have advantages such as excellent γ-selectivity toward allyl acetate, good to excellent yields, and broad substrate scope. PMID:27351917

  14. Fumigation of wheat using liquid ethyl formate plus methyl isothiocyanate in 50-tonne farm bins.

    PubMed

    Ren, Yonglin; Lee, Byungho; Mahon, Daphne; Xin, Ni; Head, Matthew; Reid, Robin

    2008-04-01

    Australian Standard White wheat, Triticum aestivum L. (a marketing grade with mixed grain hardness),with a moisture content of 12.5% was fumigated with a new ethyl formate formulation (95% ethyl formate plus 5% methyl isothiocyanate) identified and developed by Commonwealth Scientific and Industrial Research Organization Entomology, Canberra, Australia. Wheat was fumigated with the formulation at a calculated application rate of 80 g/m3 in two 50-tonne sealed metal vertical silos located at Fisherman Islands, Queensland, Australia. Access was gained through the top of the silo where the application of the formulation was completed within a few minutes by pouring it onto the top of the wheat. After 2 h of recirculation, using a 0.5-kW fan, the in-bin concentrations of ethyl formate achieved equilibrium with a concentration variation < 7%. The ethyl formate concentration, in both silos 1 and 2, during the first day's exposure period remained above 10 g/m3. The concentration of ethyl formate by time product achieved was 790 and 650 g h/m3 in silos 1 and 2, respectively. In silo 1, the formulation was sufficient to kill all life stages of mixed age cultures of Sitophilus oryzae (L.), Rhyzopertha dominica (F.), and Tribolium castaneum (Herbst). In silo 2, control was 100% for R. dominica and T. castaneum and 99.4% for S. oryzae. After 5 d fumigation, the silo top-hatch was opened but no forced aeration was initiated. The in-bin concentration of ethyl formate was lower than the Australian experimental threshold limit value of 100 ppm. The ethyl formate and methyl isothiocyanate residues in the grain had declined to below the Australian experimental maximum residue limit of 0.2 and 0.1 mg/kg, respectively. The workspace and environmental levels of ethyl formate and methyl isothiocyanate were less than the detection limit of 0.1 ppm. The treatment with ethyl formate formulation had no affect on the wheat germination and seed color compared with untreated controls. PMID

  15. α-Regioselective Barbier Reaction of Carbonyl Compounds and Allyl Halides Mediated by Praseodymium.

    PubMed

    Wu, San; Li, Ying; Zhang, Songlin

    2016-09-01

    The first utility of praseodymium as a mediating metal in the Barbier reaction of carbonyl compounds with allyl halides was reported in this paper. In contrast to the traditional metal-mediated or catalyzed Barbier reactions, exclusive α-adducts were obtained in this one-pot reaction with a broad scope of substrates and feasible reaction conditions. PMID:27490708

  16. Direct and Highly Regioselective and Enantioselective Allylation of β-Diketones

    PubMed Central

    Chalifoux, Wesley A.; Reznik, Samuel K.; Leighton, James L.

    2012-01-01

    The enantioselective allylation of ketones represents both a problem of fundamental importance in asymmetric reaction design and one of only a very small number of available methods to access valuable tertiary carbinols. Despite the vast amount of attention from chemists that this problem has elicited,1-8 however, success has generally been limited to just a few simple ketone types thus limiting the utility of these methods. A method for the selective allylation of functionally complex ketones would be expected to increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective, and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by the co-optation of their enol form to provide the necessary Brønsted acid activation. This unprecedented reaction thus not only significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed, but also overturns more than a century of received wisdom regarding the reactivity of β-diketones. PMID:22763452

  17. Amide α,β-Dehydrogenation Using Allyl-Palladium Catalysis and a Hindered Monodentate Anilide.

    PubMed

    Chen, Yifeng; Turlik, Aneta; Newhouse, Timothy R

    2016-02-01

    A practical and direct method for the α,β-dehydrogenation of amides is reported using allyl-palladium catalysis. Critical to the success of this process was the synthesis and application of a novel lithium N-cyclohexyl anilide (LiCyan). The reaction conditions tolerate a wide variety of substrates, including those with acidic heteroatom nucleophiles. PMID:26790471

  18. Stereoselectivity of nitrile oxide cycloadditions to chiral allylic fluorides: experiment and theory.

    PubMed

    Prakesch, Michael; Grée, Danielle; Grée, René; Carter, Jennifer; Washington, Ilyas; Houk, K N

    2003-11-21

    The cycloadditions of nitrile oxides with new and previously studied allylic fluorides were examined. The 1,3-dipolar cycloaddition reactions were also investigated theoretically with density functional theory (B3LYP) based transition-state modelling. The predictions provided reasonable agreement with experiment, indicating that both steric and electronic effects have important influences on the stereoselectivities of these reactions. PMID:14639650

  19. Allylic and benzylic sp3 C-H oxidation in water.

    PubMed

    Ang, Wei Jie; Lam, Yulin

    2015-01-28

    A copper-catalyzed method for the oxidation of allylic and benzylic sp(3) C-H by aqueous tert-butyl hydroperoxide (T-Hydro) in water using a recyclable fluorous ligand has been developed. The reaction procedure is tolerant to additional functional groups and the fluorous ligand could be reused with little loss of catalytic activity. PMID:25412371

  20. GALLIUM-MEDIATED ALLYLATION OF CARBONYL COMPOUNDS IN WATER. (R828129)

    EPA Science Inventory

    Ga-mediated allylation of aldehydes or ketones in distilled or tap water generated the corresponding homoallyl alcohols in high yields without the assistance of either acidic media or sonication.


    Grap...

  1. The Defense Metabolite, Allyl Glucosinolate, Modulates Arabidopsis thaliana Biomass Dependent upon the Endogenous Glucosinolate Pathway

    PubMed Central

    Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A.; Lin, Catherine; Kerwin, Rachel; Burow, Meike; Kliebenstein, Daniel J.

    2016-01-01

    Glucosinolates (GSLs) play an important role in plants as direct mediators of biotic and abiotic stress responses. Recent work is beginning to show that the GSLs can also inducing complex defense and growth networks. However, the physiological significance of these GSL-induced responses and the molecular mechanisms by which GSLs are sensed and/or modulate these responses are not understood. To identify these potential mechanisms within the plant and how they may relate to the endogenous GSLs, we tested the regulatory effect of exogenous allyl GSL application on growth and defense metabolism across sample of Arabidopsis thaliana accessions. We found that application of exogenous allyl GSL had the ability to initiate changes in plant biomass and accumulation of defense metabolites that genetically varied across accessions. This growth effect was related to the allyl GSL side-chain structure. Utilizing this natural variation and mutants in genes within the GSL pathway we could show that the link between allyl GSL and altered growth responses are dependent upon the function of known genes controlling the aliphatic GSL pathway. PMID:27313596

  2. Biomonitoring the intake of garlic via urinary excretion of allyl mercapturic acid.

    PubMed

    Verhagen, H; Hageman, G J; Rauma, A L; Versluis-de Haan, G; van Herwijnen, M H; de Groot, J; Törrönen, R; Mykkänen, H

    2001-08-01

    Allium vegetables (onions, leeks, chives) and in particular garlic have been claimed to have health-promoting potential. This study was conducted to get insight into the perspectives for monitoring the intake of garlic by a biomarker approach. Chemically, the biomarker results from exposure to gamma-glutamyl-S-allyl-l-cysteine, which is first hydrolysed by gamma-glutamine-transpeptidase resulting in the formation of S-allyl-l-cysteine. The latter compound is subsequently N-acetylated by N-acetyltransferase into S-allyl-mercapturic acid (ALMA) and excreted into urine. The mercapturic acid was measured in urine using gaschromatography with mass spectrometry. Thus the intake of garlic was determined to check the compliance of garlic intake in a placebo-controlled intervention study. Results indicate that S-allyl-mercapturic acid could be detected in 15 out of 16 urine samples of garlic supplement takers, indicating good compliance. In addition, the intake of garlic was also monitored in a cross-section study of vegans versus controls in Finland, in which no differences in garlic consumption nor in ALMA output were recorded between vegans and controls. These data indicate good possibilities for further studies in the field of biomarkers to investigate the putative chemopreventive effects of garlic and garlic-containing products. PMID:11520428

  3. Catalytic enantioselective synthesis of naturally occurring butenolides via hetero-allylic alkylation and ring closing metathesis.

    PubMed

    Mao, Bin; Geurts, Koen; Fañanás-Mastral, Martín; van Zijl, Anthoni W; Fletcher, Stephen P; Minnaard, Adriaan J; Feringa, Ben L

    2011-03-01

    An efficient catalytic asymmetric synthesis of chiral γ-butenolides was developed based on the hetero-allylic asymmetric alkylation (h-AAA) in combination with ring closing metathesis (RCM). The synthetic potential of the h-AAA-RCM protocol was illustrated with the facile synthesis of (-)-whiskey lactone, (-)-cognac lactone, (-)-nephrosteranic acid, and (-)-roccellaric acid. PMID:21268603

  4. Method of preparing water purification membranes. [polymerization of allyl amine as thin films in plasma discharge

    NASA Technical Reports Server (NTRS)

    Hollahan, J. R.; Wydeven, T. J., Jr. (Inventor)

    1974-01-01

    Allyl amine and chemically related compounds are polymerized as thin films in the presence of a plasma discharge. The monomer compound can be polymerized by itself or in the presence of an additive gas to promote polymerization and act as a carrier. The polymerized films thus produced show outstanding advantages when used as reverse osmosis membranes.

  5. Total synthesis of (±)-leuconolam: intramolecular allylic silane addition to a maleimide carbonyl group

    PubMed Central

    Izgu, Enver Cagri

    2014-01-01

    A concise total synthesis of the plant alkaloid (±)-leuconolam (1) has been achieved. A regio- and diastereoselective Lewis-acid mediated allylative cyclization was used to establish, simultaneously, two adjacent tetrasubstituted carbon centers. Furthermore, an essential arene cross-coupling to a hindered haloalkene was enabled by the use of a novel 2-anilinostannane. PMID:25419448

  6. Dietary phenethyl isothiocyanate inhibition of androgen-responsive LNCaP prostate cancer cell tumor growth correlates with decreased angiogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenethyl isothiocyanate (PEITC), found in certain cruciferous vegetables, has antitumor activity in several cancer models, including prostate cancer. In our xenograft model, dietary administration of PEITC (100-150 mg/kg/d) inhibited androgen-responsive LNCaP human prostate cancer cell tumor growth...

  7. Structural Interactions Dictate the Kinetics of Macrophage Migration Inhibitory Factor Inhibition by Different Cancer-Preventive Isothiocyanates

    PubMed Central

    Crichlow, Gregg V.; Fan, Chengpeng; Keeler, Camille; Hodsdon, Michael; Lolis, Elias J.

    2012-01-01

    Regulation of cellular processes by dietary nutrients is known to affect the likelihood of cancer development. One class of cancer preventive nutrients, isothiocyanates (ITCs) derived from consumption of cruciferous vegetables, is known to have various effects on cellular biochemistry. One target of ITCs is macrophage migration inhibitory factor (MIF), a widely expressed protein with known inflammatory, pro-tumorigenic, pro-angiogenic, and anti-apoptotic properties. MIF is covalently inhibited by a variety of ITCs, which in part, may explain how they exert their cancer-preventive effects. We report the crystallographic structures of human MIF bound to phenethylisothiocyanate and to L-sulforaphane (dietary isothiocyanates derived from watercress and broccoli, respectively), and correlate structural features of these two isothiocyanates with their second-order rate constants for MIF inactivation. We also characterize changes in the MIF structure using NMR HSQC spectra of these complexes and observe many changes at the subunit interface. While a number of chemical shifts do not change, many of those that change do not have similar features in magnitude or direction for the two isothiocyanates. The difference in the binding modes of these two ITCs provides a means of using structure-activity relationships to reveal insights into MIF biological interactions. The results of this study provide a framework for the development of therapeutics that target MIF. PMID:22931430

  8. Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer-preventive isothiocyanates.

    PubMed

    Crichlow, Gregg V; Fan, Chengpeng; Keeler, Camille; Hodsdon, Michael; Lolis, Elias J

    2012-09-25

    Regulation of cellular processes by dietary nutrients is known to affect the likelihood of cancer development. One class of cancer-preventive nutrients, isothiocyanates (ITCs), derived from the consumption of cruciferous vegetables, is known to have various effects on cellular biochemistry. One target of ITCs is macrophage migration inhibitory factor (MIF), a widely expressed protein with known inflammatory, pro-tumorigenic, pro-angiogenic, and anti-apoptotic properties. MIF is covalently inhibited by a variety of ITCs, which in part may explain how they exert their cancer-preventive effects. We report the crystallographic structures of human MIF bound to phenethylisothiocyanate and to l-sulforaphane (dietary isothiocyanates derived from watercress and broccoli, respectively) and correlate structural features of these two isothiocyanates with their second-order rate constants for MIF inactivation. We also characterize changes in the MIF structure using nuclear magnetic resonance heteronuclear single-quantum coherence spectra of these complexes and observe many changes at the subunit interface. While a number of chemical shifts do not change, many of those that change do not have features similar in magnitude or direction for the two isothiocyanates. The difference in the binding modes of these two ITCs provides a means of using structure-activity relationships to reveal insights into MIF biological interactions. The results of this study provide a framework for the development of therapeutics that target MIF. PMID:22931430

  9. DNA Microarray Highlights Nrf2-Mediated Neuron Protection Targeted by Wasabi-Derived Isothiocyanates in IMR-32 Cells.

    PubMed

    Trio, Phoebe Zapanta; Fujisaki, Satoru; Tanigawa, Shunsuke; Hisanaga, Ayami; Sakao, Kozue; Hou, De-Xing

    2016-01-01

    6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), 6-(methylthio)hexyl isothiocyanate (6-MTITC), and 4-(methylsulfinyl)butyl isothiocyanate (4-MSITC) are isothiocyanate (ITC) bioactive compounds from Japanese Wasabi. Previous in vivo studies highlighted the neuroprotective potential of ITCs since ITCs enhance the production of antioxidant-related enzymes. Thus, in this present study, a genome-wide DNA microarray analysis was designed to profile gene expression changes in a neuron cell line, IMR-32, stimulated by these ITCs. Among these ITCs, 6-MSITC caused the expression changes of most genes (263), of which 100 genes were upregulated and 163 genes were downregulated. Gene categorization showed that most of the differentially expressed genes are involved in oxidative stress response, and pathway analysis further revealed that Nrf2-mediated oxidative stress pathway is the top of the ITC-modulated signaling pathway. Finally, real-time polymerase chain reaction (PCR) and Western blotting confirmed the gene expression and protein products of the major targets by ITCs. Taken together, Wasabi-derived ITCs might target the Nrf2-mediated oxidative stress pathway to exert neuroprotective effects. PMID:27547033

  10. DNA Microarray Highlights Nrf2-Mediated Neuron Protection Targeted by Wasabi-Derived Isothiocyanates in IMR-32 Cells

    PubMed Central

    Trio, Phoebe Zapanta; Fujisaki, Satoru; Tanigawa, Shunsuke; Hisanaga, Ayami; Sakao, Kozue; Hou, De-Xing

    2016-01-01

    6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), 6-(methylthio)hexyl isothiocyanate (6-MTITC), and 4-(methylsulfinyl)butyl isothiocyanate (4-MSITC) are isothiocyanate (ITC) bioactive compounds from Japanese Wasabi. Previous in vivo studies highlighted the neuroprotective potential of ITCs since ITCs enhance the production of antioxidant-related enzymes. Thus, in this present study, a genome-wide DNA microarray analysis was designed to profile gene expression changes in a neuron cell line, IMR-32, stimulated by these ITCs. Among these ITCs, 6-MSITC caused the expression changes of most genes (263), of which 100 genes were upregulated and 163 genes were downregulated. Gene categorization showed that most of the differentially expressed genes are involved in oxidative stress response, and pathway analysis further revealed that Nrf2-mediated oxidative stress pathway is the top of the ITC-modulated signaling pathway. Finally, real-time polymerase chain reaction (PCR) and Western blotting confirmed the gene expression and protein products of the major targets by ITCs. Taken together, Wasabi-derived ITCs might target the Nrf2-mediated oxidative stress pathway to exert neuroprotective effects. PMID:27547033

  11. Aggresome-like structure induced by isothiocyanates is novel proteasome-dependent degradation machinery

    SciTech Connect

    Mi, Lixin; Gan, Nanqin; Chung, Fung-Lung

    2009-10-16

    Unwanted or misfolded proteins are either refolded by chaperones or degraded by the ubiquitin-proteasome system (UPS). When UPS is impaired, misfolded proteins form aggregates, which are transported along microtubules by motor protein dynein towards the juxta-nuclear microtubule-organizing center to form aggresome, a single cellular garbage disposal complex. Because aggresome formation results from proteasome failure, aggresome components are degraded through the autophagy/lysosome pathway. Here we report that small molecule isothiocyanates (ITCs) can induce formation of aggresome-like structure (ALS) through covalent modification of cytoplasmic {alpha}- and {beta}-tubulin. The formation of ALS is related to neither proteasome inhibition nor oxidative stress. ITC-induced ALS is a proteasome-dependent assembly for emergent removal of misfolded proteins, suggesting that the cell may have a previously unknown strategy to cope with misfolded proteins.

  12. Myrosinase-dependent and -independent formation and control of isothiocyanate products of glucosinolate hydrolysis.

    PubMed

    Angelino, Donato; Dosz, Edward B; Sun, Jianghao; Hoeflinger, Jennifer L; Van Tassell, Maxwell L; Chen, Pei; Harnly, James M; Miller, Michael J; Jeffery, Elizabeth H

    2015-01-01

    Brassicales contain a myrosinase enzyme that hydrolyzes glucosinolates to form toxic isothiocyanates (ITC), as a defense against bacteria, fungi, insects and herbivores including man. Low levels of ITC trigger a host defense system in mammals that protects them against chronic diseases. Because humans typically cook their brassica vegetables, destroying myrosinase, there is a great interest in determining how human microbiota can hydrolyze glucosinolates and release them, to provide the health benefits of ITC. ITC are highly reactive electrophiles, binding reversibly to thiols, but accumulating and causing damage when free thiols are not available. We found that addition of excess thiols released protein-thiol-bound ITC, but that the microbiome supports only poor hydrolysis unless exposed to dietary glucosinolates for a period of days. These findings explain why 3-5 servings a week of brassica vegetables may provide health effects, even if they are cooked. PMID:26500669

  13. Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate.

    PubMed

    Tarozzi, Andrea; Marchetti, Chiara; Nicolini, Benedetta; D'Amico, Massimo; Ticchi, Nicole; Pruccoli, Letizia; Tumiatti, Vincenzo; Simoni, Elena; Lodola, Alessio; Mor, Marco; Milelli, Andrea; Minarini, Anna

    2016-07-19

    Epidermal growth factor receptor inhibitors (EGFR-TKIs) represent a class of compounds widely used in anticancer therapy. An increasing number of studies reports on combination therapies in which the block of the EGFR-TK activity is associated with inhibition of its downstream pathways, as PI3K-Akt. Sulforaphane targets the PI3K-Akt pathway whose dysregulation is implicated in many functions of cancer cells. According to these considerations, a series of multitarget molecules have been designed by combining key structural features derived from an EGFR-TKI, PD168393, and the isothiocyanate sulforaphane. Among the obtained molecules 1-6, compound 6 emerges as a promising lead compound able to exert antiproliferative and proapoptotic effects in A431 epithelial cancer cell line by covalently binding to EGFR-TK, and reducing the phosphorylation of Akt without affecting the total Akt levels. PMID:27135370

  14. Myrosinase-dependent and –independent formation and control of isothiocyanate products of glucosinolate hydrolysis

    PubMed Central

    Angelino, Donato; Dosz, Edward B.; Sun, Jianghao; Hoeflinger, Jennifer L.; Van Tassell, Maxwell L.; Chen, Pei; Harnly, James M.; Miller, Michael J.; Jeffery, Elizabeth H.

    2015-01-01

    Brassicales contain a myrosinase enzyme that hydrolyzes glucosinolates to form toxic isothiocyanates (ITC), as a defense against bacteria, fungi, insects and herbivores including man. Low levels of ITC trigger a host defense system in mammals that protects them against chronic diseases. Because humans typically cook their brassica vegetables, destroying myrosinase, there is a great interest in determining how human microbiota can hydrolyze glucosinolates and release them, to provide the health benefits of ITC. ITC are highly reactive electrophiles, binding reversibly to thiols, but accumulating and causing damage when free thiols are not available. We found that addition of excess thiols released protein-thiol-bound ITC, but that the microbiome supports only poor hydrolysis unless exposed to dietary glucosinolates for a period of days. These findings explain why 3–5 servings a week of brassica vegetables may provide health effects, even if they are cooked. PMID:26500669

  15. Early events in herpes simplex virus type 1 infection: photosensitivity of fluorescein isothiocyanate-treated virions

    SciTech Connect

    DeLuca, N.; Bzik, D.; Person, S.; Snipes, W.

    1981-02-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyanate (FITC). The inactivation of FITC-treated virions upon subsequent exposure to light is inhibited by the presence of sodium azide, suggesting the involvement of singlet oxygen in the process. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that treatment with FITC plus light induces crosslinks in viral envelope glycoproteins. Treatment of virions with high concentrations of FITC (50 ..mu..g/ml) plus light causes a reduction in the adsorption of the virus to monolayers of human embryonic lung cells. For lower concentrations of FITC (10 ..mu..g/ml) plus light, treated virions adsorb to the host cells, but remain sensitive to light until entry occurs. The loss of light sensitivity coincides with the development of resistance to antibodies. These results are most consistent with a mechanism of entry for herpes simplex virus involving fusion of the viral membrane with the plasma membrane of the host cell.

  16. Isothiocyanates may chemically detoxify mutagenic amines formed in heat processed meat.

    PubMed

    Lewandowska, Anna; Przychodzeń, Witold; Kusznierewicz, Barbara; Kołodziejski, Dominik; Namieśnik, Jacek; Bartoszek, Agnieszka

    2014-08-15

    Meat consumption represents a dietary risk factor increasing the incidence of common cancers, probably due to carcinogenic amines (HAAs) formed upon meat heating. Interestingly, cancers whose incidence is increased by meat consumption, are decreased in populations consuming brassica vegetables regularly. This inverse correlation is attributed to brassica anticarcinogenic components, especially isothiocyanates (ITCs) that stimulate detoxification of food carcinogens. However, ITC reactivity towards amines generating stable thioureas, may also decrease mutagenicity of processed meat. We confirmed here that combining meat with cabbage (fresh or lyophilized), in proportions found in culinary recipes, limited by 17-20% formation of HAAs and significantly lowered mutagenic activity of fried burgers. Moreover, MeIQx mutagenicity was lowered in the presence of ITCs, as well as for synthetic ITC-MeIQx conjugates. This suggests that formation of thioureas could lead to chemical detoxification of food carcinogens, reducing the cancer risk associated with meat consumption. PMID:24679758

  17. The direct arylation of allylic sp3 C-H bonds via organic and photoredox catalysis

    NASA Astrophysics Data System (ADS)

    Cuthbertson, James D.; MacMillan, David W. C.

    2015-03-01

    The direct functionalization of unactivated sp3 C-H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts, the establishment of general and mild strategies for the engagement of sp3 C-H bonds in C-C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C-H bonds (that is, C-H bonds where an adjacent carbon is involved in a C = C bond) have become widely established, the engagement of allylic substrates in C-C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug's action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C-H arylation. This C-C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C-H bonds.

  18. The direct arylation of allylic sp(3) C-H bonds via organic and photoredox catalysis.

    PubMed

    Cuthbertson, James D; MacMillan, David W C

    2015-03-01

    The direct functionalization of unactivated sp(3) C-H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts, the establishment of general and mild strategies for the engagement of sp(3) C-H bonds in C-C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C-H bonds (that is, C-H bonds where an adjacent carbon is involved in a C = C bond) have become widely established, the engagement of allylic substrates in C-C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug's action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C-H arylation. This C-C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C-H bonds. PMID:25739630

  19. Gold(I)-Catalyzed Intramolecular Hydroamination of N-Allylic,N'-Aryl Ureas to form Imidazolidin-2-ones.

    PubMed

    Li, Hao; Song, Feijie; Widenhoefer, Ross A

    2011-04-18

    Treatment of N-allylic,N'-aryl ureas with a catalytic 1:1 mixture of di-tert-butyl-o-biphenylphoshphine gold(I) chloride and silver hexafluorophosphate (1 mol %) in chloroform at room temperature led to 5-exo hydroamination to form the corresponding imidazolidin-2-ones in excellent yield. In the case of N-allylic ureas that possessed an allylic alkyl, benzyloxymethyl, or acetoxymethyl substituent, gold(I)-catalyzed 5-exo hydroamination leads to formation of the corresponding trans-3,4-disubstituted imidazolidin-2-ones in excellent yield with ≥50:1 diastereoselectivity. PMID:21709731

  20. Pharmacokinetics and pharmacodynamics of phenethyl isothiocyanate: implications in breast cancer prevention.

    PubMed

    Morris, Marilyn E; Dave, Rutwij A

    2014-07-01

    Phenethyl isothiocyanate (PEITC)-a naturally occurring isothiocyanate in cruciferous vegetables-has been extensively studied as a chemopreventive agent in several preclinical species and in humans. Pharmacokinetic features of unchanged PEITC are (I) linear and first-order absorption, (II) high protein binding and capacity-limited tissue distribution, and (III) reversible metabolism and capacity-limited hepatic elimination. Membrane transport of PEITC is mediated by BCRP, multidrug resistance-associated protein (MRP) 1, and MRP2 transporters belonging to the ATP-binding-cassette (ABC) family. PEITC is metabolized by glutathione S-transferase (GST) in the liver, with the glutathione conjugate of PEITC undergoing further conversion to mercapturic acid by N-acetyl transferase in rats and humans. PEITC modulates the activity and expression of numerous phase I and phase II drug-metabolizing enzymes and can inhibit the metabolism of procarcinogens to form carcinogens and increase carcinogen elimination. In recent years, several in vitro and in vivo studies have elucidated molecular mechanisms underlying the pharmacodynamics of PEITC in breast cancer that include cancer cell apoptosis by upregulation of apoptotic genes, cell cycle arrest at G2/M phase by generation of reactive oxygen species and depletion of intracellular glutathione, downregulation of the estrogen receptor, decrease in sensitivity to estrogen, and inhibition of tumor metastasis. Inhibition of angiogenesis is one of the recently reported mechanisms of breast cancer prevention by PEITC. Complex pharmacokinetics and pharmacodynamics of PEITC necessitate a systems-biology approach in parallel with PK/PD modeling to develop PEITC as a therapeutic agent for treating cancers. PMID:24821055

  1. Short-form RON overexpression augments benzyl isothiocyanate-induced apoptosis in human breast cancer cells.

    PubMed

    Sehrawat, Anuradha; Singh, Shivendra V

    2016-05-01

    Chemoprevention of breast cancer is feasible with the use of non-toxic phytochemicals from edible and medicinal plants. Benzyl isothiocyanate (BITC) is one such plant compound that prevents mammary cancer development in a transgenic mouse model in association with tumor cell apoptosis. Prior studies from our laboratory have demonstrated a role for reactive oxygen species (ROS)-dependent Bax activation through the intermediary of c-Jun N-terminal kinases in BITC-induced apoptosis in human breast cancer cells. The present study demonstrates that truncated Recepteur d'Origine Nantais (sfRON) is a novel regulator of BITC-induced apoptosis in breast cancer cells. Overexpression of sfRON in MCF-7 and MDA-MB-361 cells resulted in augmentation of BITC-induced apoptosis when the apoptotic fraction was normalized against vehicle control for each cell type (untransfected and sfRON overexpressing cells). ROS generation and G2 /M phase cell cycle arrest resulting from BITC treatment were significantly attenuated in sfRON overexpressing cells after normalization with vehicle control for each cell type. Increased BITC-induced apoptosis by sfRON overexpression was independent of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase hyperphosphorylation. On the other hand, activation of Bax and Bak following BITC exposure was markedly more pronounced in sfRON overexpressing cells than in controls. sfRON overexpression also augmented apoptosis induction by structurally diverse cancer chemopreventive phytochemicals including withaferin A, phenethyl isothiocyanate, and D,L-sulforaphane. In conclusion, the present study provides novel mechanistic insights into the role of sfRON in apoptosis regulation by BITC and other electrophilic phytochemicals. © 2015 Wiley Periodicals, Inc. PMID:25857724

  2. A new class of isothiocyanate-based irreversible inhibitors of Macrophage Migration Inhibitory Factor (MIF)

    PubMed Central

    Ouertatani-Sakouhi, Hajer; El-Turk, Farah; Fauvet, Bruno; Roger, Thierry; Le Roy, Didier; Karpinar, Damla Pinar; Leng, Lin; Bucala, Richard; Zweckstetter, Markus; Calandra, Thierry; Lashuel, Hilal A.

    2013-01-01

    Macrophage migration inhibitory factor (MIF) is a homotrimeric multifunctional proinflammatory cytokine that has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Current therapeutic strategies for targeting MIF focus on developing inhibitors of its tautomerase activity or modulating its biological activities using anti-MIF neutralizing antibodies. Herein we report a new class of isothiocyanate (ITC)-based irreversible inhibitors of MIF. Modification by benzyl isothiocyanate (BITC) and related analogues occurred at the N-terminal catalytic proline residue without affecting the oligomerization state of MIF. Different alkyl and arylalkyl ITCs-modified MIF with nearly the same efficiency as BITC. To elucidate the mechanism of action, we performed detailed biochemical, biophysical, and structural studies to determine the effect of BITC and its analogues on the conformational state, quaternary structure, catalytic activity, receptor binding and biological activity of MIF. Light scattering, analytical ultracentrifugation and NMR studies on unmodified and ITC-modified MIF demonstrated that modification of Pro1 alters the tertiary, but not the secondary or quaternary, structure of the trimer without affecting its thermodynamic stability. BITC induced drastic effects on the tertiary structure of MIF, in particular residues that cluster around Pro1 and constitute the tautomerase active site. These changes in tertiary structure and loss of catalytic activity translated into reduction in MIF receptor binding activity, MIF-mediated glucocorticoid overriding and MIF-induced Akt phosphorylation. Together, these findings highlight the role of tertiary structure in modulating the biochemical and biological activities of MIF and present new opportunities for modulating MIF biological activities in vivo. PMID:19737008

  3. Unusual Allylpalladium Carboxylate Complexes: Identification of the Resting State of Catalytic Enantioselective Decarboxylative Ketone Allylic Alkylation Reactions**

    PubMed Central

    Sherden, Nathaniel H.; Behenna, Douglas C.; Virgil, Scott C.

    2010-01-01

    Palladium poprocks: Hold on to your CO2! Enantioselective Pd-catalyzed decarboxylative alkylation of ketone enolates proceeds via η1-σ-allyl Pd-carboxylate complexes by slow loss of CO2. PMID:19672907

  4. Gaussian density functional calculations on the allyl and polyene radicals: C3H5 to C11H13

    NASA Astrophysics Data System (ADS)

    Sim, Fiona; Salahub, Dennis R.; Chin, Steven; Dupuis, Michel

    1991-09-01

    The electronic structure of the allyl radical C3H5 and the polyene radicals C5H7, C7H9, C9H11, and C11H13 have been calculated using the linear combination of Gaussian-type orbitals-local spin density method. In contrast to the results obtained using the Hartree-Fock model, which show large errors, the geometries are in excellent agreement with multiconfiguration self-consistent-field calculations and with experiment. LSD yields a C2v symmetry for the allyl radical, while the polyenes C5H7 to C11H13 have C-C bonds alternating between single and double bonds. The harmonic vibrational frequencies were calculated for the allyl radical and C5H7 (the 1,4-pentadienyl radical). The unscaled vibrational frequencies calculated for the allyl radical are in excellent agreement with experiment.

  5. Intramolecular [4 + 2] cycloaddition reaction of six- and seven-membered cyclic N-allyl-C-arylethynyl iminium salts.

    PubMed

    Herz, H G; Schatz, J; Maas, G

    2001-05-01

    N-Allyl-2-(het)arylethynyl-3,4,5,6-tetrahydropyridinium triflates 1c,d,e and N-allyl-2-(het)aryl-4,5,6,7-tetrahydro-3H-azepinium triflates 1g,h undergo a thermal isomerization reaction leading to derivatives of [a,f]-annulated isoindolium salts 2 in good yields. Similarly, N-allyl-2-phenylethynyl-pyridinium triflate 4 is transformed into the condensed pyridinium salt 5. An intramolecular [4 + 2] cycloaddition reaction, in which the (het)arylethynyl moiety acts as the 4pi component, is considered as the key step of this transformation. In contrast, the related N-allyl-4,5-dihydro-3H-pyrrolium salts 1a,b and N-homoallyl-3,4,5,6-tetrahydropyridinium salt 1f undergo unspecific decomposition under thermal impact. PMID:11325285

  6. Highly regio- and enantioselective synthesis of N-substituted 2-pyridones: iridium-catalyzed intermolecular asymmetric allylic amination.

    PubMed

    Zhang, Xiao; Yang, Ze-Peng; Huang, Lin; You, Shu-Li

    2015-02-01

    The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98% yield and 99% ee. PMID:25504907

  7. Enantioselective Allylic C-H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis.

    PubMed

    Ammann, Stephen E; Liu, Wei; White, M Christina

    2016-08-01

    The enantioselective synthesis of isochroman motifs has been accomplished by palladium(II)-catalyzed allylic C-H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C-H oxidation reaction proceeds with the broadest scope and highest levels of asymmetric induction reported to date (avg. 92 % ee, 13 examples with greater than 90 % ee). PMID:27376625

  8. Iridium-Catalyzed Allylic Amination Route to α-Aminoboronates: Illustration of the Decisive Role of Boron Substituents

    PubMed Central

    Touchet, Sabrina; Molander, Gary A.; Carboni, Bertrand; Bouillon, Alexandre

    2012-01-01

    The development of a new route to α-aminoboronates using an iridium-catalyzed allylic amination on boronated substrates is described. Unlike the boronate group, the trifluoroborato substituent was found to govern the regioselectivity exclusively in favor of branched products. The transformation of an allylic substitution product into an α-aminoboronic ester in an efficient way validated the implementation of this approach. PMID:22350584

  9. Expanding insight into asymmetric palladium-catalyzed allylic alkylation of N-heterocyclic molecules and cyclic ketones.

    PubMed

    Bennett, Nathan B; Duquette, Douglas C; Kim, Jimin; Liu, Wen-Bo; Marziale, Alexander N; Behenna, Douglas C; Virgil, Scott C; Stoltz, Brian M

    2013-04-01

    Eeny, meeny, miny ... enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates. PMID:23447555

  10. Allylic Oxidations Catalyzed by Dirhodium Caprolactamate via Aqueous tert-Butyl Hydroperoxide: The Role of the tert-Butylperoxy Radical

    PubMed Central

    McLaughlin, Emily C.; Choi, Hojae; Wang, Kan; Chiou, Grace; Doyle, Michael P.

    2009-01-01

    Dirhodium(II) caprolactamate exhibits optimal efficiency for the production of the tert-butylperoxy radical, which is a selective reagent for hydrogen atom abstraction. These oxidation reactions occur with aqueous tert-butyl hydroperoxide (TBHP) without rapid hydrolysis of the caprolactamate ligands on dirhodium. Allylic oxidations of enones yield the corresponding enedione in moderate to high yields, and applications include allylic oxidations of steroidal enones. Although methylene oxidation to a ketone is more effective, methyl oxidation to a carboxylic acid can also be achieved. The superior efficiency of dirhodium(II) caprolactamate as a catalyst for allylic oxidations by TBHP (mol % catalyst, % conversion) is described in comparative studies with other metal catalysts that are also reported to be effective for allylic oxidations. That different catalysts produce essentially the same mixture of products with the same relative yields suggests that the catalyst is not involved in product forming steps. Mechanistic implications arising from studies of allylic oxidation with enones provide new insights into factors that control product formation. A previously undisclosed disproportionation pathway, catalyzed by the tert-butoxy radical, of mixed peroxides for the formation of ketone products via allylic oxidation has been uncovered. PMID:19072696

  11. Kappa Opioid Receptor Agonist and Brain Ischemia

    PubMed Central

    Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

    2014-01-01

    Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Rheology and viscosity scaling of gelatin/1-allyl-3-methylimidazolium chloride solution

    NASA Astrophysics Data System (ADS)

    Qiao, Congde; Li, Tianduo; Zhang, Ling; Yang, Xiaodeng; Xu, Jing

    2014-05-01

    Gelatin/1-allyl-3-methylimidazolium chloride solutions are prepared by using the ionic liquid 1-allyl-3-methylimidazolium chloride as solvent. The rheological properties of the gelatin solutions have been investigated by steady shear and oscillatory shear measurements. In the steady shear measurements, the gelatin solutions with high concentration show a shear-thinning flow behavior at high shear rates, while another shear thinning region can be found in the dilute gelatin solutions at low shear rates. The overlap concentration of gelatin in [amim]Cl is 1.0 wt% and the entanglement concentration is a factor of 4 larger (4.0 wt%). The high intrinsic viscosity (295 mL/g) indicates that the gelatin chains dispersed freely in the ionic liquid and no aggregation phenomenon occurs in dilute gelatin solution. The frequency dependences of modulus changed obviously with an increase in gelatin concentration. The empirical time-temperature superposition principle holds true at the experimental temperatures.

  15. Mechanistic Study on Oxorhenium-Catalyzed Deoxydehydration and Allylic Alcohol Isomerization.

    PubMed

    Wu, Di; Zhang, Yugen; Su, Haibin

    2016-05-20

    The reaction mechanism of 1,2×n-deoxydehydration (DODH; n=1, 2, 3 …) reactions with 1-butanol as a reductant in the presence of methyltrioxorhenium(VII) catalyst has been investigated by DFT. The reduced rhenium compound, methyloxodihydroxyrhenium(V), serves as the catalytically relevant species in both allylic alcohol isomerization and subsequent DODH processes. Compared with three-step pathway A, involving [1,3]-transposition of allylic alcohols, direct two-step pathway B is an alternative option with lower activation barriers. The rate-limiting step of the DODH reaction is the first hydrogen transfer in methyltrioxorhenium(VII) reduction. Moreover, the increase in the distance between two hydroxyl groups in direct 1,2×n-DODH reactions for C4 and C6 diols results in a higher barrier height. PMID:26991093

  16. Simple strategy for synthesis of optically active allylic alcohols and amines by using enantioselective organocatalysis

    PubMed Central

    Jiang, Hao; Holub, Nicole; Anker Jørgensen, Karl

    2010-01-01

    A simple organocatalytic one-pot protocol for the construction of optically active allylic alcohols and amines using readily available reactants and catalyst is presented. The described reaction is enabled by an enantioselective enone epoxidation/aziridination-Wharton-reaction sequence affording two highly privileged and synthetically important classes of compounds in an easy and benign way. The advantages of the described sequence include easy generation of stereogenic allylic centers, also including quaternary stereocenters, with excellent enantio- and diastereomeric-control and high product diversity. Furthermore, using monosubstituted enones as substrates, having moderate enantiomeric excess, the one-pot reaction sequence proceeds with an enantioenrichment of the products and high diastereoselectivity was achieved. PMID:20547884

  17. Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins

    SciTech Connect

    Sarkar, Ruma; Mukherjee, Sutapa; Biswas, Jaydip; Roy, Madhumita

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer HSPs (27, 70 and 90) and HSF1 are overexpressed in MCF-7 and MDA-MB-231 cells. Black-Right-Pointing-Pointer Sulphoraphane, a natural isothiocyanate inhibited HSPs and HSF1 expressions. Black-Right-Pointing-Pointer Inhibition of HSPs and HSF1 lead to regulation of apoptotic proteins. Black-Right-Pointing-Pointer Alteration of apoptotic proteins activate of caspases particularly caspase 3 and 9 leading to induction of apoptosis. Black-Right-Pointing-Pointer Alteration of apoptotic proteins induce caspases leading to induction of apoptosis. -- Abstract: Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport and/or stabilization by acting as a molecular chaperone, leading to inhibition of apoptosis by both caspase dependent and/or independent pathways. HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion and metastasis. HSPs particularly 27, 70, 90 and the transcription factor heat shock factor1 (HSF1) play key roles in the etiology of breast cancer and can be considered as potential therapeutic target. The present study was designed to investigate the role of sulphoraphane, a natural isothiocyanate on HSPs (27, 70, 90) and HSF1 in two different breast cancer cell lines MCF-7 and MDA-MB-231 cells expressing wild type and mutated p53 respectively, vis-a-vis in normal breast epithelial cell line MCF-12F. It was furthermore investigated whether modulation of HSPs and HSF1 could induce apoptosis in these cells by altering the expressions of p53, p21 and some apoptotic proteins like Bcl-2, Bax, Bid, Bad, Apaf-1 and AIF. Sulphoraphane was found to down-regulate the expressions of HSP70, 90 and HSF1, though the effect on HSP27 was not pronounced. Consequences of HSP inhibition was upregulation of p21 irrespective of p53 status. Bax, Bad, Apaf-1, AIF were upregulated followed by down-regulation of Bcl-2 and this effect was prominent

  18. Experimental and Kinetic Modeling Study of 2-Methyl-2-Butene: Allylic Hydrocarbon Kinetics.

    PubMed

    Westbrook, Charles K; Pitz, William J; Mehl, Marco; Glaude, Pierre-Alexandre; Herbinet, Olivier; Bax, Sarah; Battin-Leclerc, Frederique; Mathieu, Olivier; Petersen, Eric L; Bugler, John; Curran, Henry J

    2015-07-16

    Two experimental studies have been carried out on the oxidation of 2-methyl-2-butene, one measuring ignition delay times behind reflected shock waves in a stainless steel shock tube, and the other measuring fuel, intermediate, and product species mole fractions in a jet-stirred reactor (JSR). The shock tube ignition experiments were carried out at three different pressures, approximately 1.7, 11.2, and 31 atm, and at each pressure, fuel-lean (ϕ = 0.5), stoichiometric (ϕ = 1.0), and fuel-rich (ϕ = 2.0) mixtures were examined, with each fuel/oxygen mixture diluted in 99% Ar, for initial postshock temperatures between 1330 and 1730 K. The JSR experiments were performed at nearly atmospheric pressure (800 Torr), with stoichiometric fuel/oxygen mixtures with 0.01 mole fraction of 2M2B fuel, a residence time in the reactor of 1.5 s, and mole fractions of 36 different chemical species were measured over a temperature range from 600 to 1150 K. These JSR experiments represent the first such study reporting detailed species measurements for an unsaturated, branched hydrocarbon fuel larger than iso-butene. A detailed chemical kinetic reaction mechanism was developed to study the important reaction pathways in these experiments, with particular attention on the role played by allylic C-H bonds and allylic pentenyl radicals. The results show that, at high temperatures, this olefinic fuel reacts rapidly, similar to related alkane fuels, but the pronounced thermal stability of the allylic pentenyl species inhibits low temperature reactivity, so 2M2B does not produce "cool flames" or negative temperature coefficient behavior. The connections between olefin hydrocarbon fuels, resulting allylic fuel radicals, the resulting lack of low-temperature reactivity, and the gasoline engine concept of octane sensitivity are discussed. PMID:25822578

  19. Highly efficient aminocarbonylation of iodoarenes at atmospheric pressure catalyzed by a robust acenaphthoimidazolyidene allylic palladium complex.

    PubMed

    Fang, Weiwei; Deng, Qinyue; Xu, Mizhi; Tu, Tao

    2013-07-19

    A robust allylic palladium-NHC complex was developed and exhibited extremely high catalytic activity toward aminocarbonylation of various (hetero)aryl iodides under atmospheric carbon monoxide pressure, in which a broad range of secondary and primary amines were well tolerated. In addition, the concise synthesis of an anticancer drug tamibarotene was accomplished even in a gram scale, further highlighting the practical applicability of the protocol. PMID:23829496

  20. Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

    PubMed Central

    Yan, Lin; Han, Zhiqiang; Zhu, Bo; Yang, Caiyun

    2013-01-01

    Summary In the presence of a commercially available Cinchona alkaloid as catalyst, the asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates, with α-fluoro-β-keto esters as nucleophiles, have been successfully developed. A series of important fluorinated adducts, with chiral quaternary carbon centres containing a fluorine atom, was achieved in good yields (up to 93%), with good to excellent enantioselectivities (up to 96% ee) and moderate diastereoselectivities (up to 4:1 dr). PMID:24062852

  1. Iridium-Catalyzed Allylation of Chiral β-Stereogenic Alcohols: Bypassing Discrete Formation of Epimerizable Aldehydes

    PubMed Central

    Schmitt, Daniel C.; Dechert-Schmitt, Anne-Marie R.; Krische, Michael J.

    2012-01-01

    The cyclometallated π-allyliridium 3,4-dinitro-C,O-benzoate complex modified by (R)- or (S)-Cl,MeO-BIPHEP promotes the transfer hydrogenative coupling of allyl acetate to β-stereogenic alcohols with good to excellent levels of catalyst-directed diastereoselectivity to furnish homoallylic alcohols. Remote electronic effects of the C,O-benzoate of the catalyst play a critical role in suppressing epimerization of the transient α-stereogenic aldehyde. PMID:23231774

  2. Chiral sulfoxides in the enantioselective allylation of aldehydes with allyltrichlorosilane: a kinetic study.

    PubMed

    Monaco, Guglielmo; Vignes, Chiara; De Piano, Francesco; Bosco, Assunta; Massa, Antonio

    2012-12-28

    The mechanism of the allylation of aldehydes in the presence of allyltrichlorosilane employing the commercially available (R)-methyl p-tolyl sulfoxide as a Lewis base has been investigated. The combination of kinetic measurements, conductivity analysis and quantum chemical calculations indicates that the reaction proceeds through a dissociative pathway in which an octahedral cationic complex with two sulfoxides is involved. The lack of turnover is ascribed to the formation of neutral sulfurane derivatives. PMID:23139050

  3. An Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

    PubMed

    Ye, Ke-Yin; Cheng, Qiang; Zhuo, Chun-Xiang; Dai, Li-Xin; You, Shu-Li

    2016-07-01

    A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand. PMID:27162135

  4. Characterization of CM572, a Selective Irreversible Partial Agonist of the Sigma-2 Receptor with Antitumor Activity.

    PubMed

    Nicholson, Hilary; Comeau, Anthony; Mesangeau, Christophe; McCurdy, Christopher R; Bowen, Wayne D

    2015-08-01

    The sigma-2 receptors are promising therapeutic targets because of their significant upregulation in tumor cells compared with normal tissue. Here, we characterize CM572 [3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)-6-isothiocyanatobenzo[d]oxazol-2(3H)-one] (sigma-1 Ki ≥ 10 µM, sigma-2 Ki = 14.6 ± 6.9 nM), a novel isothiocyanate derivative of the putative sigma-2 antagonist, SN79 [6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one]. CM572 bound irreversibly to sigma-2 receptors by virtue of the isothiocyanate moiety but not to sigma-1. Studies in human SK-N-SH neuroblastoma cells revealed that CM572 induced an immediate dose-dependent increase in cytosolic calcium concentration. A 24-hour treatment of SK-N-SH cells with CM572 induced dose-dependent cell death, with an EC50 = 7.6 ± 1.7 µM. This effect was sustained over 24 hours even after a 60-minute pretreatment with CM572, followed by extensive washing to remove ligand, indicating an irreversible effect consistent with the irreversible binding data. Western blot analysis revealed that CM572 also induced cleavage activation of proapoptotic BH3-interacting domain death agonist. These data suggest irreversible agonist-like activity. Low concentrations of CM572 that were minimally effective were able to attenuate significantly the calcium signal and cell death induced by the sigma-2 agonist CB-64D [(+)-1R,5R-(E)-8-benzylidene-5-(3-hydroxyphenyl)-2-methylmorphan-7-one]. CM572 was also cytotoxic against PANC-1 pancreatic and MCF-7 breast cancer cell lines. The cytotoxic activity of CM572 was selective for cancer cells over normal cells, being much less potent against primary human melanocytes and human mammary epithelial cells. Taken together, these data show that CM572 is a selective, irreversible sigma-2 receptor partial agonist. This novel irreversible ligand may further our understanding of the endogenous role of this receptor, in addition to having potential use in targeted

  5. Dinuclear Pd(I) complexes with bridging allyl and related ligands.

    PubMed

    Hazari, Nilay; Hruszkewycz, Damian P

    2016-05-21

    There are many important synthetic methods that utilize palladium catalysts. In most of these reactions, the palladium species are proposed to exist exclusively in either the Pd(0) or Pd(II) oxidation states. However, in the last decade, dinuclear Pd(I) complexes have repeatedly been isolated from reaction mixtures previously suggested to involve only species in the Pd(0) and Pd(II) oxidation states. As a consequence, in order to design improved catalysts there is considerable interest in understanding the chemistry of dinuclear Pd(I) complexes. A significant proportion of the known dinuclear Pd(I) complexes are supported by bridging allyl or related ligands such as cyclopentadienyl or indenyl ligands. This review provides a detailed account of the synthesis, electronic structure and stoichiometric reactivity of dinuclear Pd(I) complexes with bridging allyl and related ligands. Additionally, it describes recent work where dinuclear Pd(I) complexes with bridging allyl ligands have been detected in catalytic reactions, such as cross-coupling, and discusses the potential implications for catalysis. PMID:27051890

  6. The soft X-ray absorption spectrum of the allyl free radical.

    PubMed

    Alagia, M; Bodo, E; Decleva, P; Falcinelli, S; Ponzi, A; Richter, R; Stranges, S

    2013-01-28

    The first experimental study of the X-ray absorption spectrum (XAS) of the allyl free radical, CH(2)CHCH(2), is reported. A supersonic He seeded beam of hyperthermal allyl radicals was crossed by a high resolution synchrotron radiation (SR) in the focus of a 3D ion momentum imaging time-of-flight (TOF) spectrometer to investigate the soft X-ray absorption and fragmentation processes. The XAS, recorded as Total-Ion-Yield (TIY), is dominated by C1s electron excitations from either the central carbon atom, C(C), or the two terminal carbon atoms, C(T), to the frontier orbitals, the semi-occupied-molecular-orbital (SOMO) and the lowest-unoccupied-molecular-orbital (LUMO). All of the intense features in the XAS could only be assigned with the aid of ab initio spectral simulation at the Multi-Configuration Self-Consistent-Field (MCSCF) level of theory, this level being required because of the multi-reference nature of the core-excited state wavefunctions of the open shell molecule. The ionization energies (IEs) of the singlet and triplet states of the C1s ionized allyl radical (XPS) were also calculated at the MCSCF level. PMID:23232557

  7. Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

    NASA Astrophysics Data System (ADS)

    Sidera, Mireia; Fletcher, Stephen P.

    2015-11-01

    Csp2-Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. Csp2-Csp3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective Csp2-Csp3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

  8. A glutathione S-transferase inducer from papaya: rapid screening, identification and structure-activity relationship of isothiocyanates.

    PubMed

    Nakamura, Y; Morimitsu, Y; Uzu, T; Ohigashi, H; Murakami, A; Naito, Y; Nakagawa, Y; Osawa, T; Uchida, K

    2000-09-01

    We have developed a simple system for rapid detection and measurement of glutathione S-transferase placental form (GSTP1) that detoxify polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, (RL34) cells. Survey of fruit extracts for GST inducing ability identified both papaya and avocado as significant sources. Benzyl isothiocyanate (BITC) was isolated from papaya methanol extract as a principal inducer of GST activity. Further, the GST inducing ability of a total of 20 isothiocyanates (ITCs) and their derivatives was investigated. Some ITCs showed significant induction, and BITC was one of the most potent inducers among all compounds tested in the present study. The modification of isothiocyanate group (-NCS) or introduction of substituent group to the alpha-carbon modifies GST induction. Moreover, a significant correlation (P<0.01, r=0.913) between the GST activity enrichment and GSTP1 protein induction by ITCs was observed. We also indicated that phenethyl ITC and nitrophenyl ITC, potently inducing GST activity, but not inactive benzyl isocyanate, are potential inducers of intracellular reactive oxygen intermediates (ROIs). Our system of GSTP1 induction is appropriate for the chemical research such as screening and identification of novel type of inducers as well as the structure-activity relationship studies, providing mechanistic insight into essential structural elements for GSTP1 induction. PMID:10936680

  9. Preclinical Evaluation of 4-Methylthiobutyl Isothiocyanate on Liver Cancer and Cancer Stem Cells with Different p53 Status

    PubMed Central

    Lamy, Evelyn; Hertrampf, Anke; Herz, Corinna; Schüler, Julia; Erlacher, Miriam; Bertele, Daniela; Bakare, Adekunle; Wagner, Meike; Weiland, Timo; Lauer, Ulrich; Drognitz, Oliver; Huber, Roman; Rohn, Sascha; Giesemann, Torsten; Mersch-Sundermann, Volker

    2013-01-01

    Isothiocyanates from plants of the order Brassicales are considered promising cancer chemotherapeutic phytochemicals. However, their selective cytotoxicity on liver cancer has been barely researched. Therefore, in the present study, we systematically studied the chemotherapeutic potency of 4-methylthiobutyl isothiocyanate (MTBITC). Selective toxicity was investigated by comparing its effect on liver cancer cells and their chemoresistant subpopulations to normal primary hepatocytes and liver tissue slices. Additionally, in a first assessment, the in vivo tolerability of MTBITC was investigated in mice. Growth arrest at G2/M and apoptosis induction was evident in all in vitro cancer models treated with MTBITC, including populations with cancer initiating characteristics. This was found independent from TP53; however cell death was delayed in p53 compromised cells as compared to wt-p53 cells which was probably due to differential BH3 only gene regulation i. e. Noxa and its antagonist A1. In normal hepatocytes, no apoptosis or necrosis could be detected after repeated administration of up to 50 µM MTBITC. In mice, orally applied MTBITC was well tolerated over 18 days of treatment for up to 50 mg/kg/day, the highest dose tested. In conclusion, we could show here that the killing effect of MTBITC has a definite selectivity for cancer cells over normal liver cells and its cytotoxicity even applies for chemoresistant cancer initiating cells. Our study could serve for a better understanding of the chemotherapeutic properties of isothiocyanates on human liver-derived cancer cells. PMID:23936472

  10. Plasmids from the gut microbiome of cabbage root fly larvae encode SaxA that catalyses the conversion of the plant toxin 2-phenylethyl isothiocyanate.

    PubMed

    Welte, Cornelia U; de Graaf, Rob M; van den Bosch, Tijs J M; Op den Camp, Huub J M; van Dam, Nicole M; Jetten, Mike S M

    2016-05-01

    Cabbage root fly larvae (Delia radicum) cause severe crop losses (≥ 50%) of rapeseed/ canola and cabbages used in the food and biofuel industries. These losses occur despite the fact that cabbages produce insecticidal toxins such as isothiocyanates. Here we describe the cabbage root fly larval gut microbiome as a source of isothiocyanate degrading enzymes. We sequenced the microbial gut community of the larvae and analysed phylogenetic markers and functional genes. We combined this with the isolation of several microbial strains representing the phylogenetic distribution of the metagenome. Eleven of those isolates were highly resistant towards 2-phenylethyl isothiocyanate, a subset also metabolized 2-phenylethyl isothiocyanate. Several plasmids appeared to be shared between those isolates that metabolized the toxin. One of the plasmids harboured a saxA gene that upon transformation gave resistance and enabled the degradation of 2-phenylethyl isothiocyanate in Escherichia coli. Taken together, the results showed that the cabbage root fly larval gut microbiome is capable of isothiocyanate degradation, a characteristic that has not been observed before, and may help us understand and design new pest control strategies. PMID:26234684

  11. Evaluation of Fluorescein Isothiocyanate-labeled Whole Antiserum in the Immunofluorescent Identification of Microorganisms

    PubMed Central

    Sweet, George H.; Schindler, Charles A.

    1967-01-01

    Portions of a whole antiserum to Histoplasma capsulatum were reacted with amounts of fluorescein isothiocyanate (FITC) that ranged from 50 to 400 μg/mg of protein. Portions of the globulin from the same antiserum were reacted with amounts of FITC that ranged from 12.5 to 50 μg of FITC per mg of protein. The globulin conjugates (postlabeled globulins), the whole serum conjugates, and the globulins from the whole serum conjugates (prelabeled globulins) were compared with respect to their fluorescein-protein (F:P) ratios and fluorescent-antibody (FA) activities. The whole serum sample treated with 50 μg of FITC per mg of protein was least reactive in FA tests, and its globulin had the lowest F:P. All other conjugates had globulins with F:P ratios that were considered to be adequate for high FA activity. It was found, however, that the prelabeled globulins were considerably less reactive than the postlabeled globulins or the whole serum conjugates. A larger amount of brightly staining reagent per milliliter of original serum could be obtained from labeled whole serum than from postlabeled globulin. Lissamine-rhodamine conjugated to bovine serum albumin (LRBSA) was evaluated as a counterstain to be used in conjunction with FITC-labeled whole antisera. The counterstain was effective in masking nonspecific FITC fluorescence in Formalin-fixed tissues and in culture smears of fungi. Masking was incomplete in culture smears of a bacterium and in blood smears containing a protozoan. Images PMID:5337774

  12. Involvement of the Electrophilic Isothiocyanate Sulforaphane in Arabidopsis Local Defense Responses1

    PubMed Central

    Andersson, Mats X.; Nilsson, Anders K.; Johansson, Oskar N.; Boztaş, Gülin; Adolfsson, Lisa E.; Pinosa, Francesco; Petit, Christel Garcia; Aronsson, Henrik; Mackey, David; Tör, Mahmut; Hamberg, Mats; Ellerström, Mats

    2015-01-01

    Plants defend themselves against microbial pathogens through a range of highly sophisticated and integrated molecular systems. Recognition of pathogen-secreted effector proteins often triggers the hypersensitive response (HR), a complex multicellular defense reaction where programmed cell death of cells surrounding the primary site of infection is a prominent feature. Even though the HR was described almost a century ago, cell-to-cell factors acting at the local level generating the full defense reaction have remained obscure. In this study, we sought to identify diffusible molecules produced during the HR that could induce cell death in naive tissue. We found that 4-methylsulfinylbutyl isothiocyanate (sulforaphane) is released by Arabidopsis (Arabidopsis thaliana) leaf tissue undergoing the HR and that this compound induces cell death as well as primes defense in naive tissue. Two different mutants impaired in the pathogen-induced accumulation of sulforaphane displayed attenuated programmed cell death upon bacterial and oomycete effector recognition as well as decreased resistance to several isolates of the plant pathogen Hyaloperonospora arabidopsidis. Treatment with sulforaphane provided protection against a virulent H. arabidopsidis isolate. Glucosinolate breakdown products are recognized as antifeeding compounds toward insects and recently also as intracellular signaling and bacteriostatic molecules in Arabidopsis. The data presented here indicate that these compounds also trigger local defense responses in Arabidopsis tissue. PMID:25371552

  13. Comparison of the Photobleaching and Photostability Traits of Alexa Fluor 568- and Fluorescein Isothiocyanate- conjugated Antibody

    PubMed Central

    Mahmoudian, Jafar; Hadavi, Reza; Jeddi-Tehrani, Mahmood; Mahmoudi, Ahmad Reza; Bayat, Ali Ahmad; Shaban, Elham; Vafakhah, Mohtaram; Darzi, Maryam; Tarahomi, Majid; Ghods, Roya

    2011-01-01

    Objective: Synthetic fluorescent dyes that are conjugated to antibodies are useful tools to probe molecules. Based on dye chemical structures, their photobleaching and photostability indices are quite diverse. It is generally believed that among different fluorescent dyes, Alexa Fluor family has greater photostability than traditional dyes like fluorescein isothiocyanate (FITC) and Cy5. Alexa Fluor 568 is a member of Alexa Fluor family presumed to have superior photostability and photobleahing profiles than FITC. Materials and Methods: In this experimental study, we conjugated Alexa Fluor 568 and FITC dyes to a mouse anti-human nestin monoclonal antibody (ANM) to acquire their photobleaching profiles and photostability indices. Then, the fluorophore/antibody ratios were calculated using a spectrophotometer. The photobleaching profiles and photostability indices of conjugated antibodies were subsequently studied by immunocytochemistry (ICC). Samples were continuously illuminated and digital images acquired under a fluorescent microscope. Data were processed by ImageJ software. Results: Alexa Fluor 568 has a brighter fluorescence and higher photostability than FITC. Conclusion: Alexa Fluor 568 is a capable dye to use in photostaining techniques and it has a longer photostability when compared to FITC. PMID:23508937

  14. Reduction of methyl isothiocyanate atmospheric emissions after application of metam sodium by shank injection.

    PubMed

    Ajwa, Husein A; Sullivan, David A; Holdsworth, Mark T; Sullivan, Ryan D; Nelson, Shad D

    2013-11-01

    Regulatory initiatives in the United States have created the impetus to reassess application methods for metam sodium (sodium -methyldithiocarbamate), a methyl isothiocyanate (MITC) generator, to reduce flux to the atmosphere. This paper compares flux rates in the years 1990 through 2002 with flux rates based on four studies conducted during the period 2008 through 2010 in California, Michigan, Wisconsin, and Washington using current shank-injection/compaction methods. Up to a 100-fold reduction in peak flux rates and total loss of MITC have been observed. A combination of the following factors led to these reductions in flux: soil moisture goals set at 70% of the field water holding capacity; improved design of shank-injection systems to break up the voids after injection; effective shank compaction to further reduce volatilization; and the use of water sealing, where applicable. These refinements in the application methods for metam sodium provide a means to merge environmental and agricultural goals in the United States and in other countries that use metam sodium. This paper documents the reduced atmospheric emissions of MITC under commercial production conditions when applied using good agricultural practices. This research also shows that MITC flux can be effectively managed without the use of high barrier tarp material. PMID:25602406

  15. Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate.

    PubMed

    Thaler, Roman; Maurizi, Antonio; Roschger, Paul; Sturmlechner, Ines; Khani, Farzaneh; Spitzer, Silvia; Rumpler, Monika; Zwerina, Jochen; Karlic, Heidrun; Dudakovic, Amel; Klaushofer, Klaus; Teti, Anna; Rucci, Nadia; Varga, Franz; van Wijnen, Andre J

    2016-03-25

    Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2,Col1a1,Bglap2,Sp7,Atf4, andAlpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of theTet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorptionin vivo Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis. PMID:26757819

  16. [Effect of phenylhexyl isothiocyanate on Wnt/beta-catenin signaling pathway in Jurkat cell line].

    PubMed

    Lin, Juan; Huang, Yi-Qun; Ma, Xu-Dong

    2013-04-01

    This study was purposed to investigate the effect of phenylhexyl isothiocyanate (PHI) on Wnt/β-catenin signaling pathway, histone acetylation, histone methylation and cell apoptosis in Jurkat cell line. The viability of Jurkat cells after treatment with PHI was tested by MTT. Apoptotic rate of Jurkat cells was measured by flow cytometry. The levels of Wnt/β-catenin related proteins including β-catenin, TCF, c-myc, and cyclinD1, histone acetylated H3 and H4, histone methylated H3K9 and H3K4 were detected by Western blot. The results showed that PHI inhibited the cell growth and induced apoptosis in Jurkat cells in time-and dose-dependent manners. Its IC50 at 48 h was about 20 µmol/L. Expression of histone acetylated H3, H4 and histone methylated H3k4 increased after exposure to PHI for 3 h, while histone methylated H3K9 decreased. Expression of β-catenin was not changed after exposure to PHI for 3 h, but expression of β-catenin, and its cell cycle-related genes such as TCF, c-myc and cyclinD1 decreased after exposure to PHI for 7 h. It is concluded that PHI regulates acetylation and methylation of histone, inhibits Wnt/β-catenin signal pathway, and is able to induce apoptosis and inhibits growth of Jurkat cells. PMID:23628033

  17. Isothiocyanate from the Tunisian radish (Raphanus sativus) prevents genotoxicity of Zearalenone in vivo and in vitro.

    PubMed

    Ben Salah-Abbès, Jalila; Abbès, Samir; Ouanes, Zouhour; Abdel-Wahhab, Mosaad A; Bacha, Hassen; Oueslati, Ridha

    2009-01-01

    Zearalenone (ZEN) is a naturally occurring contaminant of animal feed that has been implicated in several mycotoxicoses in farm livestock. Recently some information has become available indicating that ZEN caused cancer or at least increased its prevalence, although the mechanism of action is unknown. Many papers mentioned that exposure to ZEN results in genotoxicity and DNA damage. Therefore, we investigated the chemo-preventive role of 4-(methylthio)-3-butenyl isothiocyanate (MTBITC) extracted from Tunisian Raphanus sativus (radish) on the cytogenetic effect of ZEN in Balb/c mice and in in vitro cultures of mouse lymphocytes isolated from mouse spleen. We determined chromosome aberrations and micronuclei as well as the mitotic index and DNA fragmentation following ZEN treatment alone or in combination with MTBITC. This report is the first to provide evidence of a statistically significant decrease of structural chromosome aberrations and micronuclei associated with an augmentation of the mitotic index and prevention of DNA fragmentation in all mice treated with ZEN-MTBITC and in mouse lymphocyte cultures. The MTBITC alone was safe and succeeded in reducing the toxicity of ZEN by counteracting its deleterious effect, thus protecting against the genotoxicity and clastogenicity from ZEN. PMID:19501672

  18. Honey-Induced Protein Stabilization as Studied by Fluorescein Isothiocyanate Fluorescence

    PubMed Central

    Abdul Kadir, Habsah; Tayyab, Saad

    2013-01-01

    Protein stabilizing potential of honey was studied on a model protein, bovine serum albumin (BSA), using extrinsic fluorescence of fluorescein isothiocyanate (FITC) as the probe. BSA was labelled with FITC using chemical coupling, and urea and thermal denaturation studies were performed on FITC-labelled BSA (FITC-BSA) both in the absence and presence of 10% and 20% (w/v) honey using FITC fluorescence at 522 nm upon excitation at 495 nm. There was an increase in the FITC fluorescence intensity upon increasing urea concentration or temperature, suggesting protein denaturation. The results from urea and thermal denaturation studies showed increased stability of protein in the presence of honey as reflected from the shift in the transition curve along with the start point and the midpoint of the transition towards higher urea concentration/temperature. Furthermore, the increase in ΔGDH2O and ΔGD25°C in presence of honey also suggested protein stabilization. PMID:24222758

  19. Lacosamide Isothiocyanate-based Agents: Novel Agents to Target and Identify Lacosamide Receptors

    PubMed Central

    Park, Ki Duk; Morieux, Pierre; Salomé, Christophe; Cotten, Steven W.; Reamtong, Onrapak; Eyers, Claire; Gaskell, Simon J.; Stables, James P.; Liu, Rihe; Kohn, Harold

    2009-01-01

    (R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide), has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique. A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogs, 3, that contain “affinity bait (AB)” and “chemical reporter (CR)” functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with an appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent seizure protection in mice and, like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. PMID:19795888

  20. Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance and hepatic gluconeogenesis in mice

    PubMed Central

    Waterman, Carrie; Rojas-Silva, Patricio; Tumer, Tugba Boyunegmez; Kuhn, Peter; Richard, Allison J.; Wicks, Shawna; Stephens, Jacqueline M.; Wang, Zhong; Mynatt, Randy; Cefalu, William; Raskin, Ilya

    2015-01-01

    Scope Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. Methods and results C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti- diabetic effects observed. Conclusion Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes. PMID:25620073

  1. Phenethyl isothiocyanate induces apoptosis and inhibits cell proliferation and invasion in Hep-2 laryngeal cancer cells.

    PubMed

    Dai, Meng-Yuan; Wang, Yan; Chen, Chen; Li, Fen; Xiao, Bo-Kui; Chen, Shi-Ming; Tao, Ze-Zhang

    2016-05-01

    The dietary compound phenethyl isothiocyanate (PEITC), an important tumoricidal component found in cruciferous vegetables, exhibits strong anticancer and chemopreventive effects in a variety of tumors. However, its role in human laryngeal cancer is unclear. The aim of the present study was to investigate whether PEITC exhibits anticancer properties in human laryngeal carcinoma Hep-2 cells in vitro and to identify the potential molecular mechanisms. The results showed that treatment of Hep-2 cells with PEITC significantly inhibited cell proliferation in a dose- and time-dependent manner, promoted apoptosis with concurrent G2/M cell cycle arrest and inhibited cell invasion in a dose-dependent manner. These effects were accompanied by significant alterations in the expression levels of key proteins associated with pro-survival signaling pathways, including PI3K, Akt, ERK, NF-κB, Bcl, Bax, cyclin B, CDK4 and CDK6. Importantly, these effects were not reflected in 16HBE normal human bronchial epithelial cells, suggesting a safe range of treatment concentrations between 0 and 10 µM PEITC. In summary, PEITC exhibited significant anticancer effects against human laryngeal cancer cells in vitro with low toxicological impact on normal bronchial epithelial cells. This was achieved through dysregulation of key proteins involved in the occurrence and development of tumors, thereby offering a valuable contribution to future strategies for the treatment and screening of patients with laryngocarcinoma. PMID:26986926

  2. Effects of hyperthermia, irradiation, and cytotoxic drugs on fluorescein isothiocyanate staining intensity for flow cytofluorometry

    SciTech Connect

    Dyson, J.E.; McLaughlin, J.B.; Surrey, C.R.; Simmons, D.M.; Daniel, J.

    1987-01-01

    Measurement of fluorescein isothiocyanate (FITC) staining intensity of cultured lymphoblastoid cells following hyperthermia showed large increases without concomitant increases in nuclear protein. Similar measurements of cells following incubation with cytotoxic drugs showed fluorescent intensity increases that exceeded the increases in nuclear protein that were due to the cell cycle blocking action of the drug. The reverse, however, was true for cells following irradiation. In contrast, FITC staining intensity and nuclear protein measurements of cells proceeding through the cell cycle after removal of the cycle blocking agent showed nearly parallel changes, although there were reproducible minor differences, especially following blocking with hydroxyurea. These results suggest that FITC staining intensity is a function not only of nuclear protein content but also of stain access to the reaction sites of the protein constituents of the chromatin. Thus, it is possible that FITC staining may be used as a probe of changes in chromatin structure following experimental manipulation of cells in vitro or treatment of tumors in vivo.

  3. α-Allyl-α-aryl α-Amino Esters in the Asymmetric Synthesis of Acyclic and Cyclic Amino Acid Derivatives by Alkene Metathesis

    PubMed Central

    2015-01-01

    Allylating agents were explored for the asymmetric synthesis of α-allyl-α-aryl α-amino acids by tandem N-alkylation/π-allylation. Cross-metathesis of the tandem product was developed to provide allylic diversity not afforded in the parent reaction; the synthesis of homotyrosine and homoglutamate analogues was completed. Cyclic α-amino acid derivatives could be accessed by ring-closing metathesis presenting a viable strategy to higher ring homologue of enantioenriched α-substituted proline. The eight-membered proline analogue was successfully converted to the pyrrolizidine natural product backbone. PMID:24828423

  4. Theoretical Comparative Study of the Structure, Dynamics and Electronic Properties of Five Ally Molecules: Allicin, Methyl Propyl Disulfide (MPD), Allyl Methyl Sulfide (AMS), S-allyl cysteine (SAC) and S-allyl mercaptocysteine (SAMC)

    NASA Astrophysics Data System (ADS)

    Deniz Calisir, Emine; Erkoc, Sakir; Yildirim, Handan; Kara, Abdelkader; Rahman, Talat S.; Selvi, Mahmut; Erkoc, Figen

    2006-03-01

    The structural, dynamics and electronic properties of five allyl molecules have been investigated theoretically by performing semi-empirical molecular orbital (AM1 and PM3), ab-initio (RHF) and density functional theory calculations. The geometry of the molecules have been optimized, the vibrational spectra and the electronic properties of the molecules have been calculated in their ground states in gas phase. For each molecule, we found that the optimized geometries resulting from calculations based on the three levels of accuracy, to be very similar. However, we found that an accurate description of the vibrational properties of these molecules necessitates calculations at the ab-initio level. The electronic structures of these molecules were performed at the DFT level, resulting in an accurate description of the HOMO-LUMO gap and the local charges.

  5. Synthesis, Characterization, and Some Properties of Cp*W(NO)(H)(η(3)-allyl) Complexes.

    PubMed

    Baillie, Rhett A; Holmes, Aaron S; Lefèvre, Guillaume P; Patrick, Brian O; Shree, Monica V; Wakeham, Russell J; Legzdins, Peter; Rosenfeld, Devon C

    2015-06-15

    Sequential treatment at low temperatures of Cp*W(NO)Cl2 in THF with 1 equiv of a binary magnesium allyl reagent, followed by an excess of LiBH4, affords three new Cp*W(NO)(H)(η(3)-allyl) complexes, namely, Cp*W(NO)(H)(η(3)-CH2CHCMe2) (1), Cp*W(NO)(H)(η(3)-CH2CHCHPh) (2), and Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3). Complexes 1-3 are isolable as air-stable, analytically pure yellow solids in good to moderate yields by chromatography or fractional crystallization. In solutions, complex 1 exists as two coordination isomers in an 83:17 ratio differing with respect to the endo/exo orientation of the allyl ligand. In contrast, complexes 2 and 3 each exist as four coordination isomers, all differing by the orientation of their allyl ligands which can have either an endo or an exo orientation with the phenyl or methyl groups being either proximal or distal to the nitrosyl ligand. A DFT computational analysis using the major isomer of Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3a) as the model complex has revealed that its lowest-energy thermal-decomposition pathway involves the intramolecular isomerization of 3a to the 16e η(2)-alkene complex, Cp*W(NO)(η(2)-CH2═CHCH2Me). Such η(2)-alkene complexes are isolable as their 18e PMe3 adducts when compounds 1-3 are thermolyzed in neat PMe3, the other organometallic products formed during these thermolyses being Cp*W(NO)(PMe3)2 (5) and, occasionally, Cp*W(NO)(H)(η(1)-allyl)(PMe3). All new complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them have been established by single-crystal X-ray crystallographic analyses. PMID:26000552

  6. The Biosynthesis of Some Isothiocyanates and Oxazolidinethiones in Rape (Brassica campestris L.) 1

    PubMed Central

    Chisholm, M. D.; Wetter, L. R.

    1967-01-01

    The incorporation of the radioactivity from acetate-1-14C, acetate-2-14C, dl-methionine-1-14C, dl-methionine-2-14C, dl-methionine-3,4-14C, dl-homomethionine-2-14C, dl-allyl-glycine-2-14C, and dl-2-amino-5-hydroxyvalerate-2-14C into the aglycones of progoitrin, gluconapin, and glucobrassicanapin of maturing rape plants (Brassica campestris L.) was investigated. Radioactivity from dl-methionine-2-14C, dl-methionine-3,4-14C, dl-homomethionine-2-14C, and acetate-2-14C were incorporated into the 3 major thioglucosides. The other organic compounds were poorly incorporated except for dl-allylglycine-2-14C into glucobrassicanapin. The results obtained suggest that the rape plant can synthesize amino acids by the condensation of acetate (as acetyl CoA) to α-keto acids to yield a homologue of the original amino acid. These newly formed amino acids are then employed to synthesize the 3 major thioglucosides. PMID:16656711

  7. Part 1: synthesis of irreversible inhibitors of aldose reductase with subsequent development of a carbon-13 NMR protein probe. Part 2: synthesis of selenium analogs of dopamine as potential dopamine receptor agonists

    SciTech Connect

    Ares, J.J.

    1986-01-01

    Aldose reductase converts glucose into sorbitol using NADPH as a cofactor. Sorbitol accumulation in various tissues is believed to play a major role in the development of debilitating complications of diabetes; thus, much effort has been directed toward the preparation of aldose reductase inhibitors. Of the compounds prepared, the most active are the isothiocyanate and azide analogs of the reversible aldose reductase inhibitor alrestatin. The potency of the alrestatin isothiocyanate prompted the authors to examine the possibility that isothiocyanates enriched with carbon-13 could be used as carbon-13 NMR protein probes. Toward this end, a synthesis of carbon-13 enriched phenylisothiocyanate has been developed. This reagent has been successfully utilized to study peptides via carbon-13 NMR spectroscopy. Research in their laboratory over the years has focused on answering two fundamental questions regarding the interaction of dopamine with its receptor. First, can the concept of bioisosterism be applied to dopamine agonists. Secondly, what is the actual molecular species of dopamine which interacts with the dopamine receptor. In an effort to answer these questions, methyl selenide and dimethyl selenonium analogs of dopamine have been synthesized.

  8. Beta-agonists and animal welfare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  9. β2-agonist therapy in lung disease.

    PubMed

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  10. From allylic alcohols to aldols through a new nickel-mediated tandem reaction: synthetic and mechanistic studies.

    PubMed

    Cuperly, David; Petrignet, Julien; Crévisy, Christophe; Grée, René

    2006-04-12

    Nickel hydride type complexes have been successfully developed as catalysts for the tandem isomerization-aldolization reaction of allylic alcohols with aldehydes. Optimization of the reaction conditions has shown that a cocatalyst, such as MgBr2, has a very positive effect on the kinetics of the reaction and in the yields of aldols. Under such optimized conditions {[NiHCl(dppe)] + MgBr(2) at 3-5 mol %)}, this reaction affords the aldols in good to excellent yields. It is a full-atom-economy-type reaction that occurs under mild conditions. Furthermore, it has a broad scope for the allylic alcohols and it is compatible with a wide range of aldehydes, including very bulky derivatives. The reaction is completely regioselective, but it exhibits a low stereoselectivity, except for allylic alcohols with a bulky substituent at the carbinol center. The use of chiral nonracemic catalysts was not successful, affording only racemic compounds. However, it was possible to use asymmetric synthesis for the preparation of optically active aldols. Various mechanistic studies have been performed using, for instance, a deuterated alcohol or a deuterated catalyst. They gave strong support to a mechanism involving first a transition-metal-mediated isomerization of the allylic alcohol into the free enol, followed by the addition of the latter intermediate onto the aldehyde in an "hydroxyl-carbonyl-ene" type reaction. These results confirm that allylic alcohols can be considered as new and useful partners in the development of the aldol reaction. PMID:16506253

  11. Genome Wide Association Mapping in Arabidopsis thaliana Identifies Novel Genes Involved in Linking Allyl Glucosinolate to Altered Biomass and Defense

    PubMed Central

    Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A.; Lin, Catherine; Kerwin, Rachel E.; Burow, Meike; Kliebenstein, Daniel J.

    2016-01-01

    A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis. PMID:27462337

  12. One-Pot Multicomponent Coupling Methods for the Synthesis of Diastereo- and Enantioenriched (Z)-Trisubstituted Allylic Alcohols

    PubMed Central

    Kerrigan, Michael H.; Jeon, Sang-Jin; Chen, Young K.; Salvi, Luca; Carroll, Patrick J.; Walsh, Patrick J.

    2009-01-01

    (Z)-Trisubstituted allylic alcohols are widespread structural motifs in natural products and biologically active compounds but are difficult to directly prepare. Introduced herein is a general one-pot multicomponent coupling method for the synthesis of (Z)-α,α,β-trisubstituted allylic alcohols. (Z)-Trisubstituted vinylzinc reagents are formed in situ by initial hydroboration of 1-bromo-1-alkynes. Addition of dialkylzinc reagents induces a 1,2-metallate rearrangement that is followed by a boron-to-zinc transmetallation. The resulting vinylzinc reagents add to a variety of prochiral aldehydes to produce racemic (Z)-trisubstituted allylic alcohols. When enantioenriched aldehyde substrates are employed (Z)-trisubstituted allylic alcohols are isolated with high dr (>20:1 in many cases). For example, vinylation of enantioenriched benzyl protected α- and β-hydroxy propanal derivatives furnished the expected anti-Felkin addition products via chelation control. Surprisingly, silyl protected α-hydroxy aldehydes also afford anti-Felkin addition products. A protocol for the catalytic asymmetric addition of (Z)-trisubstituted vinylzinc reagents to prochiral aldehydes with a (−)-MIB-based catalyst has also been developed. Several additives were investigated as inhibitors of the Lewis acidic alkylzinc halide byproducts, which promote the background reaction to form the racemate. α-Ethyl and α-cyclohexyl (Z)-trisubstituted allylic alcohols can now be synthesized with excellent levels of enantioselectivity in the presence of diamine inhibitors. PMID:19476375

  13. Dietary chemopreventative benzyl isothiocyanate inhibits breast cancer stem cells in vitro and in vivo.

    PubMed

    Kim, Su-Hyeong; Sehrawat, Anuradha; Singh, Shivendra V

    2013-08-01

    A small subset of mammary tumor-initiating cells (also known as breast cancer stem cells; bCSC), characterized by expression of different markers [CD44(high)/CD24(low)/epithelial-specific antigen (ESA)+], aldehyde dehydrogenase-1 (ALDH1) activity, and ability to form mammospheres under ultra-low attachment culture conditions, are suspected to evade conventional therapies leading to disease recurrence. Elimination of both therapy-sensitive epithelial tumor cells and therapy-resistant bCSC is therefore necessary for prevention of breast cancer. We have shown previously that a nontoxic small-molecule constituent of edible cruciferous vegetables (benzyl isothiocyanate; BITC) inhibits mammary cancer development in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice by causing epithelial tumor cell apoptosis. The present study shows efficacy of BITC against bCSC in vitro and in vivo. Mammosphere formation frequency and CD44(high)/CD24(low)/ESA+ and/or ALDH1+ populations in cultured MCF-7 (estrogen receptor-positive) and SUM159 (triple-negative) human breast cancer cells were decreased significantly in the presence of plasma achievable concentrations of BITC. BITC administration in the diet (3 μmol BITC/g diet for 29 weeks) resulted in a marked decrease in bCSCs in the MMTV-neu mice tumors in vivo. Overexpression of full-length Ron as well as its truncated form (sfRon), but not urokinase-type plasminogen activator receptor, conferred near complete protection against BITC-mediated inhibition of bCSCs in MCF-7 cells. The BITC treatment downregulated protein levels of Ron and sfRon in cultured breast cancer cells and in tumor xenografts. Ron overexpression resulted in upregulation of bCSC-associated genes Oct-4, SOX-2, and Nanog. In conclusion, the present study indicates that BITC treatment eliminates bCSCs in vitro and in vivo. PMID:23661606

  14. Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

    PubMed Central

    Nikhil, Kumar; Sharan, Shruti; Singh, Abhimanyu K.; Chakraborty, Ajanta; Roy, Partha

    2014-01-01

    Trans-3,5-dimethoxy-4′-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway. PMID:25119466

  15. Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

    PubMed

    Guzmán-Pérez, Valentina; Bumke-Vogt, Christiane; Schreiner, Monika; Mewis, Inga; Borchert, Andrea; Pfeiffer, Andreas F H

    2016-01-01

    Nasturtium (Tropaeolum majus L.) contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC)-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1). FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i) the insulin-signaling pathway, ii) the intracellular localization of FOXO1 and, iii) the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS) with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein) were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB) and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived)-like2 (NRF2) and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1). The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance. PMID:27622707

  16. Bim contributes to phenethyl isothiocyanate-induced apoptosis in breast cancer cells.

    PubMed

    Hahm, Eun-Ryeong; Singh, Shivendra V

    2012-06-01

    Phenethyl isothiocyanate (PEITC) is a highly promising cancer chemopreventive constituent of cruciferous vegetables (e.g., watercress) with in vivo efficacy in experimental rodent cancer models. Research thus far implicates apoptosis induction in cancer chemopreventive response to PEITC, but the mechanism of proapoptotic effect is not fully understood. The present study demonstrates that p53 upregulated modulator of apoptosis (PUMA)-independent apoptosis by PEITC is mediated by B-cell lymphoma 2 interacting mediator of cell death (Bim). Exposure of a cell line (BRI-JM04) derived from spontaneously developing mammary tumor of a MMTV-neu transgenic mouse to pharmacological concentrations of PEITC resulted in decreased cell viability coupled with apoptosis induction, characterized by release of histone-associated DNA fragments into the cytosol and cleavage of poly-(ADP-ribose)-polymerase and procaspase-3. The PEITC-induced apoptosis in BRI-JM04 cells was associated with up-regulation of Bak, PUMA, and Bim (long and short forms of Bim), increased S65 phosphorylation of BimEL (extra-long form), and down-regulation of Bcl-xL and Bcl-2. On the other hand, a non-tumorigenic human mammary epithelial cell line (MCF-10A) was significantly more resistant to PEITC-induced apoptosis compared with BRI-JM04 despite induction of Bax and PUMA due to concomitant overexpression of anti-apoptotic proteins, including Bcl-xL, Bcl-2, and Mcl-1. Wild-type HCT-116 cells and its isogenic PUMA knockout variant exhibited comparable sensitivity to PEITC-induced apoptosis. On the other hand, small interfering RNA knockdown of Bim protein imparted partial but statistically significant protection against PEITC-induced apoptosis in BRI-JM04, MCF-7, and MDA-MB-231 cells. In conclusion, the present study provides novel insight into the mechanism of PEITC-induced apoptosis involving Bim. PMID:21739479

  17. Urinary isothiocyanate excretion, brassica consumption, and gene polymorphisms among women living in Shanghai, China.

    PubMed

    Fowke, Jay H; Shu, Xiao-Ou; Dai, Qi; Shintani, Ayumi; Conaway, C Clifford; Chung, Fung-Lung; Cai, Qiuyin; Gao, Yu-Tang; Zheng, Wei

    2003-12-01

    Alternative measures of Brassica vegetable consumption (e.g., cabbage) may clarify the association between Brassica and cancer risk. Brassica isothiocyanates (ITCs) are excreted in urine and may provide a sensitive and food-specific dietary biomarker. However, the persistence of ITCs in the body may be brief and dependent on the activity of several Phase II enzymes, raising questions about the relationship between a single ITC measure and habitual dietary patterns. This study investigates the association between urinary ITC excretion and habitual Brassica consumption, estimated by a food frequency questionnaire, among healthy Chinese women enrolled in the Shanghai Breast Cancer Study. Participants (n = 347) completed a validated food frequency questionnaire querying habitual dietary intake during the prior 5 years and provided a fasting first-morning urine specimen. Genetic deletion of glutathione S-transferases (GSTM1/GSTT1), and single nucleotide substitutions in GSTP1 (A313G) and NAD(P)H:quinone oxidoreductase 1 (NQO1: C609T), were identified from blood DNA. Urinary ITC excretion levels were marginally higher with the GSTT1-null or GSTP1-G/G genotypes (P = 0.07, P = 0.05, respectively). Mean habitual Brassica intake was 98.3 g/day, primarily as bok choy, and Brassica intake significantly increased across quartile categories of ITC levels. The association between habitual Brassica intake and urinary ITC levels was stronger among women with GSTT1-null or GSTP1-A/A genotypes, or NQO1 T-allele, and the interaction was statistically significant across GSTP1 genotype. In conclusion, a single urinary ITC measure, in conjunction with markers of Phase II enzyme activity, provides a complementary measure of habitual Brassica intake among Shanghai women. PMID:14693750

  18. Benefits and Risks of the Hormetic Effects of Dietary Isothiocyanates on Cancer Prevention

    PubMed Central

    Bao, Yongping; Wang, Wei; Zhou, Zhigang; Sun, Changhao

    2014-01-01

    The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1–5 µM) to promote cell proliferation to 120–143% of the controls in a number of human cell lines, whilst at high levels (10–40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10–20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint. PMID:25532034

  19. Urinary total isothiocyanates and colorectal cancer: a prospective study of men in Shanghai, China

    PubMed Central

    Moy, Kristin A.; Yuan, Jian-Min; Chung, Fung-Lung; Van Den Berg, David; Wang, Renwei; Gao, Yu-Tang; Yu, Mimi C.

    2008-01-01

    Laboratory and epidemiological evidence suggest that dietary isothiocyanates (ITCs) may have a chemopreventive effect on cancer. Humans are exposed to ITCs primarily through ingestion of cruciferous vegetables which contain glucosinolates, the precursors to ITCs. The association between urinary total ITC level and colorectal cancer risk was examined in a cohort of 18,244 men in Shanghai, China, with 16 years of follow-up. Urinary total ITCs were quantified on 225 incident cases of colorectal cancer and 1119 matched controls. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated using logistic regression models. High levels of urinary total ITCs were associated with a reduced risk of colorectal cancer five years after baseline measurements of ITCs whereas a statistically nonsignificant increase in the risk of colorectal cancer was observed for cases within five years of post-enrollment (OR=1.93; 95% CI =0.85, 4.39 for the upper three quartiles of urinary ITCs versus the lowest quartile). The inverse ITC-colorectal cancer association became stronger with a longer duration of follow-up. Compared with the first quartile, ORs (95% CIs) for the second, third, and fourth quartiles of total ITCs in urine collected 10 or more years before cancer diagnosis were 0.61 (0.35, 1.05), 0.51 (0.29, 0.92), and 0.46 (0.25, 0.83), respectively, for risk of colorectal cancer (P for trend = 0.006). The present study suggests that dietary ITCs may exert tumor inhibitory effects, especially during earlier stages of the multistage process of carcinogenesis. PMID:18559550

  20. The effects and mode of action of biochar on the degradation of methyl isothiocyanate in soil.

    PubMed

    Fang, Wensheng; Wang, Qiuxia; Han, Dawei; Liu, Pengfei; Huang, Bin; Yan, Dongdong; Ouyang, Canbin; Li, Yuan; Cao, Aocheng

    2016-09-15

    Biochar is used as a new type of fertilizer in agriculture; however, its effect on the fate of fumigants in soil is not fully understood. The objective of this study was to investigate the effects of biochar on methyl isothiocyanate (MITC) degradation in soil in laboratory incubation experiments, including the effects of biochar composition, amendment rate, moisture, temperature, soil sterilization and soil type. The dissipation pathways of MITC in biochars included adsorption and chemical degradation. The adsorption of MITC by biochars was positively correlated with the specific surface area (SSA) of the biochar. Biochar with a high SSA and low H/C value (such as biochar type BC-1) reduced MITC degradation in soil substantially; following BC-1 amendment, the degradation rate was 73.9% slower than in unamended soil. The degradation of MITC was positively correlated with the H/C value of biochar, and MITC degradation in soil increased 2.2-31.1 times following amendment with biochars with higher H/C values (e.g. biochar types BC-3-6). The biochar with the lowest organic matter and low H/C value did not affect the fate of MITC in soil. Biochars affect abiotic degradation processes more than biodegradation. When soil samples had a higher water content (>10%), higher temperature (40°C), and lower organic matter, the addition of BC-1 biochar reduced MITC degradation substantially; and this did not change significantly when the amendment rate increased. However, BC-4 biochar accelerated MITC degradation with increasing amendment rate, increasing temperature, and decreasing soil water content. The differences in degradation rates due to soil type were minimized by amendment with BC-4, but significant differences in BC-1. The results showed that the rational use of biochar has the potential to reduce MITC emission by accelerated degradation and adsorption. PMID:27177140

  1. ER stress contributes to alpha-naphthyl isothiocyanate-induced liver injury with cholestasis in mice.

    PubMed

    Yao, Xiaomin; Li, Yue; Cheng, Xiaoyan; Li, Hongwei

    2016-06-01

    Endoplasmic reticulum (ER) stress is involved in the development of several liver diseases and tumors. This study investigated the underlying mechanisms of α-naphthyl isothiocyanate (ANIT)-induced liver injury with cholestasis in mice and found ER stress contributes to the injury. All animals were randomly divided into three groups. In the ANIT-intoxicated group, mice were intragastrically given 100mg/kg ANIT (dissolved in corn oil), while the other groups received an equal volume of vehicle as control. After 24 and 48h of ANIT administration, blood samples and liver tissues of all animals were collected for serum biochemistry and hepatic histopathological examinations to evaluate liver injuries with cholestasis. Hepatocellular apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression of hepatic ER stress-related markers was determined by real-time PCR, immunohistochemical assay and Western blot. ANIT was found to significantly induce liver injury with cholestasis compared with control mice as evidenced by the increase of serum transaminases and total bilirubin (TBil), and histopathological changes in mice. ANIT remarkably induced hepatocellular apoptosis, upregulated the expression of caspase-9 and cytochrome c, and inhibited the gene and protein expression of proliferating cell nuclear antigen (PCNA). The gene expression of ER stress-related markers, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), eukaryotic initiation factor 2α (eIF2α), inositol requiring enzyme-1α (IRE-1α) and activating transcription factor 6 (ATF6) was upregulated by ANIT in mice. ANIT also upregulated the protein expression of GRP78 and activated the phosphorylation of IRE1. These results suggested that ANIT induced liver injury with cholestasis partly due to its ability to activate the ER stress pathway. PMID:27173049

  2. Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells.

    PubMed

    Lee, Chang-Min; Lee, Dae-Sung; Jung, Won-Kyo; Yoo, Jong Su; Yim, Mi-Jin; Choi, Yung Hyun; Park, Saegwang; Seo, Su-Kil; Choi, Jung Sik; Lee, Young-Min; Park, Won Sun; Choi, Il-Whan

    2016-09-01

    Inflammasomes are multi-protein complexes that play a crucial role in innate immune responses. Benzyl isothiocyanate (BITC) is a naturally occurring compound found in cruciferous vegetables, and BITC exhibits potential as a chemopreventive agent. However, whether BITC exerts inflammasome-mediated regulatory effects on neuroinflammation is unknown. In this study, we examined the effects of BITC on inflammasome-mediated interleukin-1β (IL-1β) production in E. coli lipopolysaccharide (LPS)-stimulated BV2 microglial cells. IL-1β production is tightly regulated at the post-translational level through the inflammasoume. We measured the levels of IL-1β produced from the LPS-exposed BV2 microglial cells using enzyme-linked immunosorbent assays (ELISAs). The BITC regulatory mechanisms in inflammasome-mediated cellular signaling pathways were examined by RT-PCR, western blot analysis and electrophoretic mobility shift assays. BITC inhibited the secretion of IL-1β induced by LPS in the BV2 microglial cells. BITC inhibited inflammasome activation and NLR family, pyrin domain containing 3 (NLRP3)-mediated caspase-1 activation, and decreased the levels of inflammasome activation pro-inflammatory mediators, including mitochondrial reactive oxygen species (ROS) and adenosine triphosphate (ATP) secretion in the LPS-stimulated BV2 microglial cells. Furthermore, we demonstrated that nuclear factor-κB (NF-κB) activation induced by LPS was inhibited by BITC, which may contribute to the attenuated secretion of IL-1β. These BITC-mediated inhibitory effects on IL-1β expression may thus regulate neuroinflammation through the inflammasome-mediated signaling pathway. PMID:27430883

  3. Aspirin metabolites are GPR35 agonists.

    PubMed

    Deng, Huayun; Fang, Ye

    2012-07-01

    Aspirin is widely used as an anti-inflammatory, anti-platelet, anti-pyretic, and cancer-preventive agent; however, the molecular mode of action is unlikely due entirely to the inhibition of cyclooxygenases. Here, we report the agonist activity of several aspirin metabolites at GPR35, a poorly characterized orphan G protein-coupled receptor. 2,3,5-Trihydroxybenzoic acid, an aspirin catabolite, was found to be the most potent GPR35 agonist among aspirin metabolites. Salicyluric acid, the main metabolite of aspirin, was also active. These results suggest that the GPR35 agonist activity of certain aspirin metabolites may contribute to the clinical features of aspirin. PMID:22526472

  4. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism

    PubMed Central

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji

    2013-01-01

    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism. PMID:24062606

  5. Characterization of two distinct allyl pyrophosphatase activities from rat liver microsomes.

    PubMed

    Bansal, V S; Vaidya, S

    1994-12-01

    We have identified and characterized two novel allyl pyrophosphatase activities from rat liver microsomes. One specifically hydrolyzes farnesyl pyrophosphate (FPP) to farnesol and the other converts geranylgeranyl pyrophosphate (GGPP) to geranylgeranol. Hence, we named them farnesyl pyrophosphatase (FPPase) and geranylgeranyl pyrophosphatase (GGPPase) activities, respectively. Other allyl pyrophosphates, i.e., isopentenyl pyrophosphate, dimethyl allyl pyrophosphate, and geranyl pyrophosphate, did not act as substrates for these activities. Both activities are metal ion independent and exhibit acidic pH optima (5.5 and 6.0). Microsomal FPPase has a Km for FPP of 7 microM and a specific activity of 6.8 nmol/min/mg protein at pH 5.5. GGPP is a potent noncompetitive inhibitor of FPPase. FPP has no inhibitory effect on GGPPase activity. Microsomal GGPPase has a Km for GGPP of 12 microM and a specific activity of 14 nmol/min/mg protein. The Km of FPPase activity for FPP increases with an increase in pH. The GGPPase activity remains unaffected with an increase in pH. Metal ions Zn2+ and Mn2+ are potent inhibitors of GGPPase activity. Zaragozic acid B is a weak inhibitor of FPPase/GGPPase activities as compared to squalene synthase. GGPPase activity is inhibited with a fourfold higher IC50 (20 microM) as compared to FPPase (5 microM). Hence, the FPPase and GGPPase activities can be differentiated by zaragozic acid B inhibition. Kinetic analysis of inhibition of FPPase by zaragozic acid B further indicates that it is a mixed type noncompetitive inhibitor. PMID:7986083

  6. Pressure-resistant plane disk viewports from allyl diglycol carbonate plastic for hyperbaric chambers

    SciTech Connect

    Stachiw, J.D.; Stachiw, M.A.

    1986-12-01

    Acrylic plastic viewports have been used for over 40 yr in pressure vessels for human occupancy without any catastrophic failure resulting in a loss of life. However, there are special applications, such as for example in hyperbaric chambers for medical purposes, where the susceptibility of flexure stressed acrylic plastic to surface crazing and cracking in the presence of common organic solvents contained in antibacterial sprays is a distinct disadvantage. To solve this problem, a search has been initiated for transparent plastics that are not attacked by organic solvents and can be cast economically in thick sections. Allyl diglycol carbonate plastic appears not only to satisfy to foregoing requirement, but also to provide better resistance to abrasion, pitting, and X-ray or gamma irradiation than acrylic plastic. Short-term, long-term, and cyclic pressure testing has been conducted on over one hundred allyl diglycol carbonate plane disk viewports with t/D/sub 0/ ratio in the 0.06 to 0.4 range and temperature in the 4/sup 0/C to +52/sup 0/C (+40F to 125/sup 0/F) range. It appears that plane disks cast from allyl diglycol carbonate plastic can perform safely as pressure-resistant viewports in pressure vessels for human occupancy. It is recommended that for such an application their design temperature be limited to under 52/sup 0/C (125/sup 0/F), and that their design pressure at 52/sup 0/C (125/sup 0/F) design temperature not exceed 4 percent of their (STCP) short-term critical pressure at 24/sup 0/C (75/sup 0/F).

  7. A Spectroscopic and Theoretical Study of Weak Intramolecular OH\\cdots π Interactions in Allyl Carbinol and Methallyl Carbinol

    NASA Astrophysics Data System (ADS)

    Schroeder, Sidsel D.; Mackeprang, Kasper; Kjaergaard, Henrik G.

    2013-06-01

    The weak intramolecular OH\\cdots π interactions in allyl carbinol and methallyl carbinol have been studied using a combination of NIR spectroscopy and theory. The third OH-stretching overtone region of vapor phase allyl carbinol and methallyl carbinol have been recorded with intracavity laser photoacoustic spectroscopy to study the effect of an enhanced OH\\cdots π interaction in methallyl carbinol arising from the electron donating methyl group. Local mode calculations were employed to assign the observed bands. The OH-stretching transition frequency of methallyl carbinol was observed to be red shifted relative to the OH-stretching transition frequency of allyl carbinol. A red shift of the transition frequency is in this context normally interpreted as a signature of hydrogen bonding. Whether the OH\\cdots π interaction can be categorized as a hydrogen bond will be discussed in this talk.

  8. Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study

    PubMed Central

    Barker, Graeme; Johnson, David G; Young, Paul C; Macgregor, Stuart A; Lee, Ai-Lan

    2015-01-01

    Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au–allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive. PMID:26248980

  9. A computational study on the insertion of CO2 into (PSiP)palladium allyl σ-bond.

    PubMed

    Wang, Qin; Guo, Cai-Hong; Ren, Ying; Wu, Hai-Shun

    2015-05-01

    The insertion of CO2 into the (PSiP)palladium-allyl bond has been investigated using DFT. Three possible modes of CO2 insertion into (PSiP)Pd-allyl bond have been calculated, that is, direct 1.2-insertion mode, metallo-ene mode, and SE2 mode. The metallo-ene mode is the most favorable via the six-membered ring transition state. The results of calculations are consistent with the regioselectivity observed experimentally. The steric and electronic effects of different phosphine substituents have been evaluated by ONIOM and energy decomposition analysis (EDA) methods. For the phosphine substituents P(i-Pr)2 and PPh2, the contribution of electronic effect is greater than that of steric effect for the CO2 insertion into (PSiP)Pd-allyl bond; while for the phosphine substituent PMe2, the contribution of steric effect is slightly greater than that of electronic effect. PMID:25893517

  10. Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism.

    PubMed

    Bai, Da-Chang; Yu, Fei-Le; Wang, Wan-Ying; Chen, Di; Li, Hao; Liu, Qing-Rong; Ding, Chang-Hua; Chen, Bo; Hou, Xue-Long

    2016-01-01

    The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination. PMID:27283477

  11. Self-assembled line growth of allyl alcohol on the H-terminated Si(100)-(2 × 1) surface

    NASA Astrophysics Data System (ADS)

    Choi, Yun-Ki; Choi, Jin-Ho; Cho, Jun-Hyung

    2012-02-01

    Using first-principles density-functional calculations, we investigate the growth mechanism of allyl alcohol (ALA) line on the H-terminated Si(100)-(2 × 1) surface. Unlike the allyl mercaptan (CH2 = CH - CH2 - SH) line, which was observed to grow across the Si dimer rows, we find that ALA (CH2 = CH - CH2 - OH) has the line growth along the Si dimer row. The self-assembled growth of ALA line occurs via the radical chain reaction mechanism, similar to the case of a typical alkene molecule, styrene. Our calculated energy profile along the reaction pathway shows that the different growth direction of ALA line compared with that of allyl mercaptan line is ascribed to the great instability of the oxygen radical intermediate, which prevents the line growth across the dimer rows.

  12. Enhanced performance of the catalytic conversion of allyl alcohol to 3-hydroxypropionic acid using bimetallic gold catalysts.

    PubMed

    Falletta, Ermelinda; Della Pina, Cristina; Rossi, Michele; He, Qian; Kiely, Christopher J; Hutchings, Graham J

    2011-01-01

    One of the strategic building blocks in organic synthesis is 3-hydroxypropionic acid, which is particularly important for the manufacture of high performance polymers. However, to date, despite many attempts using both biological and chemical routes, no large scale effective process for manufacturing 3-hydroxypropionic acid has been developed. One potentially useful starting point is from allyl alcohol, as this can be obtained in principle from the dehydration of glycerol, thereby presenting a bio-renewable green pathway to this important building block. The catalytic transformation of allyl alcohol to 3-hydroxypropionic acid presents interesting challenges in catalyst design, particularly with respect to the control of selectivity among the products that can be expected, as acrylic acid, acrolein and glyceric acid can also be formed. In this paper, we present a novel eco-sustainable catalytic pathway leading to 3-hydroxypropionic acid, which highlights the outstanding potential of gold-based and bimetallic catalysts in the aerobic oxidation of allyl alcohol. PMID:22455056

  13. Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

    PubMed Central

    Bai, Da-Chang; Yu, Fei-Le; Wang, Wan-Ying; Chen, Di; Li, Hao; Liu, Qing-Rong; Ding, Chang-Hua; Chen, Bo; Hou, Xue-Long

    2016-01-01

    The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism—nucleophilic attack of enolate oxygen on Palladium followed by C–C bond-forming [3,3']-reductive elimination. PMID:27283477

  14. Non-thermal plasma destruction of allyl alcohol in waste gas: kinetics and modelling

    NASA Astrophysics Data System (ADS)

    DeVisscher, A.; Dewulf, J.; Van Durme, J.; Leys, C.; Morent, R.; Van Langenhove, H.

    2008-02-01

    Non-thermal plasma treatment is a promising technique for the destruction of volatile organic compounds in waste gas. A relatively unexplored technique is the atmospheric negative dc multi-pin-to-plate glow discharge. This paper reports experimental results of allyl alcohol degradation and ozone production in this type of plasma. A new model was developed to describe these processes quantitatively. The model contains a detailed chemical degradation scheme, and describes the physics of the plasma by assuming that the fraction of electrons that takes part in chemical reactions is an exponential function of the reduced field. The model captured the experimental kinetic data to less than 2 ppm standard deviation.

  15. Mild and selective vanadium-catalyzed oxidation of benzylic, allylic, and propargylic alcohols using air.

    PubMed

    Hanson, Susan K; Wu, Ruilian; Silks, L A Pete

    2011-04-15

    Transition metal-catalyzed aerobic alcohol oxidation is an attractive method for the synthesis of carbonyl compounds, but most catalytic systems feature precious metals and require pure oxygen. The vanadium complex (HQ)(2)V(V)(O)(O(i)Pr) (2 mol %, HQ = 8-quinolinate) and NEt(3) (10 mol %) catalyze the oxidation of benzylic, allylic, and propargylic alcohols with air. The catalyst can be easily prepared under air using commercially available reagents and is effective for a wide range of primary and secondary alcohols. PMID:21434606

  16. Study of intermolecular interaction of allyl chloride with acetone through dielectric and volumetric properties

    NASA Astrophysics Data System (ADS)

    Sudake, Y. S.; Kamble, S. P.; Maharolkar, A. P.; Patil, S. S.; Khirade, P. W.

    2012-06-01

    The static dielectric constant (ɛs)and relaxation time (τ) are determined from complex permittivity spectra of Allyl Chloride (ALC) with Acetone (ACE), which are obtained using the Time Domain Reflectometry (TDR) technique in microwave frequency range 10 MHz to 10 GHz. Density (ρ) and refractive index (nD) were also measured. These parameters are used to determine excess dielectric constant, excess molar volume, and excess molar refraction. The excess parameter is fitted to Redlich-Kister(RK) equation. The values of excess parameters are positive in ALC rich region whereas in ACE rich region are negative.

  17. Thermophysical properties and reaction kinetics of γ-irradiated poly allyl diglycol carbonates nuclear track detector

    NASA Astrophysics Data System (ADS)

    Elmaghraby, Elsayed K.; Seddik, Usama

    2015-07-01

    Kinetic thermogravimetric technique was used to study the effect of gamma irradiation on the poly allyl diglycol carbonates (PADC) within the dose range from 50 to ? Gy. The approach of Coats-Redfern was used to analyze the data. Results showed that low doses around 50 Gy make the polymer slightly more resistive to heat treatment. Higher radiation doses cause severe effects in the samples accompanied by the formation of lower molecular mass species and consequent crosslinking. Results support the domination of re-polymerization and crosslinking for the γ radiation interaction PADC at dose below about ? Gy, while the situation is inverted above ? Gy in which chain secession dominates.

  18. Comparative investigation of the mutagenicity of propenylic and allylic asarone isomers in the Ames fluctuation assay.

    PubMed

    Berg, Kerstin; Bischoff, Roland; Stegmüller, Simone; Cartus, Alexander; Schrenk, Dieter

    2016-07-01

    α-, β- and γ-asarone are naturally occurring phenylpropenes that occur in different plant families, mainly in Aristolochiaceae, Acoraceae and Lauraceae. Plants containing asarones are used as flavouring ingredients in alcoholic beverages (bitters), traditional phytomedicines and the rhizome of e.g. Acorus calamus is used to prepare tea. Although α- and β-asarone show a potential in the treatment of several diseases, previous studies have shown carcinogenicity in rodents (duodenum, liver). However, the mechanism of action remained unclear. Studies on the mutagenicity of propenylic α- and β-asarone are inconsistent and data on carcinogenicity and genotoxicity of allylic γ-asarone are lacking completely. Thus, the present study determined the mutagenicity of the three asarone isomers using the Ames fluctuation assay with and without exogenous metabolic activation (S9 mix) in the standard Salmonella typhimurium strains TA98 and TA100. A concentration dependent increase in mutagenicity could be verified for α- and β-asarone in strain TA100 in the presence of rat liver homogenate. The side-chain epoxides of α- and β-asarone, major metabolites formed in liver microsomes, caused mutations in TA100, supporting the hypothesis that epoxidation of the side chain plays a key role in mutagenicity of the propenylic alkenylbenzenes. The allylic γ-asarone, not undergoing detectable side-chain epoxidation in liver microsomes, was supposed to be activated via side-chain hydroxylation and further sulphonation, a typical pathway for other allylic alkenylbenzenes like estragole or methyleugenol. However, neither y-asarone nor 1'-OH-γ-asarone showed any mutagenic effect even in the human SULT-expressing Salmonella strains (TA100-hSULT1A1 and TA100-hSULT1C2), while 1'-OH-methyleugenol used as a positive control was mutagenic under these conditions. These results indicate that the propenylic asarones are genotoxic via metabolic formation of side-chain epoxides while the side

  19. Enantioselective synthesis of dialkylated N-heterocycles by palladium-catalyzed allylic alkylation.

    PubMed

    Numajiri, Yoshitaka; Jiménez-Osés, Gonzalo; Wang, Bo; Houk, K N; Stoltz, Brian M

    2015-03-01

    The enantioselective synthesis of α-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted α-positions. Broad functional group tolerance was explored at the α-position in the morpholinone series. We demonstrate the utility of this method by performing various transformations on our useful products to readily access a number of enantioenriched compounds. PMID:25714704

  20. Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-Catalysis Using Air as the Sole Oxidant.

    PubMed

    Ortgies, Stefan; Depken, Christian; Breder, Alexander

    2016-06-17

    A new metal-free catalysis protocol for the oxidative coupling of nonactivated alkenes with simple carboxylic acids has been established. This method is predicated on the cooperative interaction of a diselane and a photoredox catalyst, which allows for the use of ambient air or pure O2 as the terminal oxidant. Under the title conditions, a range of both functionalized and nonfunctionalized alkenes can be readily converted into the corresponding allylic ester products with good yields (up to 89%) and excellent regioselectivity as well as good functional group tolerance. PMID:27257803

  1. In vitro antiproliferative activity of isothiocyanates and nitriles generated by myrosinase-mediated hydrolysis of glucosinolates from seeds of cruciferous vegetables.

    PubMed

    Nastruzzi, C; Cortesi, R; Esposito, E; Menegatti, E; Leoni, O; Iori, R; Palmieri, S

    2000-08-01

    A comparison of the effect of isothiocyanates and nitriles derived from some glucosinolates, namely, epi-progoitrin, sinalbin, glucotropaeolin, glucocheirolin, and glucoraphenin, on human erythroleukemic in vitro cultured cells was studied. Many studies have in fact evidenced that a consumption of vegetable containing glucosinolates could reduce the development of colorectal cancer. In the experimental conditions used, the production of isothiocyanates and nitriles from glucosinolates is almost quantitative as confirmed by HPLC or GC-MS analysis. The obtained results demonstrated that in general nitriles are considerably less potent than the corresponding isothiocyanates in inhibiting cancer cell growth. Particularly, the isothiocyanates inhibitory activity on K562 cells growth is higher in the case of products derived from epi-progoitrin, glucotropaeolin, glucoraphenin, and glucocheirolin; while for nitriles the higher activity in inhibiting K562 cells growth is showed by sinalbin-derived product. Considering the antiproliferative activity found for isothiocyanates and nitriles, further studies will be aimed to the possible application of glucosinolate-derived products as chemopreventive cancer agents for the reduction of colorectal cancer. PMID:10956152

  2. Monoterpenoid agonists of TRPV3

    PubMed Central

    Vogt-Eisele, A K; Weber, K; Sherkheli, M A; Vielhaber, G; Panten, J; Gisselmann, G; Hatt, H

    2007-01-01

    Background and purpose: Transient receptor potential (TRP) V3 is a thermosensitive ion channel expressed predominantly in the skin and neural tissues. It is activated by warmth and the monoterpene camphor and has been hypothesized to be involved in skin sensitization. A selection of monoterpenoid compounds was tested for TRPV3 activation to establish a structure-function relationship. The related channel TRPM8 is activated by cool temperatures and a number of chemicals, among them the monoterpene (-)-menthol. The overlap of the receptor pharmacology between the two channels was investigated. Experimental approach: Transfected HEK293 cells were superfused with the test substances. Evoked currents were measured in whole cell patch clamp measurements. Dose-response curves for the most potent agonists were obtained in Xenopus laevis oocytes. Key results: Six monoterpenes significantly more potent than camphor were identified: 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol and (+)-borneol. Their EC50 is up to 16 times lower than that of camphor. All of these compounds carry a ring-located hydroxyl group and neither activates TRPM8 to a major extent. Conclusions and implications: Terpenoids have long been recognized as medically and pharmacologically active compounds, although their molecular targets have only partially been identified. TRPV3 activation may be responsible for several of the described effects of terpenoids. We show here that TRPV3 is activated by a number of monoterpenes and that a secondary hydroxyl-group is a structural requirement. PMID:17420775

  3. A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor.

    PubMed

    Prescott, Thomas A K; Panaretou, Barry; Veitch, Nigel C; Simmonds, Monique S J

    2014-01-31

    The phosphatase enzyme calcineurin controls gene expression in a variety of biological contexts however few potent inhibitors are currently available. A screen of 360 plant extracts for inhibition of calcineurin-dependent gene expression in the model organism Saccharomyces cerevisiae identified the compound 3,4,5-trimethoxybenzyl isothiocyanate as an inhibitor. The compound was subsequently shown to inhibit human calcineurin via a mixed inhibition mechanism. To gain further mechanistic insight a yeast haploinsufficiency screen of 1152 deletion strains was carried out using a novel liquid medium screening method. The resulting haploinsufficiency profile is similar to that reported for the known calcineurin inhibitor FK506. PMID:24374339

  4. Efficient fluorescence energy transfer system between fluorescein isothiocyanate and CdTe quantum dots for the detection of silver ions.

    PubMed

    Feng, Yueshu; Liu, Liwei; Hu, Siyi; Zou, Peng; Zhang, Jiaqi; Huang, Chen; Wang, Yue; Wang, Sihan; Zhang, Xihe

    2016-03-01

    We report a fluorescence resonance energy transfer (FRET) system in which the fluorescent donor is fluorescein isothiocyanate (FITC) dye and the fluorescent acceptor is CdTe quantum dot (QDs). Based on FRET quenching theory, we designed a method to detect the concentration of silver ions (Ag(+)). The results revealed a good linear trend over Ag(+) concentrations in the range 0.01-8.96 nmol/L, a range that was larger than with other methods; the quenching coefficient is 0.442. The FRET mechanism and physical mechanisms responsible for dynamic quenching are also discussed. PMID:26277997

  5. From a Sequential to a Concurrent Reaction in Aqueous Medium: Ruthenium-Catalyzed Allylic Alcohol Isomerization and Asymmetric Bioreduction.

    PubMed

    Ríos-Lombardía, Nicolás; Vidal, Cristian; Liardo, Elisa; Morís, Francisco; García-Álvarez, Joaquín; González-Sabín, Javier

    2016-07-18

    The ruthenium-catalyzed redox isomerization of allylic alcohols was successfully coupled with the enantioselective enzymatic ketone reduction (mediated by KREDs) in a concurrent process in aqueous medium. The overall transformation, formally the asymmetric reduction of allylic alcohols, took place with excellent conversions and enantioselectivities, under mild reaction conditions, employing commercially and readily available catalytic systems, and without external coenzymes or cofactors. Optimization resulted in a multistep approach and a genuine cascade reaction where the metal catalyst and biocatalyst coexist from the beginning. PMID:27258838

  6. (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol inhibits growth of colon tumors in mice

    PubMed Central

    Son, Dong Ju; Choi, Min Gi; Choi, Jeong Soon; Nam, Kyung Tak; Kim, Hae Deun; Rodriguez, Kevin; Gann, Benjamin; Ham, Young Wan; Han, Sang Bae; Hong, Jin Tae

    2015-01-01

    In our previous study, we found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal showed anti-cancer effect, but it showed lack of stability and drug likeness. We have prepared several (E)-2,4-bis(p-hydroxyphenyl)-2-butenal analogues by Heck reaction. We selected two compounds which showed significant inhibitory effect of colon cancer cell growth. Thus, we evaluated the anti-cancer effects and possible mechanisms of one compound (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol in vitro and in vivo. In this study, we found that (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol induced apoptotic cell death in a dose dependent manner (0-15 μg/ml) through activation of Fas and death receptor (DR) 3 in HCT116 and SW480 colon cancer cell lines. Moreover, the combination treatment with (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol and nuclear factor κB (NF-κB) inhibitor, phenylarsine oxide (0.1 μM) or signal transducer and activator of transcription 3 (STAT3) inhibitor, Stattic (50 μM) increased the expression of Fas and DR3 more significantly. In addition, (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol suppressed the DNA binding activity of both STAT3 and NF-κB. Knock down of STAT3 or NF-κB p50 subunit by STAT3 small interfering RNA (siRNA) or p50 siRNA magnified (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol-induced inhibitory effect on colon cancer cell growth. Besides, the expression of Fas and DR3 was increased in STAT3 siRNA or p50 siRNA transfected cells. Moreover, docking model and pull-down assay showed that (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol directly bound to STAT3 and NF-κB p50 subunit. Furthermore, (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol inhibited colon tumor growth in a dose dependent manner (2.5 mg/kg-5 mg/kg) in mice. Therefore, these findings indicated that (E)-4-(3-(3,5-dimethoxyphenyl)allyl)-2-methoxyphenol may be a promising anti-cancer agent for colon cancer with more advanced research. PMID

  7. Iodine-Catalyzed Decarboxylative Amidation of β,γ-Unsaturated Carboxylic Acids with Chloramine Salts Leading to Allylic Amides.

    PubMed

    Kiyokawa, Kensuke; Kojima, Takumi; Hishikawa, Yusuke; Minakata, Satoshi

    2015-10-26

    The iodine-catalyzed decarboxylative amidation of β,γ-unsaturated carboxylic acids with chloramine salts is described. This method enables the regioselective synthesis of allylic amides from various types of β,γ-unsaturated carboxylic acids containing substituents at the α- and β-positions. In the reaction, N-iodo-N-chloroamides, generated by the reaction of a chloramine salt with I2 , function as a key active species. The reaction provides an attractive alternative to existing methods for the synthesis of useful secondary allylic amine derivatives. PMID:26493878

  8. Cobalt-Catalyzed Cross-Coupling of Grignards with Allylic and Vinylic Bromides: Use of Sarcosine as a Natural Ligand.

    PubMed

    Frlan, Rok; Sova, Matej; Gobec, Stanislav; Stavber, Gaj; Časar, Zdenko

    2015-08-01

    Sarcosine was discovered to be an excellent ligand for cobalt-catalyzed carbon-carbon cross-coupling of Grignard reagents with allylic and vinylic bromides. The Co(II)/sarcosine catalytic system is shown to perform efficiently when phenyl and benzyl Grignards are coupled with alkenyl bromides. Notably, previously unachievable Co-catalyzed coupling of allylic bromides with Grignards to linearly coupled α-products was also realized with Co(II)/sarcosine catalyst. This method was used for efficient preparation of the key intermediate in an alternative synthesis of the antihyperglycemic drug sitagliptin. PMID:26158563

  9. γ-Selective Allylation of (E)-Alkenylzinc Iodides Prepared by Reductive Coupling of Arylacetylenes with Alkyl Iodides.

    PubMed

    Zhurkin, Fedor E; Hu, Xile

    2016-07-01

    The first examples of Cu-catalyzed γ-selective allylic alkenylation using organozinc reagents are reported. (E)-Alkenylzinc iodides were prepared by Fe-catalyzed reductive coupling of terminal arylalkynes with alkyl iodides. In the presence of a copper catalyst, these reagents reacted with allylic bromides derived from Morita-Baylis-Hillman alcohols to give 1,4-dienes in high yields. The reactions are highly γ-selective (generally γ/α > 49:1) and tolerate a wide range of functional groups such as ester, cyano, keto, and nitro. PMID:27285459

  10. Preparation of Allyl and Vinyl Silanes via the Palladium-Catalyzed Silylation of Terminal Olefins: A Silyl-Heck Reaction**

    PubMed Central

    McAtee, Jesse R.; Martin, Sara E. S.; Ahneman, Derek T.; Johnson, Keywan A.

    2012-01-01

    A high-yielding protocol for the palladium-catalyzed silylation of terminal alkenes using silyl halides is reported. This method allows facile conversion of styrenes to E-β-silyl styrenes using either TMSI or TMSCl/LiI. Terminal allyl silanes with good E:Z ratios are also readily accessed from α-olefins by this method. When combined with existing technology, this transformation provides a powerful strategy to selectively functionalize the vinyl or allylic position of terminal alkenes. PMID:22383447

  11. A SeCSe-Pd(II) pincer complex as a highly efficient catalyst for allylation of aldehydes with allyltributyltin.

    PubMed

    Yao, Qingwei; Sheets, Matthew

    2006-07-01

    An air- and moisture-stable SeCSe-Pd(II) pincer complex was synthesized and found to catalyze the nucleophilic allylation of aldehydes with allyltributyltin. The allylation of a variety of aromatic and aliphatic aldehydes to give the corresponding homoallyl alcohols was performed at room temperature to 60 degrees C in yields ranging from 50% (for typical aliphatic aldehydes) to up to 97% (for aromatic aldehydes) using 5 x 10(-3) to 1 mol % of the Pd catalyst. NMR spectroscopic study indicated that a sigma-allylpalladium intermediate was formed and possibly functions as the nucleophilic species that undergoes addition to the aldehydes. PMID:16808533

  12. Allyl Ligand Reactivity in Tantalum(V) Compounds: Experimental and Computational Evidence for Allyl Transfer to the Formamidinate Ligand in fac-Ta(NMe2)3( 1-allyl)[iPrNC(H)NHiPr] via a Metallo-Claisen Rearrangement

    SciTech Connect

    Huang, Shih-Huang Huang; Wang, Xiaoping; Nesterov, Vladimir; Hrovat, David A.; Hall, Michael B.; Richmond, Michael G.

    2011-01-01

    Treatment of TaCl(NMe{sub 2})4 (1) with allyl MgCl furnishes the allyl-substituted compound Ta(NMe{sub 2})4({eta}{sup 1}-allyl) (2) in moderate yield. The X-ray structure of 2 reveals a trigonal-bipyramidal geometry at the tantalum center with an equatorially situated {eta}{sup 1}-allyl moiety. VT {sup 1}H NMR measurements confirm that the molecule is fluxional in solution over the temperature range 298-193 K, and DFT calculations indicate that the time-averaged environment exhibited by the allyl moiety in fluid solution derives from a rapid {eta}{sup 1}-to-{eta}{sup 3} equilibration, with Ta(NMe{sub 2})4({eta}{sup 3}-allyl) serving as the transition state for this process. 1 reacts rapidly with the formamidine {sup i}PrNC(H)N{sup i}Pr to yield fac-TaCl(NMe{sub 2}){sub 3}[{sup i}PrNC(H)N{sup i}Pr] (5) and Me{sub 2}NH, and the tantalum product has been characterized by NMR spectroscopy and X-ray diffraction analysis. The five-coordinate compound Ta(NMe{sub 2}){sub 3}[{sup i}PrNCH(allyl)N{sup i}Pr] (7), whose origin is traced to the putative octahedral species fac-Ta(NMe{sub 2}){sub 3}({eta}{sup 1}-allyl)[{sup i}PrNC(H)N{sup i}Pr] (6), has been obtained from the reaction of 2 with {sup i}PrNC(H)N{sup i}Pr; 7 may also be prepared from the reaction of 5 with allylMgCl. The rearrangement of the allyl moiety in fac-Ta(NMe{sub 2}){sub 3}({eta}{sup 1}-allyl)[{sup i}PrNC(H)N{sup i}Pr] to the formamidinate carbon atom in 7 has been investigated by DFT calculations. Here the DFT calculations have provided crucial insight into the reaction mechanism and the composition of those transient species that do not lend themselves to direct spectroscopic observation. The computed barrier for this metallo-Claisen rearrangement is sensitive to the nature of the density functional employed, and the barrier computed using the meta-GGA TPSS functional provides the best agreement with the experimental conditions. The related alkenyl derivatives Ta(NMe{sub 2})4({eta}{sup 1}-3-butenyl) (3

  13. Piperidine derivatives as nonprostanoid IP receptor agonists.

    PubMed

    Hayashi, Ryoji; Sakagami, Hideki; Koiwa, Masakazu; Ito, Hiroaki; Miyamoto, Mitsuko; Isogaya, Masafumi

    2016-05-01

    The discovery of a new class of nonprostanoid prostaglandin I2 receptor (IP receptor) agonists is reported. Among them, the unique piperidine derivative 31b (2-((1-(2-(N-(4-tolyl)benzamido)ethyl)piperidin-4-yl)oxy)acetic acid) was a good IP receptor agonist and was 50-fold more selective for the human IP receptor than for other human prostanoid receptors. This compound showed good pharmacokinetic properties in dog. PMID:26996371

  14. Urinary Isothiocyanate Levels and Lung Cancer Risk Among Non-Smoking Women: a Prospective Investigation

    PubMed Central

    Fowke, Jay H.; Gao, Yu-Tang; Chow, Wong-Ho; Cai, Qiuyin; Shu, Xiao-Ou; Li, Hong-lan; Ji, Bu-Tian; Rothman, Nat; Yang, Gong; Chung, Fung-Lung; Zheng, Wei

    2010-01-01

    Background Aside from tobacco carcinogen metabolism, isothiocyanates (ITC) from cruciferous vegetables may induce apoptosis or steroid metabolism to reduce lung cancer risk. To separate the effect of these divergent mechanisms of action, we investigated the association between urinary ITC levels and lung cancer risk among non-smoking women. Methods We conducted a nested case-control within the Shanghai Women’s Health Study. Subjects included 209 incident lung cancer cases who never used tobacco, and 787 individually matched non-smoking controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) summarizing the association between urinary ITC levels and lung cancer. Secondary analyses stratified the ITC-lung cancer analyses by menopausal status, exposure to environmental tobacco smoke, and GSTM1 and GSTT1 genotypes. Results Urinary ITC levels were not significantly associated with lower lung cancer risk among non-smoking women, regardless of exposure to environmental tobacco smoke or menopausal status. Furthermore, this association was not modified by GSTT1 genotype. However, an inverse association was suggested among women with a GSTM1-positive genotype (Q1: OR=1.0 (reference); Q2: OR=0.35 (0.14, 0.89); Q3: OR=0.47 (0.20, 1.10); Q4: OR=0.63 (0.35, 1.54), p-trend = 0.38)). In contrast, lung cancer risk was positively associated with urinary ITC levels among women with the GSTM1-null genotype (Q1: OR=1.0 (reference); Q2: OR=1.67 (0.80, 3.50); Q3: OR=1.54 (0.71, 3.33); Q4: OR=2.22 (1.05, 4.67), p-trend = 0.06)). Conclusion Urinary ITC levels were not associated overall with lower lung cancer risk among non-smoking women, but secondary analyses suggested an interaction between urinary ITC levels, GSTM1 genotype, and lung cancer risk. PMID:21122939

  15. Nrf2 Knockout Attenuates the Anti-Inflammatory Effects of Phenethyl Isothiocyanate and Curcumin

    PubMed Central

    2015-01-01

    The role of phytochemicals in preventive and therapeutic medicine is a major area of scientific research. Several studies have illustrated the mechanistic roles of phytochemicals in Nrf2 transcriptional activation. The present study aims to examine the importance of the transcription factor Nrf2 by treating peritoneal macrophages from Nrf2+/+ and Nrf2–/– mice ex vivo with phenethyl isothiocyanate (PEITC) and curcumin (CUR). The peritoneal macrophages were pretreated with the drugs and challenged with lipopolysaccharides (LPSs) alone and in combination with PEITC or CUR to assess their anti-inflammatory and antioxidative effects based on gene and protein expression in the treated cells. LPS treatment resulted in an increase in the expression of inflammatory markers such as cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in both Nrf2+/+ and Nrf2–/– macrophages, detected by quantitative polymerase chain reaction (qPCR). Nrf2+/+ macrophages treated with PEITC and CUR exhibited a significant decrease in the expression of these anti-inflammatory genes along with an increase in the expression of hemeoxygenase-1 (HO-1), which is an antioxidative stress gene downstream of the Nrf2 transcription factor battery. Although there was no significant decrease in the expression of the anti-inflammatory genes or an increase in HO-1 expression in Nrf2–/– macrophages treated with either PEITC or CUR, there was a significant decrease in the protein expression of COX-2 and an increase in the expression of HO-1 in Nrf2+/+ macrophages treated with PEITC compared to that with CUR treatment. No significant changes were observed in the macrophages from knockout animals. Additionally, there was a significant decrease in LPS-induced IL-6 and TNF-α production following PEITC treatment compared with that following CUR in Nrf2+/+ macrophages, whereas no change was observed in the macrophages from knockout

  16. Bis[3-allyl-1-(4-cyanobenzyl)-2-methylbenzimidazolium] di-μ-bromido-bis[bromidocuprate(I)

    PubMed Central

    Xu, Guang-Hai; Wang, Wei

    2008-01-01

    The asymmetric unit of the title compound, (C19H18N3)2[Cu2Br4], contains one cation and one half-anion; there is a centre of symmetry mid-way between the two Cu atoms. In the cation, the nearly planar benzimidazole ring system is oriented at dihedral angles of 75.31 (3) and 21.39 (3)° with respect to the cyano­benzyl and allyl groups, respectively. The dihedral angle between cyano­benzyl and allyl groups is 87.94 (3)°. In the crystal structure, inter­molecular C—H⋯Br hydrogen bonds link the mol­ecules. There is a C—H⋯π contact between the cyano­benzyl ring and the anion; π—π contacts also exist between the benzimidazole ring systems as well as between the anion and the cyano­benzyl ring [centroid–centroid distances = 4.024 (1) and 4.617 (1) Å, respectively]. PMID:21201637

  17. Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

    PubMed Central

    Porter, David; Poon, Belinda M-L

    2015-01-01

    Summary Iron(II) complexes of the tetradentate amines tris(2-pyridylmethyl)amine (TPA) and N,N′-bis(2-pyridylmethyl)-N,N′-dimethylethane-1,2-diamine (BPMEN) are established catalysts of C–O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C–N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with either FeTPA (1 mol %) or FeBPMEN (10 mol %) converts cyclohexene to the allylic hydroxylamine (tert-butyl cyclohex-2-en-1-yl(hydroxy)carbamate) in moderate yields. Spectroscopic studies and trapping experiments suggest the reaction proceeds via a nitroso–ene mechanism, with involvement of a free N-Boc-nitroso intermediate. Asymmetric induction is not observed using the chiral tetramine ligand (+)-(2R,2′R)-1,1′-bis(2-pyridylmethyl)-2,2′-bipyrrolidine ((R,R′)-PDP). PMID:26734101

  18. Loop-Grafted Old Yellow Enzymes in the Bienzymatic Cascade Reduction of Allylic Alcohols.

    PubMed

    Reich, Sabrina; Nestl, Bettina M; Hauer, Bernhard

    2016-04-01

    The enzymatic reduction of C=C bonds in allylic alcohols with Old Yellow Enzymes represents a challenging task, due to insufficient activation through the hydroxy group. In our work, we coupled an alcohol dehydrogenase with three wild-type ene reductases-namely nicotinamide-dependent cyclohex-2-en-1-one reductase (NCR) from Zymomonas mobilis, OYE1 from Saccharomyces pastorianus and morphinone reductase (MR) from Pseudomonas putida M10-and four rationally designed β/α loop variants of NCR in the bienzymatic cascade hydrogenation of allylic alcohols. Remarkably, the wild type of NCR was not able to catalyse the cascade reaction whereas MR and OYE1 demonstrated high to excellent activities. Through the rational loop grafting of two intrinsic β/α surface loop regions near the entrance of the active site of NCR with the corresponding loops from OYE1 or MR we successfully transferred the cascade reduction activity from one family member to another. Further we observed that loop grafting revealed certain influences on the interaction with the nicotinamide cofactor. PMID:27037735

  19. X-ray structural and dynamic behaviour study of allyl palladium compounds with fluorinated benzenethiolate bridges

    NASA Astrophysics Data System (ADS)

    Redón, Rocío.; Torrens, Hugo; Ekkehardt Hahn, F.; Lügger, Thomas; Hernández-Ortega, Simón; Toscano, Ruben A.; Morales-Morales, David

    2003-08-01

    In solution, allyl palladium homobimetallic complexes bridged by fluorinated benzenethiolates, [{Pd(μ-SR)(η 3-C 3H 5)} 2] where R=C 6F 5, 1; C 6HF 4-4, 2; C 6H 4F-2, 3; C 6H 4F-3, 4 and C 6H 4F-4, 5, are found as a mixture of syn/ anti and cis/ trans isomers. The variable temperature 1H and 19F NMR study of these compounds show that the four isomers undergo interconversion through two probable mechanisms, allyl rotation assisted by the solvent and inversion of the configuration at the sulphur atoms. The X-ray crystal structure determination of [{Pd(μ-SC 6F 5)(η 3-C 3H 5)} 2] and [{Pd(μ-S C 6HF 4-4)(η 3-C 3H 5)} 2] shown both complexes to be bimetallic with the metal centres found in a slightly distorted square planar environments.

  20. Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

    PubMed Central

    Shakoori, Alireza; Bremner, John B; Abdel-Hamid, Mohammed K; Willis, Anthony C; Haritakun, Rachada

    2015-01-01

    Summary Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H)-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring-closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system. PMID:25977722

  1. Flavor, glucosinolates, and isothiocyanates of nau (Cook's scurvy grass, Lepidium oleraceum) and other rare New Zealand Lepidium species.

    PubMed

    Sansom, Catherine E; Jones, Veronika S; Joyce, Nigel I; Smallfield, Bruce M; Perry, Nigel B; van Klink, John W

    2015-02-18

    The traditionally consumed New Zealand native plant nau, Cook's scurvy grass, Lepidium oleraceum, has a pungent wasabi-like taste, with potential for development as a flavor ingredient. The main glucosinolate in this Brassicaceae was identified by LC-MS and NMR spectroscopy as 3-butenyl glucosinolate (gluconapin, 7-22 mg/g DM in leaves). The leaves were treated to mimic chewing, and the headspace was analyzed by solid-phase microextraction and GC-MS. This showed that 3-butenyl isothiocyanate, with a wasabi-like flavor, was produced by the endogenous myrosinase. Different postharvest treatments were used to create leaf powders as potential flavor products, which were tasted and analyzed for gluconapin and release of 3-butenyl isothiocyanate. A high drying temperature (75 °C) did not give major glucosinolate degradation, but did largely inactivate the myrosinase, resulting in no wasabi-like flavor release. Drying at 45 °C produced more pungent flavor than freeze-drying. Seven other Lepidium species endemic to New Zealand were also analyzed to determine their flavor potential and also whether glucosinolates were taxonomic markers. Six contained mostly gluconapin, but the critically endangered Lepidium banksii had a distinct composition including isopropyl glucosinolate, not detected in the other species. PMID:25625566

  2. Catalytic asymmetric reductive coupling of alkynes and aldehydes: enantioselective synthesis of allylic alcohols and alpha-hydroxy ketones.

    PubMed

    Miller, Karen M; Huang, Wei-Sheng; Jamison, Timothy F

    2003-03-26

    A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes is described. Allylic alcohols are afforded with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process is complementary to existing methods of enantioselective alpha-hydroxy ketone synthesis. PMID:12643701

  3. The NBS Reaction: A Simple Explanation for the Predominance of Allylic Substitution over Olefin Addition by Bromine at Low Concentrations.

    ERIC Educational Resources Information Center

    Wamser, Carl C.; Scott, Lawrence T.

    1985-01-01

    Examines mechanisms related to use of N-bromosuccinimide (NBS) for bromination at an allylic position. Also presents derived rate laws for three possible reactions of molecular bromine with an alkene: (1) free radical substitution; (2) free radical addition; and (3) electrophilic addition. (JN)

  4. A metal-free dyotropic-like rearrangement of 2-oxa allylic alcohols in the presence of organoboronic acids.

    PubMed

    Ye, Weimin; Li, Wenbo; Zhang, Junliang

    2014-09-01

    The first example of a dyotropic-like rearrangement of 2-oxa allylic alcohols in the presence of catalytic amounts of Selectfluor and DABCO was reported, which provides a facile access to organoboronates. This reaction represents an unprecedented dyotropic rearrangement consisting of cleavage of two vicinal bonds (one C-C bond and one C=C bond). PMID:25026497

  5. Organoselenium-catalyzed, hydroxy-controlled regio- and stereoselective amination of terminal alkenes: efficient synthesis of 3-amino allylic alcohols.

    PubMed

    Deng, Zhimin; Wei, Jialiang; Liao, Lihao; Huang, Haiyan; Zhao, Xiaodan

    2015-04-17

    An efficient route to prepare 3-amino allylic alcohols in excellent regio- and stereoselectivity in the presence of bases by orangoselenium catalysis has been developed. In the absence of bases α,β-unsaturated aldehydes were formed in up to 97% yield. Control experiments reveal that the hydroxy group is crucial for the direct amination. PMID:25849818

  6. Diastereoselective Allylation of "N"-"Tert"-Butanesulfinyl Imines: An Asymmetric Synthesis Experiment for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Chen, Xiao-Yang; Sun, Li-Sen; Gao, Xiang; Sun, Xing-Wen

    2015-01-01

    An asymmetric synthetic experiment that encompasses both diastereoselectivity and enantioselectivity is described. In this experiment, Zn-mediated allylation of an ("R")-"N"-"tert"-butanesulfinyl imine is first performed to obtain either diastereomer using two different solvent systems, followed by oxidation of the…

  7. Visible-light induced oxidant-free oxidative cross-coupling for constructing allylic sulfones from olefins and sulfinic acids.

    PubMed

    Zhang, Guoting; Zhang, Lingling; Yi, Hong; Luo, Yi; Qi, Xiaotian; Tung, Chen-Ho; Wu, Li-Zhu; Lei, Aiwen

    2016-08-16

    An oxidant-free dehydrogenative sulfonylation of α-methyl-styrene derivatives was developed for the construction of allylic sulfones by using eosin Y as a photosensitizer in conjunction with a cobaloxime catalyst. The process features a low-cost metal catalyst and atom economy, which provides an appealing strategy for future synthetic chemistry. PMID:27481529

  8. Isovanillin derived N-(un)substituted hydroxylamines possessing an ortho-allylic group: valuable precursors to bioactive N-heterocycles.

    PubMed

    Dulla, Balakrishna; Tangellamudi, Neelima D; Balasubramanian, Sridhar; Yellanki, Swapna; Medishetti, Raghavender; Kumar Banote, Rakesh; Hari Chaudhari, Girish; Kulkarni, Pushkar; Iqbal, Javed; Reiser, Oliver; Pal, Manojit

    2014-04-28

    The intramolecular 1,3-dipolar cycloaddition of isovanillin derived N-aryl hydroxylamines possessing ortho-allylic dipolarophiles affords novel benzo analogues of tricyclic isoxazolidines that can be readily transformed into functionalized lactams, γ-aminoalcohols and oxazepines. The corresponding N-unsubstituted hydroxylamines give rise to tetrahydroisoquinolines. Anxiogenic properties of these compounds are tested in zebra fish. PMID:24576957

  9. Anti-Inflammatory and Antioxidant Effects of Repeated Exposure to Cruciferous Allyl Nitrile in Sensitizer-Induced Ear Edema in Mice

    PubMed Central

    Tanii, Hideji; Sugitani, Kayo; Saijoh, Kiyofumi

    2016-01-01

    Background Skin sensitizers induce allergic reactions through the induction of reactive oxygen species. Allyl nitrile from cruciferous vegetables has been reported to induce antioxidants and phase II detoxification enzymes in various tissues. We assessed the effects of repeated exposure to allyl nitrile on sensitizer-induced allergic reactions. Material/Methods Mice were dosed with allyl nitrile (0–200 μmol/kg), and then received a dermal application of 1 of 3 sensitizers on the left ear or 1 of 2 vehicles on the right ear. Quantitative assessment of edema was carried out by measuring the difference in weight between the portions taken from the right and left ears. We tested enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) in ears. Results Repeated exposure to allyl nitrile reduced edemas induced by glutaraldehyde and by 2, 4-dinitrochlorobenzene (DNCB), but not by formaldehyde. The repeated exposure decreased levels of TBARS, a marker of oxidative stress, induced by glutaraldehyde and by DNCB, but not by formaldehyde. Allyl nitrile elevated SOD levels for the 3 sensitizers, and CAT levels for formaldehyde and DNCB. Allyl nitrile also increased GPx levels for formaldehyde and DNCB, but not for glutaraldehyde. The reduced edemas were associated with changes in oxidative stress levels and antioxidant enzymes. Conclusions Repeated exposure to allyl nitrile reduced allergic reactions induced by glutaraldehyde and by DNCB, but not by formaldehyde. This reduction was associated with changes in ROS levels and antioxidant enzyme activities. PMID:26932717

  10. Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis

    PubMed Central

    Banks, Matthew L.; Roma, Peter G.; Folk, John E.; Rice, Kenner C.

    2012-01-01

    Rationale Delta-opioid agonists enhance the antinociceptive efficacy of methadone and other mu-opioid agonists. However, relatively little is known about the degree to which delta agonists might enhance the abuse-related effects of mu agonists. Objective This study used a behavioral economic approach to examine effects of the delta agonist SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxy-benzyl]-N,N-diethylbenzamide] on the reinforcing effects of methadone in a drug self-administration assay. Interactions between SNC80 and cocaine were also examined for comparison. Methods Rhesus monkeys (n=4), surgically implanted with indwelling intravenous catheters, were tested in two phases. In phase 1, drug self-administration dose-effect curves for methadone (0.0032–0.1 mg/kg/injection (inj)) and cocaine (0.0032–0.32 mg/kg/inj) alone were determined under a fixed-ratio 10 (FR 10) schedule of reinforcement. In phase 2, FR values were increased every 3 days (FR 1–FR 1800) during availability of methadone alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.1:1, 0.3:1, and 0.9:1 SNC80/methadone) or of cocaine alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.33:1, 1:1, and 3:1 SNC80/ cocaine). Demand curves related drug intake to FR price, and measures of reinforcement were derived. Results Methadone and cocaine alone each functioned as a reinforcer. SNC80 did not alter measures of reinforcement for either methadone or cocaine. Conclusions SNC80 at proportions previously shown to enhance methadone-induced antinociception did not enhance the abuse-related effects of methadone. These results support the proposition that delta agonists may selectively enhance mu agonist analgesic effects without enhancing mu agonist abuse liability. PMID:21369752

  11. Effects of the selective delta opioid agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys.

    PubMed

    Do Carmo, Gail Pereira; Mello, Nancy K; Rice, Kenner C; Folk, John E; Negus, S Stevens

    2006-10-10

    Delta agonists such as SNC80 ((+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) produce some cocaine-like behavioral effects and warrant evaluation as candidate "agonist" medications for cocaine abuse. The present study examined acute and chronic effects of the systemically active delta agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys. Acute SNC80 (0.32-3.2 mg/kg, i.m.) pretreatment dose-dependently decreased cocaine self-administration (0.0032 mg/kg/injection), but doses of SNC80 that decreased cocaine self-administration also decreased food-maintained responding. In chronic studies, SNC80 (0.32-3.2 mg/kg/h, i.v.) was delivered for 7 days, and food or cocaine (0.01 mg/kg/injection) was available during 4 daily components of food availability and 4 daily components of drug availability. Chronic SNC80 (1.8 mg/kg/h) tended to decrease cocaine self-administration but produced greater reductions in food-maintained responding. A higher dose of 3.2 mg/kg/h SNC80 eliminated both cocaine- and food-maintained responding and produced profound sedation in one monkey and was not tested in other monkeys. These findings indicate that SNC80 produced dose-dependent and non-selective reductions in cocaine self-administration. These results suggest that SNC80 is unlikely to be useful as a treatment for cocaine dependence. PMID:16934797

  12. Antitumor activity of phenethyl isothiocyanate in HER2-positive breast cancer models

    PubMed Central

    2012-01-01

    Background HER2 is an oncogene, expression of which leads to poor prognosis in 30% of breast cancer patients. Although trastuzumab is apparently an effective therapy against HER2-positive tumors, its systemic toxicity and resistance in the majority of patients restricts its applicability. In this study we evaluated the effects of phenethyl isothiocyanate (PEITC) in HER2-positive breast cancer cells. Methods MDA-MB-231 and MCF-7 breast cancer cells stably transfected with HER2 (high HER2 (HH)) were used in this study. The effect of PEITC was evaluated using cytotoxicity and apoptosis assay in these syngeneic cells. Western blotting was used to delineate HER2 signaling. SCID/NOD mice were implanted with MDA-MB-231 (HH) xenografts. Results Our results show that treatment of MDA-MB-231 and MCF-7 cells with varying concentrations of PEITC for 24 h extensively reduced the survival of the cells with a 50% inhibitory concentration (IC50) of 8 μM in MDA-MB-231 and 14 μM in MCF-7 cells. PEITC treatment substantially decreased the expression of HER2, epidermal growth factor receptor (EGFR) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr-705. The expression of BCL-2-associated × (BAX) and BIM proteins were increased, whereas the levels of B cell lymphoma-extra large (BCL-XL) and X-linked inhibitor of apoptosis protein (XIAP) were significantly decreased in both the cell lines in response to PEITC treatment. Substantial cleavage of caspase 3 and poly-ADP ribose polymerase (PARP) were associated with PEITC-mediated apoptosis in MDA-MB-231 and MCF-7 cells. Notably, transient silencing of HER2 decreased and overexpressing HER2 increased the effects of PEITC. Furthermore, reactive oxygen species (ROS) generation, mitochondrial depolarization and apoptosis by PEITC treatment were much higher in breast cancer cells expressing higher levels of HER2 (HH) as compared to parent cell lines. The IC50 of PEITC following 24 h of treatment was

  13. beta2-Agonists at the Olympic Games.

    PubMed

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  14. Introduction of a single isomer beta agonist.

    PubMed

    Rau, J L

    2000-08-01

    The release of levalbuterol offers the first approved single-isomer beta agonist for oral inhalation. Data from in vitro studies support the concept that S albuterol is not inactive and may have properties antagonistic to bronchodilation. There is some variability in the results of clinical studies with the separate isomers of albuterol, which suggests the need for further study. The introduction of levalbuterol into general clinical use in managing asthma and chronic obstructive disease should begin to offer additional information on the effects of a single isomer beta agonist in comparison to previous racemic mixtures. PMID:10963321

  15. Isothiocyanate-functionalized bifunctional chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) complexes for targeting uPAR in prostate cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developing strategies to rapidly incorporate the fac-[MI(CO)3]+ (M = Re, 99mTc) core into biological targeting vectors is a growing realm in radiopharmaceutical development. This work presents the preparation of a novel isothiocyanate-functionalized bifunctional chelate based on 2,2´-dipicolylamine ...

  16. Development of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous analysis of intact glucosinolates and isothiocyanates in Brassicaceae seeds and functional foods.

    PubMed

    Franco, P; Spinozzi, S; Pagnotta, E; Lazzeri, L; Ugolini, L; Camborata, C; Roda, A

    2016-01-01

    A new high pressure liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of glucosinolates, as glucoraphanin and glucoerucin, and the corresponding isothiocyanates, as sulforaphane and erucin, was developed and applied to quantify these compounds in Eruca sativa defatted seed meals and enriched functional foods. The method involved solvent extraction, separation was achieved in gradient mode using water with 0.5% formic acid and acetonitrile with 0.5% formic acid and using a reverse phase C18 column. The electrospray ion source operated in negative and positive mode for the detection of glucosinolates and isothiocyanates, respectively, and the multiple reaction monitoring (MRM) was selected as acquisition mode. The method was validated following the ICH guidelines. Replicate experiments demonstrated a good accuracy (bias%<10%) and precision (CV%<10%). Detection limits and quantification limits are in the range of 1-400ng/mL for each analytes. Calibration curves were validated on concentration ranges from 0.05 to 50μg/mL. The method proved to be suitable for glucosinolates and isothiocyanates determination both in biomasses and in complex matrices such as food products enriched with glucosinolates, or nutraceutical bakery products. In addition, the developed method was applied to the simultaneous determination of glucosinolates and isothiocyanates in bakery product enriched with glucosinolates, to evaluate their thermal stability after different industrial processes from cultivation phases to consumer processing. PMID:26363943

  17. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

    NASA Astrophysics Data System (ADS)

    Behenna, Douglas C.; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E.; Virgil, Scott C.; Stoltz, Brian M.

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.

  18. Regio- and Stereoselective Monoepoxidation of Dienes using Methyltrioxorhenium: Synthesis of Allylic Epoxides

    PubMed Central

    2015-01-01

    Methyltrioxorhenium (MTO) complexed with pyridine was shown to be a highly effective catalyst for the regioselective monoepoxidation of conjugated di- and trienes using 30% H2O2 at or below room temperature. The resultant allylic epoxides, and the triols derived from them, are versatile synthetic intermediates as well as substructures present in many bioactive natural products. The site of epoxidation was dependent upon olefin substitution, olefin geometry (Z vs E), and the presence of electron-withdrawing substituents on adjacent carbons. For 1-acyl(silyl)oxypenta-2,4-dienes, epoxidation of the distal olefin was generally favored in contrast to the adjacent regioselectivity characteristic of Sharpless, peracid, and other directed epoxidations of hydroxylated dienes. PMID:25321319

  19. Catalytic asymmetric carbon-carbon bond formation via allylic alkylations with organolithium compounds

    NASA Astrophysics Data System (ADS)

    Pérez, Manuel; Fañanás-Mastral, Martín; Bos, Pieter H.; Rudolph, Alena; Harutyunyan, Syuzanna R.; Feringa, Ben L.

    2011-05-01

    Carbon-carbon bond formation is the basis for the biogenesis of nature's essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C-C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C-C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon-carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species.

  20. Allyl alcohol and garlic (Allium sativum) extract produce oxidative stress in Candida albicans

    PubMed Central

    Lemar, Katey M.; Passa, Ourania; Aon, Miguel A.; Cortassa, Sonia; Müller, Carsten T.; Plummer, Sue; O’Rourke, Brian; Lloyd, David

    2009-01-01

    Both the growth and respiration of Candida albicans are sensitive to extracts of Allium sativum and investigations into the anticandidal activities are now focussing on the purified constituents to determine the targets of inhibition. Of particular interest is allyl alcohol (AA), a metabolic product that accumulates after trituration of garlic cloves. Putative targets for AA were investigated by monitoring changes in intracellular responses after exposure of C. albicans cells to AA or a commercially available garlic extract. Two-photon laser scanning microscopy and other techniques were used. Changes typical of oxidative stress – NADH oxidation and glutathione depletion, and increased reactive oxygen species – were observed microscopically and by flow cytometry. Known targets for AA are alcohol dehydrogenases Adh1 and 2 (in the cytosol) and Adh3 (mitochondrial), although the significant decrease in NAD(P)H after addition of AA is indicative of another mechanism of action. PMID:16207909

  1. Separation and recovery of cellulose from Zoysia japonica by 1-allyl-3-methylimidazolium chloride.

    PubMed

    Li, Wei-Zun; Ju, Mei-Ting; Wang, Yan-Nan; Liu, Le; Jiang, Yang

    2013-01-30

    We investigated the use of ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AMIMCl) for extracting cellulose from Zoysia japonica by using Fourier transform infrared spectroscopy, nuclear magnetic resonance, scanning electron microscopy and thermogravimetric analysis to analyze the IL and its effects on cellulose extraction. After water pretreatment at 121 °C for several minutes, cellulose extraction rate was 71% under optimized conditions, and the yield of cellulose was >99% by AMIMCl. The effectiveness of AMIMCl as an extraction agent can be attributed to the prevalence of intra- and inter-molecular hydrogen bonding in cellulose. By contrast, hemicelluloses were not recovered by AMIMCl because hemicelluloses in plant cell walls are connected to lignin by covalent bonding. Results also showed that the regenerated cellulose was exactly the same as untreated cellulose, except for the degree of crystallinity. PMID:23218288

  2. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams.

    PubMed

    Behenna, Douglas C; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E; Virgil, Scott C; Stoltz, Brian M

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. PMID:22270628

  3. Divergent C—H Insertion–Cyclization Cascades of N‐Allyl Ynamides

    PubMed Central

    Adcock, Holly V.; Chatzopoulou, Elli

    2015-01-01

    Abstract Gold carbene reactivity patterns were accessed by ynamide insertion into a C(sp3)—H bond. A substantial increase in molecular complexity occurred through the cascade polycyclization of N‐allyl ynamides to form fused nitrogen‐heterocycle scaffolds. Exquisite selectivity was observed despite several competing pathways in an efficient gold‐catalyzed synthesis of densely functionalized C(sp3)‐rich polycycles and a copper‐catalyzed synthesis of fused pyridine derivatives. The respective gold–keteniminium and ketenimine activation pathways have been explored through a structure–reactivity study, and isotopic labeling identified turnover‐limiting C—H bond‐cleavage in both processes. PMID:26515958

  4. Theoretical study on the gas phase reaction of allyl chloride with hydroxyl radical.

    PubMed

    Zhang, Yunju; Chao, Kai; Sun, Jingyu; Zhang, Wanqiao; Shi, Haijie; Yao, Cen; Su, Zhongmin; Pan, Xiumei; Zhang, Jingping; Wang, Rongshun

    2014-02-28

    The reaction of allyl chloride with the hydroxyl radical has been investigated on a sound theoretical basis. This is the first time to gain a conclusive insight into the reaction mechanism and kinetics for important pathways in detail. The reaction mechanism confirms that OH addition to the C=C double bond forms the chemically activated adducts, IM1 (CH2CHOHCH2Cl) and IM2 (CH2OHCHCH2Cl) via low barriers, and direct H-abstraction paths may also occur. Variational transition state model and multichannel RRKM theory are employed to calculate the temperature-, pressure-dependent rate constants. The calculated rate constants are in good agreement with the experimental data. At 100 Torr with He as bath gas, IM6 formed by collisional stabilization is the major products in the temperature range 200-600 K; the production of CH2CHCHCl via hydrogen abstractions becomes dominant at high temperatures (600-3000 K). PMID:24588171

  5. Copper-catalyzed oxidative dehydrogenative carboxylation of unactivated alkanes to allylic esters via alkenes.

    PubMed

    Tran, Ba L; Driess, Matthias; Hartwig, John F

    2014-12-10

    We report copper-catalyzed oxidative dehydrogenative carboxylation (ODC) of unactivated alkanes with various substituted benzoic acids to produce the corresponding allylic esters. Spectroscopic studies (EPR, UV-vis) revealed that the resting state of the catalyst is [(BPI)Cu(O2CPh)] (1-O2CPh), formed from [(BPI)Cu(PPh3)2], oxidant, and benzoic acid. Catalytic and stoichiometric reactions of 1-O2CPh with alkyl radicals and radical probes imply that C-H bond cleavage occurs by a tert-butoxy radical. In addition, the deuterium kinetic isotope effect from reactions of cyclohexane and d12-cyclohexane in separate vessels showed that the turnover-limiting step for the ODC of cyclohexane is C-H bond cleavage. To understand the origin of the difference in products formed from copper-catalyzed amidation and copper-catalyzed ODC, reactions of an alkyl radical with a series of copper-carboxylate, copper-amidate, and copper-imidate complexes were performed. The results of competition experiments revealed that the relative rate of reaction of alkyl radicals with the copper complexes follows the trend Cu(II)-amidate > Cu(II)-imidate > Cu(II)-benzoate. Consistent with this trend, Cu(II)-amidates and Cu(II)-benzoates containing more electron-rich aryl groups on the benzamidate and benzoate react faster with the alkyl radical than do those with more electron-poor aryl groups on these ligands to produce the corresponding products. These data on the ODC of cyclohexane led to preliminary investigation of copper-catalyzed oxidative dehydrogenative amination of cyclohexane to generate a mixture of N-alkyl and N-allylic products. PMID:25389772

  6. Copper-Catalyzed Oxidative Dehydrogenative Carboxylation of Unactivated Alkanes to Allylic Esters via Alkenes

    PubMed Central

    2015-01-01

    We report copper-catalyzed oxidative dehydrogenative carboxylation (ODC) of unactivated alkanes with various substituted benzoic acids to produce the corresponding allylic esters. Spectroscopic studies (EPR, UV–vis) revealed that the resting state of the catalyst is [(BPI)Cu(O2CPh)] (1-O2CPh), formed from [(BPI)Cu(PPh3)2], oxidant, and benzoic acid. Catalytic and stoichiometric reactions of 1-O2CPh with alkyl radicals and radical probes imply that C–H bond cleavage occurs by a tert-butoxy radical. In addition, the deuterium kinetic isotope effect from reactions of cyclohexane and d12-cyclohexane in separate vessels showed that the turnover-limiting step for the ODC of cyclohexane is C–H bond cleavage. To understand the origin of the difference in products formed from copper-catalyzed amidation and copper-catalyzed ODC, reactions of an alkyl radical with a series of copper–carboxylate, copper–amidate, and copper–imidate complexes were performed. The results of competition experiments revealed that the relative rate of reaction of alkyl radicals with the copper complexes follows the trend Cu(II)–amidate > Cu(II)–imidate > Cu(II)–benzoate. Consistent with this trend, Cu(II)–amidates and Cu(II)–benzoates containing more electron-rich aryl groups on the benzamidate and benzoate react faster with the alkyl radical than do those with more electron-poor aryl groups on these ligands to produce the corresponding products. These data on the ODC of cyclohexane led to preliminary investigation of copper-catalyzed oxidative dehydrogenative amination of cyclohexane to generate a mixture of N-alkyl and N-allylic products. PMID:25389772

  7. Blood–brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate

    PubMed Central

    Shityakov, Sergey; Salvador, Ellaine; Pastorin, Giorgia; Förster, Carola

    2015-01-01

    In this study, the ability of a multiwalled carbon nanotube functionalized with fluorescein isothiocyanate (MWCNT–FITC) was assessed as a prospective central nervous system-targeting drug delivery system to permeate the blood–brain barrier. The results indicated that the MWCNT–FITC conjugate is able to penetrate microvascular cerebral endothelial monolayers; its concentrations in the Transwell® system were fully equilibrated after 48 hours. Cell viability test, together with phase-contrast and fluorescence microscopies, did not detect any signs of MWCNT–FITC toxicity on the cerebral endothelial cells. These microscopic techniques also revealed presumably the intracellular localization of fluorescent MWCNT–FITCs apart from their massive nonfluorescent accumulation on the cellular surface due to nanotube lipophilic properties. In addition, the 1,000 ps molecular dynamics simulation in vacuo discovered the phenomenon of carbon nanotube aggregation driven by van der Waals forces via MWCNT–FITC rapid dissociation as an intermediate phase. PMID:25784800

  8. Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

    PubMed Central

    Szabo, Jan; Karger, Kerstin; Bucher, Nicolas

    2014-01-01

    Summary 1,2,3-Triaminoguanidinium chloride was combined with benzaldehyde and hydratropic aldehyde to furnish the corresponding tris(imines), which were converted into 1,2,3-tris(benzylamino)guanidinium salts by catalytic hydrogenation in the former, and by borane reduction in the latter case. The resulting alkyl-substituted triaminoguanidinium salts underwent a threefold carbamoylation with aryl isocyanates to furnish 1,2,3-tris(ureido)guanidinium salts, while p-toluenesulfonyl isocyanate led only to a mono-ureido guanidinium salt. With aryl isothiocyanates, 3-hydrazino-1H-1,2,4-triazole-5(4H)-thione derivatives were obtained. Compounds 7a and 8 show interesting solid-state structures with intra- and intermolecular hydrogen bonds. PMID:25298792

  9. Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates.

    PubMed

    Szabo, Jan; Karger, Kerstin; Bucher, Nicolas; Maas, Gerhard

    2014-01-01

    1,2,3-Triaminoguanidinium chloride was combined with benzaldehyde and hydratropic aldehyde to furnish the corresponding tris(imines), which were converted into 1,2,3-tris(benzylamino)guanidinium salts by catalytic hydrogenation in the former, and by borane reduction in the latter case. The resulting alkyl-substituted triaminoguanidinium salts underwent a threefold carbamoylation with aryl isocyanates to furnish 1,2,3-tris(ureido)guanidinium salts, while p-toluenesulfonyl isocyanate led only to a mono-ureido guanidinium salt. With aryl isothiocyanates, 3-hydrazino-1H-1,2,4-triazole-5(4H)-thione derivatives were obtained. Compounds 7a and 8 show interesting solid-state structures with intra- and intermolecular hydrogen bonds. PMID:25298792

  10. Inhibition of mutagenicity of food-derived heterocyclic amines by sulphoraphene--an isothiocyanate isolated from radish.

    PubMed

    Shishu; Singla, A K; Kaur, I P

    2003-02-01

    The naturally derived isothiocyanate, sulphoraphene [4-isothiocyanato-(1R)-(methylsulphinyl)-1-(E)-butene], isolated from seeds of radish ( Raphanus sativus L., Cruciferae) was investigated for its antigenotoxic effects against a battery of cooked food mutagens (heterocyclic amines) in the Ames Salmonella/reversion assay using Salmonella typhimurium TA98 (frame-shift mutation sensitive) and TA100 (base -pair mutation sensitive) bacterial strains in the presence of Aroclor 1254 induced rat liver S9. Results of the present in vitro anti-mutagenicity studies using the base-pair mutation sensitive strain TA100, strongly suggest that sulphoraphene is a potent inhibitor of the S9-mediated mutagenicity of all the tested heterocyclic amines (60 - 75 % inhibition at a dose of 500 nmol/plate). PMID:12624832

  11. Fluorescein Isothiocyanate-Labeled Lectin Analysis of the Surface of the Nitrogen-Fixing Bacterium Azospirillum brasilense by Flow Cytometry

    PubMed Central

    Yagoda-Shagam, Janet; Barton, Larry L.; Reed, William P.; Chiovetti, Robert

    1988-01-01

    The cell surface of Azospirillum brasilense was probed by using fluorescein isothiocyanate (FITC)-labeled lectins, with binding determined by fluorescence-activated flow cytometry. Cells from nitrogen-fixing or ammonium-assimilating cultures reacted similarly to FITC-labeled lectins, with lectin binding in the following order: Griffonia simplicifolia II agglutinin > Griffonia simplicifolia I agglutinin > Triticum vulgaris agglutinin > Glycine max agglutinin > Canavalia ensiformis agglutinin > Limax flavus agglutinin > Lotus tetragonolobus agglutinin. The fluorescence intensity of cells labeled with FITC-labeled G. simplicifolia I, C. ensiformis, T. vulgaris, and G. max agglutinins was influenced by lectin concentration. Flow cytometry measurements of lectin binding to cells was consistent with measurements of agglutination resulting from lectin-cell interaction. Capsules surrounding nitrogen-fixing and ammonium-assimilating cells were readily demonstrated by light and transmission electron microscopies. Images PMID:16347693

  12. Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells.

    PubMed

    Abe, N; Hou, D-X; Munemasa, S; Murata, Y; Nakamura, Y

    2014-01-01

    Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress β-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in β-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased β-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited β-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and β-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells. PMID:25412312

  13. Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore.

    PubMed

    Zhao, B; Seow, A; Lee, E J; Poh, W T; Teh, M; Eng, P; Wang, Y T; Tan, W C; Yu, M C; Lee, H P

    2001-10-01

    Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have cancer-protective effects. This class of compounds is metabolized by the glutathione S-transferase family of enzymes, which are also involved in the detoxification of tobacco-related carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development. PMID:11588132

  14. Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells

    PubMed Central

    Abe, N; Hou, D-X; Munemasa, S; Murata, Y; Nakamura, Y

    2014-01-01

    Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress β-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in β-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased β-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited β-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and β-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells. PMID:25412312

  15. Iron depletion in HCT116 cells diminishes the upregulatory effect of phenethyl isothiocyanate on heme oxygenase-1.

    PubMed

    Bolloskis, Michael P; Carvalho, Fabiana P; Loo, George

    2016-04-15

    Some of the health-promoting properties of cruciferous vegetables are thought to be partly attributed to isothiocyanates. These phytochemicals can upregulate the expression of certain cytoprotective stress genes, but it is unknown if a particular nutrient is involved. Herein, the objective was to ascertain if adequate iron is needed for enabling HCT116 cells to optimally express heme oxygenase-1 (HO-1) when induced by phenethyl isothiocyanate (PEITC). PEITC increased HO-1 expression and also nuclear translocation of Nrf2, which is a transcription factor known to activate the HO-1 gene. However, in HCT116 cells that were made iron-deficient by depleting intracellular iron with deferoxamine (DFO), PEITC was less able to increase HO-1 expression and nuclear translocation of Nrf2. These suppressive effects of DFO were overcome by replenishing the iron-deficient cells with the missing iron. To elucidate these findings, it was found that PEITC-induced HO-1 upregulation can be inhibited with thiol antioxidants (glutathione and N-acetylcysteine). Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin) and a superoxide scavenger (Tiron) each inhibited PEITC-induced HO-1 upregulation. In doing so, diphenyleneiodonium was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf2. Collectively, the results imply that the HO-1 upregulation by PEITC involves an iron-dependent, oxidant signaling pathway. Therefore, it is concluded that ample iron is required to enable PEITC to fully upregulate HO-1 expression in HCT116 cells. As such, it is conceivable that iron-deficient individuals may not reap the full health benefits of eating PEITC-containing cruciferous vegetables that via HO-1 may help protect against multiple chronic diseases. PMID:26945724

  16. From allylic alcohols to aldols by using iron carbonyls as catalysts: computational study on a novel tandem isomerization-aldolization reaction.

    PubMed

    Branchadell, Vicenç; Crévisy, Christophe; Grée, René

    2004-11-01

    The tandem isomerization-aldolization reaction between allyl alcohol and formaldehyde mediated by [Fe(CO)3] was studied with the density functional B3LYP method. Starting from the key [(enol)Fe(CO)3] complex, several reaction paths for the reaction with formaldehyde were explored. The results show that the most favorable reaction path involves first an enol/allyl alcohol ligand-exchange process followed by direct condensation of formaldehyde with the free enol. During this process, formation of the new C-C bond takes place simultaneously with a proton transfer between the enol and the aldehyde. Therefore, the role of [Fe(CO)3] is to catalyze the allyl alcohol to enol isomerization affording the free enol, which adds to the aldehyde in a carbonyl-ene type reaction. Similar results were obtained for the reaction between allyl alcohol and acetaldehyde. PMID:15472940

  17. Reciprocity of agonistic support in ravens

    PubMed Central

    Fraser, Orlaith N.; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim’s likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID:22298910

  18. Multiple tyrosine metabolites are GPR35 agonists

    PubMed Central

    Deng, Huayun; Hu, Haibei; Fang, Ye

    2012-01-01

    Both kynurenic acid and 2-acyl lysophosphatidic acid have been postulated to be the endogenous agonists of GPR35. However, controversy remains whether alternative endogenous agonists exist. The molecular targets accounted for many nongenomic actions of thyroid hormones are mostly unknown. Here we report the agonist activity of multiple tyrosine metabolites at the GPR35. Tyrosine metabolism intermediates that contain carboxylic acid and/or catechol functional groups were first selected. Whole cell dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor were then used to characterize their agonist activity in native HT-29. Molecular assays including β-arrestin translocation, ERK phosphorylation and receptor internalization confirmed that GPR35 functions as a receptor for 5,6-dihydroxyindole-2-carboxylic acid, 3,3′,5′-triiodothyronine, 3,3′,5-triiodothyronine, gentisate, rosmarinate, and 3-nitrotyrosine. These results suggest that multiple tyrosine metabolites are alternative endogenous ligands of GPR35, and GPR35 may represent a druggable target for treating certain diseases associated with abnormality of tyrosine metabolism. PMID:22523636

  19. Small molecule TSHR agonists and antagonists.

    PubMed

    Neumann, S; Gershengorn, M C

    2011-04-01

    TSH activates the TSH receptor (TSHR) thereby stimulating the function of thyroid follicular cells (thyrocytes) leading to biosynthesis and secretion of thyroid hormones. Because TSHR is involved in several thyroid pathologies, there is a strong rationale for the design of small molecule "drug-like" ligands. Recombinant human TSH (rhTSH, Thyrogen(®)) has been used in the follow-up of patients with thyroid cancer to increase the sensitivity for detection of recurrence or metastasis. rhTSH is difficult to produce and must be administered by injection. A small molecule TSHR agonist could produce the same beneficial effects as rhTSH but with greater ease of oral administration. We developed a small molecule ligand that is a full agonist at TSHR. Importantly for its clinical potential, this agonist elevated serum thyroxine and stimulated thyroidal radioiodide uptake in mice after its absorption from the gastrointestinal tract following oral administration. Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate TSHR. We identified the first small molecule TSHR antagonists that inhibited TSH- and TSAb-stimulated signalling in primary cultures of human thyrocytes. Our results provide proof-of-principle for effectiveness of small molecule agonists and antagonists for TSHR. We suggest that these small molecule ligands are lead compounds for the development of higher potency ligands that can be used as probes of TSHR biology with therapeutic potential. PMID:21511239

  20. Reciprocity of agonistic support in ravens.

    PubMed

    Fraser, Orlaith N; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID:22298910

  1. The synthesis of (Z)-trisubstituted allylic alcohols by the selective 1,4-hydrogenation of dienol esters: improved synthesis of (-)-β-santalol.

    PubMed

    Fehr, Charles; Magpantay, Iris; Vuagnoux, Magali; Dupau, Philippe

    2011-01-24

    (E)-Trisubstituted allylic alcohols are commonly prepared from the corresponding (E)-enals, themselves readily accessible by a simple aldol condensation reaction. We demonstrate that these very same (E)-enals can be converted into (Z)-trisubstituted allylic acetates (and thus alcohols) by a ruthenium-catalyzed 1,4-hydrogenation of the corresponding dienol acetates. This simple solution to a long-lasting problem was applied to an industrially feasible synthesis of (-)-β-santalol. PMID:21243692

  2. Kinetic resolution of 2-substituted 2,3-dihydro-4-pyridones by palladium-catalyzed asymmetric allylic alkylation: catalytic asymmetric total synthesis of indolizidine (-)-209I.

    PubMed

    Lei, Bai-Lin; Zhang, Qing-Song; Yu, Wei-Hua; Ding, Qiu-Ping; Ding, Chang-Hua; Hou, Xue-Long

    2014-04-01

    The kinetic resolution of 2-substituted-2,3-dihydro-4-pyridones was realized via a Pd-catalyzed allylic substitution reaction using a commercially available (S)-P-Phos as a ligand, affording optically active dihydropyridones and C-allylated dihydropyridones in high yields and good enantioselectivities with the S-factor up to 43. With this protocol, a catalytic asymmetric total synthesis of indolizidine (-)-209I was realized for the first time. PMID:24661080

  3. A chemical assessment of the suitability of allyl- iso-propyltelluride as a Te precursor for metal organic vapour phase epitaxy

    NASA Astrophysics Data System (ADS)

    Hails, Janet E.; Cole-Hamilton, David J.; Stevenson, John; Bell, William; Foster, Douglas F.; Ellis, David

    2001-04-01

    The chemical studies, which led to the testing of allyl- iso-propyltelluride (allylTePr i) as a Te precursor in metal organic vapour phase epitaxy are presented. The pyrolysis in hydrogen of allylTePr i gave products including 1,5-hexadiene, propane and propene. Co-pyrolysis of dimethylcadmium (Me 2Cd) and allylTePr i gave the hydrocarbons expected from the pyrolysis of the individual precursors plus additional hydrocarbons including 2-methylpropane and 1-butene. Plots of percentage decomposition versus temperature, which proved extremely useful in determining the likely growth temperatures for both CdTe and HgTe, showed that allylTePr i is less stable than both Pr 2iTe (di- iso-propyltelluride) and Me 2Cd. The possible role of Hg in the growth of CdTe is also discussed. The chemistry of allylTePr i is well suited for use as an efficient precursor for epitaxial growth of tellurium containing semiconductors since there is very little formation of other organotellurium compounds on pyrolysis.

  4. Characterization of an Allylic/Benzyl Alcohol Dehydrogenase from Yokenella sp. Strain WZY002, an Organism Potentially Useful for the Synthesis of α,β-Unsaturated Alcohols from Allylic Aldehydes and Ketones

    PubMed Central

    Ying, Xiangxian; Wang, Yifang; Xiong, Bin; Wu, Tingting; Xie, Liping; Yu, Meilan

    2014-01-01

    A novel whole-cell biocatalyst with high allylic alcohol-oxidizing activities was screened and identified as Yokenella sp. WZY002, which chemoselectively reduced the C=O bond of allylic aldehydes/ketones to the corresponding α,β-unsaturated alcohols at 30°C and pH 8.0. The strain also had the capacity of stereoselectively reducing aromatic ketones to (S)-enantioselective alcohols. The enzyme responsible for the predominant allylic/benzyl alcohol dehydrogenase activity was purified to homogeneity and designated YsADH (alcohol dehydrogenase from Yokenella sp.), which had a calculated subunit molecular mass of 36,411 Da. The gene encoding YsADH was subsequently expressed in Escherichia coli, and the purified recombinant YsADH protein was characterized. The enzyme strictly required NADP(H) as a coenzyme and was putatively zinc dependent. The optimal pH and temperature for crotonaldehyde reduction were pH 6.5 and 65°C, whereas those for crotyl alcohol oxidation were pH 8.0 and 55°C. The enzyme showed moderate thermostability, with a half-life of 6.2 h at 55°C. It was robust in the presence of organic solvents and retained 87.5% of the initial activity after 24 h of incubation with 20% (vol/vol) dimethyl sulfoxide. The enzyme preferentially catalyzed allylic/benzyl aldehydes as the substrate in the reduction of aldehydes/ketones and yielded the highest activity of 427 U mg−1 for benzaldehyde reduction, while the alcohol oxidation reaction demonstrated the maximum activity of 79.9 U mg−1 using crotyl alcohol as the substrate. Moreover, kinetic parameters of the enzyme showed lower Km values and higher catalytic efficiency for crotonaldehyde/benzaldehyde and NADPH than for crotyl alcohol/benzyl alcohol and NADP+, suggesting the nature of being an aldehyde reductase. PMID:24509923

  5. Characterization of an allylic/benzyl alcohol dehydrogenase from Yokenella sp. strain WZY002, an organism potentially useful for the synthesis of α,β-unsaturated alcohols from allylic aldehydes and ketones.

    PubMed

    Ying, Xiangxian; Wang, Yifang; Xiong, Bin; Wu, Tingting; Xie, Liping; Yu, Meilan; Wang, Zhao

    2014-04-01

    A novel whole-cell biocatalyst with high allylic alcohol-oxidizing activities was screened and identified as Yokenella sp. WZY002, which chemoselectively reduced the C=O bond of allylic aldehydes/ketones to the corresponding α,β-unsaturated alcohols at 30°C and pH 8.0. The strain also had the capacity of stereoselectively reducing aromatic ketones to (S)-enantioselective alcohols. The enzyme responsible for the predominant allylic/benzyl alcohol dehydrogenase activity was purified to homogeneity and designated YsADH (alcohol dehydrogenase from Yokenella sp.), which had a calculated subunit molecular mass of 36,411 Da. The gene encoding YsADH was subsequently expressed in Escherichia coli, and the purified recombinant YsADH protein was characterized. The enzyme strictly required NADP(H) as a coenzyme and was putatively zinc dependent. The optimal pH and temperature for crotonaldehyde reduction were pH 6.5 and 65°C, whereas those for crotyl alcohol oxidation were pH 8.0 and 55°C. The enzyme showed moderate thermostability, with a half-life of 6.2 h at 55°C. It was robust in the presence of organic solvents and retained 87.5% of the initial activity after 24 h of incubation with 20% (vol/vol) dimethyl sulfoxide. The enzyme preferentially catalyzed allylic/benzyl aldehydes as the substrate in the reduction of aldehydes/ketones and yielded the highest activity of 427 U mg(-1) for benzaldehyde reduction, while the alcohol oxidation reaction demonstrated the maximum activity of 79.9 U mg(-1) using crotyl alcohol as the substrate. Moreover, kinetic parameters of the enzyme showed lower Km values and higher catalytic efficiency for crotonaldehyde/benzaldehyde and NADPH than for crotyl alcohol/benzyl alcohol and NADP(+), suggesting the nature of being an aldehyde reductase. PMID:24509923

  6. One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

    PubMed Central

    Silveira-Dorta, Gastón; Álvarez-Méndez, Sergio J; Martín, Víctor S

    2016-01-01

    Summary An improved protocol for the synthesis of enantiomerically pure allylic amines is reported. N-Protected α-amino esters derived from natural amino acids were submitted to a one-pot tandem reduction–olefination process. The sequential reduction with DIBAL-H at −78 °C and subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner–Wadsworth–Emmons organophosphorus reagents. A better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The (dia)stereoselectivity of the process was affected neither by the reaction solvent nor by the amount of DIBAL-H employed. The method is compatible with the presence of free hydroxy groups as shown with serine and threonine derivatives. PMID:27340486

  7. One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters.

    PubMed

    Silveira-Dorta, Gastón; Álvarez-Méndez, Sergio J; Martín, Víctor S; Padrón, José M

    2016-01-01

    An improved protocol for the synthesis of enantiomerically pure allylic amines is reported. N-Protected α-amino esters derived from natural amino acids were submitted to a one-pot tandem reduction-olefination process. The sequential reduction with DIBAL-H at -78 °C and subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner-Wadsworth-Emmons organophosphorus reagents. A better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The (dia)stereoselectivity of the process was affected neither by the reaction solvent nor by the amount of DIBAL-H employed. The method is compatible with the presence of free hydroxy groups as shown with serine and threonine derivatives. PMID:27340486

  8. The pure rotational spectrum of a Claisen rearrangement precursor Allyl Phenyl Ether using CP-FTMW spectroscopy

    NASA Astrophysics Data System (ADS)

    Grubbs, G. S.; Frank, Derek S.; Obenchain, Daniel A.; Cooke, S. A.; Novick, Stewart E.

    2016-06-01

    The pure rotational spectrum of a Claisen rearrangement precursor, Allyl Phenyl Ether (APE), has been measured on a chirped pulse Fourier transform microwave (CP-FTMW) spectrometer in the 8-14 GHz region. Rotational and centrifugal distortion constants for multiple conformations have been determined and are reported for the first time. This is the first study of a phenyl-containing ether where multiple conformers were experimentally observed all within their ground vibrational states. Quantum chemical calculations have been performed to isolate low energy geometries of APE and are implemented to aid in spectral assignment. Other structural parameters such as planar moments and inertial defects for the Allyl Phenyl Ether conformers are presented and compared to similar molecules.

  9. Enantioselective Synthesis of α-Quaternary Mannich Adducts by Palladium-Catalyzed Allylic Alkylation: Total Synthesis of (+)-Sibirinine

    PubMed Central

    2016-01-01

    A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of “thermodynamic” enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N–H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine. PMID:25578104

  10. Rh(III)-catalyzed dehydrogenative alkylation of (hetero)arenes with allylic alcohols, allowing aldol condensation to indenes.

    PubMed

    Shi, Zhuangzhi; Boultadakis-Arapinis, Mélissa; Glorius, Frank

    2013-07-25

    Efficient Rh(III)-catalyzed C-H activation of different classes of (hetero)arenes such as 2-phenylpyridine, indoles, aryl ketones and acetanilide and their dehydrogenative cross-coupling with allylic alcohols are described. Several important skeletons such as β-aryl aldehydes and ketones, 2-acetylindenes, 3,4-dihydro-1H-quinolin-2-one and quinoline could be produced using this protocol. PMID:23765402

  11. Synthesis of chiral biphenol-based diphosphonite ligands and their application in palladium-catalyzed intermolecular asymmetric allylic amination reactions.

    PubMed

    Shi, Ce; Chien, Chih-Wei; Ojima, Iwao

    2011-02-01

    A library of new 2,2'-bis(diphenylphosphinoyloxy)-1,1'-binaphthyl (binapo)-type chiral diphosphonite ligands was designed and synthesized based on chiral 3,3',5,5',6,6'-hexasubstituted biphenols. These bop ligands have exhibited excellent efficiency in a palladium-catalyzed intermolecular allylic amination reaction, which provides a key intermediate for the total synthesis of Strychnos indole alkaloids with enantiopurities of up to 96% ee. PMID:21254441

  12. Dual Catalysis Using Boronic Acid and Chiral Amine: Acyclic Quaternary Carbons via Enantioselective Alkylation of Branched Aldehydes with Allylic Alcohols.

    PubMed

    Mo, Xiaobin; Hall, Dennis G

    2016-08-31

    A ferrocenium boronic acid salt activates allylic alcohols to generate transient carbocations that react with in situ-generated chiral enamines from branched aldehydes. The optimized conditions afford the desired acyclic products embedding a methyl-aryl quaternary carbon center with up to 90% yield and 97:3 enantiomeric ratio, with only water as the byproduct. This noble-metal-free method complements alternative methods that are incompatible with carbon-halogen bonds and other sensitive functional groups. PMID:27518200

  13. Direct Conversion of Aldehydes and Ketones to Allylic Halides by a NbX5-[3,3] Rearrangement

    PubMed Central

    Fleming, Fraser F.; Ravikumar, P. C.; Yao, Lihua

    2009-01-01

    Sequential addition of vinylmagnesium bromide and NbCl5, or NbBr5, to a series of aldehydes and ketones directly provides homologated, allylic halides. Transposition of the intermediate vinyl alkoxide is envisaged through a metalla-halo-[3,3] rearrangement with concomitant delivery of the halogen to the terminal carbon. The [3,3] rearrangement is equally effective for the conversion of a propargyllic alcohol to the corresponding allenyl bromide. PMID:20046989

  14. Enantioselective Synthesis of α-Secondary and α-Tertiary Piperazin-2-ones and Piperazines by Catalytic Asymmetric Allylic Alkylation

    PubMed Central

    Korch, Katerina M.; Eidamshaus, Christian; Behenna, Douglas C.; Nam, Sangkil; Horne, David

    2014-01-01

    The asymmetric Pd-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows for the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogs. The introduction of these chiral tertiary piperazines resulted in imatinib analogs that exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts. PMID:25382664

  15. Hydroxymethylation beyond Carbonylation: Enantioselective Iridium-Catalyzed Reductive Coupling of Formaldehyde with Allylic Acetates via Enantiotopic π-Facial Discrimination.

    PubMed

    Garza, Victoria J; Krische, Michael J

    2016-03-23

    Chiral iridium complexes modified by SEGPHOS catalyze the 2-propanol-mediated reductive coupling of branched allylic acetates 1a-1o with formaldehyde to form primary homoallylic alcohols 2a-2o with excellent control of regio- and enantioselectivity. These processes, which rely on enantiotopic π-facial discrimination of σ-allyliridium intermediates, represent the first examples of enantioselective formaldehyde C-C coupling beyond aldol addition. PMID:26958737

  16. Rhodium(III)-catalyzed C-C coupling of 7-azaindoles with vinyl acetates and allyl acetates.

    PubMed

    Li, Shuai-Shuai; Wang, Cheng-Qi; Lin, Hui; Zhang, Xiao-Mei; Dong, Lin

    2016-01-01

    The behaviour of electron-rich alkenes with 7-azaindoles in rhodium(III)-catalyzed C-H activation is investigated. Various substituted vinyl acetates and allyl acetates as coupling partners reacted smoothly providing a wide variety of 7-azaindole derivatives, and the selectivity of the coupling reaction is alkene-dependent. In addition, the approaches of rhodium(III)-catalyzed dehydrogenative Heck-type reaction (DHR) and carbonylation reaction were quite novel and simple. PMID:26553424

  17. Directed Growth of Polymer Nanorods Using Surface-Initiated Ring-Opening Polymerization of N-Allyl N-Carboxyanhydride.

    PubMed

    Lu, Lu; Lahasky, Samuel H; Zhang, Donghui; Garno, Jayne C

    2016-02-17

    A stepwise chemistry route was used to prepare arrays of polymer nanostructures of poly(N-allyl glycine) on Si(111) using particle lithography. The nanostructures were used for studying surface reactions with advanced measurements of atomic force microscopy (AFM). In the first step to fabricate the surface platform, isolated nanopores were prepared within a thin film of octadecyltrichlorosilane (OTS). The OTS served as a surface resist, and the areas of nanopores provided multiple, regularly shaped sites for further reaction. An initiator, (3-aminopropyl)triethoxysilane (APTES), was grown selectively inside the nanopores to define sites for polymerization. The initiator attached selectively to the sites of nanopores indicating OTS prevented nonspecific adsorption. Surface-initiated ring-opening polymerization of N-allyl N-carboxyanhydride with APTES produced polymer nanorods on the nanodots of APTES presenting amine functional groups. The surface changes for each step were monitored using high resolution atomic force microscopy (AFM). Slight variations in the height of the poly(N-allyl glycine) nanorods were observed which scale correspondingly to the initial dimensions of nanopores. The distance between adjacent polymer nanorods was controlled by the size of mesoparticle masks used in the experiment. This surface platform has potential application in biotechnology for smart coatings or biosensors. PMID:26789943

  18. Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

    DOE PAGESBeta

    Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying; Chen, Di; Li, Hao; Liu, Qing -Rong; Ding, Chang -Hua; Chen, Bo; Hou, Xue -Long

    2016-06-10

    The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanistic studiesmore » by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.« less

  19. Synchrotron Photoionization Mass Spectrometry Measurements of Kinetics and Product Formation in the Allyl Radical (H2CCHCH2)Self Reaction

    NASA Technical Reports Server (NTRS)

    Selby, Talitha M.; Melini, giovanni; Goulay, Fabien; Leone, Stephen R.; Fahr, Askar; Taatjes, Craig A.; Osborn, David L.

    2008-01-01

    Product channels for the self-reaction of the resonance-stabilized allyl radical, C3H5 + C3H5, have been studied with isomeric specificity at temperatures from 300-600 K and pressures from 1-6 Torr using time-resolved multiplexed photoionization mass spectrometry. Under these conditions 1,5-hexadiene was the only C6H10 product isomer detected. The lack of isomerization of the C6H10 product is in marked contrast to the C6H6 product in the related C3H3 + C3H3 reaction, and is due to the more saturated electronic structure of the C6H10 system. The disproportionation product channel, yielding allene + propene, was also detected, with an upper limit on the branching fraction relative to recombination of 0.03. Analysis of the allyl radical decay at 298 K yielded a total rate coefficient of (2.7 +/- 0.8) x 10(exp -11) cu cm/molecule/s, in good agreement with pre.vious experimental measurements using ultraviolet kinetic absorption spectroscopy and a recent theoretical determination using variable reaction coordinate transition state theory. This result provides independent indirect support for the literature value of the allyl radical ultraviolet absorption cross-section near 223 nm.

  20. HERG1 Channel Agonists and Cardiac Arrhythmia

    PubMed Central

    Sanguinetti, Michael

    2014-01-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  1. HERG1 channel agonists and cardiac arrhythmia.

    PubMed

    Sanguinetti, Michael C

    2014-04-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  2. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

    Scheel, David; Godfrey-Smith, Peter; Lawrence, Matthew

    2016-02-01

    Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits. PMID:26832440

  3. Melanocortin 1 Receptor Agonists Reduce Proteinuria

    PubMed Central

    Ebefors, Kerstin; Johansson, Martin E.; Stefánsson, Bergur; Granqvist, Anna; Arnadottir, Margret; Berg, Anna-Lena; Nyström, Jenny; Haraldsson, Börje

    2010-01-01

    Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown. Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P < 0.01). Furthermore, treatment with MC1R agonists improved podocyte morphology and reduced oxidative stress. In summary, podocytes express MC1R, and MC1R agonism reduces proteinuria, improves glomerular morphology, and reduces oxidative stress in nephrotic rats with PHN. These data may explain the proteinuria-reducing effects of ACTH observed in patients with membranous nephropathy, and MC1R agonists may provide a new therapeutic option for these patients. PMID:20507942

  4. Benzyl isothiocyanate alters the gene expression with cell cycle regulation and cell death in human brain glioblastoma GBM 8401 cells.

    PubMed

    Tang, Nou-Ying; Chueh, Fu-Shin; Yu, Chien-Chih; Liao, Ching-Lung; Lin, Jen-Jyh; Hsia, Te-Chun; Wu, King-Chuen; Liu, Hsin-Chung; Lu, Kung-Wen; Chung, Jing-Gung

    2016-04-01

    Glioblastoma multiforme (GBM) is a highly malignant devastating brain tumor in adults. Benzyl isothiocyanate (BITC) is one of the isothiocyanates that have been shown to induce human cancer cell apoptosis and cell cycle arrest. Herein, the effect of BITC on cell viability and apoptotic cell death and the genetic levels of human brain glioblastoma GBM 8401 cells in vitro were investigated. We found that BITC induced cell morphological changes, decreased cell viability and the induction of cell apoptosis in GBM 8401 cells was time-dependent. cDNA microarray was used to examine the effects of BITC on GBM 8401 cells and we found that numerous genes associated with cell death and cell cycle regulation in GBM 8401 cells were altered after BITC treatment. The results show that expression of 317 genes was upregulated, and two genes were associated with DNA damage, the DNA-damage-inducible transcript 3 (DDIT3) was increased 3.66-fold and the growth arrest and DNA-damage-inducible α (GADD45A) was increased 2.34-fold. We also found that expression of 182 genes was downregulated and two genes were associated with receptor for cell responses to stimuli, the EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1) was inhibited 2.01-fold and the TNF receptor-associated protein 1 (TRAP1) was inhibited 2.08-fold. BITC inhibited seven mitochondria ribosomal genes, the mitochondrial ribosomal protein; tumor protein D52 (MRPS28) was inhibited 2.06-fold, the mitochondria ribosomal protein S2 (MRPS2) decreased 2.07-fold, the mitochondria ribosomal protein L23 (MRPL23) decreased 2.08-fold, the mitochondria ribosomal protein S2 (MRPS2) decreased 2.07-fold, the mitochondria ribosomal protein S12 (MRPS12) decreased 2.08-fold, the mitochondria ribosomal protein L12 (MRPL12) decreased 2.25-fold and the mitochondria ribosomal protein S34 (MRPS34) was decreased 2.30-fold in GBM 8401 cells. These changes of gene expression can provide the effects of BITC on the genetic level and are

  5. Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

    NASA Astrophysics Data System (ADS)

    You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P.

    2015-01-01

    The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

  6. On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update.

    PubMed

    Colín-González, Ana Laura; Ali, Syed F; Túnez, Isaac; Santamaría, Abel

    2015-10-01

    Therapeutic approaches based on isolated compounds obtained from natural products to handle central and peripheral disorders involving oxidative stress and inflammation are more common nowadays. The validation of nutraceutics vs. pharmaceutics as tools to induce preventive and protective profiles in human health alterations is still far of complete acceptance, but the basis to start more solid experimental and clinical protocols with natural products has already begun. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound exhibiting a considerable number of positive actions in cell models and living systems. An update, in the form of review, is needed from time to time to get access to the state-of-the-art on this topic. In this review we visited recent and refreshing evidence of new already proven and potential targets to explain the benefits of using SAC against toxic and pathological conditions. The broad spectrum of protective actions covered by this molecule comprises antioxidant, redox modulatory and anti-inflammatory activities, accompanied by anti-apoptotic, pro-energetic and signaling capacities. Herein, we detail the evidence on these aspects to provide the reader a more complete overview on the promising aspects of SAC in research. PMID:26122973

  7. Crystal structure of allyl­ammonium hydrogen succinate at 100 K

    PubMed Central

    Dziuk, Błażej; Zarychta, Bartosz; Ejsmont, Krzysztof

    2014-01-01

    The asymmetric unit of the title compound, C2H8N+·C4H5O4 −, consists of two allyl­ammonium cations and two hydrogen succinate anions (Z′ = 2). One of the cations has a near-perfect syn-periplanar (cis) conformation with an N—C—C—C torsion angle of 0.4 (3)°, while the other is characterized by a gauche conformation and a torsion angle of 102.5 (3)°. Regarding the anions, three out of four carboxilic groups are twisted with respect to the central C–CH2–CH2–C group [dihedral angles = 24.4 (2), 31.2 (2) and 40.4 (2)°], the remaining one being instead almost coplanar, with a dihedral angle of 4.0 (2)°. In the crystal, there are two very short, near linear O—H⋯O hydrogen bonds between anions, with the H atoms shifted notably from the donor O towards the O⋯O midpoint. These O—H⋯O hydrogen bonds form helical chains along the [011] which are further linked to each other through N—H⋯O hydrogen bonds (involving all the available NH groups), forming layers lying parallel to (100). PMID:25309251

  8. Antibacterial activity of starch/acrylamide/allyl triphenyl phosphonium bromide copolymers synthesized by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Song, Weiqiang; Guo, Zhengchao; Zhang, Linqi; Zheng, Hongjuan; Zhao, Zhiwei

    2013-10-01

    Starch/acrylamide/allyl triphenyl phosphonium bromide (St/AM/TP) copolymers were synthesized by simultaneous gamma irradiation and characterized by FTIR and 1H NMR techniques, weight measurement and titration method. Moreover, their antibacterial activities against Staphylococcus aureus were explored by the viable cell counting method in sterile distilled water. At St/AM/TP 6:8.4:5.6 g, copolymers with higher graft ratio (G) and higher (AM+TP) graft efficiency (EAM+TP) were obtained at 3 and 6 kGy, while cationic degree (CD) and TP graft efficiency (ETP) continuously increased with absorbed dose from 1 to 6 kGy. All of the copolymers were capable of killing >99.75% of 107 CFU/ml S. aureus within 30 mins. Moreover, at 3 kGy, G, EAM+TP and ETP increased with AM/TP from 0:14 to 11.2:2.8 g at St/(AM+TP) 6:14 g, while the optimum CD and antibacterial activity were achieved at AM/TP 7:7 and 8.4:5.6 g. In addition, at 3 kGy, G, EAM+TP and CD increased with St/(AM+TP) from 6:3 to 6:18 g at AM/TP 8.4:5.6 g, while the optimum antibacterial activity was achieved at 6:10 to 6:18 g, and the optimum ETP was achieved at 6:14.

  9. Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

    SciTech Connect

    Asermely, K.E.; O'Neill, J.J.

    1986-03-01

    The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37/sup 0/C in buffers containing tritium choline (5 ..mu..M 0.124 ..mu..C/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10/sup -5/ M compared with 50% inhibition on brain synaptosomes. At 5 x 10/sup -4/ M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K/sup +/-ion (25 mM) were unsuccessful; tissue /sup 3/H-choline uptake appeared to oscillate over a 30 min period.

  10. Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation.

    PubMed

    You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P

    2015-01-15

    The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of ≥50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods. PMID:25592541

  11. Novel 3-hydroxypropyl bonded phase by direct hydrosilylation of allyl alcohol on amorphous hydride silica

    PubMed Central

    Gómez, Jorge E.; Navarro, Fabián H.; Sandoval, Junior E.

    2015-01-01

    A novel 3-hydroxypropyl (propanol) bonded silica phase has been prepared by hydrosilylation of allyl alcohol on a hydride silica intermediate, in the presence of platinum (0)-divinyltetramethyldisiloxane (Karstedt's catalyst). The regio-selectivity of this synthetic approach had been correctly predicted by previous reports involving octakis(dimethylsiloxy)octasilsesquioxane (Q8M8H) and hydrogen silsesquioxane (T8H8), as molecular analogs of hydride amorphous silica. Thus, C-silylation predominated (~ 94%) over O-silylation, and high surface coverages of propanol groups (5±1 µmol/m2) were typically obtained in this work. The propanol-bonded phase was characterized by spectroscopic (IR and solid state NMR on silica microparticles), contact angle (on fused-silica wafers) and CE (on fused-silica tubes) techniques. CE studies of the migration behavior of pyridine, caffeine, tris(2,2’-bipyridine)Ru(II) chloride and lysozyme on propanol-modified capillaries were carried out. The adsorption properties of these select silanol-sensitive solutes were compared to those on the unmodified and hydride-modified tubes. It was found that hydrolysis of the SiH species underlying the immobilized propanol moieties leads mainly to strong ion-exchange based interactions with the basic solutes at pH 4, particularly with lysozyme. Interestingly, and in agreement with water contact angle and electroosmotic mobility figures, the silanol-probe interactions on the buffer-exposed (hydrolyzed) hydride surface are quite different from those of the original unmodified tube. PMID:24934906

  12. Protective effect of allyl methyl disulfide on acetaminophen-induced hepatotoxicity in mice.

    PubMed

    Zhang, Yongchun; Zhang, Fang; Wang, Kaiming; Liu, Guangpu; Yang, Min; Luan, Yuxia; Zhao, Zhongxi

    2016-04-01

    Multiple sulfur compounds of garlic have shown versatile medicinal activities in the prevention and treatment of various diseases. Allyl methyl disulfide (AMDS) was identified as one of the bioactive components in fresh garlic paste in our previous study. The purpose of this study was to investigate the hepatoprotective effect of AMDS against acetaminophen (APAP)-induced acute liver damage in mice. Results reveal that AMDS significantly alleviates APAP-induced elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in mice. Furthermore, AMDS significantly (p < 0.05) reduced the maleic dialdehyde (MDA) level in liver tissues and restored the activities of antioxidant enzymes SOD, GSH-PX and GSH towards normal levels. IL-6 and TNF-alpha (TNF-α) levels in the serum and liver were clearly increased by acetaminophen-damage (p < 0.05) and AMDS intake significantly suppressed acetaminophen-induced increase of the two cytokines (p < 0.05). The immunohistochemical and pathological analyses showed that AMDS could ameliorate the liver injury through the strong attenuation of the CD45 expression and HNE formation. All the results indicate that AMDS had the ability to protect hepatocytes from APAP-induced liver damage. PMID:26969520

  13. Allylic amination reactivity of Ni, Pd, and Pt heterobimetallic and monometallic complexes.

    PubMed

    Carlsen, Ryan W; Ess, Daniel H

    2016-06-14

    Transition metal heterobimetallic complexes with dative metal-metal interactions have the potential for novel fast reactivity. There are few studies that both compare the reactivity of different metal centers in heterobimetallic complexes and compare bimetallic reactivity to monometallic reactivity. Here we report density-functional calculations that show the reactivity of [Cl2Ti(N(t)BuPPh2)2M(II)(η(3)-methallyl)] heterobimetallic complexes for allylic amination follows M = Ni > Pd > Pt. This reactivity trend was not anticipated since the amine addition transition state involves M(II) to M(0) reduction and this could disadvantage Ni. Comparison of heterobimetallic complexes to the corresponding monometallic (CH2)2(N(t)BuPPh2)2M(II)(η(3)-methallyl) complexes reveals that this reactivity trend is due to the bimetallic interaction and that the bimetallic interaction significantly lowers the barrier height for amine addition by >10 kcal mol(-1). The impact of the early transition metal center on the amination addition barrier height depends on the late transition metal center. The lowest barrier heights for this reaction occur when late and early transition metal centers are from the same periodic table row. PMID:26893287

  14. Theoretical kinetic estimates for the recombination of hydrogen atoms with propargyl and allyl radicals

    SciTech Connect

    Harding, L. B.; Klippenstein, S. J.

    2000-01-12

    Ab initio quantum chemical simulations are coupled with variational transition state theory in estimating rate constants for the H+C{sub 3}H{sub 3} and H+C{sub 3}H{sub 5} recombination reactions. The energy of interaction between the H atom and each of the radicals is evaluated at the CAS+1+2 level for the range of separations and relative orientations spanning the transition state region. An analytic representation of these interaction energies is then implemented in variable reaction coordinate transition state theory calculations of the high pressure limit recombination rate constant for temperatures ranging from 200 to 2000 K. For the propargyl reaction the overall addition rate is separated into contributions correlating with the initial formation of allene and propyne. These theoretical results are compared with the available experimental data as well as with corresponding theoretical estimates for the H+C{sub 2}H{sub 3} and H+C{sub 2}H{sub 5} reactions. The H+propargyl and H+allyl total recombination rates are remarkably similar, with both being greater than the H+vinyl and H+ethyl rates, due to the presence of twice as many addition channels.

  15. Merging allylic carbon-hydrogen and selective carbon-carbon bond activation

    NASA Astrophysics Data System (ADS)

    Masarwa, Ahmad; Didier, Dorian; Zabrodski, Tamar; Schinkel, Marvin; Ackermann, Lutz; Marek, Ilan

    2014-01-01

    Since the nineteenth century, many synthetic organic chemists have focused on developing new strategies to regio-, diastereo- and enantioselectively build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. Ideal syntheses should use the least number of synthetic steps, with few or no functional group transformations and by-products, and maximum atom efficiency. One potentially attractive method for the synthesis of molecular skeletons that are difficult to prepare would be through the selective activation of C-H and C-C bonds, instead of the conventional construction of new C-C bonds. Here we present an approach that exploits the multifold reactivity of easily accessible substrates with a single organometallic species to furnish complex molecular scaffolds through the merging of otherwise difficult transformations: allylic C-H and selective C-C bond activations. The resulting bifunctional nucleophilic species, all of which have an all-carbon quaternary stereogenic centre, can then be selectively derivatized by the addition of two different electrophiles to obtain more complex molecular architecture from these easily available starting materials.

  16. Glucosinolate-derived isothiocyanates impact mitochondrial function in fungal cells and elicit an oxidative stress response necessary for growth recovery

    PubMed Central

    Calmes, Benoit; N’Guyen, Guillaume; Dumur, Jérome; Brisach, Carlos A.; Campion, Claire; Iacomi, Béatrice; Pigné, Sandrine; Dias, Eva; Macherel, David; Guillemette, Thomas; Simoneau, Philippe

    2015-01-01

    Glucosinolates are brassicaceous secondary metabolites that have long been considered as chemical shields against pathogen invasion. Isothiocyanates (ITCs), are glucosinolate-breakdown products that have negative effects on the growth of various fungal species. We explored the mechanism by which ITCs could cause fungal cell death using Alternaria brassicicola, a specialist Brassica pathogens, as model organism. Exposure of the fungus to ICTs led to a decreased oxygen consumption rate, intracellular accumulation of reactive oxygen species (ROS) and mitochondrial-membrane depolarization. We also found that two major regulators of the response to oxidative stress, i.e., the MAP kinase AbHog1 and the transcription factor AbAP1, were activated in the presence of ICTs. Once activated by ICT-derived ROS, AbAP1 was found to promote the expression of different oxidative-response genes. This response might play a significant role in the protection of the fungus against ICTs as mutants deficient in AbHog1 or AbAP1 were found to be hypersensitive to these metabolites. Moreover, the loss of these genes was accompanied by a significant decrease in aggressiveness on Brassica. We suggest that the robust protection response against ICT-derived oxidative stress might be a key adaptation mechanism for successful infection of host plants by Brassicaceae-specialist necrotrophs like A. brassicicola. PMID:26089832

  17. Effect of glutathione-S-transferase polymorphisms on the cancer preventive potential of isothiocyanates: an epidemiological perspective.

    PubMed

    Seow, Adeline; Vainio, Harri; Yu, Mimi C

    2005-12-30

    Isothiocyanates (ITCs) are widely distributed in cruciferous vegetables and are biologically active against chemical carcinogenesis due to their ability to induce phase II conjugating enzymes. Among these is the glutathione-S-transferase (GST) family of enzymes, which in turn catalyzes the metabolism of ITCs, for which it has high substrate specificity. A recent body of epidemiologic data on the inverse association between cruciferous vegetable/ITC intake and cancers of the colo-rectum, lung and breast, also support that this protective effect is greater among individuals who possess the GSTM1 or T1 null genotype, and who would be expected to accumulate higher levels of ITC at the target tissue level, a pre-requisite for their enzyme-inducing effects. The association between ITC and cancer, and its modification by GST status, is most consistent for lung cancer and appears to be strongest among current smokers. Within limits, a comparison between groups which have been stratified by GST genotype may be less susceptible to confounding by other variables, given the random assortment of genes in gametogenesis. While a more complete understanding of the overall effects on health will need to take into account other components such as indoles and anti-oxidants, the interaction between ITC intake and GST genotype may provide a firmer basis to support a biologically significant role for ITC in cruciferous vegetables. PMID:16019037

  18. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC.

    PubMed

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-12-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level. PMID:25256442

  19. Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases.

    PubMed

    Wang, Yating; Wei, Sixi; Wang, Jishi; Fang, Qin; Chai, Qixiang

    2014-07-01

    Phenethyl isothiocyanate (PEITC), a potential cancer chemopreventive constituent of cruciferous vegetables, including watercress, has been reported to inhibit cancer cell growth by arresting the cell cycle and inducing apoptosis in various human cancer cell models. However, the role of PEITC in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms have yet to be elucidated. In the present study, PEITC was found to induce cell death through the induction of reactive oxygen species (ROS) stress and oxidative damage. Heme oxygenase‑1 (HO‑1), which participates in the development of numerous tumors and the sensitivity of these tumors to chemotherapeutic drugs, plays a protective role by modulating oxidative injury. Therefore, the present study assessed the inhibitory effect of PEITC on K562 cells and whether HO‑1 facilitated cell apoptosis and ROS generation. PEITC was found to suppress cell growth and cause apoptosis by promoting Fas and Fas ligand expression, increasing ROS generation and by the successive release of cytochrome c as well as the activation of caspase‑9 and caspase‑3. PEITC was also combined with the HO‑1 inhibitor zinc protoporphyrin IX and the inducer hemin to assess whether HO‑1 determines cell survival and ROS generation. The results of the present study suggest that PEITC may be a potential anti‑tumor compound for CML therapy, and that HO‑1 has a critical function in PEITC‑induced apoptosis and ROS generation. PMID:24788892

  20. Phenylethyl isothiocyanate reverses cisplatin resistance in biliary tract cancer cells via glutathionylation-dependent degradation of Mcl-1.

    PubMed

    Li, Qiwei; Zhan, Ming; Chen, Wei; Zhao, Benpeng; Yang, Kai; Yang, Jie; Yi, Jing; Huang, Qihong; Mohan, Man; Hou, Zhaoyuan; Wang, Jian

    2016-03-01

    Biliary tract cancer (BTC) is a highly malignant cancer. BTC exhibits a low response rate to cisplatin (CDDP) treatment, and therefore, an understanding of the mechanism of CDDP resistance is urgently needed. Here, we show that BTC cells develop CDDP resistance due, in part, to upregulation of myeloid cell leukemia 1 (Mcl-1). Phenylethyl isothiocyanate (PEITC), a natural compound found in watercress, could enhance the efficacy of CDDP by degrading Mcl-1. PEITC-CDDP co-treatment also increased the rate of apoptosis of cancer stem-like side population (SP) cells and inhibited xenograft tumor growth without obvious toxic effects. In vitro, PEITC decreased reduced glutathione (GSH), which resulted in decreased GSH/oxidized glutathione (GSSG) ratio and increased glutathionylation of Mcl-1, leading to rapid proteasomal degradation of Mcl-1. Furthermore, we identified Cys16 and Cys286 as Mcl-1 glutathionylation sites, and mutating them resulted in PEITC-mediated degradation resistant Mcl-1 protein. In conclusion, we demonstrate for the first time that CDDP resistance is partially associated with Mcl-1 in BTC cells and we identify a novel mechanism that PEITC can enhance CDDP-induced apoptosis via glutathionylation-dependent degradation of Mcl-1. Hence, our results provide support that dietary intake of watercress may help reverse CDDP resistance in BTC patients. PMID:26848531

  1. Phenylethyl isothiocyanate reverses cisplatin resistance in biliary tract cancer cells via glutathionylation-dependent degradation of Mcl-1

    PubMed Central

    Li, Qiwei; Zhan, Ming; Chen, Wei; Zhao, Benpeng; Yang, Kai; Yang, Jie; Yi, Jing; Huang, Qihong; Mohan, Man; Hou, Zhaoyuan; Wang, Jian

    2016-01-01

    Biliary tract cancer (BTC) is a highly malignant cancer. BTC exhibits a low response rate to cisplatin (CDDP) treatment, and therefore, an understanding of the mechanism of CDDP resistance is urgently needed. Here, we show that BTC cells develop CDDP resistance due, in part, to upregulation of myeloid cell leukemia 1 (Mcl-1). Phenylethyl isothiocyanate (PEITC), a natural compound found in watercress, could enhance the efficacy of CDDP by degrading Mcl-1. PEITC-CDDP co-treatment also increased the rate of apoptosis of cancer stem-like side population (SP) cells and inhibited xenograft tumor growth without obvious toxic effects. In vitro, PEITC decreased reduced glutathione (GSH), which resulted in decreased GSH/oxidized glutathione (GSSG) ratio and increased glutathionylation of Mcl-1, leading to rapid proteasomal degradation of Mcl-1. Furthermore, we identified Cys16 and Cys286 as Mcl-1 glutathionylation sites, and mutating them resulted in PEITC-mediated degradation resistant Mcl-1 protein. In conclusion, we demonstrate for the first time that CDDP resistance is partially associated with Mcl-1 in BTC cells and we identify a novel mechanism that PEITC can enhance CDDP-induced apoptosis via glutathionylation-dependent degradation of Mcl-1. Hence, our results provide support that dietary intake of watercress may help reverse CDDP resistance in BTC patients. PMID:26848531

  2. Numbers and phenotype of lymphocytes emigrating from sheep bone marrow after in situ labelling with fluorescein isothiocyanate.

    PubMed Central

    Pabst, R; Miyasaka, M; Dudler, L

    1986-01-01

    In normal young lambs the bone marrow was selectively labelled with fluorescein isothiocyanate by a temporary perfusion of one hind-leg. One day later, the incidence of bone marrow emigrants in different lymph nodes, spleen, Peyer's patches, thymus, non-perfused bone marrow and blood was determined. The emigrants were also phenotyped by the use of monoclonal antibodies and classified into monocytes or lymphocyte subsets. Large numbers of lymphocytes left the bone marrow of the perfused leg during 1 day. Considerable numbers of cells migrated to other bone marrow compartments. Varying numbers of mononuclear emigrants were found in peripheral lymphoid organs, with labelling indices ranging from 1.06% in the blood to 0.004% in the thymus. In the spleen, comparable numbers of B- and T-lymphocyte emigrants from the bone marrow were found, whereas in the blood, lymph nodes and jejunal Peyer's patches many more emigrants were T lymphocytes than B lymphocytes. In the prescapular lymph nodes, for instance, 90.4% of emigrants were T cells but only 9.6% were B cells. Based on the large numbers of lymphocytes emigrating from the bone marrow, their phenotypes and their entry into other bone marrow compartments, it it can be concluded that the bone marrow of young lambs is an integral part of the migratory route of lymphocytes. Images Figure 2 Figure 3 PMID:3095227

  3. Isothiocyanates Are Promising Compounds against Oxidative Stress, Neuroinflammation and Cell Death that May Benefit Neurodegeneration in Parkinson's Disease.

    PubMed

    Sita, Giulia; Hrelia, Patrizia; Tarozzi, Andrea; Morroni, Fabiana

    2016-01-01

    Parkinson's disease (PD) is recognized as the second most common neurodegenerative disorder and is characterized by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the mechanisms involved in neuronal loss are not completely understood yet; however, misfolded proteins, oxidative stress, excitotoxicity and inflammation play a pivotal role in the progression of the pathology. Neuroinflammation may have a greater function in PD pathogenesis than initially believed, taking part in the cascade of events that leads to neuronal death. To date, no efficient therapy, able to arrest or slow down PD, is available. In this context, the need to find novel strategies to counteract neurodegenerative progression by influencing diseases' pathogenesis is becoming increasingly clear. Isothiocyanates (ITCs) have already shown interesting properties in detoxification, inflammation, apoptosis and cell cycle regulation through the induction of phase I and phase II enzyme systems. Moreover, ITCs may be able to modulate several key points in oxidative and inflammatory evolution. In view of these considerations, the aim of the present review is to describe ITCs as pleiotropic compounds capable of preventing and modulating the evolution of PD. PMID:27598127

  4. Preparation and characterization of inclusion complex of benzyl isothiocyanate extracted from papaya seed with β-cyclodextrin.

    PubMed

    Li, Wenzhao; Liu, Xiaoyu; Yang, Qingfeng; Zhang, Ning; Du, Yideng; Zhu, Huaping

    2015-10-01

    The inclusion complex of benzyl isothiocyanate (BITC), extracted from papaya seed with β-cyclodextrin (β-CD), was prepared. Different analytical techniques, such as Fourier transform infrared spectroscopy, thermal analysis, X-ray diffractometry, particle size distribution analysis and (1)H Nuclear magnetic resonance analysis, were used to investigate the characterization of the inclusion complex (BITC-β-CD). All these approaches indicated that the inclusion complex was capable of being formed. The inclusion complex exhibited different spectroscopic and thermodynamic features and properties from BITC, and we deduced the possible inclusion modes for BITC-β-CD. The calculated apparent stability constant of the BITC-β-CD was 600.8l/mol, and the aqueous solubility of BITC was indistinctively improved by phase solubility studies. The results illustrated that β-CD was a proper excipient for increasing the stability and controlled release of BITC. Thus, β-CD complexation technology would be a promising approach, in expanding the application of BITC as a food antibacterial agent. PMID:25872431

  5. Low concentrations of isothiocyanates protect mesenchymal stem cells from oxidative injuries, while high concentrations exacerbate DNA damage.

    PubMed

    Zanichelli, Fulvia; Capasso, Stefania; Di Bernardo, Giovanni; Cipollaro, Marilena; Pagnotta, Eleonora; Cartenì, Maria; Casale, Fiorina; Iori, Renato; Giordano, Antonio; Galderisi, Umberto

    2012-09-01

    Isothiocyanates (ITCs) are molecules naturally present in many cruciferous vegetables (broccoli, black radish, daikon radish, and cauliflowers). Several studies suggest that cruciferous vegetable consumption may reduce cancer risk and slow the aging process. To investigate the effect of ITCs on cellular DNA damage, we evaluated the effects of two different ITCs [sulforaphane (SFN) and raphasatin (RPS)] on the biology of human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, contribute to the homeostatic maintenance of many organs. The choice of SFN and RPS relies on two considerations: they are among the most popular cruciferous vegetables in the diet of western and eastern countries, respectively, and their bioactive properties may differ since they possess specific molecular moiety. Our investigation evidenced that MSCs incubated with low doses of SFN and RPS show reduced in vitro oxidative stress. Moreover, these cells are protected from oxidative damages induced by hydrogen peroxide, while no protection was evident following treatment with the UV ray of a double strand DNA damaging drug, such as doxorubicin. High concentrations of both ITCs induced cytotoxic effects in MSC cultures and further increased DNA damage induced by peroxides. In summary, our study suggests that ITCs, at low doses, may contribute to slowing the aging process related to oxidative DNA damage. Moreover, in cancer treatment, low doses of ITCs may be used as an adjuvant to reduce chemotherapy-induced oxidative stress, while high doses may synergize with anticancer drugs to promote cell DNA damage. PMID:22684843

  6. Characterization of some amino acid derivatives of benzoyl isothiocyanate: Crystal structures and theoretical prediction of their reactivity

    NASA Astrophysics Data System (ADS)

    Odame, Felix; Hosten, Eric C.; Betz, Richard; Lobb, Kevin; Tshentu, Zenixole R.

    2015-11-01

    The reaction of benzoyl isothiocyanate with L-serine, L-proline, D-methionine and L-alanine gave 2-[(benzoylcarbamothioyl)amino]-3-hydroxypropanoic acid (I), 1-(benzoylcarbamothioyl)pyrrolidine-2-carboxylic acid (II), 2-[(benzoylcarbamothioyl)amino]-4-(methylsulfanyl)butanoic acid (III) and 2-[(benzoylcarbamothioyl)amino]propanoic acid (IV), respectively. The compounds have been characterized by IR, NMR, microanalyses and mass spectrometry. The crystal structures of all the compounds have also been discussed. Compound II showed rotamers in solution. DFT calculations of the frontier orbitals of the compounds have been carried out to ascertain the groups that contribute to the HOMO and LUMO, and to study their contribution to the reactivity of these compounds. The calculations indicated that the carboxylic acid group in these compounds is unreactive hence making the conversion to benzimidazoles via cyclization on the carboxylic acids impractical. This has been further confirmed by the reaction of compounds I-IV, respectively, with o-phenylene diamine which was unsuccessful but gave compound V.

  7. Isothiocyanate metabolism, distribution, and interconversion in mice following consumption of thermally processed broccoli sprouts or purified sulforaphane

    PubMed Central

    Bricker, Gregory V.; Riedl, Kenneth M.; Ralston, Robin A.; Tober, Kathleen L.; Oberyszyn, Tatiana M.; Schwartz, Steven J.

    2014-01-01

    Scope Broccoli sprouts are a rich source of glucosinolates, a group of phytochemicals that when hydrolyzed, are associated with cancer prevention. Our objectives were to investigate the metabolism, distribution, and interconversion of isothiocyanates (ITCs) in mice fed thermally processed broccoli sprout powders (BSPs) or the purified ITC sulforaphane. Methods and results For 1 wk, mice were fed a control diet (n = 20) or one of four treatment diets (n = 10 each) containing nonheated BSP, 60°C mildly heated BSP, 5-min steamed BSP, or 3 mmol purified sulforaphane. Sulforaphane and erucin metabolite concentrations in skin, liver, kidney, bladder, lung, and plasma were quantified using HPLC-MS/MS. Thermal intensity of BSP processing had disparate effects on ITC metabolite concentrations upon consumption. Mild heating generally resulted in the greatest ITC metabolite concentrations in vivo, followed by the nonheated and steamed BSP diets. We observed interconversion between sulforaphane and erucin species or metabolites, and report that erucin is the favored form in liver, kidney, and bladder, even when only sulforaphane is consumed. Conclusion ITC metabolites were distributed to all tissues analyzed, suggesting the potential for systemic benefits. We report for the first time tissue-dependent ratio of sulforaphane and erucin, though further investigation is warranted to assess biological activity of individual forms. PMID:24975513

  8. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC

    PubMed Central

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-01-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level. PMID:25256442

  9. Neuroprotection by 6-(methylsulfinyl)hexyl isothiocyanate in a 6-hydroxydopamine mouse model of Parkinson׳s disease.

    PubMed

    Morroni, Fabiana; Sita, Giulia; Tarozzi, Andrea; Cantelli-Forti, Giorgio; Hrelia, Patrizia

    2014-11-17

    A number of pathogenic factors have been implicated in the progression of Parkinson׳s disease (PD), including oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and signals mediating apoptosis cascade. 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major component in wasabi, a very popular spice in Japan and a member of the Brassica family of vegetables. This study was designed to investigate the neuroprotective effects of 6-MSITC in a PD mouse model. Mice were treated with 6-MSITC (5mg/kg twice a week) for four weeks after the unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). On the 28th day, 6-OHDA-injected mice showed behavioral impairments, a significant decrease in tyrosine hydroxylase (TH) and an increase in apoptosis. In addition, lesioned mice showed reduced glutathione levels and glutathione-S-transferase and glutathione reductase activities. Notably, 6-MSITC demonstrated neuroprotective effects in our experimental model strongly related to the preservation of functional nigral dopaminergic neurons, which contributed to the reduction of motor dysfunction induced by 6-OHDA. Furthermore, this study provides evidence that the beneficial effects of 6-MSITC could be attributed to the decrease of apoptotic cell death and to the activation of glutathione-dependent antioxidant systems. These findings may render 6-MSITC as a promising molecule for further pharmacological studies on the investigation for disease-modifying treatment in PD. PMID:25257035

  10. Fetal ethanol exposure attenuates aversive oral effects of TrpV1, but not TrpA1 agonists in rats

    PubMed Central

    Glendinning, John I; Simons, Yael M; Youngentob, Lisa; Youngentob, Steven L

    2012-01-01

    In humans, fetal ethanol exposure is highly predictive of adolescent ethanol use and abuse. Prior work in our labs indicated that fetal ethanol exposure results in stimulus-induced chemosensory plasticity in the taste and olfactory systems of adolescent rats. In particular, we found that increased ethanol acceptability could be attributed, in part, to an attenuated aversion to ethanol’s aversive odor and quinine-like bitter taste quality. Here, we asked whether fetal ethanol exposure also alters the oral trigeminal response of adolescent rats to ethanol. We focused on two excitatory ligand-gated ion channels, TrpV1 and TrpA1, which are expressed in oral trigeminal neurons and mediate the aversive orosensory response to many chemical irritants. To target TrpV1, we used capsaicin, and to target TrpA1, we used allyl isothiocyanate (or mustard oil). We assessed the aversive oral effects of ethanol, together with capsaicin and mustard oil, by measuring short-term licking responses to a range of concentrations of each chemical. Experimental rats were exposed in utero by administering ethanol to dams through a liquid diet. Control rats had ad libitum access to an iso-caloric iso-nutritive liquid diet. We found that fetal ethanol exposure attenuated the oral aversiveness of ethanol and capsaicin, but not mustard oil, in adolescent rats. Moreover, the increased acceptability of ethanol was directly related to the reduced aversiveness of the TrpV1-mediated orosensory input. We propose that fetal ethanol exposure increases ethanol avidity not only by making ethanol smell and taste better, but also by attenuating ethanol’s capsaicin-like burning sensations. PMID:22378825

  11. Dopamine agonist: pathological gambling and hypersexuality.

    PubMed

    2008-10-01

    (1) Pathological gambling and increased sexual activity can occur in patients taking dopaminergic drugs. Detailed case reports and small case series mention serious familial and social consequences. The frequency is poorly documented; (2) Most affected patients are being treated for Parkinson's disease, but cases have been reported among patients prescribed a dopamine agonist for restless legs syndrome or pituitary adenoma; (3) Patients treated with this type of drug, and their relatives, should be informed of these risks so that they can watch for changes in behaviour. If such disorders occur, it may be necessary to reduce the dose or to withdraw the drug or replace it with another medication. PMID:19536937

  12. Modulation of Innate Immune Responses via Covalently Linked TLR Agonists

    PubMed Central

    2015-01-01

    We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed in vivo studies using a vaccinia vaccination model. Mice vaccinated with the linked TLR agonists showed an increase in antibody depth and breadth compared to mice vaccinated with the unconjugated mixture. These studies demonstrate how activation of multiple TLRs through chemically and spatially defined organization assists in guiding immune responses, providing the potential to use chemical tools to design and develop more effective vaccines. PMID:26640818

  13. Mechanisms of agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Lin, Hong; Strange, Philip G

    2004-12-01

    In this study, we investigated the biochemical mechanisms of agonist action at the G protein-coupled D2 dopamine receptor expressed in Chinese hamster ovary cells. Stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding by full and partial agonists was determined at different concentrations of [35S]GTPgammaS (0.1 and 10 nM) and in the presence of different concentrations of GDP. At both concentrations of [35S]GTPgammaS, increasing GDP decreased the [35S]GTPgammaS binding observed with maximally stimulating concentrations of agonist, with partial agonists exhibiting greater sensitivity to the effects of GDP than full agonists. The relative efficacy of partial agonists was greater at the lower GDP concentrations. Concentration-response experiments were performed for a range of agonists at the two [35S]GTPgammaS concentrations and with different concentrations of GDP. At 0.1 nM [35S]GTPgammaS, the potency of both full and partial agonists was dependent on the GDP concentration in the assays. At 10 nM [35S]GTPgammaS, the potency of full agonists exhibited a greater dependence on the GDP concentration, whereas the potency of partial agonists was virtually independent of GDP. We concluded that at the lower [35S]GTPgammaS concentration, the rate-determining step in G protein activation is the binding of [35S]GTPgammaS to the G protein. At the higher [35S]GTPgammaS concentration, for full agonists, [35S]GTPgammaS binding remains the slowest step, whereas for partial agonists, another (GDP-independent) step, probably ternary complex breakdown, becomes rate-determining. PMID:15340043

  14. Computational modeling toward understanding agonist binding on dopamine 3.

    PubMed

    Zhao, Yaxue; Lu, Xuefeng; Yang, Chao-Yie; Huang, Zhimin; Fu, Wei; Hou, Tingjun; Zhang, Jian

    2010-09-27

    The dopamine 3 (D3) receptor is a promising therapeutic target for the treatment of nervous system disorders, such as Parkinson's disease, and current research interests primarily focus on the discovery/design of potent D3 agonists. Herein, a well-designed computational protocol, which combines pharmacophore identification, homology modeling, molecular docking, and molecular dynamics (MD) simulations, was employed to understand the agonist binding on D3 aiming to provide insights into the development of novel potent D3 agonists. We (1) identified the chemical features required in effective D3 agonists by pharmacophore modeling based upon 18 known diverse D3 agonists; (2) constructed the three-dimensional (3D) structure of D3 based on homology modeling and the pharmacophore hypothesis; (3) identified the binding modes of the agonists to D3 by the correlation between the predicted binding free energies and the experimental values; and (4) investigated the induced fit of D3 upon agonist binding through MD simulations. The pharmacophore models of the D3 agonists and the 3D structure of D3 can be used for either ligand- or receptor-based drug design. Furthermore, the MD simulations further give the insight that the long and flexible EL2 acts as a "door" for agonist binding, and the "ionic lock" at the bottom of TM3 and TM6 is essential to transduce the activation signal. PMID:20695484

  15. Does 1-Allyl-3-methylimidazolium chloride Act as a Biocompatible Solvent for Stem Bromelain?

    PubMed

    Jha, Indrani; Bisht, Meena; Venkatesu, Pannuru

    2016-06-30

    The broader scope of ILs in chemical sciences particularly in pharmaceutical, bioanalytical and many more applications is increasing day by day. Hitherto, a very less amount of research is available in the depiction of conformational stability, activity, and thermal stability of enzymes in the presence of ILs. In the present study, the perturbation in the structure, stability, and activity of stem bromelain (BM) has been observed in the presence of 1-allyl-3-methylimidazolium chloride ([Amim][Cl]) using various techniques. This is the first report in which the influence of [Amim][Cl] has been studied on the enzyme BM. Fluorescence spectroscopy has been utilized to map out the changes in the environment around tryptophan (Trp) residues of BM and also to discuss the variations in the thermal stability of BM as an outcome of its interaction with the IL at different concentrations. Further, the work delineates the denaturing effect of high concentration of IL on enzyme structure and activity. It dictates the fact that low concentrations (0.01-0.10 M) of [Amim][Cl] are only changing the structural arrangement of the protein without having harsh consequences on its activity and stability. However, high concentrations of IL proved to be totally devastating for both activity and stability of BM. The observed decrease in the stability of BM at high concentration may be due to the combined effect of cation and anion interactions with the protein residues. The present work is successful in dictating the probable mechanism of interaction between BM and [Amim][Cl]. These results can prove to be fruitful in the studies of enzymes in aqueous IL systems since the used IL is thermally stable and nonvolatile in nature thereby providing a pathway of alteration in the activity of enzymes in potentially green systems. PMID:27268069

  16. Rate of Molecular Transfer of Allyl Alcohol across an AOT Surfactant Layer Using Muon Spin Spectroscopy.

    PubMed

    Jayasooriya, Upali A; Clayden, Nigel J; Steytler, David C; Oganesyan, Vasily S; Peck, Jamie N T; Khasanov, Rustem; Scheuermann, Robert; Stoykov, Alexey

    2016-01-26

    The transfer rate of a probe molecule across the interfacial layer of a water-in-oil (w/o) microemulsion was investigated using a combination of transverse field muon spin rotation (TF-μSR), avoided level crossing muon spin resonance (ALC-μSR), and Monte Carlo simulations. Reverse microemulsions consist of nanometer-sized water droplets dispersed in an apolar solvent separated by a surfactant monolayer. Although the thermodynamic, static model of these systems has been well described, our understanding of their dynamics is currently incomplete. For example, what is the rate of solute transfer between the aqueous and apolar solvents, and how this is influenced by the structure of the interface? With an appropriate choice of system and probe molecule, μSR offers a unique opportunity to directly probe these interfacial transfer dynamics. Here, we have employed a well characterized w/o microemulsion stabilized by bis(2-ethylhexyl) sodium sulfosuccinate (Aerosol OT), with allyl alcohol (CH2═CH-CH2-OH, AA) as the probe. Resonances due to both muoniated radicals, CMuH2-C*H-CH2-OH and C*H2-CHMu-CH2-OH, were observed with the former being the dominant species. All resonances displayed solvent dependence, with those in the microemulsion observed as a single resonance located at intermediate magnetic fields to those present in either of the pure solvents. Observation of a single resonance is strong evidence for interfacial transfer being in the fast exchange limit. Monte Carlo calculations of the ΔM = 0 ALC resonances are consistent with the experimental data, indicating exchange rates greater than 10(9) s(-1), placing the rate of interfacial transfer at the diffusion limit. PMID:26716949

  17. N-allyl epiderpride: An extremely potent SPECT radioligand for the dopamine D2 receptor

    SciTech Connect

    Kessler, R.M.; Mason, N.S.; Ansari, M.S.

    1994-05-01

    We have previously reported that epidepride is a potent (K{sub D} 24pM) and specific SPECT radioligand for the dopamine D2 receptor which can be used to study striatal and extrastriatal dopamine D2 receptors in man. We have synthesized and evaluated the N-allyl analogue of epiderpride (APID) as a potential SPECT radioligand for the dopamine D2 receptor. In comparison to epidepride it is even more potent at the dopamine D2 receptor, the K{sub D} for APID being 11 frontal cortical homogenate. The lipophilicity, evaluated using the log kw pH 7.5, was 2.9 versus 2.05 for epidepride. Competitive binding studies using rat striatal, hippocampal and frontal cortical homogenates showed high affinity for only dopamine D2 like cerebellar ratio of 275:1 at 320 minutes post injection-similar to that seen with epidepride, but with nearly four times higher brain uptake. Of interest was the off-rate from the dopamine D2 receptor; it was 0.0046 min{sup -1} in vitro at 25{degrees}C-corresponding to an t 1/2 of 150 minutes. Studies in rhesus monkeys show an in vivo off rate (following 2.5 mg/kg raclopride IV) of about 0.0082 min{sup -1} seen that with epidepride. SPECT studies in rhesus monkeys reveal APID is a promising SPECT radioligand that appears to be similar to epidepride, but with higher brain uptake due to its more optimal lipophilicity for entry into brain.

  18. Mechanism of copper(I)-catalyzed allylic alkylation of phosphorothioate esters: influence of the leaving group on α regioselectivity.

    PubMed

    Sheng, Wenhao; Wang, Mian; Lein, Matthias; Jiang, Linbin; Wei, Wanxing; Wang, Jianyi

    2013-10-11

    The mechanism of Cu(I) -catalyzed allylic alkylation and the influence of the leaving groups (OPiv, SPiv, Cl, SPO(OiPr)2 ; Piv: pivavloyl) on the regioselectivity of the reaction have been explored by using density functional theory (DFT). A comprehensive comparison of many possible reaction pathways shows that [(iPr)2 Cu](-) prefers to bind first oxidatively to the double bond of the allylic substrate at the anti position with respect to the leaving group, and this is followed by dissociation of the leaving group. If the leaving group is not taken into account, the reaction then undergoes an isomerization and a reductive elimination process to give the α- or γ-selective product. If OPiv, SPiv, Cl, or SPO(OiPr)2 groups are present, the optimal route for the formation of both α- and γ-substituted products changes from the stepwise elimination to the direct process, in which the leaving group plays a stabilizing role for the reactant and destabilizes the transition state. The differences to the energy barrier for the α- and γ-substituted products are 2.75 kcal mol(-1) with SPO(OiPr)2 , 2.44 kcal mol(-1) with SPiv, 2.33 kcal mol(-1) with OPiv, and 1.98 kcal mol(-1) with Cl, respectively; these values show that α regioselectivity in the allylic alkylation follows a SPO(OiPr)2 >SPiv>OPiv>Cl trend, which is in satisfactory agreement with the experimental findings. This trend mainly originates in the differences between the attractive electrostatic forces and the repelling steric interactions of the SPO(OiPr)2 , SPiv, OPiv, and Cl groups on the Cu group. PMID:24038319

  19. Rheological and mechanical behavior of polyacrylamide hydrogels chemically crosslinked with allyl agarose for two-dimensional gel electrophoresis.

    PubMed

    Suriano, R; Griffini, G; Chiari, M; Levi, M; Turri, S

    2014-02-01

    Two-dimensional (2-D) gel electrophoresis currently represents one of the most standard techniques for protein separation. In addition to the most commonly employed polyacrylamide crosslinked hydrogels, acrylamide-agarose copolymers have been proposed as promising systems for separation matrices in 2-D electrophoresis, because of the good resolution of both high and low molecular mass proteins made possible by careful control and optimization of the hydrogel pore structure. As a matter of fact, a thorough understanding of the nature of the hydrogel pore structure as well as of the parameters by which it is influenced is crucial for the design of hydrogel systems with optimal sieving properties. In this work, a series of acrylamide-based hydrogels covalently crosslinked with different concentrations of allyl agarose (0.2-1%) is prepared and characterized by creep-recovery measurements, dynamic rheology and tensile tests, in the attempt to gain a clearer understanding of structure-property relationships in crosslinked polyacrylamide-based hydrogels. The rheological and mechanical properties of crosslinked acrylamide-agarose hydrogels are found to be greatly affected by crosslinker concentration. Dynamic rheological tests show that hydrogels with a percentage of allyl agarose between 0.2% and 0.6% have a low density of elastically effective crosslinks, explaining the good separation of high molecular mass proteins in 2-D gel electrophoresis. Over the same range of crosslinker concentration, creep-recovery measurements reveal the presence of non-permanent crosslinks in the hydrogel network that justifies the good resolution of low molecular mass proteins as well. In tensile tests, the hydrogel crosslinked with 0.4% of allyl agarose exhibits the best results in terms of mechanical strength and toughness. Our results show how the control of the viscoelastic and the mechanical properties of these materials allow the design of mechanically stable hydrogels with improved

  20. Monitoring the Reaction Products of Perfluoropropionic Acid and Allyl Phenyl Ether Using Chirped-Pulse Fourier Transform Microwave Cp-Ftmw Spectroscopy

    NASA Astrophysics Data System (ADS)

    Frank, Derek S.; Obenchain, Daniel A.; Lin, Wei; Novick, Stewart E.; Cooke, S. A.; Grubbs, G. S., II

    2014-06-01

    The pure rotational spectra of the reaction mixture of perfluoropropionic acid, CF3CF2COOH, and allyl phenyl ether, C6H5OCH2CH=CH2, have been studied by a pulsed nozzle, chirped-pulse Fourier transform microwave spectrometer in the frequency range of 8-14 GHz. Transitions corresponding to multiple species, two of which being starting materials allyl phenyl ether and perfluoropropionic acid, have been observed and analyzed. Determination of the reaction products was carried out by matching observed rotational constants with ab initio quantum chemical calculations of predicted products and will be discussed. Rotational constants, centrifugal distortion constants and the assignment of allyl phenyl ether and reaction products spectra will all be discussed.

  1. Regioselective synthesis of dihydrothiophene and thiopyran frameworks via catalyst-controlled intramolecular Cγ/Cδ-S fusion of α-allyl-β'-oxodithioesters.

    PubMed

    Chowdhury, Sushobhan; Chanda, Tanmoy; Koley, Suvajit; Anand, Namrata; Singh, Maya Shankar

    2014-11-01

    A highly efficient and atom-economic dual reaction manifold has been developed to synthesize 4H-thiopyran and 4,5-dihydrothiophene frameworks via regioselective intramolecular C-S fusion of α-allyl-β'-oxodithioesters. The ring size of the sulfur-heterocycles has been efficiently tuned by the use of two different catalytic systems. Palladium activates the Cδ-H of the allyl termini and facilitates the intramolecular Cδ-S coupling to furnish six-membered thiopyran skeletons exclusively. Conversely, the allylic double bond of the same substrate has been activated by BF3·Et2O to promote the Cγ-S cyclization leading to the formation of a five-membered dihydrothiophene nucleus. PMID:25343754

  2. Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

    PubMed Central

    Weidmann, Verena; Schaffrath, Mathias; Zorn, Holger

    2013-01-01

    Summary Allylic oxidations of olefins to enones allow the efficient synthesis of value-added products from simple olefinic precursors like terpenes or terpenoids. Biocatalytic variants have a large potential for industrial applications, particularly in the pharmaceutical and food industry. Herein we report efficient biocatalytic allylic oxidations of spirocyclic terpenoids by a lyophilisate of the edible fungus Pleurotus sapidus. This ‘’mushroom catalysis’’ is operationally simple and allows the conversion of various unsaturated spirocyclic terpenoids. A number of new spirocyclic enones have thus been obtained with good regio- and chemoselectivity and chiral separation protocols for enantiomeric mixtures have been developed. The oxidations follow a radical mechanism and the regioselectivity of the reaction is mainly determined by bond-dissociation energies of the available allylic CH-bonds and steric accessibility of the oxidation site. PMID:24204436

  3. Strategies for designing synthetic immune agonists.

    PubMed

    Wu, Tom Y-H

    2016-08-01

    Enhancing the immune system is a validated strategy to combat infectious disease, cancer and allergy. Nevertheless, the development of immune adjuvants has been hampered by safety concerns. Agents that can stimulate the immune system often bear structural similarities with pathogen-associated molecular patterns found in bacteria or viruses and are recognized by pattern recognition receptors (PRRs). Activation of these PRRs results in the immediate release of inflammatory cytokines, up-regulation of co-stimulatory molecules, and recruitment of innate immune cells. The distribution and duration of these early inflammatory events are crucial in the development of antigen-specific adaptive immunity in the forms of antibody and/or T cells capable of searching for and destroying the infectious pathogens or cancer cells. However, systemic activation of these PRRs is often poorly tolerated. Hence, different strategies have been employed to modify or deliver immune agonists in an attempt to control the early innate receptor activation through temporal or spatial restriction. These approaches include physicochemical manipulation, covalent conjugation, formulation and conditional activation/deactivation. This review will describe recent examples of discovery and optimization of synthetic immune agonists towards clinical application. PMID:27213842

  4. Proglumide exhibits delta opioid agonist properties.

    PubMed

    Rezvani, A; Stokes, K B; Rhoads, D L; Way, E L

    1987-01-01

    Recently, it was reported that proglumide, a cholecystokinin (CCK) antagonist, potentiates the analgetic effects of morphine and endogenous opioid peptides and reverses morphine tolerance by antagonizing the CCK system in the central nervous system of the rat. In order to provide additional insight into the mode of action of this agent, we assessed the effect of proglumide in the isolated guinea pig ileum and the mouse, rat and rabbit vas deferens. Furthermore, we studied the in vitro binding affinity of this substance to mouse brain synaptosomes. Our results show that proglumide inhibits, dose dependently, the electrically stimulated twitches in the mouse vas deferens and guinea pig ileum, but not in the rat or rabbit vas deferens. The inhibitory action of proglumide on the mouse vas deferens, but not on the guinea pig ileum, is antagonized by naloxone and by the selective delta-antagonist, ICI 174,864, in a competitive fashion. Other CCK antagonists were found to be devoid of such activity on the mouse vas deferens. In vitro binding studies showed that proglumide displaces D-ala-D-[leucine]5-enkephalin (DADLE), a delta agonist, but not ethylketocyclazocine (EKC), a preferentially selective kappa agonist. The effect of proglumide appeared to be elicited presynaptically since it did not alter the norepinephrine-induced contractions of the mouse vas deferens. Our results suggest that proglumide might exert its opiate-like effects by activation of delta-opioid receptors. PMID:3030338

  5. Chimpanzees Extract Social Information from Agonistic Screams

    PubMed Central

    Slocombe, Katie E.; Kaller, Tanja; Call, Josep; Zuberbühler, Klaus

    2010-01-01

    Chimpanzee (Pan troglodytes) agonistic screams are graded vocal signals that are produced in a context-specific manner. Screams given by aggressors and victims can be discriminated based on their acoustic structure but the mechanisms of listener comprehension of these calls are currently unknown. In this study, we show that chimpanzees extract social information from these vocal signals that, combined with their more general social knowledge, enables them to understand the nature of out-of-sight social interactions. In playback experiments, we broadcast congruent and incongruent sequences of agonistic calls and monitored the response of bystanders. Congruent sequences were in accordance with existing social dominance relations; incongruent ones violated them. Subjects looked significantly longer at incongruent sequences, despite them being acoustically less salient (fewer call types from fewer individuals) than congruent ones. We concluded that chimpanzees categorised an apparently simple acoustic signal into victim and aggressor screams and used pragmatics to form inferences about third-party interactions they could not see. PMID:20644722

  6. Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

    PubMed Central

    Rideau, Emeline

    2015-01-01

    Summary Asymmetric allylic alkylation is a powerful reaction that allows the enantioselective formation of C–C bonds. Here we describe the asymmetric alkylation of alkylzirconium species to racemic 3,6-dihydro-2H-pyrans. Two systems were examined: 3-chloro-3,6-dihydro-2H-pyran using linear optimization (45–93% ee, up to 33% yield, 5 examples) and 3,6-dihydro-2H-pyran-3-yl diethyl phosphate with the assistance of a design of experiments statistical approach (83% ee, 12% yield). 1H NMR spectroscopy was used to gain insight into the reaction mechanisms. PMID:26734091

  7. Allyl- iso-propyltelluride, a new MOVPE precursor for CdTe, HgTe and (Hg,Cd)Te

    NASA Astrophysics Data System (ADS)

    Hails, Janet E.; Cole-Hamilton, David J.; Stevenson, John; Bell, William

    2000-06-01

    The use of allyl- iso-propyltelluride as the tellurium precursor for the growth of CdTe, HgTe and (Hg,Cd)Te by metal organic vapour-phase epitaxy has been investigated. It has proved to be an efficient source of tellurium with growth rates for HgTe and (Hg,Cd)Te of up to 10 μm h -1 at 300°C. The best CdTe was grown at 4.5 μm h -1 under Me 2Cd-rich conditions at 300°C in the presence of Hg vapour.

  8. Palladium-catalyzed Heck-type reaction of oximes with allylic alcohols: synthesis of pyridines and azafluorenones.

    PubMed

    Zheng, Meifang; Chen, Pengquan; Wu, Wanqing; Jiang, Huanfeng

    2016-01-01

    We describe herein a palladium-catalyzed Heck-type reaction of O-acetyl ketoximes and allylic alcohols to synthesise pyridines. This protocol allows the robust synthesis of pyridines and azafluorenones in good to excellent yields with tolerance of various functional groups under mild conditions. The reaction is supposed to go through an oxidative addition of oximes to palladium(0) complexes, generating an alkylideneamino-palladium(II) species, which is utilized as a key intermediate to capture the nonbiased alkenes for carbon-carbon bond formation. PMID:26496814

  9. Catalytic Reduction of Noble Metal Salts by Sodium Hypophosphite Promoted by the Film Poly-(p-Allyl Ether Benzenesulfonic Acid).

    PubMed

    Costa, M I C F; Steter, J R; Purgato, F L S; Romero, J R

    2011-01-01

    Glassy carbon electrodes were coated with the film poly-(p-allyl ether benzenesulfonic acid) by an anodic procedure. Nickel, platinum, and palladium ions were introduced into the film by ion exchange of H(+) with the corresponding salts. These ions were catalytically reduced to their corresponding metals using the known electroless reducing agent sodium hypophosphite. Scanning electron microcopy and energy dispersive X-ray spectroscopy were carried out to demonstrate the occurrence of the catalytic process. To compare this method with another one carried out in our laboratory, the electrocatalytic reduction of H(+) was studied using the same modified electrodes. A suggested mechanism for the catalysis is proposed. PMID:24052832

  10. Catalytic Reduction of Noble Metal Salts by Sodium Hypophosphite Promoted by the Film Poly-(p-Allyl Ether Benzenesulfonic Acid)

    PubMed Central

    Costa, M. I. C. F.; Steter, J. R.; Purgato, F. L. S.; Romero, J. R.

    2011-01-01

    Glassy carbon electrodes were coated with the film poly-(p-allyl ether benzenesulfonic acid) by an anodic procedure. Nickel, platinum, and palladium ions were introduced into the film by ion exchange of H+ with the corresponding salts. These ions were catalytically reduced to their corresponding metals using the known electroless reducing agent sodium hypophosphite. Scanning electron microcopy and energy dispersive X-ray spectroscopy were carried out to demonstrate the occurrence of the catalytic process. To compare this method with another one carried out in our laboratory, the electrocatalytic reduction of H+ was studied using the same modified electrodes. A suggested mechanism for the catalysis is proposed. PMID:24052832

  11. Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study.

    PubMed

    Seow, Adeline; Yuan, Jian-Min; Sun, Can-Lan; Van Den Berg, David; Lee, Hin-Peng; Yu, Mimi C

    2002-12-01

    Dietary intake of cruciferous vegetables (Brassica spp.) has been inversely related to colorectal cancer risk, and this has been attributed to their high content of glucosinolate degradation products such as isothiocyanates (ITCs). These compounds act as anticarcinogens by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). These enzymes also metabolize ITCs, such that the protective effect of cruciferous vegetables may predicate on GST genotype. The Singapore Chinese Health Study is a prospective investigation among 63 257 middle-aged men and women, who were enrolled between April 1993 and December 1998. In this nested case-control analysis, we compared 213 incident cases of colorectal cancer with 1194 controls. Information on dietary ITC intake from cruciferous vegetables, collected at recruitment via a semi-quantitative food frequency questionnaire, was combined with GSTM1, T1 and P1 genotype from peripheral blood lymphocytes or buccal mucosa. When categorized into high (greater than median) and low (less than/equal to median) intake, dietary ITC was slightly lower in cases than controls but the difference was not significant [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.59-1.12]. There were no overall associations between GSTM1, T1 or P1 genotypes and colorectal cancer risk. However, among individuals with both GSTM1 and T1 null genotypes, we observed a 57% reduction in risk among high versus low consumers of ITC (OR 0.43, 95% CI 0.20-0.96), in particular for colon cancer (OR 0.31, 0.12-0.84). Our results are compatible with the hypothesis that ITCs from cruciferous vegetables modify risk of colorectal cancer in individuals with low GST activity. Further, this gene-diet interaction may be important in studies evaluating the effect of risk-enhancing compounds in the colorectum. PMID:12507929

  12. Comparative systems biology analysis to study the mode of action of the isothiocyanate compound Iberin on Pseudomonas aeruginosa.

    PubMed

    Tan, Sean Yang-Yi; Liu, Yang; Chua, Song Lin; Vejborg, Rebecca Munk; Jakobsen, Tim Holm; Chew, Su Chuen; Li, Yingying; Nielsen, Thomas E; Tolker-Nielsen, Tim; Yang, Liang; Givskov, Michael

    2014-11-01

    Food is now recognized as a natural resource of novel antimicrobial agents, including those that target the virulence mechanisms of bacterial pathogens. Iberin, an isothiocyanate compound from horseradish, was recently identified as a quorum-sensing inhibitor (QSI) of the bacterial pathogen Pseudomonas aeruginosa. In this study, we used a comparative systems biology approach to unravel the molecular mechanisms of the effects of iberin on QS and virulence factor expression of P. aeruginosa. Our study shows that the two systems biology methods used (i.e., RNA sequencing and proteomics) complement each other and provide a thorough overview of the impact of iberin on P. aeruginosa. RNA sequencing-based transcriptomics showed that iberin inhibits the expression of the GacA-dependent small regulatory RNAs RsmY and RsmZ; this was verified by using gfp-based transcriptional reporter fusions with the rsmY or rsmZ promoter regions. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics showed that iberin reduces the abundance of the LadS protein, an activator of GacS. Taken together, the findings suggest that the mode of QS inhibition in iberin is through downregulation of the Gac/Rsm QS network, which in turn leads to the repression of QS-regulated virulence factors, such as pyoverdine, chitinase, and protease IV. Lastly, as expected from the observed repression of small regulatory RNA synthesis, we also show that iberin effectively reduces biofilm formation. This suggests that small regulatory RNAs might serve as potential targets in the future development of therapies against pathogens that use QS for controlling virulence factor expression and assume the biofilm mode of growth in the process of causing disease. PMID:25155599

  13. Protection of humans by plant glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora.

    PubMed

    Fahey, Jed W; Wehage, Scott L; Holtzclaw, W David; Kensler, Thomas W; Egner, Patricia A; Shapiro, Theresa A; Talalay, Paul

    2012-04-01

    Plant-based diets rich in crucifers are effective in preventing cancer and other chronic diseases. Crucifers contain very high concentrations of glucosinolates (GS; β-thioglucoside-N-hydroxysulfates). Although not themselves protective, GS are converted by coexisting myrosinases to bitter isothiocyanates (ITC) which defend plants against predators. Coincidentally, ITC also induce mammalian genes that regulate defenses against oxidative stress, inflammation, and DNA-damaging electrophiles. Consequently, the efficiency of conversion of GS to ITC may be critical in controlling the health-promoting benefits of crucifers. If myrosinase is heat-inactivated by cooking, the gastrointestinal microflora converts GS to ITC, a process abolished by enteric antibiotics and bowel cleansing. When single oral doses of GS were administered as broccoli sprout extracts (BSE) to two dissimilar populations (rural Han Chinese and racially mixed Baltimoreans) patterns of excretions of urinary dithiocarbamates (DTC) were very similar. Individual conversions in both populations varied enormously, from about 1% to more than 40% of dose. In contrast, administration of ITC (largely sulforaphane)-containing BSE resulted in uniformly high (70%-90%) conversions to urinary DTC. Despite the remarkably large range of conversion efficiencies between individuals, repeated determinations within individuals were much more consistent. The rates of urinary excretion (slow or fast) were unrelated to the ultimate magnitudes (low or high) of these conversions. Although no demographic factors affecting conversion efficiency have been identified, there are clearly diurnal variations: conversion of GS to DTC was greater during the day, but conversion of ITC to DTC was more efficient at night. PMID:22318753

  14. Taste detection of the non-volatile isothiocyanate moringin results in deterrence to glucosinolate-adapted insect larvae.

    PubMed

    Müller, Caroline; van Loon, Joop; Ruschioni, Sara; De Nicola, Gina Rosalinda; Olsen, Carl Erik; Iori, Renato; Agerbirk, Niels

    2015-10-01

    Isothiocyanates (ITCs), released from Brassicales plants after hydrolysis of glucosinolates, are known for their negative effects on herbivores but mechanisms have been elusive. The ITCs are initially present in dissolved form at the site of herbivore feeding, but volatile ITCs may subsequently enter the gas phase and all ITCs may react with matrix components. Deterrence to herbivores resulting from topically applied volatile ITCs in artificial feeding assays may hence lead to ambiguous conclusions. In the present study, the non-volatile ITC moringin (4-(α-L-rhamnopyranosyloxy)benzyl ITC) and its glucosinolate precursor glucomoringin were examined for effects on behaviour and taste physiology of specialist insect herbivores of Brassicales. In feeding bioassays, glucomoringin was not deterrent to larvae of Pieris napi (Lepidoptera: Pieridae) and Athalia rosae (Hymenoptera: Tenthredinidae), which are adapted to glucosinolates. Glucomoringin stimulated feeding of larvae of the related Pieris brassicae (Lepidoptera: Pieridae) and also elicited electrophysiological activity from a glucosinolate-sensitive gustatory neuron in the lateral maxillary taste sensilla. In contrast, the ITC moringin was deterrent to P. napi and P. brassicae at high levels and to A. rosae at both high and low levels when topically applied to cabbage leaf discs (either 12, 120 or 1200 nmol moringin per leaf disc of 1cm diameter). Survival of A. rosae was also significantly reduced when larvae were kept on leaves treated with moringin for several days. Furthermore, moringin elicited electrophysiological activity in a deterrent-sensitive neuron in the medial maxillary taste sensillum of P. brassicae, providing a sensory mechanism for the deterrence and the first known ITC taste response of an insect. In simulated feeding assays, recovery of moringin was high, in accordance with its non-volatile nature. Our results demonstrate taste-mediated deterrence of a non-volatile, natural ITC to glucosinolate

  15. The MAPK Pathway Signals Telomerase Modulation in Response to Isothiocyanate-Induced DNA Damage of Human Liver Cancer Cells

    PubMed Central

    Lamy, Evelyn; Herz, Corinna; Lutz-Bonengel, Sabine; Hertrampf, Anke; Márton, Melinda-Rita; Mersch-Sundermann, Volker

    2013-01-01

    4-methylthiobutyl isothiocyanate (MTBITC), an aliphatic, sulphuric compound from Brassica vegetables, possesses in vitro and in vivo antitumor activity. Recently we demonstrated the potent growth inhibitory potential of the DNA damaging agent MTBITC in human liver cancer cells. Here we now show that MTBITC down regulates telomerase which sensitizes cells to apoptosis induction. This is mediated by MAPK activation but independent from production of reactive oxygen species (ROS). Within one hour, MTBITC induced DNA damage in cancer cells correlating to a transient increase in hTERT mRNA expression which then turned into telomerase suppression, evident at mRNA as well as enzyme activity level. To clarify the role of MAPK for telomerase regulation, liver cancer cells were pre-treated with MAPK-specific inhibitors prior to MTBITC exposure. This clearly showed that transient elevation of hTERT mRNA expression was predominantly mediated by the MAPK family member JNK. In contrast, activated ERK1/2 and P38, but not JNK, signalled to telomerase abrogation and consequent apoptosis induction. DNA damage by MTBITC was also strongly abolished by MAPK inhibition. Oxidative stress, as analysed by DCF fluorescence assay, electron spin resonance spectroscopy and formation of 4-hydroxynonenal was found as not relevant for this process. Furthermore, N-acetylcysteine pre-treatment did not impact MTBITC-induced telomerase suppression or depolarization of the mitochondrial membrane potential as marker for apoptosis. Our data therefore imply that upon DNA damage by MTBITC, MAPK are essential for telomerase regulation and consequent growth impairment in liver tumor cells and this detail probably plays an important role in understanding the potential chemotherapeutic efficacy of ITC. PMID:23382840

  16. Prevention of cigarette smoke–induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetylcysteine

    PubMed Central

    Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E.; De Flora, Silvio

    2009-01-01

    Lung cancer is the most important cause of death among neoplastic diseases worldwide, and cigarette smoke (CS) is the major risk factor for cancer. Complementarily to avoidance of exposure to CS, chemoprevention will lower the risk of cancer in passive smokers, ex-smokers, and addicted current smokers who fail to quit smoking. Unfortunately, chemoprevention clinical trials have produced disappointing results to date and, until recently, a suitable animal model evaluating CS carcinogenicity was not available. We previously demonstrated that mainstream CS induces a potent carcinogenic response when exposure of mice starts at birth. In the present study, neonatal mice (strain H) were exposed to CS for 120 consecutive days, starting at birth. The chemopreventive agents budesonide (2.4 mg/kg diet), phenethyl isothiocyanate (PEITC, 1,000 mg/kg diet), and N-acetyl-l-cysteine (NAC, 1,000 mg/kg body weight) were administered orally according to various protocols. The experiment was stopped after 210 days. Exposure to CS resulted in a high incidence and multiplicity of benign lung tumors and in significant increases of malignant lung tumors and other histopathological alterations. All three chemopreventive agents, administered to current smokers after weanling, were quite effective in protecting both male and female mice from CS pulmonary carcinogenicity. When given to ex-smokers after withdrawal of exposure to CS, the protective capacity of budesonide was unchanged, while PEITC lost part of its cancer chemopreventive activity. In conclusion, the proposed experimental model provides convincing evidence that it is possible to prevent CS-induced lung cancer by means of dietary and pharmacological agents. PMID:19816928

  17. Hydrogen-Bond Directed Regioselective Pd-Catalyzed Asymmetric Allylic Alkylation: The Construction of Chiral α-Amino Acids with Vicinal Tertiary and Quaternary Stereocenters.

    PubMed

    Wei, Xuan; Liu, Delong; An, Qianjin; Zhang, Wanbin

    2015-12-01

    A Pd-catalyzed asymmetric allylic alkylation of azlactones with 4-arylvinyl-1,3-dioxolan-2-ones was developed, providing "branched" chiral α-amino acids with vicinal tertiary and quaternary stereocenters, in high yields and with excellent selectivities. Mechanistic studies revealed that the formation of a hydrogen bond between the Pd-allylic complex and azlactone isomer is responsible for the excellent regioselectivities. This asymmetric alkylation can be carried out on a gram scale without a loss of catalytic efficiency, and the resulting product can be further transformed to a chiral azetidine in two simple steps. PMID:26575242

  18. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  19. Physical Chemistry to the Rescue: Differentiating Nicotinic and Cholinergic Agonists

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researches suggest that two agonists can bind to the same binding site of an important transmembrane protein and elicit a biological response through strikingly different binding interactions. Evidence is provided which suggests two possible types of nicotinic acetylcholine receptor agonist binding like acetlycholine (cholinergic) or like nicotine…

  20. Demonstration of HNE-related aldehyde formation via lipoxygenase-catalyzed synthesis of a bis-allylic dihydroperoxide intermediate

    PubMed Central

    Jin, Jing; Zheng, Yuxiang; Brash, Alan R.

    2013-01-01

    One of the proposed pathways to the synthesis of 4-hydroxy-nonenal (HNE) and related aldehydes entails formation of an intermediate bis-allylic fatty acid dihydroperoxide. As a first direct demonstration of such a pathway and proof of principle, herein we show that 8R-lipoxygenase (8R-LOX) catalyzes the enzymatic production of the HNE-like product (11-oxo-8-hydroperoxy-undeca-5,9-dienoic acid) via synthesis of 8,11-dihydroperoxy-eicosa-5,9,12,14-tetraenoic acid intermediate. Incubation of arachidonic acid with 8R-LOX formed initially 8R-hydroperoxyeicosatetraenoic acid (8R-HPETE) which was further converted to a mixture of products including a prominent HPNE-like enone. A new bis-allylic dihydroperoxide was trapped when the incubation was repeated on ice. Re-incubation of this intermediate with 8R-LOX successfully demonstrated its conversion to the enone products, and this reaction was greatly accelerated by co-incubation with NDGA, a reductant of the LOX iron. These findings identify a plausible mechanism that could contribute to the production of 4-hydroxy-alkenals in vivo. PMID:23668325