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Sample records for synthetic trihydroxilated chalcones

  1. Novel synthetic chalcones induces apoptosis in human glioblastoma cells.

    PubMed

    Bittencourt, Lucas Felipe Fernandes; Oliveira, Karen Andrinéia de; Cardoso, Carine Bropp; Lopes, Flávia Garcia; Dal-Cim, Tharine; Chiaradia-Delatorre, Louise Domeneghini; Mascarello, Alessandra; Maluf, Sharbel Weidner; Yunes, Rosendo Augusto; Garcez, Ricardo Castilho; Tasca, Carla Inês; Nedel, Cláudia Beatriz

    2016-05-25

    Glioblastoma multiforme is the main and most frequent tumor in adults' central nervous system. With a survival average of 5% two years after diagnosis, this type of cancer is a main health problem. Substances like the chalcones have been tested in order to develop new treatments. Here, we studied the effects of three synthetic chalcones (A23, C31 and J11) on A172 and surgery obtained-glioma cells. All chalcones showed a decrease in cell viability, mainly C31. An increase in apoptosis levels with no further increase of necrosis was observed. This augmentation may be linked to the high oxidative effect found, caused by the increased presence of reactive oxygen species and nitric oxide production. Cell cycle distribution showed an arrest at G0/G1 and S phases, suggesting that C31 interferes in cell cycle control. Our results shall aid in directing future research with this substance and its antitumor effect.

  2. Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones.

    PubMed

    de Mello, Tatiane F P; Cardoso, Bruna M; Bitencourt, Heriberto R; Donatti, Lucélia; Aristides, Sandra M A; Lonardoni, Maria V C; Silveira, Thais G V

    2016-01-01

    Cutaneous leishmaniasis has an estimated incidence of 1.5 million new cases per year and the treatment options available are old, expensive, toxic, and difficult to administer. Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms of action and drug target of this group of compounds in Leishmania. The synthetic chalcones that were evaluated in the present study were previously shown to exhibit activity against Leishmania (Viannia) braziliensis. The objective of the present study was to identify ultrastructural and morphological changes in L. (V.) braziliensis after treatment with three synthetic chalcones (1-3). Promastigotes were treated with chalcones 1-3 and evaluated by transmission and scanning electron microscopy. Cellular and nuclear morphology of the parasites, changes in membrane permeability, and DNA fragmentation in agarose electrophoresis gel were also investigated after exposure to synthetic chalcones. All three synthetic chalcones (1-3) induced ultrastructural alterations in mitochondria, intense vacuolization, two nuclei with rounding of parasites, and cellular and nuclear shrinkage. Chalcones 1-3 also induced no changes in membrane permeability, and presence of nucleosome-sized DNA fragments. Synthetic chalcones 1-3 induced ultrastructural and morphological changes, suggesting that chalcones 1-3 induce apoptosis-like cell death. Further studies should be conducted to elucidate other aspects of the action of these chalcones against Leishmania spp. and their use for the treatment of cutaneous leishmaniasis.

  3. Experimental and quantum chemical studies of a novel synthetic prenylated chalcone

    PubMed Central

    2013-01-01

    Background Chalcones are ubiquitous natural compounds with a wide variety of reported biological activities, including antitumoral, antiviral and antimicrobial effects. Furthermore, chalcones are being studied for its potential use in organic electroluminescent devices; therefore the description of their spectroscopic properties is important to elucidate the structure of these molecules. One of the main techniques available for structure elucidation is the use of Nuclear Magnetic Resonance Spectroscopy (NMR). Accordingly, the prediction of the NMR spectra in this kind of molecules is necessary to gather information about the influence of substituents on their spectra. Results A novel substituted chalcone has been synthetized. In order to identify the functional groups present in the new synthesized compound and confirm its chemical structure, experimental and theoretical 1H-NMR and 13C-NMR spectra were analyzed. The theoretical molecular structure and NMR spectra were calculated at both the Hartree-Fock and Density Functional (meta: TPSS; hybrid: B3LYP and PBE1PBE; hybrid meta GGA: M05-2X and M06-2X) levels of theory in combination with a 6-311++G(d,p) basis set. The structural parameters showed that the best method for geometry optimization was DFT:M06-2X/6-311++G(d,p), whereas the calculated bond angles and bond distances match experimental values of similar chalcone derivatives. The NMR calculations were carried out using the Gauge-Independent Atomic Orbital (GIAO) formalism in a DFT:M06-2X/6-311++G(d,p) optimized geometry. Conclusion Considering all HF and DFT methods with GIAO calculations, TPSS and PBE1PBE were the most accurate methods used for calculation of 1H-NMR and 13C-NMR chemical shifts, which was almost similar to the B3LYP functional, followed in order by HF, M05-2X and M06-2X methods. All calculations were done using the Gaussian 09 software package. Theoretical calculations can be used to predict and confirm the structure of substituted chalcones

  4. Examination of growth inhibitory properties of synthetic chalcones for which antibacterial activity was predicted.

    PubMed

    Batovska, Daniela; Parushev, Stoyan; Stamboliyska, Bistra; Tsvetkova, Iva; Ninova, Mariana; Najdenski, Hristo

    2009-05-01

    A large series of chalcones were synthesized and studied against Staphylococcus aureus and Escherichia coli. Chalcones were either unsubstituted in ring A or possessed 4'-chloro or 3',4',5'-trimethoxy groups. Their other ring B was variously substituted. It was found that the anti-staphylococcal activity of chalcones was related to the energy difference between the two highest occupied molecular orbitals (HOMO and HOMO-1). Presence of hydroxyl group in ring B was not a determinant factor for the anti-staphylococcal activity, but the lipophilicity of ring A of the hydroxyl chalcones was of importance. PMID:18584918

  5. Study on the substituents' effects of a series of synthetic chalcones against the yeast Candida albicans.

    PubMed

    Batovska, D; Parushev, St; Slavova, A; Bankova, V; Tsvetkova, I; Ninova, M; Najdenski, H

    2007-01-01

    A large series of chalcones were synthesized and studied for activity against Candida albicans. The SAR analysis showed that the antifungal activity was highly dependent on the substitution pattern of the aryl rings and correlated to a large extent with the ability of compounds to interact with sulfhydryl groups. The most active were the hydroxylated chalcones as their activity related to the location of the phenolic group in the aryl ring B as follows: o-OH>p-OH approximately 3,4-di-OH>m-OH. These and other correlations obtained strongly contribute to the knowledge for design of anticandidal chalcones. PMID:17007965

  6. Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

    PubMed Central

    de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Sechini Cordeiro, Marlon Norberto; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

    2015-01-01

    Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g−1) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment. PMID:26366075

  7. Synthetic chalcone derivatives as inhibitors of cathepsins K and B, and their cytotoxic evaluation.

    PubMed

    Ramalho, Suelem Demuner; Bernades, Aline; Demetrius, Giulio; Noda-Perez, Caridad; Vieira, Paulo Cezar; Dos Santos, Caio Yu; da Silva, James Almada; de Moraes, Manoel Odorico; Mousinho, Kristiana Cerqueira

    2013-11-01

    A series of chalcone derivatives, 1-15, were prepared by Claisen-Schmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, (E)-3-(3,4-dimethoxyphenyl)-1-phenylprop-2-en-1-one (12), (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (13), (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (14), and (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (15) showed significant cytotoxicities. The most effective compound was 15, which showed high cytotoxic activity with an IC50 value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.

  8. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

    PubMed Central

    Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

    2009-01-01

    Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. PMID:19725977

  9. Studies of synthetic chalcone derivatives as potential inhibitors of secretory phospholipase A2, cyclooxygenases, lipoxygenase and pro-inflammatory cytokines

    PubMed Central

    Jantan, Ibrahim; Bukhari, Syed Nasir Abbas; Adekoya, Olayiwola A; Sylte, Ingebrigt

    2014-01-01

    Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities involving inhibition of secretory phospholipase A2, cyclooxygenases, soybean lipoxygenase, and lipopolysaccharides-induced secretion of interleukin-6 and tumor necrosis factor-alpha in mouse RAW264.7 macrophages. The results from the above mentioned assays exhibited that the synthesized compounds were effective inhibitors of pro-inflammatory enzymes and cytokines. The results also revealed that the chalcone derivatives with 4-methlyamino ethanol substitution seem to be significant for inhibition of enzymes and cytokines. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the investigated compounds. Present findings increase the possibility that these chalcone derivatives might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents. PMID:25258510

  10. Trends in utilization of the pharmacological potential of chalcones.

    PubMed

    Batovska, Daniela Ilieva; Todorova, Iva Todorova

    2010-02-01

    Chalcones (1,3-diaryl-2-propen-1-ones) are open chain flavonoids that are widely biosynthesized in plants. They are important for the pigmentation of flowers and, hence, act as attractants to the pollinators. As flavonoids, chalcones also play an important role in defense against pathogens and insects. A longstanding scientific research has shown that chalcones also display other interesting biological properties such as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Some lead compounds with various pharmacological properties have been developed based on the chalcone skeleton. Clinical trials have shown that these compounds reached reasonable plasma concentrations and did not cause toxicity. For these reasons, chalcones became an object of continued interest in both academia and industry. Nowadays, several chalcones are used for treatment of viral disorders, cardiovascular diseases, parasitic infections, pain, gastritis, and stomach cancer, as well as like food additives and cosmetic formulation ingredients. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to describe the recent efforts of scientists in pharmacological screening of natural and synthetic chalcones, studying the mechanisms of chalcone action and relevant structure-activity relationships. Put together, these activities aimed at synthesis of pharmacologically active chalcones and their analogs. PMID:19891604

  11. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    PubMed

    Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

    2015-11-15

    Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders.

  12. A synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the TNFα-induced invasive capability of MDA-MB-231 human breast cancer cells by inhibiting NF-κB-mediated GROα expression.

    PubMed

    Lee, Da Young; Lee, Da Hyun; Jung, Jung You; Koh, Dongsoo; Kim, Geum-Soog; Ahn, Young-Sup; Lee, Young Han; Lim, Yoongho; Shin, Soon Young

    2016-01-01

    2-Hydroxy-3',5,5'-trimenthoxyochalcone (DK-139) is a synthetic chalcone-derived compound. This study evaluated the biological activity of DK-139 on the inhibition of tumor metastasis. Growth-regulated oncogene-alpha (GROα) plays an important role in the progression of tumor development by stimulating angiogenesis and metastasis. In this study, DK-139 inhibited tumor necrosis factor alpha (TNFα)-induced GROα gene promoter activity by inhibiting of IκB kinase (IKK) in MDA-MB231 cells. In addition, DK-139 prevented the TNFα-induced cell migration, F-actin formation, and invasive capability of MDA-MB-231 cells. These findings suggest that DK-139 is a potential drug candidate for the inhibition of tumor cell locomotion and invasion via the suppression of NF-κB-mediated GROα expression. PMID:26602275

  13. Inhibitory effects of chalcone glycosides isolated from Brassica rapa L. 'hidabeni' and their synthetic derivatives on LPS-induced NO production in microglia.

    PubMed

    Hara, Hirokazu; Nakamura, Yoko; Ninomiya, Masayuki; Mochizuki, Ryosuke; Kamiya, Tetsuro; Aizenman, Elias; Koketsu, Mamoru; Adachi, Tetsuo

    2011-09-15

    Activation of microglia induces the production of various inflammatory mediators including nitric oxide (NO), leading to neurodegeneration in many central nervous system diseases. In this study, we examined the effects of chalcone glycosides isolated from Brassica rapa L. 'hidabeni' on lipopolysaccharide (LPS)-induced NO production using rat immortalized microglia HAPI cells. 4'-O-β-D-Glucopyranosyl-3',4-dimethoxychalcone (A2) inhibited LPS-induced inducible NO synthase (iNOS) expression and NO production. However, A2 did not affect nuclear factor-κB and mitogen-activated protein kinase pathways. The signal transduction and activator of transcription 1 (STAT1), which is activated via production of IFN-β by LPS, is an important transcription factor responsible for LPS-induced iNOS expression. A2 suppressed LPS-induced phosphorylation and nuclear translocation of STAT1, although it had no effects on LPS-induced IFN-β expression. These results indicate that the inhibitory effect of A2 is due to the prevention of STAT signaling. Moreover, structure-activity relationship studies on newly synthesized 'hidabeni' chalcone derivatives showed that 4'-O-β-D-glucopyranosyl-3'-methoxychalcone (A11), which has no functional groups in the B-ring, inhibits LPS-induced NO production more potently than A2.

  14. Inhibition of Epithelial CC-Family Chemokine Synthesis by the Synthetic Chalcone DMPF-1 via Disruption of NF-κB Nuclear Translocation and Suppression of Experimental Asthma in Mice.

    PubMed

    Rajajendram, Revathee; Tham, Chau Ling; Akhtar, Mohamad Nadeem; Sulaiman, Mohd Roslan; Israf, Daud Ahmad

    2015-01-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The interaction between airway epithelium and inflammatory mediators plays a key role in the pathogenesis of asthma. In vitro studies evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMPF-1), a synthetic chalcone analogue, upon inflammation in the A549 lung epithelial cell line. DMPF-1 selectively inhibited TNF-α-stimulated CC chemokine secretion (RANTES, eotaxin-1, and MCP-1) without any effect upon CXC chemokine (GRO-α and IL-8) secretion. Western blot analysis further demonstrated that the inhibitory activity resulted from disruption of p65NF-κB nuclear translocation without any effects on the mitogen-activated protein kinase (MAPK) pathway. Treatment of ovalbumin-sensitized and ovalbumin-challenged BALB/c mice with DMPF-1 (0.2-100 mg/kg) demonstrated significant reduction in the secretion and gene expression of CC chemokines (RANTES, eotaxin-1, and MCP-1) and Th2 cytokines (IL-4, IL-5, and IL-13). Furthermore, DMPF-1 treatment inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total IgE, and airway hyperresponsiveness in ovalbumin-sensitized and ovalbumin-challenged mice. In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation.

  15. Inhibition of Epithelial CC-Family Chemokine Synthesis by the Synthetic Chalcone DMPF-1 via Disruption of NF-κB Nuclear Translocation and Suppression of Experimental Asthma in Mice

    PubMed Central

    Rajajendram, Revathee; Tham, Chau Ling; Akhtar, Mohamad Nadeem; Sulaiman, Mohd Roslan; Israf, Daud Ahmad

    2015-01-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The interaction between airway epithelium and inflammatory mediators plays a key role in the pathogenesis of asthma. In vitro studies evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMPF-1), a synthetic chalcone analogue, upon inflammation in the A549 lung epithelial cell line. DMPF-1 selectively inhibited TNF-α-stimulated CC chemokine secretion (RANTES, eotaxin-1, and MCP-1) without any effect upon CXC chemokine (GRO-α and IL-8) secretion. Western blot analysis further demonstrated that the inhibitory activity resulted from disruption of p65NF-κB nuclear translocation without any effects on the mitogen-activated protein kinase (MAPK) pathway. Treatment of ovalbumin-sensitized and ovalbumin-challenged BALB/c mice with DMPF-1 (0.2–100 mg/kg) demonstrated significant reduction in the secretion and gene expression of CC chemokines (RANTES, eotaxin-1, and MCP-1) and Th2 cytokines (IL-4, IL-5, and IL-13). Furthermore, DMPF-1 treatment inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total IgE, and airway hyperresponsiveness in ovalbumin-sensitized and ovalbumin-challenged mice. In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation. PMID:26300589

  16. Therapeutic potential of chalcones as cardiovascular agents.

    PubMed

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

    2016-03-01

    Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. PMID:26876916

  17. A synthetic chalcone, 2'-hydroxy-2,3,5'-trimethoxychalcone triggers unfolded protein response-mediated apoptosis in breast cancer cells.

    PubMed

    Lee, Da Hyun; Jung Jung, You; Koh, Dongsoo; Lim, Yoongho; Lee, Young Han; Shin, Soon Young

    2016-03-01

    The primary aim of this study was to find novel chemopreventive agents effective against breast cancer. Endoplasmic reticulum (ER) stress can induce apoptosis through the unfolded protein response (UPR). 2'-Hydroxy-2,3,5'-trimethoxychalcone (DK143) is a synthetic flavonoid derivative. The present study provides evidence supporting the role of the UPR in mediating the apoptotic effect of DK143. Treatment with DK143 triggered apoptosis through the activation of the caspase pathway in MDA-MB-231 breast cancer cells without affecting viability of MCF10A non-transformed breast epithelial cells. Further analysis revealed that DK143 produced reactive oxygen species (ROS) in MDA-MB-231 cells, but not in MCF10A cells, and upregulated the expression of ER stress sensors, including GRP78/BiP, IRE1α, CHOP, and Bim in MDA-MB-231 cells. In addition, UPR-related transcription factors, XBP-1 and CHOP, were activated by DK143. Moreover, silencing of IRE1α or CHOP by corresponding siRNA molecules attenuated DK143-induced apoptosis. Furthermore, DK143 suppressed mouse tumor growth in vivo. These results demonstrate that promoting ER stress in breast cancer cells via UPR induction might be a promising strategy for developing new chemotherapeutic or chemopreventive agents for breast cancer.

  18. A synthetic chalcone, 2'-hydroxy-2,3,5'-trimethoxychalcone triggers unfolded protein response-mediated apoptosis in breast cancer cells.

    PubMed

    Lee, Da Hyun; Jung Jung, You; Koh, Dongsoo; Lim, Yoongho; Lee, Young Han; Shin, Soon Young

    2016-03-01

    The primary aim of this study was to find novel chemopreventive agents effective against breast cancer. Endoplasmic reticulum (ER) stress can induce apoptosis through the unfolded protein response (UPR). 2'-Hydroxy-2,3,5'-trimethoxychalcone (DK143) is a synthetic flavonoid derivative. The present study provides evidence supporting the role of the UPR in mediating the apoptotic effect of DK143. Treatment with DK143 triggered apoptosis through the activation of the caspase pathway in MDA-MB-231 breast cancer cells without affecting viability of MCF10A non-transformed breast epithelial cells. Further analysis revealed that DK143 produced reactive oxygen species (ROS) in MDA-MB-231 cells, but not in MCF10A cells, and upregulated the expression of ER stress sensors, including GRP78/BiP, IRE1α, CHOP, and Bim in MDA-MB-231 cells. In addition, UPR-related transcription factors, XBP-1 and CHOP, were activated by DK143. Moreover, silencing of IRE1α or CHOP by corresponding siRNA molecules attenuated DK143-induced apoptosis. Furthermore, DK143 suppressed mouse tumor growth in vivo. These results demonstrate that promoting ER stress in breast cancer cells via UPR induction might be a promising strategy for developing new chemotherapeutic or chemopreventive agents for breast cancer. PMID:26742460

  19. Stereoselectivity of chalcone isomerase with chalcone derivatives: a computational study.

    PubMed

    Yao, Yuan; Zhang, Hui; Li, Ze-Sheng

    2013-11-01

    Chalcone isomerase (CHI) catalyzes the intramolecular cyclization of chalcones into flavonoids. The activity of CHI is essential for the biosynthesis of flavonoids precursors of floral pigments and phenylpropanoid plant defense compounds. In the present study, we explored the detailed binding structures and binding free energies for two different active site conformations of CHI with s-cis/s-trans conformers of three chalcone compounds by performing molecular dynamics (MD) simulations and binding free energy calculations. The computational results indicate that s-cis/s-trans conformers of chalcone compounds are orientated in the similar binding position in the active site of CHI and stabilized by the different first hydrogen bond network and the same second hydrogen bond network. The first hydrogen bond network results in much lower binding affinity of s-trans conformer of chalcone compound with CHI than that of s-cis conformer. The conformational change of the active site residue T48 from indirectly interacting with the substrate via the second hydrogen bond network to directly forming the hydrogen bond with the substrates cannot affect the binding mode of both conformers of chalcone compounds, but remarkably improves the binding affinity. These results show that CHI has a strong stereoselectivity. The calculated binding free energies for three chalcone compounds with CHI are consistent with the experimental activity data. In addition, several valuable insights are suggested for future rational design and discovery of high-efficiency mutants of CHI. PMID:23989772

  20. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

    PubMed

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  1. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

    PubMed Central

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A.; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1) and 3′-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID:26907262

  2. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

    PubMed

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID:26907262

  3. Diverse Molecular Targets for Chalcones with Varied Bioactivities

    PubMed Central

    Zhou, Bo; Xing, Chengguo

    2015-01-01

    Natural or synthetic chalcones with different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular targets and the modes of interaction with the targets, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable target-selectivity profile. This review summarizes literature evidence on chalcones’ direct molecular targets in the context of their biological activities. PMID:26798565

  4. Solvent-Free Synthesis of Chalcones

    ERIC Educational Resources Information Center

    Palleros, Daniel R.

    2004-01-01

    The synthesis of twenty different chalcones in the absence of solvent is presented. The results indicated that out of the twenty different chalcones investigated seventeen can be obtained in a matter of minutes by mixing the corresponding benzaldehyde and acetophenone in the presence of solid NaOH in a mortar with pestle.

  5. Chalcones and their potential role in inflammation.

    PubMed

    Kontogiorgis, C; Mantzanidou, M; Hadjipavlou-Litina, D

    2008-10-01

    Chalcones are a group of phenolic compounds which possess a wide variety of cytoprotective and modulatory functions. They have been shown to possess antioxidant, oxygen scavenging and anti-inflammatory properties in a variety of experimental systems and can trigger the intracellular cascade of protective pathways offering a promising stratagem for therapeutic applications. In this research we will review the anti-inflammatory effect of chalcone derivatives and new approaches. PMID:18855737

  6. Chalcone Scaffold in Anticancer Armamentarium: A Molecular Insight

    PubMed Central

    Manna, Kuntal

    2016-01-01

    Cancer is an inevitable matter of concern in the medicinal chemistry era. Chalcone is the well exploited scaffold in the anticancer domain. The molecular mechanism of chalcone at cellular level was explored in past decades. This mini review provides the most recent updates on anticancer potential of chalcones. PMID:26880913

  7. Two-photon-induced cycloreversion reaction of chalcone photodimers

    NASA Astrophysics Data System (ADS)

    Träger, J.; Härtner, S.; Heinzer, J.; Kim, H.-C.; Hampp, N.

    2008-04-01

    The photocleavage reaction of chalcone photodimers has been studied using a two-photon process. For this purpose, a novel chalcone dimer has been synthesized as a low molecular weight model substance for polymer bound chalcones and its photochemistry triggered by two-photon-absorption (2PA) has been investigated using a pulsed frequency-doubled Nd:YAG-laser. The 2PA-induced cycloreversion reaction selectively leads to the cleavage of the chalcone photodimers resulting in the formation of monomeric chalcone molecules. Hence, as an application chalcones can be used as a photosensitive linker which can be cleaved beyond an UV-absorbing barrier. The 2PA cross section of the chalcone photodimer was determined to be of 1.1 × 10 -49 cm 4 s photon -1 (11 GM).

  8. Efficacy of Organophosphorus Derivatives Containing Chalcones/Chalcone Semicarbazones Against Fungal Pathogens of Sugarcane

    PubMed Central

    Pandey, O. P.; Rao, G. P.; Singh, Priyanka

    2002-01-01

    Ten newly synthesized organophosphorus derivatives containing substituted chalcones and substituted chalcone semicarbazones were tested for their antifungal efficacy against Colletotrichum falcatum, Fusarium oxysporum, Curvularia pallescens (all sugarcane pathogens). The O,O-diethylphosphate derivatives containing 2-chlorochalcone and 2-chlorochalcone semicarbazone exhibited 70-85% mycelial inhibition against all the test fungi at 1000 ppm. The screening results were correlated with structural features of the tested compounds. PMID:18476009

  9. Chalcones as Promising Lead Compounds on Cancer Therapy.

    PubMed

    León-González, Antonio J; Acero, Nuria; Muñoz-Mingarro, Dolores; Navarro, Inmaculada; Martín-Cordero, Carmen

    2015-01-01

    Chalcones constitute a group of phenolic compounds that command an increasing interest on cancer research. Natural chalcones are widespread through the plant kingdom. The most abundant and investigated chalcones are isoliquiritigenin, flavokawain and xanthohumol, which are present in the Fabaceae, Piperaceae, Cannabaceae, and Moraceae families. These chalcones have been shown to be promising lead antitumor-chemopreventive drugs by three different activities: antioxidants, cytotoxic and apoptosis inducers. In the recent years, SAR (structure-activity relationship) has contributed towards the improvement of anticancer properties of chalcones by substituting aryl rings and introducing heterocyclic moieties. This review summarizes the anticancer activities shown by natural chalcones and the SAR and describes how different chemical moiety modifications could lead them to be therapeutically useful in the treatment of cancer.

  10. Stilbene Synthase and Chalcone Synthase 1

    PubMed Central

    Rolfs, Claus-Henning; Kindl, Helmut

    1984-01-01

    Cultured cells of Picea excelsa capable of forming stilbenes and flavanoids have been established. Unlike needles of intact plants containing piceatannol (3,3′,4′,5-tetrahydroxystilbene) and stilbene glycosides the cultured cells converted phenylalanine and p-coumaric acid primarily into resveratrol monomethyl ether (3,4′-dihydroxy-5-methoxystilbene) and naringenin. Partially purified enzyme preparations were assayed for chalcone synthase as well as for stilbene synthase activity converting malonyl-CoA plus p-coumaroyl-CoA into 3,4′,5-trihydroxystilbene (resveratrol). Although stilbene synthase and chalcone synthase use the same substrates and exhibit similar molecular properties, i.e. molecular weight and subunit molecular weight, they are two different proteins. This difference was demonstrated by gel electrophoresis and by means of monospecific antibodies. PMID:16663649

  11. Silver-catalyzed double-decarboxylative cross-coupling of α-keto acids with cinnamic acids in water: a strategy for the preparation of chalcones.

    PubMed

    Zhang, Ning; Yang, Daoshan; Wei, Wei; Yuan, Li; Nie, Fafa; Tian, Laijin; Wang, Hua

    2015-03-20

    A silver-catalyzed double-decarboxylative protocol has been proposed for the construction of chalcone derivatives via cascade coupling of substituted α-keto acids with cinnamic acids under the mild aqueous conditions. The developed method for constructing C-C bonds via double-decarboxylative reactions is efficient, practical, and environmentally benign by using the readily available starting materials. It should provide a promising synthesis candidate for the formation of diverse and useful chalcone derivatives in the fields of synthetic and pharmaceutical chemistry.

  12. MDR-reversal activity of chalcones.

    PubMed

    Ivanova, Antoaneta; Batovska, Daniela; Engi, Helga; Parushev, Stoyan; Ocsovszki, Imre; Kostova, Ivanka; Molnar, Joseph

    2008-01-01

    The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was applied as a positive control. The majority of the tested compounds were proved to be effective inhibitors of the outward transport of rhodamine-123. In the MTT test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects, with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 microg/mL, respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values in the range of 1.5-3.5 microg/mL. The antiproliferative effect was shown to be affected by the type of substitution at the p-position on ring B. Chalcone 7, with a p-chloro group on ring B, was the most effective in MDR reversal, causing a marked increase in drug accumulation from 0.4 to 40 microg/mL. In combination with epirubicin, compound 7 displayed synergistic properties while compound 3 exhibited an additive effect. The data presented here indicated that some calcone derivatives can be regarded as effective compounds for reversal of MDR. PMID:18610751

  13. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen–Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  14. Comparative Study on the MDR Reversal Effects of Selected Chalcones

    PubMed Central

    Ivanova, A. B.; Batovska, D. I.; Todorova, I. T.; Stamboliyska, B. A.; Serly, J.; Molnar, J.

    2011-01-01

    Based on the structure of three previously established lead compounds, fifteen selected chalcones were synthesized and evaluated for their multidrug resistance (MDR) reversal activity on mouse lymphoma cells. The most active chalcones were stronger revertants than the positive control, verapamil. In the model of combination chemotherapy, the interactions between the anticancer drug doxorubicin and two of the most effective compounds were measured in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction for one of these compounds was indifferent while that for the other one was additive. Furthermore, two chalcones inhibited 50% of cell proliferation in concentration of around 0.4 μg/mL and were from 2- to 100-fold more active than the most chalcones. The structure-activity relationships were obtained and discussed in view of their usefulness for the design of chalcone-like P-gp modulators and drugs able to treat resistant cancers. PMID:27516904

  15. Comparative Study on the MDR Reversal Effects of Selected Chalcones.

    PubMed

    Ivanova, A B; Batovska, D I; Todorova, I T; Stamboliyska, B A; Serly, J; Molnar, J

    2011-01-01

    Based on the structure of three previously established lead compounds, fifteen selected chalcones were synthesized and evaluated for their multidrug resistance (MDR) reversal activity on mouse lymphoma cells. The most active chalcones were stronger revertants than the positive control, verapamil. In the model of combination chemotherapy, the interactions between the anticancer drug doxorubicin and two of the most effective compounds were measured in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction for one of these compounds was indifferent while that for the other one was additive. Furthermore, two chalcones inhibited 50% of cell proliferation in concentration of around 0.4 μg/mL and were from 2- to 100-fold more active than the most chalcones. The structure-activity relationships were obtained and discussed in view of their usefulness for the design of chalcone-like P-gp modulators and drugs able to treat resistant cancers. PMID:27516904

  16. Novel carbapenem chalcone derivatives: synthesis, cytotoxicity and molecular docking studies.

    PubMed

    Kommidi, Devendar Reddy; Pagadala, Ramakanth; Rana, Surjyakanta; Singh, Parvesh; Shintre, Suhas A; Koorbanally, N A; Jonnalagadda, Sreekantha B; Moodley, Brenda

    2015-04-14

    A one-pot efficient synthetic protocol is described for the synthesis of carbapenem chalcone derivatives using AAPTMS@MCM-41 heterogeneous catalyst. Various substituted aromatic aldehydes were attached to highly chiral and reactive carbapenem using this approach. The cytotoxic activity evaluation of all synthesized compounds was performed against lung cancer cell lines (A-549) and breast cancer cell lines (MCF-7) using the MTT assay. Among the tested compounds, compound CPC-2 showed better activity against MCF-7 cell lines with an IC50 value 2.52 μM mL(-1); whereas compound CPC-4 showed good activity against A-549 cell lines with an IC50 value 1.59 μM mL(-1). In order to support the observed activity profiles, the representative compounds were flexibly docked into the active sites of the Anaplastic Lymphoma Kinase (ALK) enzyme and the Estrogen receptor (ERβ). The most active anticancer compounds exhibited stronger binding affinities for proteins. PMID:25767041

  17. Photochemistry of chalcone and the application of chalcone-derivatives in photo-alignment layer of liquid crystal display

    NASA Astrophysics Data System (ADS)

    Song, Dong-mee; Jung, Kyoung-hoon; Moon, Ji-hye; Shin, Dong-myung

    2003-01-01

    We synthesized chalcone derivatives and introduced them as a side chain unit in the backbone of polyimide for photo-alignment layers. The rate of photoreaction was followed by the disappearance of the CCCO bond in the chalcone moiety using UV-visible spectroscopy. The absorption peak at around 340 nm decreased significantly in less than a few minutes at room temperature. We studied the effect of the length of alkyl chain in chalcone derivatives and found that the alignment properties are very much dependent on the chain length.

  18. Synthesis and anti-inflammatory activity of chalcone derivatives.

    PubMed

    Herencia, F; Ferrándiz, M L; Ubeda, A; Domínguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    1998-05-19

    Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.

  19. Asymmetric cyclopropanation of chalcones using chiral phase-transfer catalysts

    PubMed Central

    Herchl, Richard; Waser, Mario

    2013-01-01

    The first phase-transfer catalyzed cyclopropanation reaction of chalcones using bromomalonates as the nucleophiles in a Michael Initiated Ring Closing reaction (MIRC) was developed. Key to success was the use of a free OH-containing cinchona alkaloid ammonium salt catalyst and carefully optimized liquid/liquid reaction conditions. The reaction performed well for electron neutral and electron deficient chalcones giving the products in yields up to 98% and with enantiomeric ratios up to 91:9. PMID:24391288

  20. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    PubMed Central

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

  1. Radiation and quantum chemical studies of chalcone derivatives.

    PubMed

    Gaikwad, P; Priyadarsini, K I; Naumov, S; Rao, B S M

    2010-08-01

    The reactions of oxidizing radicals ((*)OH, Br(2)(*-), and SO(4)(*-)) with -OH-, -CH(3)-, or -NH(2)-substituted indole chalcones and hydroxy benzenoid chalcones were studied by radiation and quantum chemical methods. The (*)OH radical was found to react by addition at diffusion-controlled rates (k = 1.1-1.7 x 10(10) dm(3) mol(-1) s(-1)), but Br(2)(*-) radical reacted by 2 orders of magnitude lower. Quantum chemical calculations at the B3LYP/6-31+G(d,p) level of theory have shown that the (C2-OH)(*), (C11-OH)(*), and (C10-OH)(*) adducts of the indole chalcones and the (C7-OH)(*) and (C8-OH)(*) adducts of the hydroxy benzenoid chalcones are more stable with DeltaH = -39 to -28 kcal mol(-1) and DeltaG = -32 to -19 kcal mol(-1). This suggests that (*)OH addition to the alpha,beta-unsaturated bond is a major reaction channel in both types of chalcones and is barrierless. The stability and lack of dehydration of the (*)OH adducts arise from two factors: strong frontier orbital interaction due to the low energy gap between interacting orbitals and the negligible Coulombic repulsion due to small absolute values of Mulliken charges. The transient absorption spectrum measured in the (*)OH radical reaction with all the indole chalcone derivatives exhibited a maximum at 390 nm, which is in excellent agreement with the computed value (394 nm). The formation of three phenolic products under steady-state radiolysis is in line with the three stable (*)OH adducts predicted by theory. Independent of the substituent, identical spectra (lambda(max) = 330-360 and approximately 580 nm) were obtained on one-electron oxidation of the three indole chalcones. MO calculations predict the deprotonation from the -NH group is more efficient than from the substituent due to the larger electron density on the N1 atom forming the chalcone indolyl radical. Its reduction potential was determined to be 0.56 V from the ABTS(*-)/ABTS(2-) couple. In benzenoid chalcones, the (*)OH adduct spectrum is

  2. Antifungal activity of chalcones: a mechanistic study using various yeast strains.

    PubMed

    Lahtchev, K L; Batovska, D I; Parushev, St P; Ubiyvovk, V M; Sibirny, A A

    2008-10-01

    We reported the synthesis, antifungal evaluation and study on substituent effects of 21 chalcones. A lot of genetically defined strains belonging to different yeast genera and species, namely Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis, were used as test organisms. Concerning the mode of the antifungal action of chalcones it was shown that DNA was probably not the main target for the chalcones. It was revealed that the yeast's intracellular glutathione and cysteine molecules play significant role as defence barrier against the chalcone action. It was also shown that chalcones may react with some proteins involved in cell separation. PMID:18280009

  3. Nitric oxide-scavenging properties of some chalcone derivatives.

    PubMed

    Herencia, Felipe; López-García, M Pilar; Ubeda, Amalia; Ferrándiz, M Luisa

    2002-03-01

    The implication of NO in many inflammatory diseases has been well documented. We have previously reported that some chalcone derivatives can control the iNOS pathway in inflammatory processes. In the present study, we have assessed the NO-scavenging capacity of three chalcone derivatives (CH8, CH11, and CH12) in a competitive assay with HbO(2), a well-known physiologically relevant NO scavenger. Our data identify these chalcones as new NO scavengers. The estimated second-order rate constants (k(s)) for the reaction of the three derivatives with NO is in the same range as the value obtained for HbO(2), with CH11 exerting the greatest effect. These results suggest an additional action of these compounds on NO regulation.

  4. Second harmonic generation and crystal growth of new chalcone derivatives

    NASA Astrophysics Data System (ADS)

    Patil, P. S.; Dharmaprakash, S. M.; Ramakrishna, K.; Fun, Hoong-Kun; Sai Santosh Kumar, R.; Narayana Rao, D.

    2007-05-01

    We report on the synthesis, crystal structure and optical characterization of chalcone derivatives developed for second-order nonlinear optics. The investigation of a series of five chalcone derivatives with the second harmonic generation powder test according to Kurtz and Perry revealed that these chalcones show efficient second-order nonlinear activity. Among them, high-quality single crystals of 3-Br-4'-methoxychalcone (3BMC) were grown by solvent evaporation solution growth technique. Grown crystals were characterized by X-ray powder diffraction (XRD), laser damage threshold, UV-vis-NIR and refractive index measurement studies. Infrared spectroscopy, thermogravimetric analysis and differential thermal analysis measurements were performed to study the molecular vibration and thermal behavior of 3BMC crystal. Thermal analysis does not show any structural phase transition.

  5. 4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene

    SciTech Connect

    Ku, Bo Mi; Ryu, Hyung Won; Lee, Yeon Kyung; Ryu, Jinhyun; Jeong, Joo Yeon; Choi, Jungil; Cho, Hee Jun; Park, Ki Hun; Kang, Sang Soo

    2010-11-19

    Research highlights: {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) has anti-cancer property for glioma. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) increased tropomyosin expreesion through activattion of PKA signaling. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) inhibits glioma cell migration and invasion. {yields} In vivo administration of 4'-acetoamido-4-hydroxychalcone (AHC) reduced tumor growth. -- Abstract: Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, and tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.

  6. An Update on Antitumor Activity of Naturally Occurring Chalcones

    PubMed Central

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

  7. An update on antitumor activity of naturally occurring chalcones.

    PubMed

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

  8. Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection.

    PubMed

    Li, Hongen; Chen, Yutao; Zhang, Bing; Niu, Xiaodi; Song, Meng; Luo, Zhaoqing; Lu, Gejin; Liu, Bowen; Zhao, Xiaoran; Wang, Jianfeng; Deng, Xuming

    2016-04-15

    The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC50 of 28.41 ± 5.34 μM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes-mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection. PMID:26826492

  9. Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection.

    PubMed

    Li, Hongen; Chen, Yutao; Zhang, Bing; Niu, Xiaodi; Song, Meng; Luo, Zhaoqing; Lu, Gejin; Liu, Bowen; Zhao, Xiaoran; Wang, Jianfeng; Deng, Xuming

    2016-04-15

    The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC50 of 28.41 ± 5.34 μM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes-mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection.

  10. Genetic control of chalcone isomerase activity in flowers of Dianthus caryophyllus.

    PubMed

    Forkmann, G; Dangelmayr, B

    1980-06-01

    In flowers of Dianthus caryophyllus (carnation), the gene I is concerned with a discrete step in flavonoid biosynthesis, Genotypes with recessive (ii) alleles produce yellow flowers, which contain the chalcone isosalipurposide (naringenin-chalcone-2'-glucoside) as the major petal pigment, but in genotypes with wild-type alleles flavonols and anthocyanins can be formed and the flowers are white or red. Enzymatic measurements on petal extracts of four strains with different flower coloration revealed a clear correlation between accumulation of chalcone in recessive genotypes and deficiency of chalcone isomerase (E.C. 5.5.1.6) activity. From the chemogenetic and enzymological evidence it can be concluded that naringenin-chalcone is the first product of the synthesis of the flavonoid skeleton and that only the conversion of naringenin-chalcone to naringenin furnishes the substrate for the further reactions to flavonol and anthocyanin.

  11. Preparing Students for Research: Synthesis of Substituted Chalcones as a Comprehensive Guided-Inquiry Experience

    NASA Astrophysics Data System (ADS)

    Vyvyan, James R.; Pavia, Donald L.; Lampman, Gary M.; Kriz, George S., Jr.

    2002-09-01

    A guided inquiry experiment involving the synthesis and characterization of substituted benzalacetophenones (chalcones) is described. The chalcones are produced in the aldol condensation of substituted benzaldehydes with substituted acetophenones. Each student is assigned a different target chalcone and conducts online and printed literature searches on the target. After completing the synthesis and purification of their product, the students compare their data with those found in the literature.

  12. Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects.

    PubMed

    Champelovier, Pierre; Chauchet, Xavier; Hazane-Puch, Florence; Vergnaud, Sabrina; Garrel, Catherine; Laporte, François; Boutonnat, Jean; Boumendjel, Ahcène

    2013-12-01

    Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (ΔΨm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found.

  13. Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects.

    PubMed

    Champelovier, Pierre; Chauchet, Xavier; Hazane-Puch, Florence; Vergnaud, Sabrina; Garrel, Catherine; Laporte, François; Boutonnat, Jean; Boumendjel, Ahcène

    2013-12-01

    Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (ΔΨm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found. PMID:24134853

  14. Molecular evolution and sequence divergence of plant chalcone synthase and chalcone synthase-Like genes.

    PubMed

    Han, Yingying; Zhao, Wenwen; Wang, Zhicui; Zhu, Jingying; Liu, Qisong

    2014-06-01

    Plant chalcone synthase (CHS) and CHS-Like (CHSL) proteins are polyketide synthases. In this study, we evaluated the molecular evolution of this gene family using representative types of CHSL genes, including stilbene synthase (STS), 2-pyrone synthase (2-PS), bibenzyl synthase (BBS), acridone synthase (ACS), biphenyl synthase (BIS), benzalacetone synthase, coumaroyl triacetic acid synthase (CTAS), and benzophenone synthase (BPS), along with their CHS homologs from the same species of both angiosperms and gymnosperms. A cDNA-based phylogeny indicated that CHSLs had diverse evolutionary patterns. STS, ACS, and 2-PS clustered with CHSs from the same species (late diverged pattern), while CTAS, BBS, BPS, and BIS were distant from their CHS homologs (early diverged pattern). The amino-acid phylogeny suggested that CHS and CHSL proteins formed clades according to enzyme function. The CHSs and CHSLs from Polygonaceae and Arachis had unique evolutionary histories. Synonymous mutation rates were lower in late diverged CHSLs than in early diverged ones, indicating that gene duplications occurred more recently in late diverged CHSLs than in early diverged ones. Relative rate tests proved that late diverged CHSLs had unequal rates to CHSs from the same species when using fatty acid synthase, which evolved from the common ancestor with the CHS superfamily, as the outgroup, while the early diverged lineages had equal rates. This indicated that late diverged CHSLs experienced more frequent mutation than early diverged CHSLs after gene duplication, allowing obtaining new functions in relatively short period of time.

  15. Role of nuclear factor-κB and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells

    PubMed Central

    Alcaraz, María José; Vicente, Ana María; Araico, Amparo; Dominguez, José N; Terencio, María Carmen; Ferrándiz, María Luisa

    2004-01-01

    The synthetic chalcone 3′,4′,5′,3,4,5-hexamethoxy-chalcone (CH) is an anti-inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10–30 μM) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μg ml−1) due to the inhibition of nuclear factor κB (NF-κB) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF-κB–IκB complex leading to inhibition of NF-κB translocation into the nucleus, DNA binding and transcriptional activity. We also demonstrate the ability of this compound to activate NfE2-related factor (Nrf2) and induce heme oxygenase-1 (HO-1). Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO-1 induction by this chalcone derivative.  This novel anti-inflammatory agent simultaneously induces a cytoprotective response (HO-1) and downregulates an inflammatory pathway (NF-κB) with a mechanism of action different from antioxidant chalcones. PMID:15249426

  16. Growth, characterization and nonlinear optical property of chalcone derivative

    NASA Astrophysics Data System (ADS)

    Indira, J.; Karat, P. Prakash; Sarojini, B. K.

    2002-07-01

    The synthesis of chalcone derivative compound is reported. The compound showed second harmonic generation conversion efficiency in powder form. Solubility of 1-(4-methoxyphenyl)-3-(phenyl)-2-propen-1-one in acetone was studied. Single crystals of the same compound was grown by slow evaporation technique using acetone as the solvent. Large crystal of size 55×33×5 mm 3 was obtained. The microhardness of the crystal was measured by Vickers hardness method.

  17. Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synthesis of chalcones and 2-pyrazoline derivatives has been an active field of research due to the established pharmacological effects of these compounds. In this study, a series of chalcone (1a-i), 2-pyrazoline-1-carbothioamides (2a-i) and 2-pyrazoline-1-carboxamide derivatives (3a-g) were synthes...

  18. New chalcones bearing a long-chain alkylphenol from the rhizomes of Alpinia galanga.

    PubMed

    Yang, Wan-Qiu; Gao, Yuan; Li, Ming; Miao, De-Ren; Wang, Fei

    2015-01-01

    Three novel chalcones bearing a long-chain alkylphenol, galanganones A-C (1-3), were isolated from the rhizomes of Alpinia galanga. Their structures were elucidated by extensive spectroscopic analysis including 2D NMR experiments. Compounds 1-3 represent the first examples of long-chain alkylphenol-coupled chalcone.

  19. Second harmonic generation and crystal growth of substituted thienyl chalcone

    NASA Astrophysics Data System (ADS)

    Goto, Yoshitaka; Hayashi, Akio; Kimura, Yasuhiro; Nakayama, Masaharu

    1991-02-01

    The second harmonic generation (SHG) of 29 kinds of thienyl chalcone derivatives with a thiophene ring were examined. A series of 1-{2-(5-bromothienyl)}-3-(4'-halophenyl)propene-3-one showed high SHG activity. Especially 1-(2-thienyl)-3-(4-methylphenyl)propene-1-one had SHG activity 15 times as large as urea and also high blue light region transparency with a cutoff wavelength of 390 nm. A large high quality single crystal of 60x15x10mm of this compound could be obtained from acetone solution. Analysis of the crystal structure identified it as a monoclinical system of space group P2 1.

  20. Synthesis and bioevaluation of substituted chalcones, coumaranones and other flavonoids as anti-HIV agents.

    PubMed

    Cole, Amy L; Hossain, Sandra; Cole, Alex M; Phanstiel, Otto

    2016-06-15

    A series of chalcone, flavone, coumaranone and other flavonoid compounds were screened for their anti HIV-1 activity in two cell culture models using TZM-bl and PM1 cells. Within the systems evaluated, the most promising compounds contained either an α- or β-hydroxy-carbonyl motif within their structure (e.g., 8 and 9). Efficacious substituents were identified and used to design new HIV inhibitors with increased potency and lower cytotoxicity. Of the scaffolds evaluated, specific chalcones were found to provide the best balance between anti-HIV potency and low host cell toxicity. Chalcone 8l was shown to inhibit different clinical isolates of HIV in a dose-dependent manner (e.g., IC50 typically⩽5μM). Inhibition of HIV infection experiments using TZM-bl cells demonstrated that chalcone 8l and flavonol 9c had IC50 values of 4.7μM and 10.4μM, respectively. These insights were used to design new chalcones 8o and 8p. Rewardingly, chalcones 8o and 8p (at 10μM) each gave >92% inhibition of viral propagation without impacting PM1 host cell viability. Inhibition of viral propagation significantly increased (60-90%) when PM1 cells were pre-incubated with chalcone 8o, but not with the related flavonol 9c. These results suggested that chalcone 8o may be of value as both a HIV prophylactic and therapy. In summary, O-benzyl-substituted chalcones were identified as promising anti-HIV agents for future investigation. PMID:27161874

  1. Effects of chalcone derivatives on players of the immune system.

    PubMed

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.

  2. Effects of chalcone derivatives on players of the immune system

    PubMed Central

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells. PMID:26316713

  3. Xanthohumol, a prenylated chalcone from Humulus lupulus L., inhibits cholesteryl ester transfer protein.

    PubMed

    Hirata, Hiroshi; Takazumi, Koji; Segawa, Shuichi; Okada, Yukio; Kobayashi, Naoyuki; Shigyo, Tatsuro; Chiba, Hitoshi

    2012-10-01

    High density lipoprotein (HDL)-cholesterol levels are correlated with a low risk of atherosclerosis. The inhibition of cholesteryl ester transfer protein (CETP), which catalyses cholesterol transfer between lipoproteins, leads to an increase in HDL-cholesterol and is expected to be the next anti-atherogenic target. This study revealed that xanthohumol, a prenylated chalcone, showed the highest inhibition against CETP from screening of natural products in various plants. We investigated the inhibitory activity of some chalcones and flavanones. Naringenin chalcone showed weak CETP inhibition compared with xanthohumol. In addition, isoxanthohumol and naringenin drastically decreased the inhibitory activity. These results suggest that the prenyl group and chalcone structure of xanthohumol were responsible for the CETP inhibitory activity. PMID:25005963

  4. Synthesis of new chalcone derivatives containing acridinyl moiety with potential antimalarial activity.

    PubMed

    Tomar, V; Bhattacharjee, G; Kamaluddin; Rajakumar, S; Srivastava, Kumkum; Puri, S K

    2010-02-01

    A series of novel chalcones bearing acridine moiety attached to the amino group in their ring A have been synthesized through noncatalyzed nucleophilic aromatic substitution reaction between various 3'-aminochalcone or 4'-aminochalcones and 9-chloroacridine. The synthesized chalcone derivatives have been characterized and screened for in vitro antimalarial activity against Plasmodium falciparum NF-54. All the chalcones showed complete inhibition at concentration of 10 microg/mL and above while three compounds showed significant inhibition at concentration of 2 microg/mL. The three most active chalcone derivatives were screened for in vivo activity as well, but no significant inhibition in parasitaemia was observed when given intraperitoneally to Plasmodium yoelii infected mice model.

  5. Bidentate coordinating behaviour of chalcone based ligands towards oxocations: VO(IV) and Mo(V)

    NASA Astrophysics Data System (ADS)

    Thaker, B. T.; Barvalia, R. S.

    2013-08-01

    We synthesized and studied the coordinating behaviour of chalcone based ligands derived from DHA and n-alkoxy benzaldehyde and their complexes of VO(IV) and MoO(V). The chalcone ligands are characterized by elemental analyses, UV-visible, IR, 1H NMR, and mass spectra. The resulting oxocation complexes are also characterized by elemental analyses, IR, 1H NMR, electronic, electron spin resonance spectra, magnetic susceptibility measurement and molar conductance studies. The IR and 1H NMR spectral data suggest that the chalcone ligands behave as a monobasic bidentate with O:O donor sequence towards metal ion. The molar conductivity data show them to be non-electrolytes. From the electronic, magnetic and ESR spectral data suggest that all the chalcone ligand complexes of VO(IV) and MoO(V) have distorted octahedral geometry.

  6. Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis.

    PubMed

    Jayasinghe, Lalith; Balasooriya, B A I S; Padmini, W Chintha; Hara, Noriyuki; Fujimoto, Yoshinori

    2004-05-01

    Antifungal activity guided fractionation of the n-butanol extract from the methanol extract of the leaves of Artocarpus nobilis furnished 2',4',4-trihydroxy-3'-geranylchalcone (1), 2 ',4',4-trihydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (2), 2',4',4-trihydroxy-3'-[2-hydroxy-7-methyl-3-methylene-6-octaenyl]chalcone (3), 2',3,4,4'-tetrahydroxy-3'-geranylchalcone (4), 2',3,4,4'-tetrahydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (5). The chalcones 3 and 5 are new natural products whereas 1 and 2 are reported first time from the family Moraceae. All these compounds showed good fungicidal activity against Cladosporium cladosporioides and high radical scavenging activity towards the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC bio-autography method.

  7. Synthesis, crystal growth and studies on non-linear optical property of new chalcones

    NASA Astrophysics Data System (ADS)

    Sarojini, B. K.; Narayana, B.; Ashalatha, B. V.; Indira, J.; Lobo, K. G.

    2006-09-01

    The synthesis, crystal growth and non-linear optical (NLO) property of new chalcone derivatives are reported. 4-Propyloxy and 4-butoxy benzaldehydes were made to under go Claisen-Schmidt condensation with 4-methoxy, 4-nitro and 4-phenoxy acetophenones to form corresponding chalcones. The newly synthesized compounds were characterized by analytical and spectral data. The Second harmonic generation (SHG) efficiency of these compounds was measured by powder technique using Nd:YAG laser. Among tested compounds three chalcones showed NLO property. The chalcone 1-(4-methoxyphenyl)-3-(4-propyloxy phenyl)-2-propen-1-one exhibited SHG conversion efficiency 2.7 times that of urea. The bulk crystal of 1-(4-methoxyphenyl)-3-(4-butoxyphenyl)-2-propen-1-one (crystal size 65×28×15 mm 3) was grown by slow-evaporation technique from acetone. Microhardness of the crystal was tested by Vicker's microhardness method.

  8. New indolizine-chalcones as potent inhibitors of human farnesyltransferase: Design, synthesis and biological evaluation.

    PubMed

    Moise, Iuliana-Monica; Ghinet, Alina; Belei, Dalila; Dubois, Joëlle; Farce, Amaury; Bîcu, Elena

    2016-08-01

    A new family of indolizine-chalcones was designed, synthesized and screened for the inhibitory potential on human farnesyltransferase in vitro to identify potent antitumor agents. The most active compound was phenothiazine 2a, exhibiting an IC50 value in the low nanomolar range, similar to that of known FTI-276, highly potent farnesyltransferase inhibitor. The newly synthesized indolizine-chalcones 2a-d constitute the most efficient inhibitors of farnesyltransferase bearing a phenothiazine unit known to date. PMID:27282741

  9. Second harmonic chalcone crystal: Synthesis, growth and characterization

    NASA Astrophysics Data System (ADS)

    D'silva, E. D.; Narayan Rao, D.; Philip, Reji; Butcher, Ray J.; Rajnikant; Dharmaprakash, S. M.

    2011-05-01

    The novel nonlinear optical chalcone derivative (2 E)-3-[4-(methylsulfanyl)phenyl]-1-(3-bromophenyl)prop-2-en-1-one (3Br4MSP) crystals have been grown by slow evaporation technique at ambient temperature. The crystal was subjected to different types of characterization method in order to study its possible application in nonlinear optics. The structure determination of the grown crystal was done by single crystal X-ray diffraction study. The morphology of the crystal is studied. The crystal was subjected to thermal analysis to find its thermal stability. The grown crystals were characterized for their optical transmission and mechanical hardness. The second harmonic generation (SHG) efficiency of the crystal is obtained by classical powdered technique. The laser damage threshold for 3Br4MSP crystal was determined using Q-switched Nd:YAG laser.

  10. 13C NMR spectra of pyridine chalcone analogs

    NASA Astrophysics Data System (ADS)

    Jovanović, B. Ž.; Mišić-Vuković, M.; Marinković, A. D.; Csanádi, J.

    1999-05-01

    13C NMR spectra of two series of pyridine chalcone analogs were determined in deuterated dimethylsulphoxide (DMSO-d 6). It was established that these compounds were in more stable E-configurations except for the 4-pyridalacetophenone which was in Z-configuration. On the basis of the Hammett correlations of 13C NMR chemical shifts of the ethylenic bond carbon atoms and the σ values for the pyridine "aza" groups, the polarization of ethylenic bonds were discussed. It was established that the opposite effect of the pyridine substituents at the electronic density distribution in pyridalacetophenone and cinnamoylpyridines depends on its direct bonding to the ethylenic carbon or the transmission electronic effects via the carbonyl group, respectively.

  11. Synthetic oils

    NASA Technical Reports Server (NTRS)

    Hatton, R. E.

    1973-01-01

    Synthetic lubricants are discussed by chemical class and their general strengths and weaknesses in terms of lubrication properties are analyzed. Comparative ratings are given for 14 chemical classes and are used as a guide for lubricant selection. The effects of chemical structure on the properties of the lubricant are described with special emphasis on thermal stability. The diversity of synthetic lubricants which is provided by the wide range of properties permits many applications, some of which are reported.

  12. Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

    PubMed

    Kil, Yun-Seo; Choi, Seul-Ki; Lee, Yun-Sil; Jafari, Mahtab; Seo, Eun-Kyoung

    2015-10-23

    Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

  13. Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

    PubMed

    Kil, Yun-Seo; Choi, Seul-Ki; Lee, Yun-Sil; Jafari, Mahtab; Seo, Eun-Kyoung

    2015-10-23

    Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer. PMID:26431394

  14. Synthetic environments

    NASA Astrophysics Data System (ADS)

    Lukes, George E.; Cain, Joel M.

    1996-02-01

    The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

  15. In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells.

    PubMed

    Zenger, Katharina; Dutta, Subhajit; Wolff, Horst; Genton, Marc G; Kraus, Birgit

    2015-10-01

    Xanthohumol (XN), the major prenylated chalcone from hops (Humulus lupulus L.), has received much attention within the last years, due to its multiple pharmacological activities including anti-proliferative, anti-inflammatory, antioxidant, pro-apoptotic, anti-bacterial and anti-adhesive effects. However, there exists a huge number of metabolites and structurally-related chalcones, which can be expected, or are already known, to exhibit various effects on cells. We have therefore analyzed the effects of XN and 18 other chalcones in a panel, consisting of multiple cell-based assays. Readouts of these assays addressed distinct aspects of cell-toxicity, like proliferation, mitochondrial health, cell cycle and other cellular features. Besides known active structural elements of chalcones, like the Michael system, we have identified several moieties that seem to have an impact on specific effects and toxicity in human liver cells in vitro. Based on these observations, we present a structure-toxicity model, which will be crucial to understand the molecular mechanisms of wanted effects and unwanted side-effects of chalcones. PMID:26201061

  16. In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells.

    PubMed

    Zenger, Katharina; Dutta, Subhajit; Wolff, Horst; Genton, Marc G; Kraus, Birgit

    2015-10-01

    Xanthohumol (XN), the major prenylated chalcone from hops (Humulus lupulus L.), has received much attention within the last years, due to its multiple pharmacological activities including anti-proliferative, anti-inflammatory, antioxidant, pro-apoptotic, anti-bacterial and anti-adhesive effects. However, there exists a huge number of metabolites and structurally-related chalcones, which can be expected, or are already known, to exhibit various effects on cells. We have therefore analyzed the effects of XN and 18 other chalcones in a panel, consisting of multiple cell-based assays. Readouts of these assays addressed distinct aspects of cell-toxicity, like proliferation, mitochondrial health, cell cycle and other cellular features. Besides known active structural elements of chalcones, like the Michael system, we have identified several moieties that seem to have an impact on specific effects and toxicity in human liver cells in vitro. Based on these observations, we present a structure-toxicity model, which will be crucial to understand the molecular mechanisms of wanted effects and unwanted side-effects of chalcones.

  17. Influence of industrial processing on orange juice flavanone solubility and transformation to chalcones under gastrointestinal conditions.

    PubMed

    Gil-Izquierdo, Angel; Gil, María Isabel; Tomas-Barberan, Francisco Abraham; Ferreres, Federico

    2003-05-01

    Orange juice manufactured at industrial scale was subjected to digestion under in vitro gastrointestinal conditions (pH, temperature, and enzyme and chemical conditions) to evaluate the influence of individual industrial processing treatments on flavanone solubility, stability, and ability to permeate through a membrane under simulated physiological conditions. Four industrial processes including squeezing, standard pasteurization, concentration, and freezing were evaluated. Hand squeezing was compared with industrial squeezing. After in vitro gastrointestinal digestion of the orange juices, the flavanones able to permeate through a dialysis membrane, and those remaining in the retentate were evaluated by HPLC as were those present in the insoluble fraction. In all of the assayed orange juices, a high content of precipitated chalcones ( approximately 70% of the total flavanones) was formed under the physiological conditions of the gastrointestinal tract. Hand squeezing provided a higher concentration of flavanones in the permeated fraction and lower transformation to chalcones than industrial squeezing. Standard pasteurization did not influence the solubility and permeability of the orange juice flavanones and chalcones. Industrial concentration did not affect the amount of flavanones able to permeate but decreased the chalcones produced. Juices produced from frozen orange juice contained considerably smaller amounts of both soluble flavanones and insoluble chalcones.

  18. The Role of Chalcones in Suppression of NF-κB-Mediated Inflammation and Cancer

    PubMed Central

    Yadav, Vivek R.; Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B.

    2010-01-01

    Although consumption of fruits, vegetables, spices, cereals and pulses has been associated with lower incidence of cancer and other chronic diseases, how these dietary agents and their active ingredients minimize these diseases, is not fully understood. Whether it is oranges, kawa, hops, water-lilly, locorice, wax apple or mulberry, they are all connected by a group of aromatic ketones, called chalcones (1,3-diaryl-2-propen-1-ones). Some of the most significant chalcones identified from these plants include flavokawin, butein, xanthoangelol, 4-hydroxyderricin, cardamonin, 2′,4′-dihydroxychalcone, isoliquiritigenin, isosalipurposide, and naringenin. These chalcones have been linked with immunomodulation, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, anticancer, and antidiabetic activities. The current review, however, deals with the role of various chalcones in inflammation that controls both the immune system and tumorigenesis. Inflammatory pathways have been shown to mediate the survival, proliferation, invasion, angiogenesis and metastasis of tumors. How these chalcones modulate inflammatory pathways, tumorigenesis and immune system is the focus of this review. PMID:21184860

  19. Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers.

    PubMed

    Hofmann, Emily; Webster, Jonathan; Do, Thuy; Kline, Reid; Snider, Lindsey; Hauser, Quintin; Higginbottom, Grace; Campbell, Austin; Ma, Lili; Paula, Stefan

    2016-02-15

    In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones' effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class.

  20. Structure and NLO property relationship in a novel chalcone co-crystal

    NASA Astrophysics Data System (ADS)

    Ravindra, H. J.; Chandrashekaran, K.; Harrison, W. T. A.; Dharmaprakash, S. M.

    2009-03-01

    Single crystals of a chalcone co-crystal (C18H19NO4/C17H16NO3Br; 0.972/0.028) have been grown by slow evaporation from solution. The powder second harmonic generation (SHG) efficiency of this chalcone co-crystal is 7 times that of urea. The dependence of second harmonic (SH) intensity on particle size revealed the existence of phase matching direction in this crystal. The large SHG efficiency observed is mainly due to the unidirectional alignment of molecular dipoles, in which the dipole moment of each molecule adds to establish a net polarization. The weak N-H ṡṡṡO hydrogen-bond interactions help to stabilize the noncentrosymmetric crystal packing and also contribute partly to the SHG. The better thermal stability, transparency and high laser damage resistance (>1.5 GW cm-2 at 532 nm, 8 ns) of this chalcone co-crystal indicate that it is a promising material for frequency doubling of diode lasers down to 470 nm. This molecule also shows a third-order NLO response and good optical limiting property of 8 ns laser pulses at 532 nm. The mechanism for optical limiting in this chalcone was attributed to two-photon induced excited state absorption that leads to reverse saturable absorption. The structure-property relationship in this chalcone and related compounds is discussed based on the experimental results and semiempherical hyperpolarizability calculations.

  1. Synthetic Jets

    NASA Technical Reports Server (NTRS)

    Milanovic, Ivana M.

    2003-01-01

    Current investigation of synthetic jets and synthetic jets in cross-flow examined the effects of orifice geometry and dimensions, momentum-flux ratio, cluster of orifices, pitch and yaw angles as well as streamwise development of the flow field. This comprehensive study provided much needed experimental information related to the various control strategies. The results of the current investigation on isolated and clustered synthetic jets with and without cross-flow will be further analyzed and documented in detail. Presentations at national conferences and publication of peer- reviewed journal articles are also expected. Projected publications will present both the mean and turbulent properties of the flow field, comparisons made with the data available in an open literature, as well as recommendations for the future work.

  2. Antioxidant activities of [60]fullerene derivatives from chalcone, flavone and flavanone: A ONIOM approach via H-atom and electron transfer mechanism

    NASA Astrophysics Data System (ADS)

    Thong, Nguyen Minh; Dao, Duy Quang; Ngo, Thi Chinh; Huyen, Trinh Le; Nam, Pham Cam

    2016-05-01

    Antioxidant properties of C60 flavonoid conjugates were computationally examined via their O-H bond dissociation enthalpies (BDEs) and ionization energies (IEs) using two-layer ONIOM and PM6 methods, respectively. Eight ONIOM((RO)B3LYP/6-311++G(2df,2p):PM6) models were evaluated by computing BDE(O-H)s of a series of polyphenol. Synthetic mechanism of C60 flavonoid conjugates was also explored via the potential energy surfaces of reaction between C60 and malonate flavonoid derivatives (chalcone, flavone and flavanone) at the B3LYP/6-31G(d)//PM6. Antioxidant activities of C60 flavonoid conjugates were discussed via hydrogen atom transfer, single electron transfer mechanisms and the effect of C60 on the BDE(O-H)s and IEs of these compounds.

  3. Transcriptional regulation of the Arabidopsis thaliana chalcone synthase gene

    SciTech Connect

    Feinbaum, R.L.; Ausubel, F.M.

    1988-05-01

    The authors cloned an Arabiodpsis thaliana chalcone synthase (CHS) gene on the basis of cross-hybridization with a Petroselinum hortense CHS cDNA clone. The protein sequence deduced from the A. thaliana CHS DNA sequence is at least 85% homologous to the CHS sequences from P. hortense, Antirrhinum majus, and Petunia hybrida. Southern blot analysis indicated that CHS is a single-copy gene in A. thaliana. High-intensity light treatment of A. thaliana plants for 24 h caused a 50-fold increase in CHS enzyme activity and an accumulation of visibly detectable levels of anthocyanin pigments in the vegetative structures of these plants. A corresponding increase in the steady-state level of CHS mRNA was detected after high-intensity light treatment for the same period of time. The accumulation of CHS mRNA in response to high-intensity light was due, at least in part, to an increased rate of transcription of the CHS gene as demonstrated by nuclear runoff experiment.

  4. Synthetic Astrobiology

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2015-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  5. Synthetic Astrobiology

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2016-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  6. Synthesis, growth, structure determination and optical properties of chalcone derivative single crystal

    SciTech Connect

    Karthi, S. Girija, E. K.

    2014-04-24

    Acquiring large nonlinear optical (NLO) efficient organic material is essential for the development of optoelectronics and photonic devices. Chalcone is the donor - Π - acceptor - Π - donor (D-Π-A-Π-D) type conjugated molecule with appreciable hyperpolarizability of potential interest in NLO applications. The addition of vinyl and electron donor groups in the chalcone molecule may enhance the second harmonic generation (SHG) efficiency. Here we report the synthesis, crystal growth and characterization of a chalcone derivative 1-(4-methylphenyl)-5-(4-methoxyphenyl)-penta-2,4-dien-1-one (MPMPP). The MPMPP crystal was grown by slow evaporation solution growth technique from acetone. The grown crystal structure was studied by single crystal X-ray diffraction. The SHG efficiency of the grown crystal was determined by Kurtz and Perry method.

  7. Bacteriocin release protein-mediated secretory expression of recombinant chalcone synthase in Escherichia coli.

    PubMed

    Zakaria, Iffah Izzati; Rahman, Raja Noor Zaliha Raja Abdul; Salleh, Abu Bakar; Basri, Mahiran

    2011-09-01

    Flavonoids are secondary metabolites synthesized by plants shown to exhibit health benefits such as anti-inflammatory, antioxidant, and anti-tumor effects. Thus, due to the importance of this compound, several enzymes involved in the flavonoid pathway have been cloned and characterized in Escherichia coli. However, the formation of inclusion bodies has become a major disadvantage of this approach. As an alternative, chalcone synthase from Physcomitrella patens was secreted into the medium using a bacteriocin release protein expression vector. Secretion of P. patens chalcone synthase into the culture media was achieved by co-expression with a psW1 plasmid encoding bacteriocin release protein in E. coli Tuner (DE3) plysS. The optimized conditions, which include the incubation of cells for 20 h with 40 ng/ml mitomycin C at OD(600) induction time of 0.5 was found to be the best condition for chalcone synthase secretion.

  8. Synthesis, growth, structure determination and optical properties of chalcone derivative single crystal

    NASA Astrophysics Data System (ADS)

    Karthi, S.; Girija, E. K.

    2014-04-01

    Acquiring large nonlinear optical (NLO) efficient organic material is essential for the development of optoelectronics and photonic devices. Chalcone is the donor - Π - acceptor - Π - donor (D-Π-A-Π-D) type conjugated molecule with appreciable hyperpolarizability of potential interest in NLO applications. The addition of vinyl and electron donor groups in the chalcone molecule may enhance the second harmonic generation (SHG) efficiency. Here we report the synthesis, crystal growth and characterization of a chalcone derivative 1-(4-methylphenyl)-5-(4-methoxyphenyl)-penta-2,4-dien-1-one (MPMPP). The MPMPP crystal was grown by slow evaporation solution growth technique from acetone. The grown crystal structure was studied by single crystal X-ray diffraction. The SHG efficiency of the grown crystal was determined by Kurtz and Perry method.

  9. Bacteriocin release protein-mediated secretory expression of recombinant chalcone synthase in Escherichia coli.

    PubMed

    Zakaria, Iffah Izzati; Rahman, Raja Noor Zaliha Raja Abdul; Salleh, Abu Bakar; Basri, Mahiran

    2011-09-01

    Flavonoids are secondary metabolites synthesized by plants shown to exhibit health benefits such as anti-inflammatory, antioxidant, and anti-tumor effects. Thus, due to the importance of this compound, several enzymes involved in the flavonoid pathway have been cloned and characterized in Escherichia coli. However, the formation of inclusion bodies has become a major disadvantage of this approach. As an alternative, chalcone synthase from Physcomitrella patens was secreted into the medium using a bacteriocin release protein expression vector. Secretion of P. patens chalcone synthase into the culture media was achieved by co-expression with a psW1 plasmid encoding bacteriocin release protein in E. coli Tuner (DE3) plysS. The optimized conditions, which include the incubation of cells for 20 h with 40 ng/ml mitomycin C at OD(600) induction time of 0.5 was found to be the best condition for chalcone synthase secretion. PMID:21633820

  10. Study on third-order nonlinear optical properties of 4-methylsulfanyl chalcone derivatives using picosecond pulses

    SciTech Connect

    D'silva, E.D.; Podagatlapalli, G. Krishna; Venugopal Rao, S.; Dharmaprakash, S.M.

    2012-11-15

    Graphical abstract: Photograph and schematic representation of Z-scan experimental setup used to investigate third order nonlinear properties of the chalcone materials. Highlights: ► Br and NO{sub 2} substituted chalcone derivatives were exposed to picosecond laser pulses. ► Third-order nonlinear optical (NLO) properties were investigated. ► Compounds show promising third-order and optical limiting properties. ► These materials found suitable for electrical and optical applications. -- Abstract: In this paper we present results from the experimental study of third-order nonlinear optical (NLO) properties of three molecules of Br and NO{sub 2} substituted chalcone derivatives namely (2E)-1-(4-bromophenyl)-3-[4(methylsulfanyl)phenyl]prop-2-en-1-one (4Br4MSP), (2E)-1-(3-bromophenyl)-3-[4-(methylsulfanyl) phenyl]prop-2-en-1-one (3Br4MSP) and (2E)-3[4(methylsulfanyl) phenyl]-1-(4-nitrophenyl)prop-2-en-1-one (4N4MSP). The NLO properties have been investigated by Z-scan technique using 2 ps laser pulses at 800 nm. The nonlinear refractive indices, nonlinear absorption coefficient, and the magnitude of third-order susceptibility have been determined. The values obtained are of the order of 10{sup −7} cm{sup 2}/GW, 10{sup −3} cm/GW and 10{sup −14} esu respectively. The molecular second hyperpolarizability for the chalcone derivatives is of the order of 10{sup −32} esu. The coupling factor, excited state cross section, ground state cross section etc. were determined. The optical limiting (OL) property was studied. The results suggest that the nonlinear properties investigated for present chalcones are comparable with some of the reported chalcone derivatives and can be desirable for NLO applications.

  11. Studies on the chalcone synthase gene of two higher plants: petroselinum hortense and matthiola incana

    SciTech Connect

    Hemleben, V.; Frey, M.; Rall, S.; Koch, M.; Kittel, M.; Kreuzaler, F.; Ragg, H.; Fautz, E.; Hahlbrock, K.

    1982-01-01

    Two higher plant systems are presented which allow to study coordinated gene expression of the light-induced metabolic pathway of flavonoid biosynthesis: tissue culture cells of Petroselinum hortense (Apiaceae) and different developmental stages of various genotypes of Matthiola incana (Brassicaceae). The gene structure of the chalcone synthase is mainly studied. A cDNA clone (pLF56) of parsley has been constructed and characterized conferring the chalcone synthase gene sequence. Strong cross hybridization between the parsley cDNA and Matthiola DNA allowed to identify a HindIII fragment (6000 bp) identical in size for parsley and different Matthiola wild type lines and a mutant line.

  12. Free Volume Related Fluorescence Properties of Electron Irradiated Chalcone Doped PMMA Films

    SciTech Connect

    Ravindrachary, Ismayil V.; Bhajantri, R. F.; Harisha, A.; Praveena, S. D.

    2011-07-15

    Effect of electron irradiation on free volume related fluorescence properties of chalcone doped Poly(methyl methacrylate)(PMMA) composite films have been studied using Positron Annihilation and Fluorescence spectroscopic techniques. In this polymer composite, enhancement of fluorescence at lower doses and reduction at higher doses has been observed under electron irradiation. From Positron annihilation studies suggests that at lower doses of irradiation induced crosslinking which affect the free volume properties and inturn hinders the chalcone molecular rotation. At higher doses chain scission process affect matrix relaxation. Under the restricted condition the chromophore molecules likely to emit enhanced fluorescence and its mobility is directly related to the free volume around it.

  13. Second-order nonlinear optical property and crystal growth of chalcone derivatives

    NASA Astrophysics Data System (ADS)

    Goto, Yoshitaka; Hayashi, Akio; Zhang, G. J.; Nakayama, M.; Kitaoka, Yasuo; Sasaki, Takatomo; Watanabe, Toshiyuki; Miyata, Seizo; Honda, K.; Goto, Midori

    1990-12-01

    300 types of "chalcone" derivatives excellent in blue light region transparency were synthesized to investigate on second harmonic generation(SHG). The results of investigation suggested that an alkoxy group, an alkylthio group and halogen were effective as a substituent. Besides, a single crystal with respect to 4-ethoxy-4 ' -methoxychalcone(C-607) and 1- (2-thienyl ) -3- (4- fflethylphenyl)propene-l-one(TC-28) were grown. The obtained crystals were high quality and large size over 5 cm. We also had the first success in continuous SHG on a intracavity of the microchip laser using this single crystal "chalcone".

  14. Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors.

    PubMed

    Hammuda, Arwa; Shalaby, Raed; Rovida, Stefano; Edmondson, Dale E; Binda, Claudia; Khalil, Ashraf

    2016-05-23

    A novel series of substituted chalcones were designed and synthesized to be evaluated as selective human MAO-B inhibitors. A combination of either methylsulfonyl or trifluoromethyl substituents on the aromatic ketone moiety with a benzodioxol ring on the other end of the chalcone scaffold was investigated. The compounds were tested for their inhibitory activities on both human MAO-A and B. All compounds appeared to be selective MAO-B inhibitors with Ki values in the micromolar to submicromolar range. Molecular modeling studies have been performed to get insight into the binding mode of the synthesized compounds to human MAO-B active site. PMID:26974383

  15. Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells.

    PubMed

    Park, Cheon-Soo; Ahn, Yongchel; Lee, Dahae; Moon, Sung Won; Kim, Ki Hyun; Yamabe, Noriko; Hwang, Gwi Seo; Jang, Hyuk Jai; Lee, Heesu; Kang, Ki Sung; Lee, Jae Wook

    2015-12-15

    Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway. PMID:26564263

  16. Synthesis and Hydrogenation of Disubstituted Chalcones: A Guided-Inquiry Organic Chemistry Project

    ERIC Educational Resources Information Center

    Mohrig, Jerry R.; Hammond, Christina Noring; Schatz, Paul F.; Davidson, Tammy A.

    2009-01-01

    Guided-inquiry experiments offer the same opportunities to participate in the process of science as classical organic qualitative analysis used to do. This three-week guided-inquiry project involves an aldol-dehydration synthesis of a chalcone chosen from a set of nine, followed by a catalytic transfer hydrogenation reaction using ammonium formate…

  17. Positive selection sites in tertiary structure of Leguminosae chalcone isomerase 1.

    PubMed

    Wang, R K; Zhan, S F; Zhao, T J; Zhou, X L; Wang, C E

    2015-03-20

    Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are unique in the Leguminosae, with diverse biological functions. Among the Leguminosae, the soybean is an important oil, protein crop, and model plant. In this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome-wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model plants was performed; the expression levels of soybean chalcone isomerases were also analyzed. By comparing positively selected sites and their protein structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of 28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1, CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase subfamily had similar expression patterns. CHI1, the unique chalcone isomerase subfamily in Leguminosae, showed signs of significant positive selection as well as special expression characteristics, indicating an accelerated evolution throughout its divergence. Eight sites were identified as undergoing positive selection with high confidence. When mapped onto the tertiary structure of CHI1, these 8 sites were observed surrounding the enzyme substrate only; some of them connected to the catalytic core of CHI. Thus, we inferred that the generation of Leguminosae CHI1 is dependent on the positively selected amino acids surrounding its catalytic substrate. In other words, the evolution of CHI1 was driven by specific selection or processing conditions within the substrate.

  18. Studies on third-order nonlinear optical properties of chalcone derivatives in polymer host

    NASA Astrophysics Data System (ADS)

    Shettigar, Seetharam; Umesh, G.; Chandrasekharan, K.; Sarojini, B. K.; Narayana, B.

    2008-04-01

    In this paper we present the experimental study of the third-order nonlinear optical properties of two chalcone derivatives, viz., 1-(4-methoxyphenyl)-3-(4-butyloxyphenyl)-prop-2-en-1-one and 1-(4-methoxyphenyl)-3-(4-propyloxyphenyl)-prop-2-en-1-one in PMMA host, with the prospective of reaching a compromise between good processability and high nonlinear optical properties. The nonlinear optical properties have been investigated by Z-scan technique using 7 ns laser pulses at 532 nm. The nonlinear refractive index, nonlinear absorption coefficient, magnitude of third-order susceptibility and the coupling factor have been determined. The values obtained are of the order of 10 -14 cm 2/W, 1 cm/GW, 10 -13 esu and 0.2, respectively. The molecular second hyperpolarizability for the chalcone derivatives in polymer is of the order of 10 -31 esu. Different guest/host concentrations have also been studied. The results suggest that the nonlinear properties of the chalcones have been improved when they are used as dopants in polymer matrix. The nonlinear parameters obtained are comparable with the reported values of II-VI compound semiconductors. Hence, these chalcons are a promising class of nonlinear optical dopant materials for optical device applications.

  19. Chemistry of isoflavone heteroanalogs. 11. Benzodioxane analogs of chalcone, flavone, and isoflavone

    SciTech Connect

    Khilya, V.P.; Aitmambetov, A.; Turov, A.V.; Kornilov, A.M.; Litkei, D.; Patonai, T.

    1986-08-01

    Benzodioxane analogs of chalcones and their epoxides have been prepared. Different types of analogs of natural flavonolignan - silibin - have been synthesized from these compounds. The PMR spectra of the new compounds and the results of the preliminary biological testings are reported and discussed.

  20. Second-harmonic generation of a new chalcone-type crystal

    NASA Astrophysics Data System (ADS)

    Zhang, G. J.; Kinoshita, T.; Sasaki, K.; Goto, Y.; Nakayama, M.

    1990-07-01

    A new type of chalcone crystal was prepared. Anisotropic indices with wavelength dispersion were measured by the Brewster angle method. The two largest second-harmonic generation (SHG) tensor components were determined by the wedge method and compared with d11 of 2-methyl-4-nitroaniline. Calculated collinear and noncollinear phase-matched SHG patterns reasonably fit the observed photographs.

  1. Synthesis, structural characterization and anti-carcinogenic activity of new cyclotriphosphazenes containing dioxybiphenyl and chalcone groups

    NASA Astrophysics Data System (ADS)

    Görgülü, Ahmet Orhan; Koran, Kenan; Özen, Furkan; Tekin, Suat; Sandal, Süleyman

    2015-05-01

    2,2-Dichloro-4,4,6,6-bis[spiro(2‧,2″-dioxy-1‧,1″-biphenylyl]cyclotriphosphazene (2) was synthesized from hexachlorocyclotriphosphazene (HCCP) and 2,2‧-dihydroxybiphenyl. The mixed substituent chalcone/dioxybiphenyl cyclophosphazenes (2a-h) were obtained from the reactions of (2) with hydroxy chalcone compounds in K2CO3/acetone system. The chalcone-cyclophosphazene compounds were characterized by elemental analysis, FT-IR, 1H, 13C, 31P NMR techniques. In vitro anti-carcinogenic activities of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Anti-carcinogenic activity of the compounds (2a-h) against androgen-dependent (LNCaP) and independent (PC-3) human prostate cancer cell lines were investigated. Our results indicate that the chalcone-phosphazene compounds (2a-h) have anti-carcinogenic activity on PC-3 and LNCaP cell lines (p < 0.05). The effective dose of the compounds was determined as 100 μM.

  2. Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV.

    PubMed

    Park, Ji-Young; Ko, Jin-A; Kim, Dae Wook; Kim, Young Min; Kwon, Hyung-Jun; Jeong, Hyung Jae; Kim, Cha Young; Park, Ki Hun; Lee, Woo Song; Ryu, Young Bae

    2016-01-01

    Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro).

  3. Synthetic Cathinones ("Bath Salts")

    MedlinePlus

    ... still unknown about how synthetic cathinones affect the human brain. Researchers do know that synthetic cathinones are chemically ... of the chemicals in synthetic cathinones affect the human brain. Synthetic cathinones can cause: nosebleeds paranoia increased sociability ...

  4. Synthetic Cannabinoids.

    PubMed

    Mills, Brooke; Yepes, Andres; Nugent, Kenneth

    2015-07-01

    Synthetic cannabinoids (SCBs), also known under the brand names of "Spice," "K2," "herbal incense," "Cloud 9," "Mojo" and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis. This is likely due to SCBs being direct agonists of the cannabinoid receptors, whereas THC is a partial agonist. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.

  5. Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

    PubMed

    Meng, Charles Q; Ni, Liming; Worsencroft, Kimberly J; Ye, Zhihong; Weingarten, M David; Simpson, Jacob E; Skudlarek, Jason W; Marino, Elaine M; Suen, Ki-Ling; Kunsch, Charles; Souder, Amy; Howard, Randy B; Sundell, Cynthia L; Wasserman, Martin A; Sikorski, James A

    2007-03-22

    Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP values and inhibitory efficacy were observed among structurally similar compounds of the series. Various substituents were found to be tolerated at several positions of the chalcone backbone as long as the compounds fell into the right range of lipophilicity. The chalcone alpha,beta-unsaturated ketone moiety seemed to be the pharmacophore required for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effects in a mouse model of allergic inflammation, indicating that this series of compounds might have therapeutic value for human asthma and other inflammatory disorders. PMID:17323940

  6. Synthetic Brainbows

    PubMed Central

    Wan, Y.; Otsuna, H.; Hansen, C.

    2014-01-01

    Brainbow is a genetic engineering technique that randomly colorizes cells. Biological samples processed with this technique and imaged with confocal microscopy have distinctive colors for individual cells. Complex cellular structures can then be easily visualized. However, the complexity of the Brainbow technique limits its applications. In practice, most confocal microscopy scans use different florescence staining with typically at most three distinct cellular structures. These structures are often packed and obscure each other in rendered images making analysis difficult. In this paper, we leverage a process known as GPU framebuffer feedback loops to synthesize Brainbow-like images. In addition, we incorporate ID shuffing and Monte-Carlo sampling into our technique, so that it can be applied to single-channel confocal microscopy data. The synthesized Brainbow images are presented to domain experts with positive feedback. A user survey demonstrates that our synthetic Brainbow technique improves visualizations of volume data with complex structures for biologists. PMID:25018576

  7. Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53.

    PubMed

    Silva, Gabriel; Marins, Mozart; Fachin, Ana Lúcia; Lee, Seong-Ho; Baek, Seung Joon

    2016-10-01

    Osteosarcoma is the most common bone cancer. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Currently, much anticancer therapy uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up-regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Building on this knowledge, we evaluated the ability of trans-chalcone to reduce viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in human osteosarcoma cell lines. We found that treatment of trans-chalcone inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with significant inhibition at 10 μM after 48 h; apoptosis was also induced in a dose-dependent manner, with 1.9- and 3.6-fold induction at 10 μM and 50 μM, respectively, compared to non-treated cells. Further experiments suggest that trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma. © 2015 Wiley Periodicals, Inc.

  8. Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53.

    PubMed

    Silva, Gabriel; Marins, Mozart; Fachin, Ana Lúcia; Lee, Seong-Ho; Baek, Seung Joon

    2016-10-01

    Osteosarcoma is the most common bone cancer. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Currently, much anticancer therapy uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up-regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Building on this knowledge, we evaluated the ability of trans-chalcone to reduce viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in human osteosarcoma cell lines. We found that treatment of trans-chalcone inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with significant inhibition at 10 μM after 48 h; apoptosis was also induced in a dose-dependent manner, with 1.9- and 3.6-fold induction at 10 μM and 50 μM, respectively, compared to non-treated cells. Further experiments suggest that trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma. © 2015 Wiley Periodicals, Inc. PMID:26294168

  9. Studies on chalcone derivatives: Complex formation, thermal behavior, stability constant and antioxidant activity

    NASA Astrophysics Data System (ADS)

    El-Sayed, Yusif S.; Gaber, M.

    2015-02-01

    The chalcone 3-[4‧-dimethylaminophenyl]-1-(2-pyridyl) prop-2-en-1-one (DMAPP) and 3-(4‧-diethylaminophenyl)-1-(2-pyridinyl) prop-2-en-1-one abbreviated as DEAPP have been synthesized and characterized with IR, 1H NMR, 13C NMR spectroscopic techniques as described previously (El-Daly et al., 2008; Gaber et al., 2009; El-Sayed, 2013). By using UV visible spectroscopy method the mole fraction ratio for copper with DMAPP and DEAPP complexes were determined and it was found to be 1:1. The stability constants of this complex have been determined by Job's method. The stability constant (Kf) of copper with DMAPP and DEAPP complexes in universal buffer pH = 3.2 was determined to be 9.9 × 104 and 5.2 × 104 respectively. The effect of Cu(II) ion on the emission spectrum of the free chalcone is also assigned. Adherence to Beer's law and Ringbom optimum concentration ranges are determined. The thermal decomposition of the metal complexes is studied by TGA technique. The kinetic parameters like activation energy, pre-exponential factor and entropy of activation are estimated. The structure of complexes was energetically optimized through molecular mechanics applying MM+ force field coupled with molecular dynamics simulation. The bond lengths and bond angles have been calculated to confirm the geometry of the ligands and their Cu(II) complexes. The mode of interaction of the chalcone to copper nanoparticles was studied. The apparent association constants of the colloidal copper nanoparticles:chalcone complexes in solution were evaluated using the spectral method and compared with the formation constant of the Cu(II) chalcone complexes. Antioxidant activity of these chalcones was evaluated by using 1,1‧-diphenyl-2-picrylhydrazyl (DPPHrad) radicals scavenging method, which showed that the antioxidant activity of DMAPP has higher value than the DEAPP. Semi-empirical study results showed that DMAPP have higher dipole moment than DEAPP [1].

  10. Synthetic and Antibacterial Studies of Quinolinylchalcones

    NASA Astrophysics Data System (ADS)

    Azad, Muhammad; Munawar, Munawar Ali; Athar, Makshoof

    A series of quinolinyl chalcones have been prepared by the condensation of N-substituted-3-acetyl-4-hydroxyquinolin-2(1H)-ones with different aromatic aldehydes using conventional heating and ultrasound-assisted methods. The percentage yields are considerably increased in ultrasound-assisted method. The prepared chalcone derivatives were assayed for antibacterial and cytotoxicity and were found to be active.

  11. Biotechnological methods for chalcone reduction using whole cells of Lactobacillus, Rhodococcus and Rhodotorula strains as a way to produce new derivatives.

    PubMed

    Stompor, Monika; Kałużny, Mateusz; Żarowska, Barbara

    2016-10-01

    Microbial strains of the genera Dietzia, Micrococcus, Pseudomonas, Rhodococcus, Gordonia, Streptomyces, Pseudomonas, Bacillus, Penicillium, Rhodotorula and Lactobacillus were screened for the ability to convert chalcones. Synthesis of chalcones was performed by the Claisen-Schmidt reaction. There were three groups of chalcones obtained as the products, which included the derivatives containing 4-substituted chalcone, 2'-hydroxychalcone and 4'-methoxychalcone. The B ring of the chalcones was substituted in the para position with different groups, such as halide, hydroxyl, nitro, methyl, ethyl and ethoxy one. The structure-activity relationship of the tested chalcones in biotransformation processes was studied. It has been proven that Gram-positive bacterial strains Rhodococcus and Lactobacillus catalyzed reduction of C=C bond in the chalcones to give respective dihydrochalcones. The strain Rhodotorula rubra AM 82 transformed chalcones into dihydrochalcones and respective secondary alcohols. These results suggest that the probiotic strain of Lactobacillus can be used for biotransformations of chalcones, which has not been described before. The structure of new metabolites 14a and 15b were established as 4-ethoxy-4'-methoxydihydrochalcone and 3-(4-bromophenyl)-1-(4'-O-methylphenyl)-2-propan-1-ol, respectively, which was confirmed by (1)H NMR and (13)C NMR analysis.

  12. Biotechnological methods for chalcone reduction using whole cells of Lactobacillus, Rhodococcus and Rhodotorula strains as a way to produce new derivatives.

    PubMed

    Stompor, Monika; Kałużny, Mateusz; Żarowska, Barbara

    2016-10-01

    Microbial strains of the genera Dietzia, Micrococcus, Pseudomonas, Rhodococcus, Gordonia, Streptomyces, Pseudomonas, Bacillus, Penicillium, Rhodotorula and Lactobacillus were screened for the ability to convert chalcones. Synthesis of chalcones was performed by the Claisen-Schmidt reaction. There were three groups of chalcones obtained as the products, which included the derivatives containing 4-substituted chalcone, 2'-hydroxychalcone and 4'-methoxychalcone. The B ring of the chalcones was substituted in the para position with different groups, such as halide, hydroxyl, nitro, methyl, ethyl and ethoxy one. The structure-activity relationship of the tested chalcones in biotransformation processes was studied. It has been proven that Gram-positive bacterial strains Rhodococcus and Lactobacillus catalyzed reduction of C=C bond in the chalcones to give respective dihydrochalcones. The strain Rhodotorula rubra AM 82 transformed chalcones into dihydrochalcones and respective secondary alcohols. These results suggest that the probiotic strain of Lactobacillus can be used for biotransformations of chalcones, which has not been described before. The structure of new metabolites 14a and 15b were established as 4-ethoxy-4'-methoxydihydrochalcone and 3-(4-bromophenyl)-1-(4'-O-methylphenyl)-2-propan-1-ol, respectively, which was confirmed by (1)H NMR and (13)C NMR analysis. PMID:27209040

  13. Synthetic peptides.

    PubMed

    Francis, M J

    1996-01-01

    Efforts to produce more stable and defined vaccines have concentrated on studying, in detail, the immune response to many infectious diseases in order to identify the antigenic sites on the pathogens that are involved in stimulating protective immumty. Armed with this knowledge, it is possible to mimic such sites by producing short chains of amino acids (peptides) and to use these as the basis for novel vaccines. The earliest documented work on peptide immunization is actually for a plant virus, tobacco mosaic virus. In 1963, Anderer (1) demonstrated that rabbit antibodies to an isolated hexapeptide fragment from the virus-coat protein coupled to bovine serum albumm would neutralize the infectious vn-us in culture. Two years later, he used a synthetically produced copy of the same peptide to confirm this observation. This was pioneering work, and it was over 10 years before the next example of a peptide that elicited antivirus antibody appeared following work by Sela and his colleagues (2) on a virus, MS2 bacteriophage, which infects bacteria. The emergence of more accessible techniques for sequencing proteins in 1977, coupled with the ability to synthesize readily peptides already developed in 1963, heralded a decade of intensive research into experimental peptide vaccines. The first demonstration that peptides could elicit protective immunity in vivo, in addition to neutralizing activity in vitro, was obtained using a peptide from the VP1 coat protein of foot-and-mouth disease virus (FMDV) in 1982, with the guinea pig as a laboratory animal model (3, 4). PMID:21359696

  14. Coumarin-Chalcone Hybrids as Peroxyl Radical Scavengers: Kinetics and Mechanisms.

    PubMed

    Mazzone, Gloria; Galano, Annia; Alvarez-Idaboy, Juan R; Russo, Nino

    2016-04-25

    The primary antioxidant activity of coumarin-chalcone hybrids has been investigated using the density functional and the conventional transition state theories. Their peroxyl radical scavenging ability was studied in solvents of different polarity and taking into account different reaction mechanisms. It was found that the activity of the hybrids increases with the polarity of the environment and the number of phenolic sites. In addition, their peroxyl radical scavenging activity is larger than those of the corresponding nonhybrid coumarin and chalcone molecules. This finding is in line with previous experimental evidence. All the investigated molecules were found to react faster than Trolox with (•)OOH, regardless of the polarity of the environment. The role of deprotonation on the overall activity of the studied compounds was assessed. The rate constants and branching ratios for the reactions of all the studied compounds with (•)OOH are reported for the first time.

  15. Cytotoxic C-benzylated chalcone and other constituents of Ellipeiopsis cherrevensis.

    PubMed

    Wirasathien, Lalita; Pengsuparp, Thitima; Moriyasu, Masataka; Kawanishi, Kazuko; Suttisri, Rutt

    2006-06-01

    A new natural C-benzylated chalcone, 2',4'-dihydroxy-3'-(2-hydroxybenzyl)-6'-methoxychalcone (2), along with two other flavonoids, tiliroside and kaempferol 3-O-rutinoside, and an oxoaporphine alkaloid, lanuginosine were isolated from the aerial parts of Ellipeiopsis cherrevensis (Annonaceae). Two known polyoxygenated cyclohexene derivatives, ferrudiol and zeylenol, and a new analog, ellipeiopsol D, were also isolated. The chalcone 2 exhibited cytotoxic activity against human small-cell lung-cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines with IC50 values of 1.40, 5.31 and 13.92 microg/mL, respectively. This compound also showed antimalarial activity against Plasmodium falciparum with an IC50 value of 7.1 microg/mL as well as antimicrobacterial activity against Mycobacterium tuberculosis with a MIC of 25 mg/mL.

  16. A quantitative analysis of weak intermolecular interactions & quantum chemical calculations (DFT) of novel chalcone derivatives

    NASA Astrophysics Data System (ADS)

    Chavda, Bhavin R.; Gandhi, Sahaj A.; Dubey, Rahul P.; Patel, Urmila H.; Barot, Vijay M.

    2016-05-01

    The novel chalcone derivatives have widespread applications in material science and medicinal industries. The density functional theory (DFT) is used to optimized the molecular structure of the three chalcone derivatives (M-I, II, III). The observed discrepancies between the theoretical and experimental (X-ray data) results attributed to different environments of the molecules, the experimental values are of the molecule in solid state there by subjected to the intermolecular forces, like non-bonded hydrogen bond interactions, where as isolated state in gas phase for theoretical studies. The lattice energy of all the molecules have been calculated using PIXELC module in Coulomb -London -Pauli (CLP) package and is partitioned into corresponding coulombic, polarization, dispersion and repulsion contributions. Lattice energy data confirm and strengthen the finding of the X-ray results that the weak but significant intermolecular interactions like C-H…O, Π- Π and C-H… Π plays an important role in the stabilization of crystal packing.

  17. Flemingin-Type Prenylated Chalcones from the Sarawak Rainforest Plant Desmodium congestum.

    PubMed

    Rees, Karlee A; Bermudez, Cindy; Edwards, David J; Elliott, Alysha G; Ripen, Jovita E; Seta, Cynthia; Huang, Johnny X; Cooper, Matthew A; Fraser, James A; Yeo, Tiong Chia; Butler, Mark S

    2015-08-28

    In an ongoing program to identify new anti-infective leads, an extract derived from whole plant material of Desmodium congestum collected in the Sarawak rainforest was found to have anti-MRSA activity. Bioassay-guided isolation led to the isolation of two new prenylated chalcones, 5'-O-methyl-3-hydroxyflemingin A (1) and 5'-O-methylflemingin C (2), which were closely related to the flemingins previously isolated from various Flemingia species. Chalcones 1 and 2, which were determined to be 4:6 enantiomeric mixtures by chiral HPLC, exhibited moderate activity against a panel of Gram-positive bacteria and were also cytotoxic to the HEK293 human embryonic kidney cell line.

  18. Chalcones, semicarbazones and pyrazolines as inhibitors of cathepsins B, H and L.

    PubMed

    Raghav, Neera; Kaur, Ravinder

    2015-09-01

    Cathepsin B [EC 3.4.22.1], cathepsin H [EC 3.4.22.16] and cathepsin L [EC 3.4.22.15] are the most versatile lysosomal cysteine proteases and are responsible for intracellular protein degradation. These are involved in a number of pathological conditions including tissue degenerative processes. In the present work, we report the synthesis and systematic evaluation of differently substituted chalcones, chalconesemicarbazones, and diarylpyrazolines on cathepsins B, H and L activity. It was found that after a preliminary screening as cysteine protease inhibitors, chalconesemicarbazones were better inhibitors to these cysteine proteases than diarylpyrazolines followed by chalcones. All the synthesized compounds were identified as the best inhibitors to cathepsin L followed by cathepsin B and then cathepsin H. The results are compared with docking studies and it was found that all the compounds resulted in decrease in energy while interacting with the active site of the enzyme. PMID:26193682

  19. Synthesis, Biological Evaluation, and Molecular Simulation of Chalcones and Aurones as Selective MAO-B Inhibitors.

    PubMed

    Morales-Camilo, Nicole; Salas, Cristian O; Sanhueza, Claudia; Espinosa-Bustos, Christian; Sepúlveda-Boza, Silvia; Reyes-Parada, Miguel; Gonzalez-Nilo, Fernando; Caroli-Rezende, Marcos; Fierro, Angélica

    2015-06-01

    A series of chalcones and aurones were synthesized and evaluated in vitro as monoamine oxidase inhibitors (MAOi). Our results show that aurones, which had not been previously reported as MAOi, are MAO-B inhibitors. Thus, both families inhibited selectively the B isoform of MAO in the micromolar range, offering novel scaffolds for the design of new and potent MAO inhibitors. The main structural requirements for their activity were characterized with the aid of 3D-QSAR and docking studies.

  20. Effect of stilbene and chalcone scaffolds incorporation in clofibric acid on PPARα agonistic activity.

    PubMed

    Giampietro, Letizia; D'Angelo, Alessandra; Giancristofaro, Antonella; Ammazzalorso, Alessandra; De Filippis, Barbara; Di Matteo, Mauro; Fantacuzzi, Marialuigia; Linciano, Pasquale; Maccallini, Cristina; Amoroso, Rosa

    2014-01-01

    In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, new compounds based on a combination of clofibric acid, the active metabolite of clofibrate, and trans-stilbene, chalcone, and other lipophilic groups were synthesized. They were evaluated for PPARα transactivation activity; all branched derivatives showed an increase of the transcriptional activity of receptor compared to the linear ones. Noteworthy, stilbene and benzophenone branched derivatives activated the PPARα better than clofibric acid. PMID:23432317

  1. Development of fluorescent lead II sensor based on an anthracene derived chalcone

    NASA Astrophysics Data System (ADS)

    Prabhu, J.; Velmurugan, K.; Nandhakumar, R.

    2015-06-01

    A simple anthracene based chalcone as a fluorescent chemosensor 1, capable of detecting Pb2+ in aqueous media, has been synthesized by the reaction between pyridine 2-carboxaldehyde and 9-acetyl anthracene. The Pb2+ recognition processes follows a photo induced electron transfer (PET) mechanism and are scarcely influenced by other coexisting metal ions. In addition, determination of lead in a variety of samples was also determined.

  2. Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma.

    PubMed

    Nishimura, Reiko; Tabata, Keiichi; Arakawa, Motoki; Ito, Yoshihisa; Kimura, Yumiko; Akihisa, Toshihiro; Nagai, Hisashi; Sakuma, Atsuko; Kohno, Hideki; Suzuki, Takashi

    2007-10-01

    Six chalcones from Angelica keiskei KOIDZUMI (Ashitaba in Japanese) and two chalcones from Humulus lupulus L. (hop) were examined for their cytotoxicity in two human neuroblastoma cell lines (IMR-32 and NB-39) and normal cells (primary culture of rat cerebellar granule cells) by [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. All chalcones exhibited cytotoxicity against neuroblastoma cells, and two of them (isobavachalcone and xanthoangelol H) had no effect on normal cells even at high concentration (10(-4) M) exposure. Typical morphologic features of apoptosis, including cell shrinkage, chromatin condensation, nuclear fragmentation and formation of apoptotic bodies, were observed in isobavachalcone-treated cells by Hoechst 33342 staining. Western blot analysis showed that isobavachalcone significantly reduced pro-caspase-3 and pro-caspase-9, and subsequently increased the level of cleaved caspase-3 and cleaved caspase-9 in both neuroblastoma cell lines. Moreover, Bax was markedly induced by isobavachalcone application. These results suggest that isobavachalcone induces apoptotic cell death in neuroblastoma via the mitochondrial pathway and has no cytotoxicity against normal cells. Therefore, isobavachalcone may be applicable as an efficacious and safe drug for the treatment of neuroblastoma.

  3. Cloning and Functional Analysis of Three Chalcone Synthases from the Flowers of Safflowers Carthamus tinctorius.

    PubMed

    Shinozaki, Junichi; Kenmoku, Hiromichi; Nihei, Kenichi; Masuda, Kazuo; Noji, Masaaki; Konno, Katsuhiro; Asakawa, Yoshinori; Kazuma, Kohei

    2016-06-01

    The flowers of safflowers (Carthamus tinctorius L.) are very important as they are the sole source of their distinct pigments, i.e. carthamus-red and -yellows, and have historically had strong connections to the cultural side of human activities such as natural dyes, rouge, and traditional medicines. The distinct pigments are quinochalcone C-glucosides, which are found specifically in the flowers of C. tinctorius. To investigate the biosynthetic pathways of quinochalcone C-glucosides, de novo assembly of the transcriptome was performed on the flowers using an Illumina sequencing platform to obtain 69,312 annotated coding DNA sequences. Three chalcone synthase like genes, CtCHS1, 2 and 3 were focused on and cloned, which might be involved in quinochalcone C-glucosides biosynthesis by establishing the C6-C3-C6 chalcone skeleton. It was demonstrated that all the recombinant CtCHSs could recognize p-coumaroyl-CoA, caffeoyl-CoA, feruloyl-CoA, and sinapoyl-CoA as starter substrates. This is the first report on the cloning and functional analysis of the three chalcone synthase genes from the flowers of C. tinctorius. PMID:27534116

  4. Ferrocenyl-cymantrenyl hetero-bimetallic chalcones: Synthesis, structure and biological properties

    NASA Astrophysics Data System (ADS)

    Mishra, Sasmita; Tirkey, Vijaylakshmi; Ghosh, Avishek; Dash, Hirak R.; Das, Surajit; Shukla, Madhulata; Saha, Satyen; Mobin, Sheikh M.; Chatterjee, Saurav

    2015-04-01

    Two new ferrocenyl-cymantrenyl bimetallic chalcones, [(CO)3Mn(η5-C5H4)C(O)CHdbnd CH(η5-C5H4)Fe(η5-C5H5)] (1) and [{(CO)3Mn(η5-C5H4)C(O)CHdbnd CH(η5-C5H4)}2Fe] (2) have been synthesized. Their reactivity study with triphenylphosphine and bis-(diphenylphosphino)ferrocene led to the isolation of phosphine substituted bimetallic chalcones (3-6). Single crystal X-ray structural characterization for 1 and its phosphine analogue (3) reveals their different conformational identity with anti-conformation for 1, while syn-conformation for 3. Investigation of antimalarial and antibacterial activities was carried out for compounds 1 and 2 against two strains of Plasmodium falciparum (3D7, K1) and four bacterial strains. TD-DFT calculation was performed for compound 1 and electrochemical properties were studied for bimetallic chalcone compounds by cyclic voltammetric technique.

  5. Cloning and Functional Analysis of Three Chalcone Synthases from the Flowers of Safflowers Carthamus tinctorius.

    PubMed

    Shinozaki, Junichi; Kenmoku, Hiromichi; Nihei, Kenichi; Masuda, Kazuo; Noji, Masaaki; Konno, Katsuhiro; Asakawa, Yoshinori; Kazuma, Kohei

    2016-06-01

    The flowers of safflowers (Carthamus tinctorius L.) are very important as they are the sole source of their distinct pigments, i.e. carthamus-red and -yellows, and have historically had strong connections to the cultural side of human activities such as natural dyes, rouge, and traditional medicines. The distinct pigments are quinochalcone C-glucosides, which are found specifically in the flowers of C. tinctorius. To investigate the biosynthetic pathways of quinochalcone C-glucosides, de novo assembly of the transcriptome was performed on the flowers using an Illumina sequencing platform to obtain 69,312 annotated coding DNA sequences. Three chalcone synthase like genes, CtCHS1, 2 and 3 were focused on and cloned, which might be involved in quinochalcone C-glucosides biosynthesis by establishing the C6-C3-C6 chalcone skeleton. It was demonstrated that all the recombinant CtCHSs could recognize p-coumaroyl-CoA, caffeoyl-CoA, feruloyl-CoA, and sinapoyl-CoA as starter substrates. This is the first report on the cloning and functional analysis of the three chalcone synthase genes from the flowers of C. tinctorius.

  6. Synthesis, characterization, and computational study of a new dimethoxy-chalcone.

    PubMed

    Ternavisk, Ricardo R; Camargo, Ademir J; Machado, Francisco B C; Rocco, José A F F; Aquino, Gilberto L B; Silva, Valter H C; Napolitano, Hamilton B

    2014-12-01

    Chalcones are an important class of medicinal compounds and are known for taking part in various biological activities as in anti-inflammatory, anti-leishmania, antimitotic, and antiviral. Chemically, chalcones consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α,β-unsaturated carbonyl system. The wide action spectrum has attracted our attention to synthesize, crystallize, and characterize the dimethoxy-chalcone C18H18O3. Aiming to understand the process of crystal lattice stabilization, a combination of technique has been used including X-ray diffraction, infrared spectroscopy and computational molecular modeling. The theoretical calculations were carried out by the density functional method (DFT) with the M06-2X functional, with the 6-311+G(d,p) basis set. The vibrational wavenumbers were calculated and the scaled values were compared with experimental FT-IR spectrum. The intermolecular interactions were quantified and intercontacts in the crystal structure were analyzed using Hirshfeld surfaces. Bond distances and angles described by the X-ray diffraction and theoretical calculation are very similar. The C-H….O contacts contributing to assemble the supramolecular architecture are also responsible for the molecular structure assembly. PMID:25420703

  7. Potent and Selective Monoamine Oxidase-B Inhibitory Activity: Fluoro- vs. Trifluoromethyl-4-hydroxylated Chalcone Derivatives.

    PubMed

    Mathew, Bijo; Mathew, Githa Elizabeth; Uçar, Gülberk; Baysal, Ipek; Suresh, Jerad; Mathew, Sincy; Haridas, Abitha; Jayaprakash, Venkatesan

    2016-08-01

    For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO-B inhibitors with a competitive mode of inhibition. The most active compound, (2E)-1-(4-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one, exhibited a Ki value of 0.33 ± 0.01 μm toward hMAO-B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H-bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO-B selectivity and potency.

  8. Dual emission of chalcone-analogue dyes emitting in the red region

    NASA Astrophysics Data System (ADS)

    Fayed, Tarek A.; Awad, Mohamed K.

    2004-08-01

    The photophysical properties of new synthesized chalcones namely; 1-(4 '-R-phenyl)-5-(4 '-dimethylaminophenyl)-2,4- pentadien-1-one, [R=H ( 1), Cl ( 2) and OCH 3 ( 3)] were studied in different solvents by using steady-state absorption and emission spectroscopy. The fluorescence spectra of these chalcones exhibit dual emission in medium and polar solvents. The dual emission was attributed to population of a polar locally excited (LE) state and a highly dipolar intramolecular charge transfer (ICT) state. The changes in dipole moments upon excitation were calculated from the solvatochromic plots. The total fluorescence quantum yields ( φf) were also determined, and their values are strongly dependent on the nature of substitutent and the solvent polarity. Semiempirical molecular orbital calculations using the atom superposition and electron delocalization molecular orbital (ASED-MO) method were also performed to investigate the molecular and electronic structures of these chalcones in both the ground and excited state. The change of the dipole moment upon excitation was explained on the basis of changes in the charge redistribution over the whole skeleton of the molecules, which agree well with the experimental results. Also, the nature and energy of the electronic transitions were elucidated and discussed in relation to the experimental data.

  9. Viscosity and medium effects on the fluorescence and photochemical behaviour of some aryl chalcones

    NASA Astrophysics Data System (ADS)

    Ebeid, El-Zeiny M.; Abdel-Kader, Mahmood H.; Issa, Raafat M.; El-Daly, Samy A.

    1988-05-01

    The emission, excitation and absorption spectra toghether with the fluorescence and photochemical quantum yields of some chalcone derivatives have been studied in organic solvents and micellar and microemulsion media. Both 4-[2-(2-pyridyl)ethenyl] ( I) and 4-[2-(4-pyridyl)ethenyl ( II) chalcones show large positive solvatochromic effects. The fluorescence quantum yields increase substantially as the medium viscosity increases with a subsequent decrease in the photochemical quatum yield. Compounds I and II undergo excited-state molecular aggregation in concentrated solutions giving excimer-like emission that coincides with emission from crystalline samples. The enthalpies of photoassociation have been estimated. The chalcone derivative I acts as an efficient quencher of the fluorescence of the laser dye 1,4-bis (β-pyridyl-2-vinyl)benzene via a long-range mechanism. The excited-state lifetimes of both I and II are short and at 20°C their τ values are less than 800 ps.

  10. HPLC of flavanones and chalcones in different species and clones of Salix.

    PubMed

    Krauze-Baranowska, Mirosława; Pobłocka-Olech, Loretta; Głód, Daniel; Wiwart, Marian; Zieliński, Jerzy; Migas, Piotr

    2013-01-01

    The SPE-HPLC method was developed to determine an isosalipurposide (5) and its derivative, 6"-O-p-coumaroyl ester (6) in the bark of eight taxa (I-VIII) belonging to three species of the genus Salix and originating from a natural habitat or cultivated for pharmaceutical purposes. The chalcones were separated by HPLC under gradient elution with the concentration of ACN increasing from 20% to 50% in 0.1% aqueous H3PO, (tG 15 min). The content of both compounds was determined by an external standardization with the use of isoliquiritigenin (7) as a reference substance - a commercially available chalcone, and also isosalipurposide (5) and its derivative, 6"-O-p-coumaroyl ester (6). The latter compound was isolated from the bark of Salix daphnoides (IV) by a CC and semi-preparative HPLC and its structure was elucidated by MS and NMR spectra. It was stated that 6"-O-p-coumaroylisosalipurposide (6), in addition to isosalipurposide (5), is a characteristic flavonoid for the S. daphnoides species. Moreover, the presence of these two chalcones was confirmed in the bark of S. acutifolia (I). Differences were observed in the results obtained from a quantitative analysis due to the type of reference substance used. The content of chalcones was varied and dependent on the species selected for analysis, namely from 22.01/21.08 mg/g in S. daphnoides clone 1095 (III) to 2.47/2.44 mg/g in S. daphnoides (II), collected from a natural habitat. Isosalipurposide (5) was determined in all the investigated species and clones of Salix, besides a number of naringenin derivatives. Separation of all flavonoids: flavanones - naringenin (1), naringenin (+)-5-O-glucoside (2), (-)-5-O-glucoside (3), 7-O-glucoside (4) and chalcones (5 and 6) was performed under gradient elution with the same solvents and changes in ACN concentration from 2% to 37% (tG 60 min). The total amount of flavanones ranged from 4.69 mg/g in S. purpurea clone 1132 (VII) to 41.93 mg/g in S. purpuea (VIII) from Herbapol Wrocław.

  11. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

    PubMed

    El-Hashash, Maher A; Rizk, Sameh A; Atta-Allah, Saad R

    2015-12-10

    A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data.

  12. Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.

    PubMed

    Wang, Hao-Meng; Zhang, Li; Liu, Jiang; Yang, Zhao-Liang; Zhao, Hong-Ye; Yang, Yao; Shen, Di; Lu, Kui; Fan, Zhen-Chuan; Yao, Qing-Wei; Zhang, Yong-Min; Teng, Yu-Ou; Peng, Yu

    2015-03-01

    Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing apoptosis. PMID:25590864

  13. Targeting Death Receptor TRAIL-R2 by Chalcones for TRAIL-Induced Apoptosis in Cancer Cells

    PubMed Central

    Szliszka, Ewelina; Jaworska, Dagmara; Kłósek, Małgorzata; Czuba, Zenon P.; Król, Wojciech

    2012-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties. PMID:23203129

  14. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

    PubMed

    El-Hashash, Maher A; Rizk, Sameh A; Atta-Allah, Saad R

    2015-01-01

    A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data. PMID:26690393

  15. Chemical modification of chalcone isomerase by mercurials and tetrathionate. Evidence for a single cysteine residue in the active site

    SciTech Connect

    Bednar, R.A.; Fried, W.B.; Lock, Y.W.; Pramanik, B. )

    1989-08-25

    Chalcone isomerase from soybean is inactivated by stoichiometric amounts of p-mercuribenzoate or HgCl{sub 2}. Spectral titration of the enzyme with p-mercuribenzoate indicates that a single thiol group is modified. Treatment of modified enzyme with KCN or thiols results in a complete restoration of enzyme activity demonstrating that the inactivation is not due to irreversible protein denaturation. A product of the enzymatic reaction, naringenin, provides complete kinetic protection against inactivation by both mercurials. The binding constant (33 microM) for naringenin determined from the concentration dependence of the protection agrees with the inhibition constant (34 microM) for naringenin as a competitive inhibitor of the catalytic reaction. This agreement demonstrates that the observed kinetic protection results from the specific binding of naringenin to the active site. Incubation of native chalcone isomerase with sodium tetrathionate (0.1 M) results in a slow time-dependent loss of enzymatic activity. The inactivation of chalcone isomerase by tetrathionate and N-ethylmaleimide becomes very rapid in the presence of 6 M urea, indicating that the native tertiary structure is responsible for the low reactivity of the enzymatic thiol. The stoichiometric modification of reduced and denatured chalcone isomerase by ({sup 3}H) N-ethylmaleimide indicates that the enzyme contains only a single cysteine residue and does not contain any disulfides. The evidence presented suggests that the only half-cystine residue in chalcone isomerase is located in the active site and thereby provides the first clue to the location of the active site in chalcone isomerase.

  16. Novel anti-inflammatory chalcone derivatives inhibit the induction of nitric oxide synthase and cyclooxygenase-2 in mouse peritoneal macrophages.

    PubMed

    Herencia, F; Ferrándiz, M L; Ubeda, A; Guillén, I; Dominguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    1999-06-18

    In a previous work, we tested a series of chalcone derivatives as possible anti-inflammatory compounds. We now investigate the effects of three of those compounds, CHI, CH8 and CH12, on nitric oxide and prostanoid generation in mouse peritoneal macrophages stimulated with lipopolysaccharide and in the mouse air pouch injected with zymosan, where they showed a dose-dependent inhibition with inhibitory concentration 50% values in the microM range. This effect was not the consequence of a direct inhibitory action on enzyme activities. Our results demonstrated that chalcone derivatives inhibited de novo inducible nitric oxide synthase and cyclooxygenase-2 synthesis, being a novel therapeutic approach for inflammatory diseases.

  17. Probing deep into the interaction of a fluorescent chalcone derivative and bovine serum albumin (BSA): an experimental and computational study.

    PubMed

    Alvim, Haline G O; Fagg, Emma L; de Oliveira, Aline L; de Oliveira, Heibbe C B; Freitas, Sonia M; Xavier, Mary-Ann E; Soares, Thereza A; Gomes, Alexandre F; Gozzo, Fabio C; Silva, Wender A; Neto, Brenno A D

    2013-08-01

    In the present manuscript, a novel fluorescent chalcone derivative is synthesized and its photophysical properties are fully characterized. The designed fluorophore is applied as a probe to study protein-dye interactions with bovine serum albumin. Circular dichroism gave interesting results on the thermodynamics of the interaction. NMR spectroscopy, especially relaxation measurements, revealed the atoms in the chalcone derivative that interacts with the protein upon binding. Molecular docking calculations indicate that the most favourable binding sites are near the two tryptophan residues. Furthermore, ab initio and DFT calculations offer insights into the reactivity and physicochemical properties of this novel fluorophore. PMID:23680860

  18. Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core.

    PubMed

    Ötvös, Sándor B; Hsieh, Chi-Ting; Wu, Yang-Chang; Li, Jih-Heng; Chang, Fang-Rong; Fülöp, Ferenc

    2016-01-01

    Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds. PMID:26959006

  19. Synthesis, growth, vibrational spectral investigations and structure-property relationship of an organic NLO crystal: 3,4-Dimethoxy chalcone

    NASA Astrophysics Data System (ADS)

    Alen, S.; Sajan, D.; Joseph, Lynnette; Chaitanya, K.; Shettigar, Venkataraya; Jothy, V. Bena

    2015-09-01

    3,4-Dimethoxy chalcone, a nonlinear optical material, was synthesized and noncentro symmetric single crystals were grown in solution by slow evaporation technique. Thermal analysis such as DSC revealed a good thermal stability of 3,4-dimethoxy chalcone. The FT-IR and FT-Raman spectral studies were carried out to investigate the structural properties of the title compound. The molecular orbitals and natural bond analysis of this material were calculated by Density Functional Theory calculations. The second harmonic conversion efficiency was determined using the Kurtz powder technique, which is 8 times that of urea.

  20. Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors.

    PubMed

    Mathew, Bijo; Haridas, Abitha; Uçar, Gülberk; Baysal, Ipek; Adeniyi, Adebayo A; Soliman, Mahmoud E S; Joy, Monu; Mathew, Githa Elizabeth; Lakshmanan, Baskar; Jayaprakash, Venkatesan

    2016-10-01

    Chalcone has been reported to be a valid scaffold for the design of monoamine oxidase (MAO) inhibitors. This scenario has amplified the momentum for the discovery of heteroaryl based chalcone MAO inhibitors. In the present study, we have synthesized a series of eleven chlorinated thienyl chalcone derivatives substituted with a different functional groups at the para- position on the ring B and investigated for their ability to inhibit human MAO-A and -B. With the exception of compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one (TC7), which was a selective MAO-A inhibitor, all the other derivatives inhibited hMAO-B potently and selectively with competitive mode of inhibition. The most potent compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-ethylphenyl)prop-2-en-1-one (TC6) was found to be the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.31±0.02μM and 16.84, respectively. All the compounds presented in the current study are completely non-toxic with 74-88% viable cells to hepatic cells at 100μM concentration. Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.2 and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO-B inhibitor TC6.

  1. In vitro and in vivo anti-glioma activity of a chalcone-quinoxaline hybrid.

    PubMed

    Loch-Neckel, Gecioni; Bicca, Maíra Assunção; Leal, Paulo César; Mascarello, Alessandra; Siqueira, Jarbas Mota; Calixto, João B

    2015-01-27

    Chalcones are important compounds that exhibit multiple biological activities, including anti-inflammatory, antimitotic and antibacterial properties. In the present study, we have analyzed the potential anti-cancer activity of a chalcone named N9 (a hybrid chalcone-quinoxaline compound) using in vitro and in vivo experimental glioma models. Here, we report N9-induced inhibition of cell proliferation and also N9-induced cell death in a concentration-dependent manner in U87-MG glioma cells. These effects of N9 appear to be associated with its ability to inhibit the expression of cell cycle-associated proteins, and also the augmentation in the expression of the p21 (p21/Cip1) protein, a cyclin-dependent kinase inhibitor. Additionally, N9 also potentiates the production of the pro-apoptotic markers Bax and p53 via inhibition of MDM2. Moreover, our results show that N9 also significantly enhanced apoptosis of U87-MG cells with disruption of mitochondrial membrane potential, generation of ROS and caspase-9 activation. In vivo experiments carried out in a murine xenograft model of U87-MG revealed that N9 produced a significant reduction of tumors volume when compared to vehicle treated mice. Collectively, data demonstrate that N9 possess in vitro and in vivo anti-cancer activity, an effect that seems to involve the induction of p53 and p21 proteins, as well as, the activation of mitochondrial apoptosis pathway associated with the inhibition of protein MDM2. Overall, this study suggests N9 is affecting a variety of intracellular pathways related to tumor apoptosis. Perhaps N9 or derivate molecules could represent new potential drugs for cancer therapeutics.

  2. Synthesis and antimicrobial evaluation of new chalcones containing piperazine or 2,5-dichlorothiophene moiety.

    PubMed

    Tomar, V; Bhattacharjee, G; Kamaluddin; Kumar, Ashok

    2007-10-01

    Two new series of chalcones have been synthesized by reacting 1-(4-piperazin-1-yl-phenyl)ethanone and 1-(2,5-dichloro-3-thienyl)-1-ethanone with different substituted benzaldehydes in turn by Claisen-Schmidt condensation. The compounds have been characterized by IR, (1)H NMR spectral and microanalysis data. All the synthesized compounds have been evaluated for antimicrobial activity. Some of these derivatives are potentially active against Gram-positive bacteria, Staphylococcus aureus and Escherichia coli while the most potent compound (1) in this study showed MIC(50) value of 2.22 microg/mL against Candida albicans.

  3. Synthesis of chlorovinyl sulfones as structural analogs of chalcones and their antiplasmodial activities.

    PubMed

    Dominguez, Jose N; Leon, Caritza; Rodrigues, Juan; Gamboa de Dominguez, Neira; Gut, Jiri; Rosenthal, Philip J

    2009-04-01

    The synthesis of novel chlorovinyl sulfone-like chalcone derivatives and their antimalarial activity against cultured Plasmodium falciparum parasites, hemozoin formation, hemoglobin hydrolysis and murine malaria model are described. Compounds were prepared via Claisen-Schmidt condensation from available chloromethylphenyl sulfones with substituted aldehydes. Antiplasmodial IC(50) activity of these compounds ranged between 0.025 and 10 microM, those that blocked P. falciparum development at low micro molar concentrations were tested in a murine Plasmodium berghei model, and these compounds delayed the progression of malaria but did not eradicate infections. Much effort and attention are needed for discovery and development of new and less toxic antimalarial drugs.

  4. Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

    NASA Astrophysics Data System (ADS)

    Baskar, R.; Baby, C.; Moni, M. S.; Subramanian, K.

    2013-05-01

    The synthesis of a novel chalcone based N-substituted morpholine derivative namely, (E)-1-(biphenyl-4-yl)-3-(4-(5-morpholinopentyloxy) phenyl) prop-2-en-1-one (BMPP), using a two step protocol is reported. The compound is characterized by FTIR, GC-MS and FTNMR spectroscopy techniques. Advanced 2D NMR techniques such as gradient enhanced COSY, HSQC, HMBC and NOESY were employed to establish through-bond and through-space correlations. Dynamic NMR measurements were carried out to obtain the energy barrier to ring inversion of the morpholine moiety.

  5. Features of the reaction of heterocyclic analogs of chalcone with lanthanide shift reagents

    SciTech Connect

    Turov, A.V.; Khilya, V.P.

    1994-10-01

    The PMR spectra of heterocyclic analogs of 2-hydroxychalcone containing thiazole, benzofuran, triazole, imidazole, benzodioxane, or pyridine rings in the presence of lanthanide shift reagents are studied. It is found that the most effective reagent for modifying the spectra of these compounds is Yb(fod)3. The broadening of the spectra of 2-hydroxy chalcones in the presence of lanthanide shift reagents is explained by the dynamic effects of complex formation. An example is given of the determination of the conformation of molecules of 2-hydroxychalcone by the simultaneous use of lanthanide shift reagents and the homonuclear Overhauser effect. 9 refs., 1 fig., 1 tab.

  6. Supramolecular architectures constructed through self-assembly of a chalcone and substituted diazo-β-diketones

    NASA Astrophysics Data System (ADS)

    Prajapati, R.; Mishra, L.; Grabowski, S. J.; Govil, G.; Dubey, S. K.

    2008-05-01

    Organic compounds namely pyridyl chalcone viz. 3-[4-(3-oxo-3-pyridin-2-yl-propenyl)-phenyl]-1-pyridin-2-yl-propenone (L 1), p-cholorophenyldiazopentane-2,4-dione (L 2) and p-methyl phenyldiazopentane-2,4-dione (L 3) have been characterized by their single-crystal X-ray crystallographic studies. Several structural motifs resulting upon their self-association through probable non-covalent interactions have been discussed. The studies of related motifs found in Cambridge Structural Database are performed and the results are related to the structural data obtained for crystal structures reported here in.

  7. The synthesis and synergistic antifungal effects of chalcones against drug resistant Candida albicans.

    PubMed

    Wang, Yuan-Hua; Dong, Huai-Huai; Zhao, Fei; Wang, Jie; Yan, Fang; Jiang, Yuan-Ying; Jin, Yong-Sheng

    2016-07-01

    To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed. PMID:27210436

  8. Plant synthetic biology.

    PubMed

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants.

  9. [SYNTHETIC PEPTIDE VACCINES].

    PubMed

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.

  10. [From synthetic biology to synthetic humankind].

    PubMed

    Nouvel, Pascal

    2015-01-01

    In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed.

  11. The solid-state emmissive chalcone (2E)-1-(5-chlorothiophen-2-yl)-3-[4-(dimethylamino)phenyl]prop-2-en-1-one.

    PubMed

    Rodríguez-Lugo, Rafael E; Urdaneta, Neudo; Pribanic, Bruno; Landaeta, Vanessa R

    2015-09-01

    Orange rectangular blocks suitable for X-ray diffraction analysis were obtained for the previously reported [Ahmad & Bano (2011). Int. J. ChemTech Res. 3, 1470-1478] title chalcone, C15H14ClNOS. This solid-emissive chalcone exhibits a planar structure and the bond parameters are compared with related compounds already described in the literature. The determination of the structure of this chalcone is quite relevant because it will play an important role in theoretical calculations to investigate potential two-photon absorption processes and could also be useful for studying the interaction of such compounds with a biological target.

  12. Antimicrobial effects of Piper hispidum extract, fractions and chalcones against Candida albicans and Staphylococcus aureus.

    PubMed

    Costa, G M; Endo, E H; Cortez, D A G; Nakamura, T U; Nakamura, C V; Dias Filho, B P

    2016-09-01

    Three chalcones, 2'-hydroxy-4,4',6'-trimethoxychalcone, 2'-hydroxy-4,4',6'-tetramethoxychalcone, and 3,2'-dihydroxy-4,4',6'-trimethoxychalcone, were isolated from the leaves of Piper hispidum in a bioguided fractionation of crude extract. The antimicrobial activity of crude extract of P. hispidum leaves was determined against bacteria Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and yeasts Candida albicans, C. parapsilosis and C. tropicalis. Fractions and chalcones were tested against C. albicans and S. aureus. The checkerboard assay was performed to assess synergic interactions between extract and antifungal drugs, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay was used to evaluate anti-biofilm effects of extract. The extract was active against yeasts, S. aureus and B. subtilis with MIC values between 15.6 and 62.5μg/mL. Synergistic effects of extract associated with fluconazole and nystatin were observed against C. albicans, with fractional inhibitory concentration indices of 0.37 and 0.24, respectively. The extract was also effective against C. albicans and S. aureus biofilm cells at concentrations of 62.5 and 200μg/mL, respectively. Thus, P. hispidum may be a possible source of bioactive substances with antimicrobial properties. PMID:27499460

  13. Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones.

    PubMed

    Konieczny, Marek T; Buɬakowska, Anita; Pirska, Danuta; Konieczny, Wojciech; Skladanowski, Andrzej; Sabisz, Michal; Wojciechowski, Marek; Lemke, Krzysztof

    2016-10-01

    Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1-(5-alkoxybenzo[d][1,3]oxathiol-6-yl)-3-phenylprop-2-en-1-ones and 1-(6-alkoxybenzo[d][1,3]oxathiol-5-yl)-3-phenylprop-2-en-1-ones are described. Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. It was found that oxidation of sulfur atom of the oxathiole-fused chalcones strongly influenced activity of the parent compounds, and that depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. For isomers with sulfur atom para to the chalcone carbonyl group, oxidation led to increase in activity, while for isomers with sulfur atom meta to the carbonyl the activity dropped down. It was demonstrated that the compounds interact with tubulin at the colchicine binding site, and the interaction was evaluated using molecular modeling. It was concluded that the observed profound influence of oxidation of the sulfur atom on cytotoxic activity cannot be solely related to interaction of the compounds with tubulin.

  14. Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis.

    PubMed

    Ngaki, Micheline N; Louie, Gordon V; Philippe, Ryan N; Manning, Gerard; Pojer, Florence; Bowman, Marianne E; Li, Ling; Larsen, Elise; Wurtele, Eve Syrkin; Noel, Joseph P

    2012-05-24

    Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence and development. CHI operates near the diffusion limit with stereospecific control. Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid biosynthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated α-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme from a non-enzymatic ancestor over a defined period of plant evolution.

  15. A Combined Experimental and Computational Investigation on Spectroscopic and Photophysical Properties of a Coumarinyl Chalcone.

    PubMed

    Al-Sehemi, Abdullah G; Pannipara, Mehboobali; Kalam, Abul; Asiri, Abdullah M

    2016-07-01

    Here, we synthesized a new coumarinyl chalcone derivative 3-[3-(3-Methyl-thiophen-2-yl)-acryloyl]-chromen-2-one (MTC) by simple and proficient method. A comprehensive study on the photophysics of a coumarinyl chalcone derivative having pi-conjugated potential chromophore system 3-[3-(3-Methyl-thiophen-2-yl)-acryloyl]-chromen-2-one (MTC) has been carried out spectroscopically. The electronic absorption and emission characteristic of MTC were studied in different protic and aprotic solvents using absorption and steady-state fluorescence techniques. The spectral behavior of this compound is found to be extremely sensitive to the polarity and hydrogen bonding nature of the solvent. The compound shows very strong solvent polarity dependent changes in their photophysical characteristics, namely, remarkable red shift in the emission spectra with increasing solvent polarity, change in Stokes shift, significant reduction in the fluorescence quantum yield; indicating that the fluorescence states of these compounds are of intramolecular charge transfer (ICT) character. The solvent effect on the photophysical parameters such as singlet absorption, molar absorptivity, oscillator strength, dipole moment, fluorescence spectra, and fluorescence quantum yield of the compound has been investigated in detail. The difference between the excited and ground state dipole moments (Δμ) were estimated from solvatochromic methods using Lippert-Mataga and Reichardt's correlations. The prepared compound was also studied by density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results revealed that it could be easily reproduce by computational means. PMID:27307021

  16. Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols.

    PubMed

    Muir, S R; Collins, G J; Robinson, S; Hughes, S; Bovy, A; Ric De Vos, C H; van Tunen, A J; Verhoeyen, M E

    2001-05-01

    Tomatoes are an excellent source of the carotenoid lycopene, a compound that is thought to be protective against prostate cancer. They also contain small amounts of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are very potent antioxidants, and an increasing body of epidemiological data suggests that high flavonoid intake is correlated with a decreased risk for cardiovascular disease. We have upregulated flavonol biosynthesis in the tomato in order to generate fruit with increased antioxidant capacity and a wider range of potential health benefit properties. This involved transformation of tomato with the Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an accumulation of rutin. No gross phenotypical differences were observed between high-flavonol transgenic and control lines. The phenotype segregated with the transgene and demonstrated a stable inheritance pattern over four subsequent generations tested thus far. Whole-fruit flavonol levels in the best of these lines are similar to those found in onions, a crop with naturally high levels of flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of flavonols present in the fresh fruit were retained in the processed paste, supporting their potential as raw materials for tomato-based functional food products. PMID:11329019

  17. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides.

    PubMed

    Nguyen, G T T; Erlenkamp, G; Jäck, O; Küberl, A; Bott, M; Fiorani, F; Gohlke, H; Groth, G

    2016-01-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2',3',4',3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2',3',4'-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

  18. Role of a chalcone isomerase-like protein in flavonoid biosynthesis in Arabidopsis thaliana

    PubMed Central

    Jiang, Wenbo; Yin, Qinggang; Wu, Ranran; Zheng, Guangshun; Liu, Jinyue; Dixon, Richard A.; Pang, Yongzhen

    2015-01-01

    Flavonoids are important natural products for plant defence and human health. Although almost all the flavonoid pathway genes have been well-documented by biochemical and/or genetic approaches, the role of the Arabidopsis chalcone isomerase-like (CHIL) gene remains unclear. Two chil mutants with a seed colour similar to that of wild-type Arabidopsis have been identified here, but in sharp contrast to the characteristic transparent testa seed phenotype associated with other known flavonoid pathway genes. CHIL loss-of-function mutations led to a strong reduction in the proanthocyanidin and flavonol levels in seeds, but not in the anthocyanin levels in leaves. CHIL over-expression could partially recover the mutant phenotype of the chil mutant and increased both proanthocyanidin and flavonol accumulation in wild-type Arabidopsis. However, the CHIL gene could not rescue the mutant phenotype of TT5 that encodes the intrinsic chalcone isomerase in Arabidopsis. Parallel phenotypical and metabolic analyses of the chil, tt5, chs, and f3h mutants revealed that, genetically, CHIL functions at the same step as TT5. Moreover, it is demonstrated that CHIL co-expresses, co-localizes, and interacts with TT5 in Arabidopsis for flavonoid production. Based on these genetic and metabolic studies, it is concluded that CHIL functions with TT5 to promote flavonoid production, which is a unique enhancer in the flavonoid pathway. PMID:26347569

  19. Prenylated chalcones and flavonoids for the prevention and treatment of cancer.

    PubMed

    Venturelli, Sascha; Burkard, Markus; Biendl, Martin; Lauer, Ulrich M; Frank, Jan; Busch, Christian

    2016-01-01

    Prenylated chalcones and flavonoids gained increasing attention not only in nutrition but also in cancer prevention because of their biological and molecular activities in humans, which have been extensively investigated in vitro or in preclinical studies. These naturally occurring compounds exhibit antioxidant effects, modulate metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes, and display antiinflammatory properties. In particular, their potential to prevent proliferation of tumor cells is noteworthy. Some representatives of this subclass of secondary plant compounds exert pronounced anti-tumor-initiating capacities and directly inhibit growth of cancer cells, whereas their toxic effects on healthy tissues are remarkably low. These promising pharmacologic characteristics are countered by low ingestion, low bioavailability, and little knowledge of their metabolism. This review focuses on the great potential of these plant- and nutrient-derived compounds for cancer prevention and therapy. Provided here is a comprehensive summary of the current knowledge and inherent modes of action, focusing on the prenylated chalcones xanthohumol, desmethylxanthohumol, and xanthogalenol, as well as the prenylated flavonoids isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin, 6-geranylnaringenin, 8-geranylnaringenin, and pomiferin. PMID:27238957

  20. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    PubMed Central

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-01-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2′,3′,4′,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2′,3′,4′-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme. PMID:27263468

  1. Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols.

    PubMed

    Muir, S R; Collins, G J; Robinson, S; Hughes, S; Bovy, A; Ric De Vos, C H; van Tunen, A J; Verhoeyen, M E

    2001-05-01

    Tomatoes are an excellent source of the carotenoid lycopene, a compound that is thought to be protective against prostate cancer. They also contain small amounts of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are very potent antioxidants, and an increasing body of epidemiological data suggests that high flavonoid intake is correlated with a decreased risk for cardiovascular disease. We have upregulated flavonol biosynthesis in the tomato in order to generate fruit with increased antioxidant capacity and a wider range of potential health benefit properties. This involved transformation of tomato with the Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an accumulation of rutin. No gross phenotypical differences were observed between high-flavonol transgenic and control lines. The phenotype segregated with the transgene and demonstrated a stable inheritance pattern over four subsequent generations tested thus far. Whole-fruit flavonol levels in the best of these lines are similar to those found in onions, a crop with naturally high levels of flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of flavonols present in the fresh fruit were retained in the processed paste, supporting their potential as raw materials for tomato-based functional food products.

  2. Enzymatic Properties and Mutational Studies of Chalcone Synthase from Physcomitrella patens

    PubMed Central

    Rahman, Raja Noor Zaliha Raja Abdul; Zakaria, Iffah Izzati; Salleh, Abu Bakar; Basri, Mahiran

    2012-01-01

    PpCHS is a member of the type III polyketide synthase family and catalyses the synthesis of the flavonoid precursor naringenin chalcone from p-coumaroyl-CoA. Recent research reports the production of pyrone derivatives using either hexanoyl-CoA or butyryl-CoA as starter molecule. The Cys-His-Asn catalytic triad found in other plant chalcone synthase predicted polypeptides is conserved in PpCHS. Site directed mutagenesis involving these amino acids residing in the active-site cavity revealed that the cavity volume of the active-site plays a significant role in the selection of starter molecules as well as product formation. Substitutions of Cys 170 with Arg and Ser amino acids decreased the ability of the PpCHS to utilize hexanoyl-CoA as a starter molecule, which directly effected the production of pyrone derivatives (products). These substitutions are believed to have a restricted number of elongations of the growing polypeptide chain due to the smaller cavity volume of the mutant’s active site. PMID:22949824

  3. Role of direction of charge transfer on the nonlinear optical behavior of pyridine substituted chalcone derivatives

    NASA Astrophysics Data System (ADS)

    Menezes, Anthoni Praveen; Jayarama, A.

    2014-10-01

    High quality single crystals of an efficient novel nonlinear optical (NLO) chalcone derivative 3-(4-nitrophenyl)-1-(pyridine-3-yl) prop-2-en-1-one (4NP3AP) that are transparent in the entire visible and infrared region are grown by the slow evaporation solution growth method at ambient temperature. The single crystal XRD studies reveal that the crystal belongs to monoclinic system with the noncentrosymmetric space group P21. The presence of functional groups in the compound is confirmed by different spectroscopic techniques. The surface morphology of the crystal is studied by scanning electron microscopy. The second harmonic generation (SHG) efficiency of 4NP3AP determined by Perry and Kurtz method is 56% that of potassium dihydrogen phosphate (KDP) single crystals. The static and frequency dependent molecular hyperpolarizabilities were computed using MOPAC 2012. Thermal analysis confirms that the crystal is thermally stable up to 177 °C. The origin of nonlinearity and the role of charge transfer direction on the nonlinearity of the chalcone have been discussed in detail.

  4. Nonlinear optical studies on 1,3-disubstituent chalcones doped polymer films

    NASA Astrophysics Data System (ADS)

    Poornesh, P.; Shettigar, Seetharam; Umesh, G.; Manjunatha, K. B.; Prakash Kamath, K.; Sarojini, B. K.; Narayana, B.

    2009-04-01

    We report the measurements of the third-order nonlinear optical properties of recently synthesized and characterized two different 1,3-disubstituent chalcones doped PMMA films, with the prospective of reaching a good compromise between processability and high nonlinear optical properties. The measurements were done using nanosecond Z-scan at 532 nm. The Z-scan spectra reveal a large negative nonlinear refraction coefficient n2 of the order 10 -11 esu and the molecular two photon absorption cross section is 10 -46 cm 4 s/photon. The doped films exhibit good optical power limiting property under nanosecond regime and the two photon absorption (TPA) is the dominating process leading to the nonlinear behavior. The improvement in the nonlinear properties has been observed when methylenedioxy group is replaced by dimethoxy group due to increase in conjugation length. The observed nonlinear parameters of chalcone derivatives doped PMMA film is comparable with stilbazolieum derivatives, a well-known class of optical materials for photonics and biophotonics applications, which suggests that, these moieties have potential for the application of all-optical limiting and switching devices.

  5. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    NASA Astrophysics Data System (ADS)

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-06-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2‧,3‧,4‧,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2‧,3‧,4‧-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

  6. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides.

    PubMed

    Nguyen, G T T; Erlenkamp, G; Jäck, O; Küberl, A; Bott, M; Fiorani, F; Gohlke, H; Groth, G

    2016-01-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2',3',4',3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2',3',4'-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme. PMID:27263468

  7. Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones.

    PubMed

    Konieczny, Marek T; Buɬakowska, Anita; Pirska, Danuta; Konieczny, Wojciech; Skladanowski, Andrzej; Sabisz, Michal; Wojciechowski, Marek; Lemke, Krzysztof

    2016-10-01

    Synthesis, in vitro cytotoxic activity, and interaction with tubulin of oxidized, isomeric 1-(5-alkoxybenzo[d][1,3]oxathiol-6-yl)-3-phenylprop-2-en-1-ones and 1-(6-alkoxybenzo[d][1,3]oxathiol-5-yl)-3-phenylprop-2-en-1-ones are described. Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. It was found that oxidation of sulfur atom of the oxathiole-fused chalcones strongly influenced activity of the parent compounds, and that depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. For isomers with sulfur atom para to the chalcone carbonyl group, oxidation led to increase in activity, while for isomers with sulfur atom meta to the carbonyl the activity dropped down. It was demonstrated that the compounds interact with tubulin at the colchicine binding site, and the interaction was evaluated using molecular modeling. It was concluded that the observed profound influence of oxidation of the sulfur atom on cytotoxic activity cannot be solely related to interaction of the compounds with tubulin. PMID:27198732

  8. Chalcone synthesis and hydroxylation of flavonoids in 3'-position with enzyme preparations from flowers of Dianthus caryophyllus L. (carnation).

    PubMed

    Spribille, R; Forkmann, G

    1982-07-01

    Chalcone synthase activity was demonstrated in enzyme preparations from flowers of defined genotypes of Dianthus caryophyllus L. (carnation). In the absence of chalcone isomerase activity, which could be completely excluded by genetic methods, the first product formed from malonyl-CoA and 4-coumaroyl-CoA proved to be naringenin chalcone, followed by formation of naringenin as a result of chemical cyclization. In the presence of chalcone isomerase activity, however, naringenin was the only product of the synthase reaction. In vitro, both 4-coumaryl-CoA and caffeoyl-CoA were found to be used as substrates for the condensation reaction with respective pH optima of 8.0 and 7.0. The results of chemogenetic and enzymatic studies, however, showed that in vivo only 4-coumaroyl-CoA serves as substrate for the formation of the flavonoid skeleton. In confirmation of these results, an NADPH-dependent microsomal 3'-hydroxylase activity could be demonstrated, catalyzing hydroxylation of naringenin and dihydrokaempferol in 3'-position. Furthermore, a strict correlation was found between 3'-hydroxylase activity and the gene r which is known to control the formation of 3', 4'-hydroxylated flavonoid compounds.

  9. Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents.

    PubMed

    Bacharaju, Keerthana; Jambula, Swathi Reddy; Sivan, Sreekanth; Jyostnatangeda, Saritha; Manga, Vijjulatha

    2012-05-01

    A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have been designed synthesised and evaluated for their antimitotic activity. Compounds 4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 μM and 1.52 μM respectively.

  10. Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents.

    PubMed

    Bacharaju, Keerthana; Jambula, Swathi Reddy; Sivan, Sreekanth; Jyostnatangeda, Saritha; Manga, Vijjulatha

    2012-05-01

    A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have been designed synthesised and evaluated for their antimitotic activity. Compounds 4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 μM and 1.52 μM respectively. PMID:22460028

  11. Allelic variants from Dahlia variabilis encode flavonoid 3'-hydroxylases with functional differences in chalcone 3-hydroxylase activity.

    PubMed

    Schlangen, Karin; Miosic, Silvija; Halbwirth, Heidi

    2010-02-01

    In the petals of Dahlia variabilis, hydroxylation of chalcones at position 3 can be detected, except the well-known flavonoid 3'-hydroxylation. Although the reaction is well characterized at the enzymatic level, it remained unclear whether it is catalyzed by a flavonoid 3'-hydroxylase (F3'H, EC1.14.13.21, CYP75B) with broad substrate specificity. Two novel allelic variants of F3'H were cloned from D. variabilis, which differ only in three amino acids within their 508 residues. The corresponding recombinant enzymes show significant differences in their chalcone 3-hydroxylase (CH3H) activity. A substitution of alanine at position 425 with valine enables CH3H activity, whereas the reciprocal substitution leads to a loss of CH3H activity. Interaction of the valine at position 425 with not yet identified structural properties seems to be decisive for chalcone acceptance. This is the first identification of an F3'H which is able to catalyze chalcone 3-hydroxylation to a physiologically relevant extent from any plant species. PMID:19931222

  12. Chalcones from Angelica keiskei attenuate the inflammatory responses by suppressing nuclear translocation of NF-κB.

    PubMed

    Chang, Hee Ryun; Lee, Hwa Jin; Ryu, Jae-Ha

    2014-12-01

    The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones (1-7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine (1), xanthoangelol E (2), xanthokeismin A (4), and xanthoangelol B (5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory-κBα (I-κBα) and the translocation of nuclear factor κB (NF-κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones (1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I-κBα and nuclear translocation of NF-κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents.

  13. Inhibitory Effect of 3-(4-Hydroxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one, a Chalcone Derivative on MCP-1 Expression in Macrophages via Inhibition of ROS and Akt Signaling

    PubMed Central

    Kim, Mi Jin; Kadayat, Taraman; Um, Yeon Ji; Jeong, Tae Cheon; Lee, Eung-Seok; Park, Pil-Hoon

    2015-01-01

    Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TII-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-κB (NF-κB) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation. PMID:25767679

  14. Molecular structures of chalcone podands: A prognosis of photoinduced transformations in the crystals

    NASA Astrophysics Data System (ADS)

    Ovchinnikova, I. G.; Fedorova, O. V.; Slepukhin, P. A.; Litvinov, I. A.; Rusinov, G. L.

    2009-01-01

    A series of chalcone podands with the propenone group in the ortho position of the bridging aryl substituent with respect to the oxyethylene fragment is synthesized. The influence of the preorganization of the chalcone podand molecules in crystals on their ability to participate in topochemical reactions is investigated. From analyzing the X-ray structural data, the highest probability of the solid-state photochemical [2 + 2]cycloaddition is predicted for podands with phenyl substituents and the oxyethylene fragment containing two or three oxygen atoms. The X-ray structural data for the chalcone podand C32H26O4 ( 3a) are as follows: a = 7.904(9) Å, b = 14.92(2) Å, c = 21.30(3) Å, β = 91.7(1)°, monoclinic system, space group P21/ c, Z = 4, V = 2510(5) Å3, ρ = 1.26 g/cm3, and R = 0.046; C34H30O5 ( 3b): a = 15.738(9) Å, b = 11.889(2) Å, c = 15.0830(15) Å, β = 105.47(14)°, monoclinic system, space group C2/ c, Z = 4, V = 2720.0(9) Å3, ρ = 1.266 g/cm3, and R = 0.0418; C32H24N2O8 ( 4a): a = 17.9416(18) Å, b = 10.9703(8) Å, c = 41.699(2) Å, β = 105.970(11)°, monoclinic system, space group P21/ c, Z = 4, V = 2781.4(5) Å3, ρ = 1.348 g/cm3, and R = 0.0426; C36H32N2O10 ( 4c): a = 7.6286(5)Å, b = 17.9398(10) Å, c = 11.5890(3)Å, β = 95.287(4)°, monoclinic system, space group P21/ n, Z = 2, V = 1579.27(14) Å3, ρ = 1.372 g/cm3, and R = 0.0377; and C28H22O6 ( 5a): a = 15.6032(10) Å, b = 8.1131(5) Å, c = 17.7334(11) Å, β = 91.381(5)°, monoclinic system, space group C2/ c, Z = 4, V = 2244.2(2) Å3, ρ = 1.345 g/cm3, and R = 0.0309.

  15. Evolvable synthetic neural system

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  16. Synthetic cathinone abuse

    PubMed Central

    Capriola, Michael

    2013-01-01

    The abuse of synthetic cathinones, widely known as bath salts, has been increasing since the mid-2000s. These substances are derivatives of the naturally occurring compound cathinone, which is the primary psychoactive component of khat. The toxicity of synthetic cathinones includes significant sympathomimetic effects, as well as psychosis, agitation, aggression, and sometimes violent and bizarre behavior. Mephedrone and methylenedioxypyrovalerone are currently the predominantly abused synthetic cathinones. PMID:23869180

  17. [SYNTHETIC PEPTIDE VACCINES].

    PubMed

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested. PMID:27145593

  18. Chalcone synthase gene lineage diversification confirms allopolyploid evolutionary relationships of European rostrate violets.

    PubMed

    van den Hof, Kevin; van den Berg, Ronald G; Gravendeel, Barbara

    2008-10-01

    Phylogenetic relationships among and within the subsections of the genus Viola are still far from resolved. We present the first organismal phylogeny of predominantly western European species of subsection Rostratae based on the plastid trnS-trnG intron and intergenic spacer and the nuclear low-copy gene chalcone synthase (CHS) sequences. CHS is a key enzyme in the synthesis of flavonoids, which are important for flower pigmentation. Genes encoding for CHS are members of a multigene family. In Viola, 3 different CHS copies are present. CHS gene lineages obtained confirmed earlier hypotheses about reticulate relationships between species of Viola subsection Rostratae based on karyotype data. Comparison of the CHS gene lineage tree and the plastid species phylogeny of Viola reconstructed in this study indicates that the different CHS copies present in Viola are the products of both recent and more ancient duplications.

  19. Elucidation of the methyl transfer mechanism catalyzed by chalcone O-methyltransferase: a density functional study.

    PubMed

    Cui, Feng-Chao; Pan, Xiao-Liang; Liu, Wei; Liu, Jing-Yao

    2011-11-15

    The mechanism of the methyl transfer catalyzed by chalcone O-methyltransferase has been computationally investigated by employing the hybrid functional B3LYP. Two models are constructed based on the two conformations of the substrate isoliquiritigenin in the X-ray structure. Our calculations show that the overall reaction is divided into two elementary steps: the water-assisted deprotonation of the substrate by His278 as a catalytic base, followed by the methyl transfer from S-adenosyl-L-methionine (SAM) to the substrate. The calculated rate-limiting barriers for the methyl-transfer step indicate that the catalytic reactions are energetically feasible for both conformations adopted by the substrate. PMID:21815175

  20. Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl chalcones

    NASA Astrophysics Data System (ADS)

    Prasath, R.; Bhavana, P.; Sarveswari, S.; Ng, Seik Weng; Tiekink, Edward R. T.

    2015-02-01

    Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method. The compounds were characterized using IR, 1H NMR and ESI-MS spectroscopic methods and, for representative compounds, by X-ray crystallography. An E-configuration about the Cdbnd C ethylene bond has been established via 1H NMR spectroscopy and X-ray crystallography. These compounds show promising anti-microbial properties, with 4a and 3e being the most potent against bacterial and fungal strains, respectively and the methoxy substituted compounds showed moderate anti-oxidant activity.

  1. Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.

    PubMed

    Li, Haoxin; Jean, Stéphanie; Webster, Duncan; Robichaud, Gilles A; Calhoun, Larry A; Johnson, John A; Gray, Christopher A

    2015-11-25

    Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 μM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 μM, respectively).

  2. Outer-sphere residues influence the catalytic activity of a chalcone synthase from Polygonum cuspidatum.

    PubMed

    Shen, Yalin; Li, Xing; Chai, Tuanyao; Wang, Hong

    2016-06-01

    We have previously cloned a chalcone synthase (PcCHS1) from Polygonum cuspidatum and biochemically identified its enzymatic dynamic properties. Here, we found that the outer sphere residues, Q82 and R105, could affect the catalytic activity and product profile of PcCHS1. Both Q82P and R105Q mutations of PcCHS1 could also change the pH dependence activity as well as the product profile of PcCHS1. Moreover, the Q82P/C198F double mutant could rescue the complete loss of enzyme activity caused by the C198F single mutation. Our study demonstrated that these outer-sphere residues of PcCHS1 play important roles both in structural maintenance and enzyme activity. PMID:27419064

  3. Enantioselective Friedel-Crafts alkylation of pyrrole with chalcones catalyzed by a dinuclear zinc catalyst.

    PubMed

    Hua, Yuan-Zhao; Han, Xing-Wang; Yang, Xiao-Chao; Song, Xixi; Wang, Min-Can; Chang, Jun-Biao

    2014-12-01

    A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of β-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions. The absolute stereochemistry of the products was determined to be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a weak negative nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible mechanism was proposed to explain the origin of the asymmetric induction. PMID:25392948

  4. Superior characteristics of organic chalcone single crystals as efficient nonlinear optical material

    NASA Astrophysics Data System (ADS)

    Kiran, A. John; Kim, H. C.; Kim, K.; Rotermund, F.; Ravindra, H. J.; Dharmaprakash, S. M.; Lim, H.

    2008-03-01

    High-quality biaxial single crystals of chalcone derivatives were grown by solution growth technique. Their molecular structures were designed to possess large second-order nonlinearities by choosing proper donor/acceptor groups while retaining a high transparency in the visible and infrared spectral regions. The second-order nonlinear optical coefficients, determined by applying the Maker fringe technique, were found to be much larger than those of LiB3O5, KTiOPO4, KH2PO4, and urea. The advantages, such as easy synthesis and crystal growth, low cutoff wavelength (<450nm ), large optical nonlinearity, and high damage threshold (>7.2GW/cm2), make these organic crystals promising for efficient frequency doubling.

  5. Third order nonlinear optical effects in a new chalcone derivative embedded in a polymer host

    NASA Astrophysics Data System (ADS)

    Shetty, T. Chandra Shekhara; Raghavendra, S.; Dharmaprakaskh, S. M.

    2015-06-01

    A new organic nonlinear optical (NLO) material from the chalcone family: (2E)-1-(3,4-dichlorophenyl)-3-[4-(methylsulfanyl)phenyl]prop-2-en-1-one (DPMS) is crystallised in DMF solution. The functional groups in DPMS are identified by FTIR spectra. The thermal stability is studied using TGA/DTA. The polymethylmethacrylate (PMMA) film doped with DPMS was prepared. Direct and indirect band gap energy of DPMS doped PMMA is determined using U. V. Visible spectra. The nonlinear absorption coefficient and optical power limiting of the film was studied using Z-scan technique. The film exhibits a self focussing effect at a wavelength of 532nm. The results of optical limiting studies, shows that the film possesses reverse saturable absorption due to excited state absorption. The nonlinear optical properties of DPMS have been retained in the presence of a polymer material.

  6. Substituent Dependence of Third-Order Optical Nonlinearity in Chalcone Derivatives

    NASA Astrophysics Data System (ADS)

    Kiran, Anthony John; Satheesh Rai, Nooji; Chandrasekharan, Keloth; Kalluraya, Balakrishna; Rotermund, Fabian

    2008-08-01

    The third-order nonlinear optical properties of derivatives of dibenzylideneacetone were investigated using the single beam z-scan technique at 532 nm. A strong dependence of third-order optical nonlinearity on electron donor and acceptor type of substituents was observed. An enhancement in χ(3)-value of one order of magnitude was achieved upon the substitution of strong electron donors compared to that of the molecule substituted with an electron acceptor. The magnitude of nonlinear refractive index of these chalcones is as high as of 10-11 esu. Their nonlinear optical coefficients are larger than those of widely used thiophene oligomers and trans-1-[p-(p-dimethylaminobenzyl-azo)-benzyl]-2-(N-methyl-4-pyridinium)-ethene iodide (DABA-PEI) organic compounds.

  7. Separation of two major chalcones from Angelica keiskei by high-speed counter-current chromatography.

    PubMed

    Kil, Yun-Seo; Nam, Joo-Won; Lee, Jun; Seo, Eun Kyoung

    2015-08-01

    Angelica keiskei (Shin-sun cho) is an edible higher plant with the beneficial preventive effects on cancer, hypertension, and coronary heart disease. Two bioactive chalcones of Shin-sun cho, xanthoangelol (1) and 4-hydroxyderricin (2), were separated simultaneously by using high-speed counter-current chromatography with a two-phase solvent system composed of n-hexane-EtOAc-MeOH-H2O (9:5:9:4). Only nonconsuming processes, solvent fractionations and Sephadex LH-20 column chromatography, were conducted as presteps. Xanthoangelol (1, 35.9 mg, 99.9 % purity at 254 and 365 nm) and 4-hydroxyderricin (2, 4.4 mg, 98.7 % purity at 254 nm and 98.8 % purity at 365 nm) were successfully purified from 70 mg of the processed extract from A. keiskei. The structures of two compounds were confirmed by (1)H- and (13)C-NMR analysis.

  8. Design, synthesis and antiproliferative activity studies of novel dithiocarbamate-chalcone derivates.

    PubMed

    Fu, Dong-Jun; Zhang, Sai-Yang; Liu, Ying-Chao; Zhang, Li; Liu, Jun-Ju; Song, Jian; Zhao, Ruo-Han; Li, Feng; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-08-15

    A series of novel dithiocarbamate-chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC50 values of 2.03μM and 2.46μM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase. PMID:27423479

  9. Synthesis and Biological Evaluation of 1,2,3-triazole tethered Pyrazoline and Chalcone Derivatives.

    PubMed

    Hussaini, Syed Mohammed Ali; Yedla, Poornachandra; Babu, Korrapati Suresh; Shaik, Thokhir B; Chityal, Ganesh Kumar; Kamal, Ahmed

    2016-07-01

    A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin-A4(CA-4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 μm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 μm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis. PMID:26854643

  10. Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

    PubMed

    Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

    2016-07-01

    A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound. PMID:27217001

  11. Solid state structural and theoretical investigations of a biologically active chalcone

    NASA Astrophysics Data System (ADS)

    Abbas, Asghar; Gökce, Halil; Bahceli, Semiha; Bolte, Michael; Naseer, Muhammad Moazzam

    2016-05-01

    The computational methods are presently emerging as an efficient and reliable tool for predicting structural properties of biologically important compounds. In the present manuscript, the solid state structural and theoretical investigations of a biologically active chalcone i-e (E)-3-(4-(hexyloxy)phenyl)-1-phenylprop-2-en-1-one (6c) have been reported. The solid state structure of 6c was measured by X-ray crystallographic technique whereas the optimized molecular geometry, vibrational frequencies, the simulated UV-vis spectra (in gas and in methanol solvent), 1H and 13C NMR chemical shift (in gas and in chloroform solvent) values, HOMO-LUMO analysis, the molecular electrostatic potential (MEP) surface and thermodynamic parameters were calculated by using DFT/B3LYP method with 6-311++G(d,p) basis set in ground state. The results of the theoretical investigations were found to be in good agreement with experimental data.

  12. Structure and catalytic mechanism of the evolutionarily unique bacterial chalcone isomerase.

    PubMed

    Thomsen, Maren; Tuukkanen, Anne; Dickerhoff, Jonathan; Palm, Gottfried J; Kratzat, Hanna; Svergun, Dmitri I; Weisz, Klaus; Bornscheuer, Uwe T; Hinrichs, Winfried

    2015-04-01

    Flavonoids represent a large class of secondary metabolites produced by plants. These polyphenolic compounds are well known for their antioxidative abilities, are antimicrobial phytoalexins responsible for flower pigmentation to attract pollinators and, in addition to other properties, are also specific bacterial regulators governing the expression of Rhizobium genes involved in root nodulation (Firmin et al., 1986). The bacterial chalcone isomerase (CHI) from Eubacterium ramulus catalyses the first step in a flavanone-degradation pathway by ring opening of (2S)-naringenin to form naringenin chalcone. The structural biology and enzymology of plant CHIs have been well documented, whereas the existence of bacterial CHIs has only recently been elucidated. This first determination of the structure of a bacterial CHI provides detailed structural insights into the key step of the flavonoid-degradation pathway. The active site could be confirmed by co-crystallization with the substrate (2S)-naringenin. The stereochemistry of the proposed mechanism of the isomerase reaction was verified by specific (1)H/(2)H isotope exchange observed by (1)H NMR experiments and was further supported by mutagenesis studies. The active site is shielded by a flexible lid, the varying structure of which could be modelled in different states of the catalytic cycle using small-angle X-ray scattering data together with the crystallographic structures. Comparison of bacterial CHI with the plant enzyme from Medicago sativa reveals that they have unrelated folds, suggesting that the enzyme activity evolved convergently from different ancestor proteins. Despite the lack of any functional relationship, the tertiary structure of the bacterial CHI shows similarities to the ferredoxin-like fold of a chlorite dismutase and the stress-related protein SP1.

  13. Variable Synthetic Capacitance

    NASA Technical Reports Server (NTRS)

    Kleinberg, L. L.

    1986-01-01

    Feedback amplifier circuit synthesizes electronically variable capacitance. Variable Synthetic Capacitor is amplifier circuit with follower/feedback configuration. Effective input capacitance depends on input set current. If synthetic capacitor is connected across resonant element of oscillator, oscillator frequency controlled via input set current. Circuit especially suitable for fine frequency adjustments of piezoelectric-crystal or inductor/capacitor resonant oscillators.

  14. Antibacterial activity of two chalcones, xanthoangelol and 4-hydroxyderricin, isolated from the root of Angelica keiskei KOIDZUMI.

    PubMed

    Inamori, Y; Baba, K; Tsujibo, H; Taniguchi, M; Nakata, K; Kozawa, M

    1991-06-01

    Two chalcones, xanthoangelol (I) and 4-hydroxyderricin (II), isolated from the root of Angelica keiskei KOIDZUMI (Umbelliferae) showed antibacterial activity against gram-positive pathogenic bacteria. The activity of I on Micrococcus luteus IFO-12708 (minimum inhibitory concentration (MIC), 0.76 microgram/ml) was the same potency as that of gentamicin, which is used as a standard. Although the activity of both chalcones on plant-pathogenic bacteria was lower than that of streptomycin sulfate, used as a positive control, they also exhibited growth-inhibitory effects. The antibacterial activity of I isolated from Angelica keiskei KOIDZUMI is being reported here for the first time. The growth-inhibitory effect of II on plant-pathogenic bacteria is also reported for the first time in this paper.

  15. Theoretical study on the structural and antioxidant properties of some recently synthesised 2,4,5-trimethoxy chalcones.

    PubMed

    Wang, Guirong; Xue, Yunsheng; An, Lin; Zheng, Youguang; Dou, Yunyan; Zhang, Ling; Liu, Yi

    2015-03-15

    The free radical scavenging activity of a series of 2,4,5-trimethoxy chalcones has been computationally explored using the density functional theory (DFT) method. Three potential working mechanisms, hydrogen atom transfer (HAT), stepwise electron transfer proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) have been investigated. The physiochemical parameters including O-H bond dissociation enthalpy (BDE), ionisation potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA) and electron transfer enthalpy (ETE) have been calculated in gas phase and solvents. The order of antioxidant efficiencies predicted theoretically in this work is in good agreement with that reported by experimental results. The results obtained demonstrate that HAT would be the most favourable mechanism in the gas and benzene phases, whereas the SPLET mechanism is the thermodynamically preferred pathway in polar media. In addition, the importance of the A-ring on the radical scavenging capabilities of chalcones was also confirmed.

  16. Theoretical and Experimental Study of Inclusion Complexes of β-Cyclodextrins with Chalcone and 2',4'-Dihydroxychalcone.

    PubMed

    Sancho, Matias I; Andujar, Sebastian; Porasso, Rodolfo D; Enriz, Ricardo D

    2016-03-31

    The inclusion complexes formed by chalcone and 2',4'-dihydroxychalcone with β-cyclodextrin have been studied combining experimental (phase solubility diagrams, Fourier transform infrared spectroscopy) and molecular modeling (molecular dynamics, quantum mechanics/molecular mechanics calculations) techniques. The formation constants of the complexes were determined at different temperatures, and the thermodynamic parameters of the process were obtained. The inclusion of chalcone in β-cyclodextrin is an exothermic process, while the inclusion of 2',4'-dihydroxychalcone is endothermic. Free energy profiles, derived from umbrella sampling using molecular dynamics simulations, were constructed to analyze the binding affinity and the complexation reaction at a molecular level. Hybrid QM/MM calculations were also employed to obtain a better description of the energetic and structural aspects of the complexes. The intermolecular interactions that stabilize both inclusion complexes were characterized by means of quantum atoms in molecules theory and reduce density gradient method. The calculated interactions were experimentally observed using FTIR. PMID:26950264

  17. Protein preparation, crystallization and preliminary X-ray analysis of Polygonum cuspidatum bifunctional chalcone synthase/benzalacetone synthase.

    PubMed

    Lu, Heshu; Yang, Mingfeng; Liu, Chunmei; Lu, Ping; Cang, Huaixing; Ma, Lanqing

    2013-08-01

    The chalcone synthase (CHS) superfamily of type III polyketide synthases (PKSs) generate the backbones of a variety of plant secondary metabolites. An active bifunctional chalcone synthase/benzalacetone synthase (CHS/BAS) from Polygonum cuspidatum was overexpressed in Escherichia coli as a C-terminally polyhistidine-tagged fusion protein, purified to homogeneity and crystallized using polyethylene glycol 4000 as a precipitant. The production of well shaped crystals of the complex between PcPKS1 and benzalacetone was dependent on the presence of sorbitol and barium chloride as additives. The crystals belonged to the orthorhombic space group P2₁2₁2₁, with unit-cell parameters a = 80.23, b = 81.01, c = 122.89 Å, and diffracted X-rays to at least 2.0 Å resolution. PMID:23908031

  18. Synthesis, crystal structure and spectral characteristics of highly fluorescent chalcone-based coumarin in solution and in polymer matrix

    NASA Astrophysics Data System (ADS)

    Ghouili, Afef; Dusek, Michal; Petricek, Vaclav; Ayed, Taïcir Ben; Hassen, Rached Ben

    2014-02-01

    A new coumarin chalcone 3-((2E)-3-(2-hydroxyphenyl) prop-2-enoyl)-4-hydroxy-2(H)-chromen-2-one was synthesized using the Claisen Schmidt reaction by the condensation of 3-acetyl-4-hydroxycoumarin and 2-hydroxybenzaldehyde using a mild organic base. This novel compound was characterized by 1H NMR, FT-IR and UV-vis spectroscopy. Single crystal X-ray diffraction investigation at low temperature (T=120 K) shows that this compound exhibits an intramolecular O3-H…O hydrogen bond, the coumarin ring and the phenyl group are nearly coplanar and the crystal packing is stabilized by intermolecular O3-H…O contacts and π-π stacking interactions. This ortho-hydroxyphenyl-4-hydroxycoumarin chalcone exhibits a strong blue-green emission under visible light excitation at 470 nm. The fluorescence behaviors of this compound doped in poly(methyl methacrylate) (PMMA) were investigated.

  19. New eco-friendly animal bone meal catalysts for preparation of chalcones and aza-Michael adducts

    PubMed Central

    2012-01-01

    Abstract Two efficient reactions were successfully carried out using Animal Bone Meal (ABM) and potassium fluoride or sodium nitrate doped ABMs as new heterogeneous catalysts under very mild conditions. After preparation and characterization of the catalysts, we first report their use in a simple and convenient synthesis of various chalcones by Claisen–Schmidt condensation and then in an aza-Michael addition involving several synthesized chalcones with aromatic amines. All the reactions were carried out at room temperature in methanol; the chalcone synthesis was also achieved in water environment under microwave irradiation. Doping ABM enhances the rate and yield at each reaction. Catalytic activities are discussed and the ability to re-use the ABM is demonstrated. Results For Claisen–Schmidt the use of ABM alone, yields never exceeded 17%. In each entry, KF/ABM and NaNO3/ABM (79-97%) gave higher yields than using ABM alone under thermic condition. Also the reaction proceeded under microwave irradiation in good yields (72-94% for KF/ABM and 81-97% for NaNO3/ABM) and high purity. For aza-Michael addition the use of ABM doped with KF or NaNO3 increased the catalytic activity remarkably. The very high yields could be noted (84-95% for KF/ABM and 81-94% for NaNO3/ABM). Conclusion The present method is an efficient and selective procedure for the synthesis of chalcones an aza-Michael adducts. The ABM and doped ABMs are a new, inexpensive and attractive solid supports which can contribute to the development of catalytic processes and reduced environmental problems. PMID:22721409

  20. Theoretical investigation on mechanism of asymmetric Michael addition of malononitrile to chalcones catalyzed by Cinchona alkaloid aluminium(III) complex.

    PubMed

    Su, Zhishan; Lee, Hai Whang; Kim, Chan Kyung

    2011-09-21

    The mechanism of Michael addition of malononitrile to chalcones catalyzed by Cinchona alkaloid aluminium(III) complex has been investigated by DFT and ONIOM methods. Calculations indicate that the reaction proceeds through a dual activation mechanism, in which Al(III) acts as a Lewis acid to activate the electrophile α,β-unsaturated carbonyl substrate while the tertiary amine in the Cinchona alkaloid works as a Lewis base to promote the activation of the malononitrile and deprotonation. A stepwise pathway involving C-C bond formation followed by proton transfer from the catalyst to the carbonyl substrate is adopted, and latter step is predicted to be the rate-determining-step in the reaction with an energy barrier of 12.4 kcal mol(-1). In the absence of the Al(III)-complex, a Cinchona alkaloid activates the carbonyl substrate by a hydrogen bonding of the hydroxyl group, involving a higher energy barrier of 30.4 kcal mol(-1). The steric repulsion between the phenyl group attached to the carbonyl group in the chalcone and isopropoxyl groups of the Al(III)-complex may play an important role in the control of stereoselectivity. The π-π stacking effect between the quinuclidine ring of the quinine and the phenyl group of the chalcones may also help the stabilization of the preferred molecular complex. These results are in agreement with experimental observations. PMID:21796318

  1. Studies of manufacturing controlled-release graphene acid and catalyzing synthesis of chalcone with Claisen-Schmidt condensation reaction

    NASA Astrophysics Data System (ADS)

    Li, Jihui; Feng, Jia; Li, Mei; Wang, Qiaolian; Su, Yumin; Jia, Zhixin

    2013-07-01

    In the paper, graphene acid (GA) was manufactured, using flake graphite as raw material, and the acidity and the structure of GA were characterized as well as. Then, chalcone was synthesized in the presence of GA, using acetophenone and benzaldehyde as the reactant. The results showed that the acidity of GA was for pH = 1.12 in aqueous solution, and it was structured by the graphene sheets with the spaces between the graphene sheet and the graphene sheet and sulfuric acid (H2SO4) and acetic acid (CH3CO2H) inside the spaces. At the same time, the results also exhibited that the chalcone yield was able to reach 60.36% when GA dosage was 5 g, and the chalcone yields could attain apart 60.36, 52.05 and 31.16% when 5 g of GA was used thrice. This shows that GA is not only a high-performance catalyst, but also a controlled-release catalyst.

  2. Saga of synthetic rubber

    SciTech Connect

    Solo, R.A.

    1980-04-01

    The proposal to establish an Energy Mobilization Board and a synthetic fuels industry is reminiscent of World War II efforts to produce synthetic rubber. To avoid the mistakes made in the earlier effort, Mr. Solo suggests that the synthetic-fuel program should (1) use a more-successful technological development project as a model; (2) commit public funding and not rely on profit-oriented private enterprise; and (3) avoid entrusting social planning to single-purpose entities that have not been sensitive to social values. (DCK)

  3. Synthetic Base Fluids

    NASA Astrophysics Data System (ADS)

    Brown, M.; Fotheringham, J. D.; Hoyes, T. J.; Mortier, R. M.; Orszulik, S. T.; Randles, S. J.; Stroud, P. M.

    The chemical nature and technology of the main synthetic lubricant base fluids is described, covering polyalphaolefins, alkylated aromatics, gas-to-liquid (GTL) base fluids, polybutenes, aliphatic diesters, polyolesters, polyalkylene glycols or PAGs and phosphate esters.Other synthetic lubricant base oils such as the silicones, borate esters, perfluoroethers and polyphenylene ethers are considered to have restricted applications due to either high cost or performance limitations and are not considered here.Each of the main synthetic base fluids is described for their chemical and physical properties, manufacture and production, their chemistry, key properties, applications and their implications when used in the environment.

  4. Building synthetic memory

    PubMed Central

    Inniss, Mara C.; Silver, Pamela A.

    2013-01-01

    Synopsis Cellular memory – conversion of a transient signal into a sustained response – is a common feature of biological systems. Synthetic biologists aim to understand and reengineer such systems in a reliable and predictable manner. Synthetic memory circuits have been designed and built in vitro and in vivo based on diverse mechanisms such as oligonucleotide hybridization, recombination, transcription, phosphorylation, and RNA editing. Thus far, building these circuits has helped us explore the basic principles required for stable memory and ask novel biological questions. Here we discuss strategies for building synthetic memory circuits, their use as research tools, and future applications of these devices in medicine and industry. PMID:24028965

  5. Requiem for synthetic fuels

    SciTech Connect

    Myers, R.

    1982-01-27

    US plans to launch a synthetic fuels industry revive whenever a price or supply crisis occurs, but industrial hopes descend as soon as the short-term market begins improving in terms of real prices. The capital requirements of a synthetic fuels project combined with fears of a noncompetitive product have caused several major oil companies to scale down or cancel their plans. In the author's view, the Reagan administration's hands-off policy and false sense of security from the current oil supply glut have further discouraged industry. The Synthetic Fuels Corporation has been slow to organize, and appears to be favoring small-size plants. (DCK)

  6. What Are Synthetic Cannabinoids?

    MedlinePlus

    ... those produced by marijuana: elevated mood relaxation altered perception —awareness of surrounding objects and conditions symptoms of ... those produced by marijuana: elevated mood relaxation altered perception symptoms of psychosis Synthetic cannabinoids can also cause ...

  7. Analysis of Synthetic Polymers.

    ERIC Educational Resources Information Center

    Smith, Charles G.; And Others

    1989-01-01

    Reviews techniques for the characterization and analysis of synthetic polymers, copolymers, and blends. Includes techniques for structure determination, separation, and quantitation of additives and residual monomers; determination of molecular weight; and the study of thermal properties including degradation mechanisms. (MVL)

  8. Synthetic battery cycling techniques

    NASA Technical Reports Server (NTRS)

    Leibecki, H.; Thaller, L. H.

    1982-01-01

    The group of techniques that as a class are referred to as synthetic battery cycling are described with reference to spacecraft battery systems. Synthetic battery cycling makes use of the capability of computer graphics to illustrate some of the basic characteristics of operation of individual electrodes within an operating electrochemical cell. It can also simulate the operation of an entire string of cells that are used as the energy storage subsystem of a power system.

  9. Synthetic approaches to monofluoroalkenes.

    PubMed

    Landelle, Grégory; Bergeron, Maxime; Turcotte-Savard, Marc-Olivier; Paquin, Jean-François

    2011-05-01

    Monofluoroalkenes are an important fluorinated class of compounds with applications in medicinal chemistry, material sciences and organic chemistry. An overview of methods allowing synthetic access to these fluorinated building blocks is provided. In particular, this critical review, which covers publications up to October 2010, will be divided according to the substitution pattern of the monofluoroalkenes, i.e. di-, tri- or tetra-substituted. Within each group, the various synthetic approaches will be divided according to the reaction type (282 references).

  10. Active synthetic soil

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W. (Inventor); Henninger, Donald L. (Inventor); Allen, Earl R. (Inventor); Golden, Dadigamuwage C. (Inventor)

    1995-01-01

    A synthetic soil/fertilizer for horticultural application having all the agronutrients essential for plant growth is disclosed. The soil comprises a synthetic apatite fertilizer having sulfur, magnesium and micronutrients dispersed in a calcium phosphate matrix, a zeolite cation exchange medium saturated with a charge of potassium and nitrogen cations, and an optional pH buffer. Moisture dissolves the apatite and mobilizes the nutrient elements from the apatite matrix and the zeolite charge sites.

  11. Active synthetic soil

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W. (Inventor); Henninger, Donald L. (Inventor); Allen, Earl R. (Inventor); Golden, Dadigamuwage C. (Inventor)

    1995-01-01

    A synthetic soil/fertilizer for horticultural application having all the agronutrients essential for plant growth is disclosed. The soil comprises a synthetic apatite fertilizer having sulfur, magnesium, and micronutrients dispersed in a calcium phosphate matrix, a zeolite cation exchange medium saturated with a charge of potassium and nitrogen cations, and an optional pH buffer. Moisture dissolves the apatite and mobilizes the nutrient elements from the apatite matrix and the zeolite charge sites.

  12. Synthetic biology and biosecurity.

    PubMed

    Robienski, Jürgen; Simon, Jürgen

    2014-01-01

    This article discusses the conflict fields and legal questions of synthetic biology, esp. concerning biosecurity. A respective jurisprudential discussion has not taken place yet in Germany apart from few statements and recommendations. But in Germany, Europe and the USA, it is generally accepted that a broad discussion is necessary. This is esp. true for the question of biosecurity and the possible dangers arising from Synthetic Biology. PMID:25845204

  13. Synthetic Vision Systems

    NASA Technical Reports Server (NTRS)

    Prinzel, L.J.; Kramer, L.J.

    2009-01-01

    A synthetic vision system is an aircraft cockpit display technology that presents the visual environment external to the aircraft using computer-generated imagery in a manner analogous to how it would appear to the pilot if forward visibility were not restricted. The purpose of this chapter is to review the state of synthetic vision systems, and discuss selected human factors issues that should be considered when designing such displays.

  14. Molecular structures of chalcone podands: A prognosis of photoinduced transformations in the crystals

    SciTech Connect

    Ovchinnikova, I. G. Fedorova, O. V.; Slepukhin, P. A.; Litvinov, I. A.; Rusinov, G. L.

    2009-01-15

    A series of chalcone podands with the propenone group in the ortho position of the bridging aryl substituent with respect to the oxyethylene fragment is synthesized. The influence of the preorganization of the chalcone podand molecules in crystals on their ability to participate in topochemical reactions is investigated. From analyzing the X-ray structural data, the highest probability of the solid-state photochemical [2 + 2]cycloaddition is predicted for podands with phenyl substituents and the oxyethylene fragment containing two or three oxygen atoms. The X-ray structural data for the chalcone podand C{sub 32}H{sub 26}O{sub 4} (3a) are as follows: a = 7.904(9) A, b = 14.92(2) A, c = 21.30(3) A, {beta} = 91.7(1){sup o}, monoclinic system, space group P2{sub 1}/c, Z = 4, V = 2510(5) A{sup 3}, {rho} = 1.26 g/cm{sup 3}, and R = 0.046; C{sub 34}H{sub 30}O{sub 5} (3b): a = 15.738(9) A, b = 11.889(2) A, c = 15.0830(15) A, {beta} = 105.47(14){sup o}, monoclinic system, space group C2/c, Z = 4, V = 2720.0(9) A{sup 3}, {rho} = 1.266 g/cm{sup 3}, and R = 0.0418; C{sub 32}H{sub 24}N{sub 2}O{sub 8} (4a): a = 17.9416(18) A, b = 10.9703(8) A, c = 41.699(2) A, {beta} = 105.970(11){sup o}, monoclinic system, space group P2{sub 1}/c, Z = 4, V = 2781.4(5) A{sup 3}, {rho} = 1.348 g/cm{sup 3}, and R = 0.0426; C{sub 36}H{sub 32}N{sub 2}O{sub 10} (4c): a = 7.6286(5)A, b = 17.9398(10) A, c = 11.5890(3)A, {beta} = 95.287(4){sup o}, monoclinic system, space group P2{sub 1}/n, Z = 2, V = 1579.27(14) A{sup 3}, {rho} = 1.372 g/cm{sup 3}, and R = 0.0377; and C{sub 28}H{sub 22}O{sub 6} (5a): a = 15.6032(10) A, b = 8.1131(5) A, c = 17.7334(11) A, {beta} = 91.381(5){sup o}, monoclinic system, space group C2/c, Z = 4, V = 2244.2(2) A{sup 3}, {rho} = 1.345 g/cm{sup 3}, and R = 0.0309.

  15. Identification of Chalcones as Fasciola hepatica Cathepsin L Inhibitors Using a Comprehensive Experimental and Computational Approach

    PubMed Central

    Ferraro, Florencia; Merlino, Alicia; dell´Oca, Nicolás; Gil, Jorge; Tort, José F.; Gonzalez, Mercedes; Cerecetto, Hugo; Cabrera, Mauricio

    2016-01-01

    Background Increased reports of human infections have led fasciolosis, a widespread disease of cattle and sheep caused by the liver flukes Fasciola hepatica and Fasciola gigantica, to be considered an emerging zoonotic disease. Chemotherapy is the main control measure available, and triclabendazole is the preferred drug since is effective against both juvenile and mature parasites. However, resistance to triclabendazole has been reported in several countries urging the search of new chemical entities and target molecules to control fluke infections. Methodology/Principle Findings We searched a library of forty flavonoid derivatives for inhibitors of key stage specific Fasciola hepatica cysteine proteases (FhCL3 and FhCL1). Chalcones substituted with phenyl and naphtyl groups emerged as good cathepsin L inhibitors, interacting more frequently with two putative binding sites within the active site cleft of the enzymes. One of the compounds, C34, tightly bounds to juvenile specific FhCL3 with an IC50 of 5.6 μM. We demonstrated that C34 is a slow-reversible inhibitor that interacts with the Cys-His catalytic dyad and key S2 and S3 pocket residues, determinants of the substrate specificity of this family of cysteine proteases. Interestingly, C34 induces a reduction in NEJ ability to migrate through the gut wall and a loss of motility phenotype that leads to NEJ death within a week in vitro, while it is not cytotoxic to bovine cells. Conclusions/Significance Up to date there are no reports of in vitro screening for non-peptidic inhibitors of Fasciola hepatica cathepsins, while in general these are considered as the best strategy for in vivo inhibition. We have identified chalcones as novel inhibitors of the two main Cathepsins secreted by juvenile and adult liver flukes. Interestingly, one compound (C34) is highly active towards the juvenile enzyme reducing larval ability to penetrate the gut wall and decreasing NEJ´s viability in vitro. These findings open new avenues

  16. Differential Synthetic Aperture Ladar

    SciTech Connect

    Stappaerts, E A; Scharlemann, E

    2005-02-07

    We report a differential synthetic aperture ladar (DSAL) concept that relaxes platform and laser requirements compared to conventional SAL. Line-of-sight translation/vibration constraints are reduced by several orders of magnitude, while laser frequency stability is typically relaxed by an order of magnitude. The technique is most advantageous for shorter laser wavelengths, ultraviolet to mid-infrared. Analytical and modeling results, including the effect of speckle and atmospheric turbulence, are presented. Synthetic aperture ladars are of growing interest, and several theoretical and experimental papers have been published on the subject. Compared to RF synthetic aperture radar (SAR), platform/ladar motion and transmitter bandwidth constraints are especially demanding at optical wavelengths. For mid-IR and shorter wavelengths, deviations from a linear trajectory along the synthetic aperture length have to be submicron, or their magnitude must be measured to that precision for compensation. The laser coherence time has to be the synthetic aperture transit time, or transmitter phase has to be recorded and a correction applied on detection.

  17. Evolution of mustard (Brassica juncea Coss) subspecies in China: evidence from the chalcone synthase gene.

    PubMed

    Chen, F B; Liu, H F; Yao, Q L; Fang, P

    2016-01-01

    To explore the phylogenetic relationship, genome donor, and evolutionary history of the polyploid mustard (Brassica juncea) from China, eighty-one sequences of the chalcone synthase gene (Chs) were analyzed in 43 individuals, including 34 B. juncea, 2 B. rapa, 1 B. nigra, 2 B. oleracea, 1 B. napus, 1 B. carinata, and 2 Raphanus sativus. A maximum likelihood analysis showed that sequences from B. juncea were separated into two well-supported groups in accordance with the A and B genomes, whereas the traditional phenotypic classification of B. juncea was not wholly supported by the molecular results. The SplitsTree analysis recognized four distinct groups of Brassicaceae, and the median-joining network analysis recognized four distinct haplotypes of Chs. The estimates of Tajima's D, Fu and Li's D, and Fu and Li's F statistic for the Chs gene in the B genome were negative, while those in the A genome were significant. The results indicated that 1) the Chs sequences revealed a high level of sequence variation in Chinese mustard, 2) both tree and reticulate evolutions existed, and artificial selection played an important role in the evolution of Chinese mustard, 3) the original parental species of Chinese mustard are B. rapa var. sinapis arvensis and B. nigra (derived from China), 4) nucleotide variation in the B genome was higher than that in the A genome, and 5) cultivated mustard evolved from wild mustard, and China is one of the primary origins of B. juncea.

  18. Cloning and expression analysis of chalcone synthase gene from Coleus forskohlii.

    PubMed

    Awasthi, Praveen; Mahajan, Vidushi; Jamwal, Vijay Lakshmi; Kapoor, Nitika; Rasool, Shafaq; Bedi, Yashbir S; Gandhi, Sumit G

    2016-09-01

    Flavonoids are an important class of secondary metabolites that play various roles in plants such as mediating defense, floral pigmentation and plant-microbe interaction. Flavonoids are also known to possess antioxidant and antimicrobial activities. Coleus forskohlii (Willd.) Briq. (Lamiaceae) is an important medicinal herb with a diverse metabolic profile, including production of a flavonoid, genkwanin. However, components of the flavonoid pathway have not yet been studied in this plant. Chalcone synthase (CHS) catalyses the first committed step of flavonoid biosynthetic pathway. Full-length cDNA, showing homology with plant CHS gene was isolated from leaves of C. forskohlii and named CfCHS (GenBank accession no. KF643243). Theoretical translation of CfCHS nucleotide sequence shows that it encodes a protein of 391 amino acids with a molecular weight of 42.75 kDa and pI 6.57. Expression analysis of CfCHS in different tissues and elicitor treatments showed that methyl jasmonate (MeJA) strongly induced its expression. Total flavonoids content and antioxidant activity of C. forskohlii also got enhanced in response to MeJA, which correlated with increased CfCHS expression. Induction of CfCHS by MeJA suggest its involvement in production of flavonoids, providing protection from microbes during herbivory or mechanical wounding. Further, our in silico predictions and experimental data suggested that CfCHS may be posttranscriptionally regulated by miR34. PMID:27659336

  19. Chalcone synthase genes from milk thistle (Silybum marianum): isolation and expression analysis.

    PubMed

    Sanjari, Sepideh; Shobbar, Zahra Sadat; Ebrahimi, Mohsen; Hasanloo, Tahereh; Sadat-Noori, Seyed-Ahmad; Tirnaz, Soodeh

    2015-12-01

    Silymarin is a flavonoid compound derived from milk thistle (Silybum marianum) seeds which has several pharmacological applications. Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoids; thereby, the identification of CHS encoding genes in milk thistle plant can be of great importance. In the current research, fragments of CHS genes were amplified using degenerate primers based on the conserved parts of Asteraceae CHS genes, and then cloned and sequenced. Analysis of the resultant nucleotide and deduced amino acid sequences led to the identification of two different members of CHS gene family,SmCHS1 and SmCHS2. Third member, full-length cDNA (SmCHS3) was isolated by rapid amplification of cDNA ends (RACE), whose open reading frame contained 1239 bp including exon 1 (190 bp) and exon 2 (1049 bp), encoding 63 and 349 amino acids, respectively. In silico analysis of SmCHS3 sequence contains all the conserved CHS sites and shares high homology with CHS proteins from other plants.Real-time PCR analysis indicated that SmCHS1 and SmCHS3 had the highest transcript level in petals in the early flowering stage and in the stem of five upper leaves, followed by five upper leaves in the mid-flowering stage which are most probably involved in anthocyanin and silymarin biosynthesis.

  20. Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship

    NASA Astrophysics Data System (ADS)

    Akhtar, Muhammad Nadeem; Sakeh, Nurshafika M.; Zareen, Seema; Gul, Sana; Lo, Kong Mun; Ul-Haq, Zaheer; Shah, Syed Adnan Ali; Ahmad, Syahida

    2015-04-01

    Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1-10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20-14.38 μM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1-3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic techniques. These findings could lead to design and discover of new tyrosinase inhibitors to control the melanine overproduction and overcome the economic loss of food industry.

  1. Integrated kinetic studies and computational analysis on naphthyl chalcones as mushroom tyrosinase inhibitors.

    PubMed

    Radhakrishnan, Sini; Shimmon, Ronald; Conn, Costa; Baker, Anthony

    2015-10-01

    Melanin helps to protect skin from the damaging ultraviolet radiation of the sun. Tyrosinase, the key enzyme in melanogenesis is responsible for coloration of skin, hair and eyes. This enzyme is considered to have a critical role in governing the quality and economics of fruits and vegetables, as tyrosinase activity can lead to spoilage through browning. Development of tyrosinase inhibitors is a promising approach to combat hyperpigmentation conditions like ephelides, lentigo, freckles and post-inflammatory hyperpigmentation. In the present study, we have used a docking algorithm to simulate binding between tyrosinase and hydroxy-substituted naphthyl chalcone oxime compounds and studied the inhibition of tyrosinase. The results of virtual screening studies indicated that the estimated free energy of binding of all the docked ligands ranged between -19.29 and -9.12 kcal/mol. Two of the oximes synthesized were identified as competitive tyrosinase inhibitors and were found to be twice as potent as the control kojic acid with their IC50 values of 12.22 μM and 19.45 μM, respectively. This strategy of integrating experimental and virtual screening methods could give better insights to explore potent depigmentation agents. PMID:26318997

  2. Structural, electrochemical and theoretical study of a new chalcone derivative containing 3-thiophene rings

    NASA Astrophysics Data System (ADS)

    Baggio, Ricardo; Brovelli, Francisco; Moreno, Yanko; Pinto, Marcela; Soto-Delgado, Jorge

    2016-11-01

    The title chalcone, 1,3-di(thiophene-3-yl)prop-2-en-1-one (C11H8OS2) is an essentially planar molecular with its terminal thiophene rings subtending an angle of 8.9°. The crystal structure consists in the π··π stacking of molecules defining columns along [010], further linked along c by non conventional Csbnd H⋯O bonds, thus determining broad planar arrays parallel to (100). In addition, there are weak S⋯S contacts connecting these weakly interacting 2D substructures. The experimental results obtained from single crystal X-ray diffraction data and the theoretical geometry calculated by molecular mechanics are in good agreement. Electrochemical records reveal an anodic profile with an unsymmetrical irreversible peak at 1.77 V and a shoulder at 1.62 V vs SCE, a behavior interpretable as due to the oxidation of reactive sites present in the molecule. On the other hand, the electrochemical reduction shows a narrow peak at -1.58 V vs SCE, a fact attributable to the carbonyl group. Finally, the values for the energy involved in the departure/arrival of electrons from border orbitals, as calculated using DFT, is compared with experimental data from cyclic voltammetry.

  3. Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.

    PubMed

    Anthwal, Amit; Rajesh, U Chinna; Rawat, M S M; Kushwaha, Bhavana; Maikhuri, Jagdamba P; Sharma, Vishnu L; Gupta, Gopal; Rawat, Diwan S

    2014-05-22

    Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 μg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.

  4. Spectral, biological screening of metal chelates of chalcone based Schiff bases of N-(3-aminopropyl) imidazole

    NASA Astrophysics Data System (ADS)

    Kalanithi, M.; Rajarajan, M.; Tharmaraj, P.; Sheela, C. D.

    2012-02-01

    Tridentate chelate complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized from the chalcone based ligands 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-(phenylallyl)]phenol( HL1), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-p-tolylallyl]phenol( HL2), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-4-nitrophenylallyl]phenol( HL3). Microanalytical data, UV-vis spectrophotometric method, magnetic susceptibility measurements, IR, 1H NMR, Mass, and EPR techniques were used to characterize the structure of chelates. The electronic absorption spectra and magnetic susceptibility measurements suggest a distorted square planar geometry for the copper(II) ion. The other metal complexes show distorted tetrahedral geometry. The coordination of the ligands with metal(II) ions was further confirmed by solution fluorescence spectrum. The antimicrobial activity of the ligands and metal(II) complexes against the species Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albigans and Aspergillus niger has been carried out and compared. The electrochemical behavior of copper(II) complex is studied by cyclic voltammetry.

  5. Quinolinyl-thienyl chalcones as monoamine oxidase inhibitors and their in silico modeling studies.

    PubMed

    Zaib, Sumera; Rizvi, Syed Umar Farooq; Aslam, Sana; Ahmad, Matloob; Ali Abid, Syed Mobasher; Al-Rashida, Mariya; Iqbal, Jamshed

    2015-01-01

    Mitochondrial enzymes monoamine oxidases were thought to be an emerging and useful therapeutic target for neurodegenerative disorders. Monoamine oxidases have two isoforms, A and B. MAO-A is related with metabolism of amine neurotransmitters in the brain whereas MAO-B is concerned with aging related neurodegenerative disorders. Therefore the identification, characterization and discovery of potent MAO-A and B inhibitors is very crucial in research. A series of quinolyl-thienyl chalcones were tested against MAO-A and B. Among the screened compounds, most of them revealed potent MAO-A and B inhibition. Compound 5i presented most potent MAO-A inhibition having IC50 values 0.047 µM, while 4l showed excellent inhibitory potency against MAO-B among all the tested compound having IC50 values 0.063 µM. Molecular modelling studies were performed against human MAO-A and MAO-B for the explanation of binding site interactions.

  6. Chalcone Synthase Promoters in Petunia Are Active in Pigmented and Unpigmented Cell Types.

    PubMed Central

    Koes, RE; Van Blokland, R; Quattrocchio, F; Van Tunen, AJ; Mol, J

    1990-01-01

    Chalcone synthase (CHS) catalyzes the first step in the biosynthesis of flavonoids that function in flower pigmentation, protection against stress, and induction of nodulation. The petunia genome contains eight complete chs genes, of which four are differentially expressed in floral tissues and UV-light-induced seedlings. The 5[prime]-flanking regions of these four chs genes were fused to the [beta]-glucuronidase (GUS) reporter gene and introduced into petunia plants by Agrobacterium-mediated transformation. We show that expression of each construct is identical to the expression of the authentic chs gene, implying that the differences in expression pattern between these chs genes are caused at least in part by their promoters. Histochemical analyses of GUS expression show that chs promoters are not only active in pigmented cell types (epidermal cells of the flower corolla and tube and [sub] epidermal cells of the flower stem) but also in a number of unpigmented cell types (mesophylic cells of the corolla, several cell types in the ovary and the seed coat). Comparison of chs-GUS expression and flavonoid accumulation patterns in anthers suggests that intercellular transport of flavonoids and enzymes occurs in this organ. Analysis of the flavonoids accumulated in tissues from mutant lines shows that only a subset of the genes that control flavonoid biosynthesis in the flower operates in the ovary and seed. This implies that (genetic) control of flavonoid biosynthesis is highly tissue specific. PMID:12354962

  7. Evolution of mustard (Brassica juncea Coss) subspecies in China: evidence from the chalcone synthase gene.

    PubMed

    Chen, F B; Liu, H F; Yao, Q L; Fang, P

    2016-01-01

    To explore the phylogenetic relationship, genome donor, and evolutionary history of the polyploid mustard (Brassica juncea) from China, eighty-one sequences of the chalcone synthase gene (Chs) were analyzed in 43 individuals, including 34 B. juncea, 2 B. rapa, 1 B. nigra, 2 B. oleracea, 1 B. napus, 1 B. carinata, and 2 Raphanus sativus. A maximum likelihood analysis showed that sequences from B. juncea were separated into two well-supported groups in accordance with the A and B genomes, whereas the traditional phenotypic classification of B. juncea was not wholly supported by the molecular results. The SplitsTree analysis recognized four distinct groups of Brassicaceae, and the median-joining network analysis recognized four distinct haplotypes of Chs. The estimates of Tajima's D, Fu and Li's D, and Fu and Li's F statistic for the Chs gene in the B genome were negative, while those in the A genome were significant. The results indicated that 1) the Chs sequences revealed a high level of sequence variation in Chinese mustard, 2) both tree and reticulate evolutions existed, and artificial selection played an important role in the evolution of Chinese mustard, 3) the original parental species of Chinese mustard are B. rapa var. sinapis arvensis and B. nigra (derived from China), 4) nucleotide variation in the B genome was higher than that in the A genome, and 5) cultivated mustard evolved from wild mustard, and China is one of the primary origins of B. juncea. PMID:27173323

  8. Novel Chalcone Derivatives as Potent Nrf2 Activators in Mice and Human Lung Epithelial Cells

    PubMed Central

    Kumar, Vineet; Kumar, Sarvesh; Hassan, Mohammad; Wu, Hailong; Thimmulappa, Rajesh K.; Kumar, Amit; Sharma, Sunil K.; Parmar, Virinder S.; Biswal, Shyam; Malhotra, Sanjay V.

    2011-01-01

    Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes, GCLM, NQO1 and HO1, in human lung epithelial cells; while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using mouse model. Our studies showed 2-trifluoromethyl-2’-methoxychalone (2b) to be a potent activator of Nrf2, both, in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure-activity relationship and proposed a possible mechanism of Nrf2 activation. PMID:21539383

  9. Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in Flavonoid Biosynthetic Pathway

    PubMed Central

    Sun, Wei; Meng, Xiangyu; Liang, Lingjie; Jiang, Wangshu; Huang, Yafei; He, Jing; Hu, Haiyan; Almqvist, Jonas; Gao, Xiang; Wang, Li

    2015-01-01

    Chalcone synthase (CHS) catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1) encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants. PMID:25742495

  10. Transient silencing of CHALCONE SYNTHASE during fruit ripening modifies tomato epidermal cells and cuticle properties.

    PubMed

    España, Laura; Heredia-Guerrero, José A; Reina-Pinto, José J; Fernández-Muñoz, Rafael; Heredia, Antonio; Domínguez, Eva

    2014-11-01

    Tomato (Solanum lycopersicum) fruit ripening is accompanied by an increase in CHALCONE SYNTHASE (CHS) activity and flavonoid biosynthesis. Flavonoids accumulate in the cuticle, giving its characteristic orange color that contributes to the eventual red color of the ripe fruit. Using virus-induced gene silencing in fruits, we have down-regulated the expression of SlCHS during ripening and compared the cuticles derived from silenced and nonsilenced regions. Silenced regions showed a pink color due to the lack of flavonoids incorporated to the cuticle. This change in color was accompanied by several other changes in the cuticle and epidermis. The epidermal cells displayed a decreased tangential cell width; a decrease in the amount of cuticle and its main components, cutin and polysaccharides, was also observed. Flavonoids dramatically altered the cuticle biomechanical properties by stiffening the elastic and viscoelastic phase and by reducing the ability of the cuticle to deform. There seemed to be a negative relation between SlCHS expression and wax accumulation during ripening that could be related to the decreased cuticle permeability to water observed in the regions silencing SlCHS. A reduction in the overall number of ester linkages present in the cutin matrix was also dependent on the presence of flavonoids.

  11. The accumulation and localization of chalcone synthase in grapevine (Vitis vinifera L.).

    PubMed

    Wang, Huiling; Wang, Wei; Zhan, JiCheng; Yan, Ailing; Sun, Lei; Zhang, Guojun; Wang, Xiaoyue; Ren, Jiancheng; Huang, Weidong; Xu, Haiying

    2016-09-01

    Chalcone synthase (CHS, E.C.2.3.1.74) is the first committed enzyme in the flavonoid pathway. Previous studies have primarily focused on the cloning, expression and regulation of the gene at the transcriptional level. Little is yet known about the enzyme accumulation, regulation at protein level, as well as its localization in grapevine. In present study, the accumulation, tissue and subcellular localization of CHS in different grapevine tissues (Vitis vinifera L. Cabernet Sauvignon) were investigated via the techniques of Western blotting, immunohistochemical localization, immunoelectron microscopy and confocal microscopy. The results showed that CHS were mainly accumulated in the grape berry skin, leaves, stem tips and stem phloem, correlated with flavonoids accumulation. The accumulation of CHS is developmental dependent in grape berry skin and flesh. Immunohistochemical analysis revealed that CHS were primarily localized in the exocarp and vascular bundles of the fruits during berry development; in palisade, spongy tissues and vascular bundles of the leaves; in the primary phloem and pith ray in the stems; in the growth point, leaf primordium, and young leaves of leaf buds; and in the endoderm and primary phloem of grapevine roots. Furthermore, at the subcellular level, the cell wall, cytoplasm and nucleus localized patterns of CHS were observed in the grapevine vegetative tissue cells. Results above indicated that distribution of CHS in grapevine was organ-specific and tissue-specific. This work will provide new insight for the biosynthesis and regulation of diverse flavonoid compounds in grapevine. PMID:27161583

  12. Genome-Wide Identification, Characterization and Expression Analysis of the Chalcone Synthase Family in Maize

    PubMed Central

    Han, Yahui; Ding, Ting; Su, Bo; Jiang, Haiyang

    2016-01-01

    Members of the chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. The metabolites play important roles in protecting land plants against various environmental stresses during the evolutionary process. Our research was conducted on comprehensive investigation of CHS genes in maize (Zea mays L.), including their phylogenetic relationships, gene structures, chromosomal locations and expression analysis. Fourteen CHS genes (ZmCHS01–14) were identified in the genome of maize, representing one of the largest numbers of CHS family members identified in one organism to date. The gene family was classified into four major classes (classes I–IV) based on their phylogenetic relationships. Most of them contained two exons and one intron. The 14 genes were unevenly located on six chromosomes. Two segmental duplication events were identified, which might contribute to the expansion of the maize CHS gene family to some extent. In addition, quantitative real-time PCR and microarray data analyses suggested that ZmCHS genes exhibited various expression patterns, indicating functional diversification of the ZmCHS genes. Our results will contribute to future studies of the complexity of the CHS gene family in maize and provide valuable information for the systematic analysis of the functions of the CHS gene family. PMID:26828478

  13. Synthesis, growth, structure and characterization of chalcone crystal: A novel organic NLO material

    NASA Astrophysics Data System (ADS)

    Agilandeshwari, R.; Meenatchi, V.; Meenakshisundaram, S. P.

    2016-08-01

    Single crystals of a chalcone, (E)-3-(4-bromophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (BHP), were grown by the slow evaporation solution growth technique. The structure is elucidated by single-crystal X-ray diffraction analysis and the crystal belongs to the monoclinic system with noncentrosymmetric space group P21. Optical studies reveal that the absorption is minimum in the visible region and the cut-off wavelength is at ∼468 nm. The band-gap energy was estimated by the application of the Kubelka-Munk algorithm. The powder X-ray diffraction pattern reveals the good crystallinity of the as-grown specimen. The vibrational patterns in FT-IR are used to identify the functional groups and thermal studies indicate the stability of the material. The second harmonic generation efficiency (SHG), as estimated by Kurtz and Perry powder technique, reveals the superior nonlinear optical character of this material. Hirshfeld surface analysis is done to quantify the intermolecular interactions, responsible for developing a nonlinear atmosphere. As-grown crystals were further characterized by SEM, NMR, mass spectrometry and elemental analysis.

  14. Single crystal x-ray diffraction: optical and micro hardness studies on chalcone derivative single crystal

    NASA Astrophysics Data System (ADS)

    Crasta, Vincent; Ravindrachary, V.; Bhajantri, R. F.; Naveen, S.; Shridar, M. A.; Shashidhara Prasad, J.

    2005-08-01

    1-(4-methylphenyl)-3-(4- N, N dimethyl amino phenyl)-2-propen-1-one, a chalcone derivative nonlinear optical material has been synthesized by standard method. FT-IR and NMR spectral studies have been performed to confirm the molecular structure of the synthesized compound. The single crystals up to a dimension of 13 x 9 x 3 mm3 were grown by slow evaporation method. The grown crystals were transparent in the entire visible region and absorbs in the UV-region. The refractive index has been measured using a He-Ne laser. The grown crystals have been subjected to single crystal X-ray diffraction studies to determine the crystal structure and hence the cell parameters of the crystal. From this study it is found that this compound crystallizes in orthorhombic system with a space group P212121 and corresponding lattice parameters are, a = 7.3610(13) Å, b = 11.651(2) Å, c = 17.6490(17) Å. The Kurtz powder second harmonic generation test shows that the compound is a potential candidate for Photonic application. The micro hardness test on these crystals were carried out and the load dependence hardness was observed

  15. Growth, characterization, and crystal structure of a new chalcone derivative single crystal

    NASA Astrophysics Data System (ADS)

    Shettigar, Venkataraya; Dharmaprakash, S. M.

    2006-09-01

    A new organic nonlinear optical (NLO) chalcone derivative viz.1- ( 4- methoxyphenyl )-3- (3,4 - dimethoxy phenyl ) - 2 - propene-1-one, has been synthesized by Claisen-Schmidt condensation method. The synthesized compound was purified by repeated recrystallization process. To confirm the identity of the synthesized compound, FTIR spectra was recorded and various functional groups present were identified. NMR spectra were recorded for structural identity and purity confirmation of the synthesized compound. Good quality single crystals were grown by solvent evaporation and slow cooling technique using acetone as solvent. The grown crystals were characterized by UV-Visible , differential thermal analysis and linear refractive index measurement. The hardness of the crystal was determined using Vicker's indentation method. The single crystal structure analysis of the crystal was performed and it is found that the crystal belongs to monoclinic system with space group P2 I. The powder second harmonic generation(SHG)frequency conversion efficiency of the crystal was determined using Nd: YAG laser(λ = 1064nm)and it is 15 times that of Urea.

  16. Genome-Wide Identification, Characterization and Expression Analysis of the Chalcone Synthase Family in Maize.

    PubMed

    Han, Yahui; Ding, Ting; Su, Bo; Jiang, Haiyang

    2016-01-01

    Members of the chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. The metabolites play important roles in protecting land plants against various environmental stresses during the evolutionary process. Our research was conducted on comprehensive investigation of CHS genes in maize (Zea mays L.), including their phylogenetic relationships, gene structures, chromosomal locations and expression analysis. Fourteen CHS genes (ZmCHS01-14) were identified in the genome of maize, representing one of the largest numbers of CHS family members identified in one organism to date. The gene family was classified into four major classes (classes I-IV) based on their phylogenetic relationships. Most of them contained two exons and one intron. The 14 genes were unevenly located on six chromosomes. Two segmental duplication events were identified, which might contribute to the expansion of the maize CHS gene family to some extent. In addition, quantitative real-time PCR and microarray data analyses suggested that ZmCHS genes exhibited various expression patterns, indicating functional diversification of the ZmCHS genes. Our results will contribute to future studies of the complexity of the CHS gene family in maize and provide valuable information for the systematic analysis of the functions of the CHS gene family. PMID:26828478

  17. Identification and characterization of chalcone synthase cDNAs (NnCHS) from Nelumbo nucifera.

    PubMed

    Dong, C; Yu, A Q; Wang, M L; Zheng, X W; Diao, Y; Xie, K Q; Zhou, M Q; Hu, Z L

    2015-01-01

    Chalcone synthase (CHS) catalyzes the first committed step in flavonoids biosynthetic pathway. In this study, six full-length cDNAs (NnCHS) encoding CHS from Nelumbo nucifera were successfully isolated, using rapid amplification cDNA end (RACE) assay. The obtained cDNAs were 1426 bp in size, containing a 1167 bp open reading frame coding 389 amino acids. Exons-intron architecture of NnCHS gene was illustrated, consisting two exons inserted by a 426 bp intron. The putative NnCHS possessed all the conserved active sites for CHS function as well as the family signature. Phylogenetic analysis revealed that NnCHS shared high homology with CHS from high plants, and the homology-based structural modeling showed that NnCHS had the typical structure of CHS. Moreover, Real-time PCR assays demonstrated that NnCHS mRNAs were expressed in various tissues of N. nucifera, with the highest expression in red flower and lowest level in the leaves. Moreover, patterns of NnCHS expression illustrated short-time wounding or low temperature significantly induced the up-regulation of NnCHS mRNA. PMID:26718438

  18. Isolation and characterization of a chalcone isomerase gene promoter from potato cultivars.

    PubMed

    Chen, M; Zhu, W J; You, X; Liu, Y D; Kaleri, G M; Yang, Q

    2015-01-01

    Chalcone isomerase (CHI) is a key enzyme involved in anthocyanin metabolism. Previous research on CHI has mainly focused on cDNA cloning and gene expression. In the current study, the 1425-bp potato CHI promoter (PCP) was isolated from four potato cultivars (Heijingang, Zhongshu 7, Désirée, and Favorita) using PCR and DNA sequencing. The PCP contained many cis-regulatory elements (CREs) related to anthocyanin metabolism, tissue specificity, light response, stress, and hormone induction. Of the PCP CREs identified, 19 were common to those found in the higher plants examined, based on plant CRE databases. Multiple sequence alignment showed six single nucleotide variation sites in PCP among the potato cultivars examined, resulting in changes in the number of CREs connected with tissue specificity, anthocyanin metabolism, and light response. The 665-bp PCP fragments from Favorita and 1425-bp PCP fragments from Heijingang were used to construct plant expression vectors, which may be a useful tool for biological engineering. A transient expression assay demonstrated that the two PCP fragments from Heijingang could direct the expression of a green fluorescent protein gene in onion epidermis and a β-glucuronidase gene in all potato tuber tissues with different colors, suggesting that the single nucleotide variation in the PCP did not affect its activity, and that silencing of the CHI gene in Favorita may be attributed to other regulatory factors. PMID:26782538

  19. Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury.

    PubMed

    Chen, Wenbo; Ge, Xiangting; Xu, Fengli; Zhang, Yali; Liu, Zhiguo; Pan, Jialing; Song, Jiao; Dai, Yuanrong; Zhou, Jianmin; Feng, Jianpeng; Liang, Guang

    2015-08-01

    Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents.

  20. Synthetic battery cycling techniques

    NASA Technical Reports Server (NTRS)

    Leibecki, H. F.; Thaller, L. H.

    1982-01-01

    Synthetic battery cycling makes use of the fast growing capability of computer graphics to illustrate some of the basic characteristics of operation of individual electrodes within an operating electrochemical cell. It can also simulate the operation of an entire string of cells that are used as the energy storage subsystem of a power system. The group of techniques that as a class have been referred to as Synthetic Battery Cycling is developed in part to try to bridge the gap of understanding that exists between single cell characteristics and battery system behavior.

  1. Synthetic guide star generation

    DOEpatents

    Payne, Stephen A.; Page, Ralph H.; Ebbers, Christopher A.; Beach, Raymond J.

    2004-03-09

    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  2. Synthetic guide star generation

    DOEpatents

    Payne, Stephen A [Castro Valley, CA; Page, Ralph H [Castro Valley, CA; Ebbers, Christopher A [Livermore, CA; Beach, Raymond J [Livermore, CA

    2008-06-10

    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  3. Excision of transposable elements from the chalcone isomerase and dihydroflavonol 4-reductase genes may contribute to the variegation of the yellow-flowered carnation (Dianthus caryophyllus).

    PubMed

    Itoh, Yoshio; Higeta, Daisuke; Suzuki, Akane; Yoshida, Hiroyuki; Ozeki, Yoshihiro

    2002-05-01

    In the "Rhapsody" cultivar of the carnation, which bears white flowers variegated with red flecks and sectors, a transposable element, dTdic1, belonging to the Ac/Ds superfamily, was found within the dihydroflavonol 4-reductase (DFR) gene. The red flecks and sectors of "Rhapsody" may be attributable to a reversion to DFR activity after the excision of dTdic1. The yellow color of the carnation petals is attributed to the synthesis and accumulation of chalcone 2'-glucoside. In several of the carnation cultivars that bear yellow flowers variegated with white flecks and sectors, both the chalcone isomerase (CHI) and DFR genes are disrupted by dTdic1.

  4. Synthesis and structure elucidation of a series of pyranochromene chalcones and flavanones using 1D and 2D NMR spectroscopy and X-ray crystallography.

    PubMed

    Pawar, Sunayna S; Koorbanally, Neil A

    2014-06-01

    A series of novel pyranochromene chalcones and corresponding flavanones were synthesized. This is the first report on the confirmation of the absolute configuration of chromene-based flavanones using X-ray crystallography. These compounds were characterized by 2D NMR spectroscopy, and their assignments are reported herein. The 3D structure of the chalcone 3b and flavanone 4g was determined by X-ray crystallography, and the structure of the flavanone was confirmed to be in the S configuration at C-2.

  5. Synthetic Visibility System

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Test pilot Lee Person evaluates a Synthetic Visibility System - in essence, two helmet-mounted eyepieces connected to video cameras that swivel in response to head movements. Photograph published in Winds of Change, 75th Anniversary NASA publication (page 113), by James Schultz.

  6. Adaptive synthetic vision

    NASA Astrophysics Data System (ADS)

    Julier, Simon J.; Brown, Dennis; Livingston, Mark A.; Thomas, Justin

    2006-05-01

    Through their ability to safely collect video and imagery from remote and potentially dangerous locations, UAVs have already transformed the battlespace. The effectiveness of this information can be greatly enhanced through synthetic vision. Given knowledge of the extrinsic and intrinsic parameters of the camera, synthetic vision superimposes spatially-registered computer graphics over the video feed from the UAV. This technique can be used to show many types of data such as landmarks, air corridors, and the locations of friendly and enemy forces. However, the effectiveness of a synthetic vision system strongly depends on the accuracy of the registration - if the graphics are poorly aligned with the real world they can be confusing, annoying, and even misleading. In this paper, we describe an adaptive approach to synthetic vision that modifies the way in which information is displayed depending upon the registration error. We describe an integrated software architecture that has two main components. The first component automatically calculates registration error based on information about the uncertainty in the camera parameters. The second component uses this information to modify, aggregate, and label annotations to make their interpretation as clear as possible. We demonstrate the use of this approach on some sample datasets.

  7. Synthetic Aperture Radar Interferometry

    NASA Technical Reports Server (NTRS)

    Rosen, P. A.; Hensley, S.; Joughin, I. R.; Li, F.; Madsen, S. N.; Rodriguez, E.; Goldstein, R. M.

    1998-01-01

    Synthetic aperture radar interferometry is an imaging technique for measuring the topography of a surface, its changes over time, and other changes in the detailed characteristics of the surface. This paper reviews the techniques of interferometry, systems and limitations, and applications in a rapidly growing area of science and engineering.

  8. Towards a Synthetic Chloroplast

    PubMed Central

    Agapakis, Christina M.; Niederholtmeyer, Henrike; Noche, Ramil R.; Lieberman, Tami D.; Megason, Sean G.; Way, Jeffrey C.; Silver, Pamela A.

    2011-01-01

    Background The evolution of eukaryotic cells is widely agreed to have proceeded through a series of endosymbiotic events between larger cells and proteobacteria or cyanobacteria, leading to the formation of mitochondria or chloroplasts, respectively. Engineered endosymbiotic relationships between different species of cells are a valuable tool for synthetic biology, where engineered pathways based on two species could take advantage of the unique abilities of each mutualistic partner. Results We explored the possibility of using the photosynthetic bacterium Synechococcus elongatus PCC 7942 as a platform for studying evolutionary dynamics and for designing two-species synthetic biological systems. We observed that the cyanobacteria were relatively harmless to eukaryotic host cells compared to Escherichia coli when injected into the embryos of zebrafish, Danio rerio, or taken up by mammalian macrophages. In addition, when engineered with invasin from Yersinia pestis and listeriolysin O from Listeria monocytogenes, S. elongatus was able to invade cultured mammalian cells and divide inside macrophages. Conclusion Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices. PMID:21533097

  9. Biodegradable synthetic bone composites

    DOEpatents

    Liu, Gao; Zhao, Dacheng; Saiz, Eduardo; Tomsia, Antoni P.

    2013-01-01

    The invention provides for a biodegradable synthetic bone composition comprising a biodegradable hydrogel polymer scaffold comprising a plurality of hydrolytically unstable linkages, and an inorganic component; such as a biodegradable poly(hydroxyethylmethacrylate)/hydroxyapatite (pHEMA/HA) hydrogel composite possessing mineral content approximately that of human bone.

  10. Synthetic Bursae for Robots

    NASA Technical Reports Server (NTRS)

    Lovchik, Christopher S.

    2005-01-01

    Synthetic bursae are under development for incorporation into robot joints that are actuated by motor-driven cables in a manner similar to that of arthropod joints actuated by muscle-driven tendons. Like natural bursae, the synthetic bursae would serve as cushions and friction reducers. A natural bursa is a thin bladder filled with synovial fluid, which serves to reduce friction and provide a cushion between a bone and a muscle or a tendon. A synthetic bursa would be similar in form and function: It would be, essentially, a compact, soft roller consisting of a bladder filled with a non-Newtonian fluid. The bladder would be constrained to approximately constant volume. The synthetic bursa would cushion an actuator cable against one of the members of a robot joint and would reduce the friction between the cable and the member. Under load, the pressure in the bladder would hold the opposite walls of the bladder apart, making it possible for them to move freely past each other without rubbing.

  11. Synthetic Confrontation Therapy.

    ERIC Educational Resources Information Center

    Gilliam, Larry

    After initially dispelling predictable fears that his paper might suggest that computers can be equated with man, the author states the problem: what part, if any, might computers play in counseling. Specifically, the possibilities for therapeutic synthetic (artificial) counseling encounters are discussed. Two propositions are significant: (1) the…

  12. Synthetic Vision Workshop 2

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J. (Compiler)

    1999-01-01

    The second NASA sponsored Workshop on Synthetic/Enhanced Vision (S/EV) Display Systems was conducted January 27-29, 1998 at the NASA Langley Research Center. The purpose of this workshop was to provide a forum for interested parties to discuss topics in the Synthetic Vision (SV) element of the NASA Aviation Safety Program and to encourage those interested parties to participate in the development, prototyping, and implementation of S/EV systems that enhance aviation safety. The SV element addresses the potential safety benefits of synthetic/enhanced vision display systems for low-end general aviation aircraft, high-end general aviation aircraft (business jets), and commercial transports. Attendance at this workshop consisted of about 112 persons including representatives from industry, the FAA, and other government organizations (NOAA, NIMA, etc.). The workshop provided opportunities for interested individuals to give presentations on the state of the art in potentially applicable systems, as well as to discuss areas of research that might be considered for inclusion within the Synthetic Vision Element program to contribute to the reduction of the fatal aircraft accident rate. Panel discussions on topical areas such as databases, displays, certification issues, and sensors were conducted, with time allowed for audience participation.

  13. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test

    PubMed Central

    Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo e

    2015-01-01

    Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties. PMID:26335560

  14. Synthetic plant defense elicitors

    PubMed Central

    Bektas, Yasemin; Eulgem, Thomas

    2015-01-01

    To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug-like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection. PMID:25674095

  15. Synthetic River Valleys

    NASA Astrophysics Data System (ADS)

    Brown, R.; Pasternack, G. B.

    2011-12-01

    The description of fluvial form has evolved from anecdotal descriptions to artistic renderings to 2D plots of cross section or longitudinal profiles and more recently 3D digital models. Synthetic river valleys, artificial 3D topographic models of river topography, have a plethora of potential applications in fluvial geomorphology, and the earth sciences in general, as well as in computer science and ecology. Synthetic river channels have existed implicitly since approximately the 1970s and can be simulated from a variety of approaches spanning the artistic and numerical. An objective method of synthesizing 3D stream topography based on reach scale attributes would be valuable for sizing 3D flumes in the physical and numerical realms, as initial input topography for morphodynamic models, stream restoration design, historical reconstruction, and mechanistic testing of interactions of channel geometric elements. Quite simply - simulation of synthetic channel geometry of prescribed conditions can allow systematic evaluation of the dominant relationships between river flow and geometry. A new model, the control curve method, is presented that uses hierarchically scaled parametric curves in over-lapping 2D planes to create synthetic river valleys. The approach is able to simulate 3D stream geometry from paired 2D descriptions and can allow experimental insight into form-process relationships in addition to visualizing past measurements of channel form that are limited to two dimension descriptions. Results are presented that illustrate the models ability to simulate fluvial topography representative of real world rivers as well as how channel geometric elements can be adjusted. The testing of synthetic river valleys would open up a wealth of knowledge as to why some 3D attributes of river channels are more prevalent than others as well as bridging the gap between the 2D descriptions that have dominated fluvial geomorphology the past century and modern, more complete, 3D

  16. Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents.

    PubMed

    Liu, Xiao-Fang; Zheng, Chang-Ji; Sun, Liang-Peng; Liu, Xue-Kun; Piao, Hu-Ri

    2011-08-01

    A series of chalcone derivatives bearing the 2,4-thiazolidinedione and benzoic acid moieties (8a-s) were synthesized, characterized, and evaluated for their anti-bacterial activity. Among the tested compounds, the most effective were 8a, 8h, 8k, 8n and 8q with MIC value in the range of 0.5-4 μg/mL against six Gram-positive bacteria (including multidrug-resistant clinical isolates). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 and E. coli 1682 at 64 μg/mL.

  17. Derivatives of Δ 2-pyrazoline-products of 1,5-diaminotetrazole interaction with chalcone: Molecular structure and spectral properties

    NASA Astrophysics Data System (ADS)

    Kolos, N. N.; Paponov, B. V.; Orlov, V. D.; Lvovskaya, M. I.; Doroshenko, A. O.; Shishkin, O. V.

    2006-03-01

    1,5-diaminotetrazole at conditions of its interaction with chalcones (1,3-diphenylpropenones) in hot DMF undergoes Dimroth rearrangement to 5-tetrazolylhydrazine, which results in formation of 1-(5-tetrazolyl)-3,5-diaryl-Δ 2-pyrazolines ( I). Structure of the obtained products was confirmed by their parallel synthesis and X-ray structural analysis. Unusual fluorescence behavior of the tetrazolopyrazolynes in polar solvents was attributed to the dissociation of their highly acidic tetrazole N-H group. The last hypothesis was confirmed at the investigation of the protolytic interactions of I with tertiary amine.

  18. A Malus crabapple chalcone synthase gene, McCHS, regulates red petal color and flavonoid biosynthesis.

    PubMed

    Tai, Deqiang; Tian, Ji; Zhang, Jie; Song, Tingting; Yao, Yuncong

    2014-01-01

    Chalcone synthase is a key and often rate-limiting enzyme in the biosynthesis of anthocyanin pigments that accumulate in plant organs such as flowers and fruits, but the relationship between CHS expression and the petal coloration level in different cultivars is still unclear. In this study, three typical crabapple cultivars were chosen based on different petal colors and coloration patterns. The two extreme color cultivars, 'Royalty' and 'Flame', have dark red and white petals respectively, while the intermediate cultivar 'Radiant' has pink petals. We detected the flavoniods accumulation and the expression levels of McCHS during petals expansion process in different cultivars. The results showed McCHS have their special expression patterns in each tested cultivars, and is responsible for the red coloration and color variation in crabapple petals, especially for color fade process in 'Radiant'. Furthermore, tobacco plants constitutively expressing McCHS displayed a higher anthocyanins accumulation and a deeper red petal color compared with control untransformed lines. Moreover, the expression levels of several anthocyanin biosynthetic genes were higher in the transgenic McCHS overexpressing tobacco lines than in the control plants. A close relationship was observed between the expression of McCHS and the transcription factors McMYB4 and McMYB5 during petals development in different crabapple cultivars, suggesting that the expression of McCHS was regulated by these transcription factors. We conclude that the endogenous McCHS gene is a critical factor in the regulation of anthocyanin biosynthesis during petal coloration in Malus crabapple. PMID:25357207

  19. Synthesis of phenstatin/isocombretastatin-chalcone conjugates as potent tubulin polymerization inhibitors and mitochondrial apoptotic inducers.

    PubMed

    Kamal, Ahmed; Kumar, G Bharath; Vishnuvardhan, M V P S; Shaik, Anver Basha; Reddy, Vangala Santhosh; Mahesh, Rasala; Sayeeda, Ibrahim Bin; Kapure, Jeevak Sopanrao

    2015-04-01

    A series of phenstatin/isocombretastatin–chalcones were synthesized and screened for their cytotoxic activity against various human cancer cell lines. Some representative compounds exhibited significant antiproliferative activity against a panel of sixty human cancer cell lines of the NCI, with GI50 values in the range of 0.11 to 19.0 μM. Three compounds (3b, 3c and 3e) showed a broad spectrum of antiproliferative efficacy on most of the cell lines in the sub-micromolar range. In addition, all the synthesized compounds (3a–l and 4a–l) displayed moderate to excellent cytotoxicity against breast cancer cells such as MCF-7 and MDA-MB-231 with IC50 values in the range of 0.5 to 19.9 μM. Moreover, the tubulin polymerization assay and immunofluorescence analysis results suggest that some of these compounds like 3c and 3e exhibited significant inhibitory effect on the tubulin assembly with an IC50 value of 0.8 μM and 0.6 μM respectively. A competitive binding assay suggested that these compounds bind at the colchicine-binding site of tubulin. A cell cycle assay revealed that these compounds arrest at the G2/M phase and lead to apoptotic cell death. Furthermore, this was confirmed by Hoechst 33258 staining, activation of caspase 9, DNA fragmentation, Annexin V-FITC and mitochondrial membrane depolarization. Molecular docking studies indicated that compounds like 3e occupy the colchicine binding site of tubulin.

  20. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    SciTech Connect

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  1. A chalcone isomerase-like protein enhances flavonoid production and flower pigmentation.

    PubMed

    Morita, Yasumasa; Takagi, Kyoko; Fukuchi-Mizutani, Masako; Ishiguro, Kanako; Tanaka, Yoshikazu; Nitasaka, Eiji; Nakayama, Masayoshi; Saito, Norio; Kagami, Takashi; Hoshino, Atsushi; Iida, Shigeru

    2014-04-01

    Flavonoids are major pigments in plants, and their biosynthetic pathway is one of the best-studied metabolic pathways. Here we have identified three mutations within a gene that result in pale-colored flowers in the Japanese morning glory (Ipomoea nil). As the mutations lead to a reduction of the colorless flavonoid compound flavonol as well as of anthocyanins in the flower petal, the identified gene was designated enhancer of flavonoid production (EFP). EFP encodes a chalcone isomerase (CHI)-related protein classified as a type IV CHI protein. CHI is the second committed enzyme of the flavonoid biosynthetic pathway, but type IV CHI proteins are thought to lack CHI enzymatic activity, and their functions remain unknown. The spatio-temporal expression of EFP and structural genes encoding enzymes that produce flavonoids is very similar. Expression of both EFP and the structural genes is coordinately promoted by genes encoding R2R3-MYB and WD40 family proteins. The EFP gene is widely distributed in land plants, and RNAi knockdown mutants of the EFP homologs in petunia (Petunia hybrida) and torenia (Torenia hybrida) had pale-colored flowers and low amounts of anthocyanins. The flavonol and flavone contents in the knockdown petunia and torenia flowers, respectively, were also significantly decreased, suggesting that the EFP protein contributes in early step(s) of the flavonoid biosynthetic pathway to ensure production of flavonoid compounds. From these results, we conclude that EFP is an enhancer of flavonoid production and flower pigmentation, and its function is conserved among diverse land plant species.

  2. Synthesis, X-ray crystal structures and catecholase activity investigation of new chalcone ligands

    NASA Astrophysics Data System (ADS)

    Thabti, Salima; Djedouani, Amel; Rahmouni, Samra; Touzani, Rachid; Bendaas, Abderrahmen; Mousser, Hénia; Mousser, Abdelhamid

    2015-12-01

    The reaction of dehydroacetic acid DHA carboxaldehyde and RCHO derivatives (R = quinoleine-8-; indole-3-; pyrrol-2- and 4-(dimethylamino)phenyl - afforded four new chalcone ligands (4-hydroxy-6-methyl-3-[(2E)-3-quinolin-8-ylprop-2-enoyl]-2H-pyran-2-one) L1, (4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one) L2, (4-hydroxy-6-methyl-3-[(2E)-3-(1H-pyrrol-2-yl)prop-2-enoyl]-2H-pyran-2-one) L3, and (3-{(2E)-3-[4-(dimethylamino)phenyl]prop-2-enoyl}-4-hydroxy-6-methyl-2H-pyran-2-one) L4. L3 and L4 were characterized by X-ray crystallography. Molecules crystallize with four and two molecules in the asymmetric unit, respectively and adopt an E conformation about the Cdbnd C bond. Both structures are stabilized by an extended network O-H … O. Furthermore, N-H … O and C-H … O hydrogen bonds are observed in L3 and L4 structures, respectively. The in situ generated copper (II) complexes of the four compounds L1, L2, L3 and L4 were examined for their catalytic activities and were found to catalyze the oxidation reaction of catechol to o-quinone under atmospheric dioxygen. The rates of this oxidation depend on three parameters: ligand, ion salts and solvent nature and the combination L2[Cu (CH3COO)2] leads to the faster catalytic process.

  3. Cyclooxygenase-2 knockdown using retinoic acid chalcone (RAC), a promising therapeutic strategy for colon cancer

    PubMed Central

    Jiang, Chao; Wang, Qiong; Xu, Zhe; Li, Wei-Su; Chen, Che; Yao, Xue-Quan; Liu, Fu-Kun

    2015-01-01

    Retinoic acid is an effective agent in the treatment of epithelial and hematological malignancies. The present study demonstrates that retinoic acid chalcone (RAC), an analogue of retinoic acid inhibits cell proliferation and induces apoptosis in HCT-15 and CT26.WT colon cancer cell lines. In HCT-15 cells the percentage of apoptotic cells increased from 32.4 ± 3, 45.0 ± 3 to 72.6 ± 5% respectively at 10, 15 and 20 μg/mL compared to 3.7% in control. Similarly in CT26.WT cells the percentage increased from 28.6 ± 3, 41.2 ± 3 to 65.4 ± 5% on treatment with 10, 15 and 20 μg/mL concentrations of RAC after 72 h compared to 2.9 ± 1% in control. Western blotting, fluorescence-activated cell sorting analysis and reverse transcription-PCR assays were used to investigate these effects. RAC inhibited the overexpression of COX-2, PGE2 and PGE2 receptor (EP1 and EP4) in the colon cancer cell lines. RAC mediated inhibition of cell growth and induction of apoptosis through COX-2 inhibition was also confirmed by treating the HCT-15 and CT26.WT colon cancer cells with COX-2 inhibitor, indomethacin and transfection of cells with COX-2 small interfering RNA. In nude mice with tumor xenografts, treatment with RAC-supplemented diet caused inhibition of COX-2, PGE2, and PGE2 receptors (EP1, EP3, and EP4) in tumors. Thus RAC can be a potential candidate for the treatment of colon cancer through the inhibition of COX-2 expression and subsequent inhibition of PGE2 and PGE2 receptors. PMID:26269760

  4. Antigiardial activity of novel triazolyl-quinolone-based chalcone derivatives: when oxygen makes the difference

    PubMed Central

    Bahadur, Vijay; Mastronicola, Daniela; Singh, Amit K.; Tiwari, Hemandra K.; Pucillo, Leopoldo P.; Sarti, Paolo; Singh, Brajendra K.; Giuffrè, Alessandro

    2015-01-01

    Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an ‘anaerobic pathogen,’ G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study [Bahadur et al. (2014) Antimicrob. Agents Chemother. 58, 543]. Here, 45 novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified, and characterized by high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to three to fourfold); the same compounds proved to be up to >100-fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds. PMID:25904901

  5. Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

    SciTech Connect

    Wu, Yang-Chang; Sureshbabu, Munisamy; Fang, Yao-Ching; Wu, Yi-Hsiu; Lan, Yu-Hsuan; Chang, Fang-Rong; Chang, Ya-Wen; Hwang, Tsong-Long

    2013-02-01

    Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changes in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.

  6. A Malus Crabapple Chalcone Synthase Gene, McCHS, Regulates Red Petal Color and Flavonoid Biosynthesis

    PubMed Central

    Song, Tingting; Yao, Yuncong

    2014-01-01

    Chalcone synthase is a key and often rate-limiting enzyme in the biosynthesis of anthocyanin pigments that accumulate in plant organs such as flowers and fruits, but the relationship between CHS expression and the petal coloration level in different cultivars is still unclear. In this study, three typical crabapple cultivars were chosen based on different petal colors and coloration patterns. The two extreme color cultivars, ‘Royalty’ and ‘Flame’, have dark red and white petals respectively, while the intermediate cultivar ‘Radiant’ has pink petals. We detected the flavoniods accumulation and the expression levels of McCHS during petals expansion process in different cultivars. The results showed McCHS have their special expression patterns in each tested cultivars, and is responsible for the red coloration and color variation in crabapple petals, especially for color fade process in ‘Radiant’. Furthermore, tobacco plants constitutively expressing McCHS displayed a higher anthocyanins accumulation and a deeper red petal color compared with control untransformed lines. Moreover, the expression levels of several anthocyanin biosynthetic genes were higher in the transgenic McCHS overexpressing tobacco lines than in the control plants. A close relationship was observed between the expression of McCHS and the transcription factors McMYB4 and McMYB5 during petals development in different crabapple cultivars, suggesting that the expression of McCHS was regulated by these transcription factors. We conclude that the endogenous McCHS gene is a critical factor in the regulation of anthocyanin biosynthesis during petal coloration in Malus crabapple. PMID:25357207

  7. Nanoparticles as synthetic vaccines.

    PubMed

    Smith, Josiah D; Morton, Logan D; Ulery, Bret D

    2015-08-01

    As vaccines have transitioned from the use of whole pathogens to only the required antigenic epitopes, unwanted side effects have been decreased, but corresponding immune responses have been greatly diminished. To enhance immunogenicity, a variety of controlled release vehicles have been proposed as synthetic vaccines, but nanoparticles have emerged as particularly impressive systems due to many exciting publications. In specific, nanoparticles have been shown capable of not only desirable vaccine release, but can also be targeted to immune cells of interest, loaded with immunostimulatory substances termed adjuvants, or even induce desirable immune activating effects on their own. In the present review, recent advances in the utilization of inorganic, polymeric, and biomolecular nanoparticles as synthetic vaccines are discussed.

  8. Synthetic Foveal Imaging Technology

    NASA Technical Reports Server (NTRS)

    Monacos, Steve P. (Inventor); Hoenk, Michael E. (Inventor); Nikzad, Shouleh (Inventor)

    2013-01-01

    Apparatuses and methods are disclosed that create a synthetic fovea in order to identify and highlight interesting portions of an image for further processing and rapid response. Synthetic foveal imaging implements a parallel processing architecture that uses reprogrammable logic to implement embedded, distributed, real-time foveal image processing from different sensor types while simultaneously allowing for lossless storage and retrieval of raw image data. Real-time, distributed, adaptive processing of multi-tap image sensors with coordinated processing hardware used for each output tap is enabled. In mosaic focal planes, a parallel-processing network can be implemented that treats the mosaic focal plane as a single ensemble rather than a set of isolated sensors. Various applications are enabled for imaging and robotic vision where processing and responding to enormous amounts of data quickly and efficiently is important.

  9. Wholly Synthetic Molecular Machines.

    PubMed

    Cheng, Chuyang; Stoddart, J Fraser

    2016-06-17

    The past quarter of a century has witnessed an increasing engagement on the part of physicists and chemists in the design and synthesis of molecular machines de novo. This minireview traces the development of artificial molecular machines from their prototypes in the form of shuttles and switches to their emergence as motors and pumps where supplies of energy in the form of chemical fuel, electrochemical potential and light activation become a minimum requirement for them to function away from equilibrium. The challenge facing this rapidly growing community of scientists and engineers today is one of putting wholly synthetic molecules to work, both individually and as collections. Here, we highlight some of the recent conceptual and practical advances relating to the operation of wholly synthetic rotary and linear motors.

  10. Engineered Asymmetric Synthetic Vesicles

    NASA Astrophysics Data System (ADS)

    Lu, Li; Chiarot, Paul

    2013-11-01

    Synthetic vesicles are small, fluid-filled spheres that are enclosed by a bilayer of lipid molecules. They can be used as models for investigating membrane biology and as delivery vehicles for pharmaceuticals. In practice, it is difficult to simultaneously control membrane asymmetry, unilamellarity, vesicle size, vesicle-to-vesicle uniformity, and luminal content. Membrane asymmetry, where each leaflet of the bilayer is composed of different lipids, is of particular importance as it is a feature of most natural membranes. In this study, we leverage microfluidic technology to build asymmetric vesicles at high-throughput. We use the precise flow control offered by microfluidic devices to make highly uniform emulsions, with controlled internal content, that serve as templates to build the synthetic vesicles. Flow focusing, dielectrophoretic steering, and interfacial lipid self-assembly are critical procedures performed on-chip to produce the vesicles. Fluorescent and confocal microscopy are used to evaluate the vesicle characteristics.

  11. EXPEDITIOUS SYNTHETIC TRANSFORMATIONS USING MICROWAVES

    EPA Science Inventory

    Microwave-expedited solvent-free synthetic processes will be described for the synthesis of a variety of industrially significant compounds and intermediates namely, enamines, nitroalkenes, enones, oxidized sulfur compounds and ionic liquids. This solvent-free synthetic methodolo...

  12. Chemical synthetic biology.

    PubMed

    Chiarabelli, Cristiano; Luisi, Pier Luigi

    2014-01-01

    Although both the most popular form of synthetic biology (SB) and chemical synthetic biology (CSB) share the biotechnologically useful aim of making new forms of life, SB does so by using genetic manipulation of extant microorganism, while CSB utilises classic chemical procedures in order to obtain biological structures which are non-existent in nature. The main query concerning CSB is the philosophical question: why did nature do this, and not that? The idea then is to synthesise alternative structures in order to understand why nature operated in such a particular way. We briefly present here some various examples of CSB, including those cases of nucleic acids synthesised with pyranose instead of ribose, and proteins with a reduced alphabet of amino acids; also we report the developing research on the "never born proteins" (NBP) and "never born RNA" (NBRNA), up to the minimal cell project, where the issue is the preparation of semi-synthetic cells that can perform the basic functions of biological cells.

  13. Optical synthetic aperture radar

    NASA Astrophysics Data System (ADS)

    Ilovitsh, Asaf; Zach, Shlomo; Zalevsky, Zeev

    2013-06-01

    A method is proposed for increasing the resolution of an object and overcoming the diffraction limit of an optical system installed on top of a moving imaging system, such as an airborne platform or satellite. The resolution improvement is obtained via a two-step process. First, three low resolution differently defocused images are captured and the optical phase is retrieved using an improved iterative Gershberg-Saxton based algorithm. The phase retrieval allows numerical back propagation of the field to the aperture plane. Second, the imaging system is shifted and the first step is repeated. The obtained optical fields at the aperture plane are combined and a synthetically increased lens aperture is generated along the direction of movement, yielding higher imaging resolution. The method resembles a well-known approach from the microwave regime called the synthetic aperture radar in which the antenna size is synthetically increased along the platform propagation direction. The proposed method is demonstrated via Matlab simulation as well as through laboratory experiment.

  14. Synthetic surgical gloves.

    PubMed

    2002-06-01

    Surgical gloves are used by healthcare workers to protect them against bloodborne pathogens and other potential infectants and to prevent wound contamination in patients. In response to the increasing prevalence of allergies to natural rubber latex (NRL) among patients and medical staff, the trend toward purchasing gloves made of synthetic materials is on the rise. However, latex continues to dominate the market, and some people still perceive synthetic gloves as providing less protection and being less comfortable than NRL gloves. For this Update Evaluation, we present our findings for three newly evaluated glove models from three manufacturers and summarize our findings for the seven previously evaluated models that are still on the market. (Our earlier Evaluation was published in the February-March 2000 Health Devices.) As in the previous Evaluation, our ratings are based on the gloves' barrier effectiveness--that is, their resistance to viral penetration and their durability--and comfort. We also compared these characteristics of the synthetic gloves to those of NRL gloves. We found that all the evaluated gloves offer adequate barrier protection but that their level of comfort varies considerably. We rate three models Preferred, five models Acceptable, and two models Not Recommended. PMID:12116503

  15. Synthetic biology in plastids.

    PubMed

    Scharff, Lars B; Bock, Ralph

    2014-06-01

    Plastids (chloroplasts) harbor a small gene-dense genome that is amenable to genetic manipulation by transformation. During 1 billion years of evolution from the cyanobacterial endosymbiont to present-day chloroplasts, the plastid genome has undergone a dramatic size reduction, mainly as a result of gene losses and the large-scale transfer of genes to the nuclear genome. Thus the plastid genome can be regarded as a naturally evolved miniature genome, the gradual size reduction and compaction of which has provided a blueprint for the design of minimum genomes. Furthermore, because of the largely prokaryotic genome structure and gene expression machinery, the high transgene expression levels attainable in transgenic chloroplasts and the very low production costs in plant systems, the chloroplast lends itself to synthetic biology applications that are directed towards the efficient synthesis of green chemicals, biopharmaceuticals and other metabolites of commercial interest. This review describes recent progress with the engineering of plastid genomes with large constructs of foreign or synthetic DNA, and highlights the potential of the chloroplast as a model system in bottom-up and top-down synthetic biology approaches.

  16. Silencing of the chalcone synthase gene in Casuarina glauca highlights the important role of flavonoids during nodulation.

    PubMed

    Abdel-Lateif, Khalid; Vaissayre, Virginie; Gherbi, Hassen; Verries, Clotilde; Meudec, Emmanuelle; Perrine-Walker, Francine; Cheynier, Véronique; Svistoonoff, Sergio; Franche, Claudine; Bogusz, Didier; Hocher, Valérie

    2013-09-01

    Nitrogen-fixing root nodulation is confined to four plant orders, including > 14,000 Leguminosae, one nonlegume genus Parasponia and c. 200 actinorhizal species that form symbioses with rhizobia and Frankia bacterial species, respectively. Flavonoids have been identified as plant signals and developmental regulators for nodulation in legumes and have long been hypothesized to play a critical role during actinorhizal nodulation. However, direct evidence of their involvement in actinorhizal symbiosis is lacking. Here, we used RNA interference to silence chalcone synthase, which is involved in the first committed step of the flavonoid biosynthetic pathway, in the actinorhizal tropical tree Casuarina glauca. Transformed flavonoid-deficient hairy roots were generated and used to study flavonoid accumulation and further nodulation. Knockdown of chalcone synthase expression reduced the level of specific flavonoids and resulted in severely impaired nodulation. Nodule formation was rescued by supplementing the plants with naringenin, which is an upstream intermediate in flavonoid biosynthesis. Our results provide, for the first time, direct evidence of an important role for flavonoids during the early stages of actinorhizal nodulation. PMID:23692063

  17. Crucial role of molecular planarity on the second order nonlinear optical property of pyridine based chalcone single crystals

    NASA Astrophysics Data System (ADS)

    Menezes, Anthoni Praveen; Jayarama, A.; Ng, Seik Weng

    2015-05-01

    An efficient nonlinear optical material 2E-3-(4-bromophenyl)-1-(pyridin-3-yl) prop-2-en-1-one (BPP) was synthesized and single crystals were grown using slow evaporation solution growth technique at room temperature. Grown crystal had prismatic morphology and its structure was confirmed by various spectroscopic studies, elemental analysis, and single crystal X-ray diffraction (XRD) technique. The single crystal XRD of the crystal showed that BPP crystallizes in monoclinic system with noncentrosymmetric space group P21 and the cell parameters are a = 5.6428(7) Å, b = 3.8637(6) Å, c = 26.411(2) Å, β = 97.568(11) deg and v = 575.82(12) Å3. The UV-Visible spectrum reveals that the crystal is optically transparent and has high optical energy band gap of 3.1 eV. The powder second harmonic generation efficiency (SHG) of BPP is 6.8 times that of KDP. From thermal analysis it is found that the crystal melts at 139 °C and decomposes at 264 °C. High optical transparency down to blue region, higher powder SHG efficiency and better thermal stability than that of urea makes this chalcone derivative a promising candidate for SHG applications. Furthermore, effect of molecular planarity on SHG efficiency and role of pyridine ring adjacent to carbonyl group in forming noncentrosymmetric crystal systems of chalcone family is also discussed.

  18. Effect of position of nitrogen in pyridine ring on structural, optical and thermal properties of chalcone single crystals

    NASA Astrophysics Data System (ADS)

    Menezes, Anthoni Praveen; Jayarama, A.

    2015-06-01

    Crystals are unacknowledged pillars of the world of contemporary technology. Single crystals of a set of three chalcone derivatives, 1-(pyridin-2-yl)-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one (C1), 1-(pyridin-3-yl)-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one (C2) and 1-(pyridin-4-yl)-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one (C3) were grown by slow evaporation technique. The thermal analysis reveals that the chalcone derivatives possess good thermal and chemical stability. Crystal C1 is nonlinear optically (NLO) active with SHG efficiency of 0.7 times that of KDP. The position of nitrogen in the pyridine ring has a significant effect on thermal, structural and NLO properties of these materials. The UV-Visible spectrum discloses that the crystals have adequate transmission in the entire visible region. Due to good thermal stability, optical transparency and SHG response, crystal C1 is an useful candidate for NLO applications such as frequency doubling down to 433 nm.

  19. IPP51, a chalcone acting as a microtubule inhibitor with in vivo antitumor activity against bladder carcinoma

    PubMed Central

    Martel-Frachet, Véronique; Keramidas, Michelle; Nurisso, Alessandra; DeBonis, Salvatore; Rome, Claire; Coll, Jean-Luc; Boumendjel, Ahcène; Skoufias, Dimitrios A.; Ronot, Xavier

    2015-01-01

    We previously identified 1-(2,4-dimethoxyphenyl)-3-(1-methylindolyl) propenone (IPP51), a new chalcone derivative that is capable of inducing prometaphase arrest and subsequent apoptosis of bladder cancer cells. Here, we demonstrate that IPP51 selectively inhibits proliferation of tumor-derived cells versus normal non-tumor cells. IPP51 interfered with spindle formation and mitotic chromosome alignment. Accumulation of cyclin B1 and mitotic checkpoint proteins Bub1 and BubR1 on chromosomes in IPP51 treated cells indicated the activation of spindle-assembly checkpoint, which is consistent with the mitotic arrest. The antimitotic actions of other chalcones are often associated with microtubule disruption. Indeed, IPP51 inhibited tubulin polymerization in an in vitro assay with purified tubulin. In cells, IPP51 induced an increase in soluble tubulin. Furthermore, IPP51 inhibited in vitro capillary-like tube formation by endothelial cells, indicating that it has anti-angiogenic activity. Molecular docking showed that the indol group of IPP51 can be accommodated in the colchicine binding site of tubulin. This characteristic was confirmed by an in vitro competition assay demonstrating that IPP51 can compete for colchicine binding to soluble tubulin. Finally, in a human bladder xenograft mouse model, IPP51 inhibited tumor growth without signs of toxicity. Altogether, these findings suggest that IPP51 is an attractive new microtubule-targeting agent with potential chemotherapeutic value. PMID:26036640

  20. IPP51, a chalcone acting as a microtubule inhibitor with in vivo antitumor activity against bladder carcinoma.

    PubMed

    Martel-Frachet, Véronique; Keramidas, Michelle; Nurisso, Alessandra; DeBonis, Salvatore; Rome, Claire; Coll, Jean-Luc; Boumendjel, Ahcène; Skoufias, Dimitrios A; Ronot, Xavier

    2015-06-10

    We previously identified 1-(2,4-dimethoxyphenyl)-3-(1-methylindolyl) propenone (IPP51), a new chalcone derivative that is capable of inducing prometaphase arrest and subsequent apoptosis of bladder cancer cells. Here, we demonstrate that IPP51 selectively inhibits proliferation of tumor-derived cells versus normal non-tumor cells. IPP51 interfered with spindle formation and mitotic chromosome alignment. Accumulation of cyclin B1 and mitotic checkpoint proteins Bub1 and BubR1 on chromosomes in IPP51 treated cells indicated the activation of spindle-assembly checkpoint, which is consistent with the mitotic arrest. The antimitotic actions of other chalcones are often associated with microtubule disruption. Indeed, IPP51 inhibited tubulin polymerization in an in vitro assay with purified tubulin. In cells, IPP51 induced an increase in soluble tubulin. Furthermore, IPP51 inhibited in vitro capillary-like tube formation by endothelial cells, indicating that it has anti-angiogenic activity. Molecular docking showed that the indol group of IPP51 can be accommodated in the colchicine binding site of tubulin. This characteristic was confirmed by an in vitro competition assay demonstrating that IPP51 can compete for colchicine binding to soluble tubulin. Finally, in a human bladder xenograft mouse model, IPP51 inhibited tumor growth without signs of toxicity. Altogether, these findings suggest that IPP51 is an attractive new microtubule-targeting agent with potential chemotherapeutic value. PMID:26036640

  1. Ultrafast optical nonlinearities and figures of merit in acceptor-substituted 3,4,5-trimethoxy chalcone derivatives: Structure-property relationships

    NASA Astrophysics Data System (ADS)

    Gu, Bing; Ji, Wei; Patil, P. S.; Dharmaprakash, S. M.

    2008-05-01

    By performing both Z-scan and transient transmission measurements with 130 fs laser pulses in the near infrared region, we investigated structure-property relationships for χ(3) in acceptor-substituted 3,4,5-trimethoxy chalcone derivatives. We determined all nonlinear parameters, including two-photon absorption (2PA) cross section, 2PA-induced excited-state absorption (ESA) cross section, microscopic second-order hyperpolarizability, and lifetime of the excited state in these molecules. We found that the microscopic second-order hyperpolarizability γR and 2PA cross section σ2PA in chalcone derivatives increase as the acceptor strength of the molecules increases, which demonstrates an enhancement in optical nonlinearities by simple structural variations. We evaluated the one-photon, two-photon, and effective three-photon figures of merit for acetone solutions of chalcone derivatives at irradiance of 100 GW/cm2. Furthermore, we observed optical limiting behavior in these compounds, which result from both 2PA and 2PA-assisted ESA. These results indicated that chalcone derivatives are a promising candidate for applications on nonlinear photonic devices.

  2. "N"-Heterocyclic Carbene-Catalyzed Reaction of Chalcone and Cinnamaldehyde to Give 1,3,4-Triphenylcyclopentene Using Organocatalysis to Form a Homoenolate Equivalent

    ERIC Educational Resources Information Center

    Snider, Barry B.

    2015-01-01

    In this experiment, students carry out a modern organocatalytic reaction using IMes·HCl and NaOH to catalyze the formation of 1,3,4-triphenylcyclopentene from cinnamaldehyde and chalcone in water. Deprotonation of IMes·HCl with NaOH forms the "N"-heterocyclic carbene IMes that reacts with cinnamaldehyde to form a homoenolate equivalent…

  3. Nucleophilic and electrophilic double aroylation of chalcones with benzils promoted by the dimsyl anion as a route to all carbon tetrasubstituted olefins.

    PubMed

    Ragno, Daniele; Bortolini, Olga; Fantin, Giancarlo; Fogagnolo, Marco; Giovannini, Pier Paolo; Massi, Alessandro

    2015-02-01

    Dimsyl anion promoted the polarity reversal of benzils in a Stetter-like reaction with chalcones to give 2-benzoyl-1,4-diones (double aroylation products), which, in turn, were converted into the corresponding tetrasubstituted olefins via aerobic oxidative dehydrogenation catalyzed by Cu(OAc)2. PMID:25542390

  4. Opportunities in plant synthetic biology.

    PubMed

    Cook, Charis; Martin, Lisa; Bastow, Ruth

    2014-05-01

    Synthetic biology is an emerging field uniting scientists from all disciplines with the aim of designing or re-designing biological processes. Initially, synthetic biology breakthroughs came from microbiology, chemistry, physics, computer science, materials science, mathematics, and engineering disciplines. A transition to multicellular systems is the next logical step for synthetic biologists and plants will provide an ideal platform for this new phase of research. This meeting report highlights some of the exciting plant synthetic biology projects, and tools and resources, presented and discussed at the 2013 GARNet workshop on plant synthetic biology.

  5. Opportunities in plant synthetic biology.

    PubMed

    Cook, Charis; Martin, Lisa; Bastow, Ruth

    2014-05-01

    Synthetic biology is an emerging field uniting scientists from all disciplines with the aim of designing or re-designing biological processes. Initially, synthetic biology breakthroughs came from microbiology, chemistry, physics, computer science, materials science, mathematics, and engineering disciplines. A transition to multicellular systems is the next logical step for synthetic biologists and plants will provide an ideal platform for this new phase of research. This meeting report highlights some of the exciting plant synthetic biology projects, and tools and resources, presented and discussed at the 2013 GARNet workshop on plant synthetic biology. PMID:24502956

  6. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  7. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  8. Progress toward synthetic cells.

    PubMed

    Blain, J Craig; Szostak, Jack W

    2014-01-01

    The complexity of even the simplest known life forms makes efforts to synthesize living cells from inanimate components seem like a daunting task. However, recent progress toward the creation of synthetic cells, ranging from simple protocells to artificial cells approaching the complexity of bacteria, suggests that the synthesis of life is now a realistic goal. Protocell research, fueled by advances in the biophysics of primitive membranes and the chemistry of nucleic acid replication, is providing new insights into the origin of cellular life. Parallel efforts to construct more complex artificial cells, incorporating translational machinery and protein enzymes, are providing information about the requirements for protein-based life. We discuss recent advances and remaining challenges in the synthesis of artificial cells, the possibility of creating new forms of life distinct from existing biology, and the promise of this research for gaining a deeper understanding of the nature of living systems. PMID:24606140

  9. Synthetic antibiofilm peptides.

    PubMed

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. PMID:26724202

  10. Entraining synthetic genetic oscillators

    NASA Astrophysics Data System (ADS)

    Wagemakers, Alexandre; Buldú, Javier M.; Sanjuán, Miguel A. F.; de Luis, Oscar; Izquierdo, Adriana; Coloma, Antonio

    2009-09-01

    We propose a new approach for synchronizing a population of synthetic genetic oscillators, which consists in the entrainment of a colony of repressilators by external modulation. We present a model where the repressilator dynamics is affected by periodic changes in temperature. We introduce an additional plasmid in the bacteria in order to correlate the temperature variations with the enhancement of the transcription rate of a certain gene. This can be done by introducing a promoter that is related to the heat shock response. This way, the expression of that gene results in a protein that enhances the overall oscillations. Numerical results show coherent oscillations of the population for a certain range of the external frequency, which is in turn related to the natural oscillation frequency of the modified repressilator. Finally we study the transient times related with the loss of synchronization and we discuss possible applications in biotechnology of large-scale production coupled to synchronization events induced by heat shock.

  11. Bifendate-chalcone hybrids: a new class of potential dual inhibitors of P-glycoprotein and breast cancer resistance protein.

    PubMed

    Gu, Xiaoke; Ren, Zhiguang; Peng, Hui; Peng, Sixun; Zhang, Yihua

    2014-12-12

    We previously described bifendate-chalcone hybrids as potent P-glycoprotein inhibitors. In the present work, we determine whether these compounds could reverse breast cancer resistance protein (BCRP, ABCG2)-mediated multidrug resistance using HEK293/BCRP cells which was BCRP-transfected stable HEK293 cells. Results indicated that compounds 8d, 8f, 8g and 8h could significantly enhance mitoxantrone accumulation in HEK293/BCRP cells via inhibiting BCRP drug efflux function. The most active compound 8g exhibited little intrinsic cytotoxicity (IC₅₀>100 μM), and could reverse BCRP-mediated drug resistance independent of decreasing BCRP expression level. Notably, 8g had little inhibitory effect on multidrug resistance-associated protein 1 (MRP1, ABCC1), another drug efflux transporter. The present findings, together with the previous results, suggest that 8g might be act as dual inhibitors of P-gp and BCRP.

  12. Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi.

    PubMed

    Murakami, S; Kijima, H; Isobe, Y; Muramatsu, M; Aihara, H; Otomo, S; Baba, K; Kozawa, M

    1990-10-01

    Two chalcone derivatives, xanthoangelol (1) and 4-hydroxyderricin (II) isolated from Angelica keiskei Koidzumi, inhibited pig gastric H+, K(+)-ATPase with IC50 values of 1.8 and 3.3 microM, respectively. The inhibition by I or II was competitive with respect to ATP and was non-competitive with respect to K+ I and II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of 1.3 and 3.5 microM, respectively. Proton transport in-vitro was inhibited by I or II, in a dose-dependent manner, 1 at 100 mg kg-1, i.p. significantly inhibited acid secretion and the formation of stress-induced gastric lesions. These results suggest that the antisecretory effect of 1 is due to the inhibition of gastric H+, K(+)-ATPase.

  13. Patterning of virus-infected Glycine max seed coat is associated with suppression of endogenous silencing of chalcone synthase genes.

    PubMed

    Senda, Mineo; Masuta, Chikara; Ohnishi, Shizen; Goto, Kazunori; Kasai, Atsushi; Sano, Teruo; Hong, Jin-Sung; MacFarlane, Stuart

    2004-04-01

    Most commercial Glycine max (soybean) varieties have yellow seeds because of loss of pigmentation in the seed coat. It has been suggested that inhibition of seed coat pigmentation in yellow G. max may be controlled by homology-dependent silencing of chalcone synthase (CHS) genes. Our analysis of CHS mRNA and short-interfering RNAs provide clear evidence that the inhibition of seed coat pigmentation in yellow G. max results from posttranscriptional rather than transcriptional silencing of the CHS genes. Furthermore, we show that mottling symptoms present on the seed coat of G. max plants infected with some viruses can be caused by suppression of CHS posttranscriptional gene silencing (PTGS) by a viral silencing suppressor protein. These results demonstrate that naturally occurring PTGS plays a key role in expression of a distinctive phenotype in plants and present a simple clear example of the elucidation of the molecular mechanism for viral symptom induction. PMID:15037735

  14. Design, synthesis and anticancer activity of matrine-1H-1,2,3-triazole-chalcone conjugates.

    PubMed

    Zhao, Lihui; Mao, Lina; Hong, Ge; Yang, Xiaojiao; Liu, Tianjun

    2015-06-15

    A series of novel matrine-1H-1,2,3-triazole-chalcone conjugates was synthesized and their anticancer activity against A549, Bel-7402, Hela, and MCF-7 cancer cells was evaluated. Most of the conjugates displayed higher potency than their components. Compounds 6h and 6i exhibited more potent anticancer activity than 5-fluorouracil against the four tested human cancer cell lines and lower cytotoxicity to NIH3T3 normal cells. Flow cytometry tests demonstrated that compound 6h could induce apoptosis of A549 cells in a concentration-dependent manner. Moreover, 6h could efficiently suppress human tumor growth in mouse xenograft model without causing obvious toxicities.

  15. Spectroscopic and nonlinear optical properties of new chalcone fluorescent probes for bioimaging applications: a theoretical and experimental study.

    PubMed

    Krawczyk, Przemysław; Pietrzak, Marek; Janek, Tomasz; Jędrzejewska, Beata; Cysewski, Piotr

    2016-06-01

    In this study, the newly synthesized non-centrosymmetric, 4-dimethylamino-3'-isothiocyanatochalcone (PKA) compound was presented. This compound belongs to the chalcone group, and its main purpose is to be used in biomedical imaging as a fluorescence dye. For this reason, the linear and nonlinear properties in solvents of different polarity were thoroughly studied. In accordance with the requirements for a fluorochrome, the PKA compound is characterized by strong absorption, large Stokes' shifts, relatively high fluorescence quantum yields and high nonlinear optical response. Moreover, the isothiocyanate reactive probe was conjugated with Concanavalin A. Conventional fluorescence microscopy imaging of Candida albicans cells incubated with the PKA-Concanavalin A, is presented. The results of this study show that the novel conjugate PKA-Concanavalin A could be a promising new probe for cellular labelling in biological and biomedical research. Graphical abstract Spectroscopic behavior of the PKA dye. PMID:27168200

  16. Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position.

    PubMed

    Winter, Evelyn; Gozzi, Gustavo Jabor; Chiaradia-Delatorre, Louise Domeneghini; Daflon-Yunes, Nathalia; Terreux, Raphael; Gauthier, Charlotte; Mascarello, Alessandra; Leal, Paulo César; Cadena, Silvia M; Yunes, Rosendo Augusto; Nunes, Ricardo José; Creczynski-Pasa, Tania Beatriz; Di Pietro, Attilio

    2014-01-01

    A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition.

  17. Benzophenone Synthase and Chalcone Synthase Accumulate in the Mesophyll of Hypericum perforatum Leaves at Different Developmental Stages

    PubMed Central

    Belkheir, Asma K.; Gaid, Mariam; Liu, Benye; Hänsch, Robert; Beerhues, Ludger

    2016-01-01

    The active medicinal constituents in Hypericum perforatum, used to treat depression and skin irritation, include flavonoids and xanthones. The carbon skeletons of these compounds are formed by chalcone synthase (CHS) and benzophenone synthase (BPS), respectively. Polyclonal antisera were raised against the polyketide synthases from Hypericum androsaemum and their IgG fractions were isolated. Immunoblotting and immunotitration were used to test the IgGs for crossreactivity and monospecificity in H. perforatum leaf protein extract. Immunofluorescence localization revealed that both CHS and BPS are located in the mesophyll. The maximum fluorescence levels were observed in approx. 0.5 and 1 cm long leaves, respectively. The fluorescence intensity observed for CHS significantly exceeded that for BPS. Using histochemical staining, flavonoids were detected in the mesophyll, indicating that the sites of biosynthesis and accumulation coincide. Our results help understand the biosynthesis and underlying regulation of active H. perforatum constituents. PMID:27446151

  18. New chalcone and pterocarpoid derivatives from the roots of Flemingia philippinensis with antiproliferative activity and apoptosis-inducing property.

    PubMed

    Kang, Wen-Jia; Li, Da-Hong; Han, Tong; Sun, Lin; Fu, Yan-Bin; Sai, Chun-Mei; Li, Zhan-Lin; Hua, Hui-Ming

    2016-07-01

    Investigation of the roots of Flemingia philippinensis resulted in the isolation of two new chalcones, flemiphilippinones B (1) and C (2), and one new pterocarpoid, demethylwedelolactone-11-methyl ether (3), together with 12 known compounds (4-15). The antiproliferative activity against PC-3 cells was evaluated and most compounds showed cytotoxicity, among which, compound 2 exhibited GI50 value of 14.12μM. The antiproliferative activity of 2 against Bel-7402 and CaEs-17 cells was also measured, with GI50 values of 1.91 and 2.58μM, respectively. Intensive mechanism study showed that 2 caused cell-cycle arrest at S/G2 phase and induced apoptosis in Bel-7402 cells through mitochondria-related pathway. PMID:27316977

  19. Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position

    PubMed Central

    Winter, Evelyn; Gozzi, Gustavo Jabor; Chiaradia-Delatorre, Louise Domeneghini; Daflon-Yunes, Nathalia; Terreux, Raphael; Gauthier, Charlotte; Mascarello, Alessandra; Leal, Paulo César; Cadena, Silvia M; Yunes, Rosendo Augusto; Nunes, Ricardo José; Creczynski-Pasa, Tania Beatriz; Di Pietro, Attilio

    2014-01-01

    A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition. PMID:24920885

  20. Benzophenone Synthase and Chalcone Synthase Accumulate in the Mesophyll of Hypericum perforatum Leaves at Different Developmental Stages.

    PubMed

    Belkheir, Asma K; Gaid, Mariam; Liu, Benye; Hänsch, Robert; Beerhues, Ludger

    2016-01-01

    The active medicinal constituents in Hypericum perforatum, used to treat depression and skin irritation, include flavonoids and xanthones. The carbon skeletons of these compounds are formed by chalcone synthase (CHS) and benzophenone synthase (BPS), respectively. Polyclonal antisera were raised against the polyketide synthases from Hypericum androsaemum and their IgG fractions were isolated. Immunoblotting and immunotitration were used to test the IgGs for crossreactivity and monospecificity in H. perforatum leaf protein extract. Immunofluorescence localization revealed that both CHS and BPS are located in the mesophyll. The maximum fluorescence levels were observed in approx. 0.5 and 1 cm long leaves, respectively. The fluorescence intensity observed for CHS significantly exceeded that for BPS. Using histochemical staining, flavonoids were detected in the mesophyll, indicating that the sites of biosynthesis and accumulation coincide. Our results help understand the biosynthesis and underlying regulation of active H. perforatum constituents. PMID:27446151

  1. Redox Behavior of Anticancer Chalcone on a Glassy Carbon Electrode and Evaluation of its Interaction Parameters with DNA

    PubMed Central

    Shah, Afzal; Khan, Asad M.; Qureshi, Rumana; Ansari, Farzana L.; Nazar, Muhammad F.; Shah, Syed S.

    2008-01-01

    The interaction of anticancer chalcone [AMC, 1-(4′-aminophenyl)-3-(4-N,N-dimethylphenyl)-2-propen-1-one] with DNA has been explored using electrochemical, spectroscopic and viscometric techniques. A shift in peak potential and decrease in peak current were observed in cyclic voltammetry and hypochromism accompanied with bathochromic shift were noticed in UV-Vis absorption spectroscopy. These findings were taken as evidence for AMC –DNA intercalation. A binding constant (K) with a value of 6.15 × 105 M−1 was obtained from CV data, which was also confirmed by UV-Vis absorption titration. Moreover, the diffusion coefficient of the drug with and without DNA (Db and Du), heterogeneous electron transfer rate constant (ko) and electron affinity (A) were also calculated from electrochemical data. PMID:19325813

  2. Redox behavior of anticancer chalcone on a glassy carbon electrode and evaluation of its interaction parameters with DNA.

    PubMed

    Shah, Afzal; Khan, Asad M; Qureshi, Rumana; Ansari, Farzana L; Nazar, Muhammad F; Shah, Syed S

    2008-08-01

    The interaction of anticancer chalcone [AMC, 1-(4'-aminophenyl)-3-(4-N,N-dimethylphenyl)-2-propen-1-one] with DNA has been explored using electrochemical, spectroscopic and viscometric techniques. A shift in peak potential and decrease in peak current were observed in cyclic voltammetry and hypochromism accompanied with bathochromic shift were noticed in UV-Vis absorption spectroscopy. These findings were taken as evidence for AMC -DNA intercalation. A binding constant (K) with a value of 6.15 x 10(5) M(-1) was obtained from CV data, which was also confirmed by UV-Vis absorption titration. Moreover, the diffusion coefficient of the drug with and without DNA (D(b) and D(u)), heterogeneous electron transfer rate constant (k(o)) and electron affinity (A) were also calculated from electrochemical data.

  3. In vivo phase II-enzymes inducers, as potential chemopreventive agents, based on the chalcone and furoxan skeletons.

    PubMed

    Cabrera, Mauricio; Mastandrea, Ignacio; Otero, Gabriel; Cerecetto, Hugo; González, Mercedes

    2016-04-15

    Cancer chemoprevention involves prevention/delay/reverse of the carcinogenic process through administration of cancer chemopreventive agents (CCA). Compounds which are able to induce detoxification-enzymes, especially monofunctional phase II enzymes, have become in excellent approaches for new CCA. Herein, we report the synthesis of new furoxanyl chalcone-like hybrid compounds as CCA. In vitro studies showed that phenylfuroxanyl derivatives 6 and 9 displayed the best activities being 9 the greatest monofunctional-inducer. Additionally, compounds were non-mutagenic against TA98 Salmonella typhimurium strain (Ames test) and could be used in the prevention of the progression of pre-malignant lesions for their cytotoxic activity against tumoral cells. In vivo proof of concept showed increment on phase II-enzymes activities in liver, colon and mammary gland having derivative 9 the best induction profiles. We probed Nrf2 nuclear translocation is operative for both compounds allowing to exert protective effects via expression of downstream phase-II enzymes.

  4. Cytotoxic effects of new geranyl chalcone derivatives isolated from the leaves of Artocarpus communis in SW 872 human liposarcoma cells.

    PubMed

    Fang, Song-Chwan; Hsu, Chin-Lin; Yu, Yu-Shen; Yen, Gow-Chin

    2008-10-01

    Breadfruit (Artocarpus communis Moraceae) is cultivated in tropical and subtropical regions as a traditional starch crop and also has potential medicinal properties. The aim of this work was to study the in vitro anticancer activity of compounds isolated from the leaves of Artocarpus communis. Three new geranyl chalcone derivatives including isolespeol (1), 5'-geranyl-2',4',4-trihydroxychalcone (2), and 3,4,2',4'-tetrahydroxy-3'-geranyldihydrochalcone (3), together with two known compounds lespeol (4) and xanthoangelol (5), were isolated from the leaves of Artocarpus communis. The structures of 1- 5 were elucidated by spectroscopy and through comparison with data reported in the literature. The effects of geranyl chalcone derivatives (1- 5) on the viability of human cancer cells (including SW 872, HT-29, COLO 205, Hep3B, PLC5, Huh7, and HepG2 cells) were investigated. The results indicate that isolespeol (1) showed the highest inhibitory activity with an IC 50 value of 3.8 muM in SW 872 human liposarcoma cells. Treatment of SW 872 human liposarcoma cells with isolespeol (1) caused the loss of mitochondrial membrane potential (DeltaPsim). Western blotting revealed that isolespeol (1) stimulated increased protein expression of Fas, FasL, and p53. The expression ratios of pro- and antiapoptotic Bcl-2 family members were also changed by isolespeol (1) treatment to subsequently induce the activation of caspase-9 and caspase-3, which was followed by cleavage of poly (ADP-ribose) polymerase (PARP). These results demonstrate that isolespeol (1) induces apoptosis in SW 872 cells through Fas- and mitochondria-mediated pathways.

  5. Endogenous, tissue-specific short interfering RNAs silence the chalcone synthase gene family in glycine max seed coats.

    PubMed

    Tuteja, Jigyasa H; Zabala, Gracia; Varala, Kranthi; Hudson, Matthew; Vodkin, Lila O

    2009-10-01

    Two dominant alleles of the I locus in Glycine max silence nine chalcone synthase (CHS) genes to inhibit function of the flavonoid pathway in the seed coat. We describe here the intricacies of this naturally occurring silencing mechanism based on results from small RNA gel blots and high-throughput sequencing of small RNA populations. The two dominant alleles of the I locus encompass a 27-kb region containing two perfectly repeated and inverted clusters of three chalcone synthase genes (CHS1, CHS3, and CHS4). This structure silences the expression of all CHS genes, including CHS7 and CHS8, located on other chromosomes. The CHS short interfering RNAs (siRNAs) sequenced support a mechanism by which RNAs transcribed from the CHS inverted repeat form aberrant double-stranded RNAs that become substrates for dicer-like ribonuclease. The resulting primary siRNAs become guides that target the mRNAs of the nonlinked, highly expressed CHS7 and CHS8 genes, followed by subsequent amplification of CHS7 and CHS8 secondary siRNAs by RNA-dependent RNA polymerase. Most remarkably, this silencing mechanism occurs only in one tissue, the seed coat, as shown by the lack of CHS siRNAs in cotyledons and vegetative tissues. Thus, production of the trigger double-stranded RNA that initiates the process occurs in a specific tissue and represents an example of naturally occurring inhibition of a metabolic pathway by siRNAs in one tissue while allowing expression of the pathway and synthesis of valuable secondary metabolites in all other organs/tissues of the plant.

  6. Design, synthesis, physicochemical studies, solvation, and DNA damage of quinoline-appended chalcone derivative: comprehensive spectroscopic approach toward drug discovery.

    PubMed

    Kumar, Himank; Chattopadhyay, Anjan; Prasath, R; Devaraji, Vinod; Joshi, Ritika; Bhavana, P; Saini, Praveen; Ghosh, Sujit Kumar

    2014-07-01

    The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state. The radiationless deactivation of the TICT state is found to be promoted strongly by hydrogen bonding. Quantum mechanical (DFT, TDDFT, and ZINDO-CI) calculations show that the ADMQ is sort of molecular rotor which undergoes intramolecular twist followed by a complete charge transfer in the optimized excited state. FTIR studies reveals that ADMQ undergoes important structural change from its native structure to a β-hydroxy keto form in water at physiological pH. The concentration-dependent DNA cleavage has been identified in agarose gel DNA electrophoresis experiment and has been further supported by MD simulation. ADMQ forms hydrogen bond with the deoxyribose sugar attached with the nucleobase adenine DA-17 (chain A) and result in significant structural changes which potentially cleave DNA double helix. The compound does not exhibit any deleterious effect or toxicity to the E. coli strain in cytotoxicity studies. The consolidated spectroscopic research described herein can provide enormous information to open up new avenues for designing and synthesizing chalcone derivatives with low systematic toxicity for medicinal chemistry research. PMID:24962605

  7. Binding mode analyses and pharmacophore model development for sulfonamide chalcone derivatives, a new class of alpha-glucosidase inhibitors.

    PubMed

    Bharatham, Kavitha; Bharatham, Nagakumar; Park, Ki Hun; Lee, Keun Woo

    2008-06-01

    Sulfonamide chalcone derivatives are a new class of non-saccharide compounds that effectively inhibit glucosidases which are the major targets in the treatment of Type 2 diabetes and HIV infection. Our aim is to explore their binding mode of interaction at the active site by comparing with the sugar derivatives and to develop a pharmacophore model which would represent the critical features responsible for alpha-glucosidase inhibitory activity. The homology modeled structure of Saccharomyces cerevisiae alpha-glucosidase was built and used for molecular docking of non-sugar/sugar derivatives. The validated docking results projected the crucial role of NH group in the binding of sugar/non-sugar derivatives to the active site. Ligplot analyses revealed that Tyr71, and Phe177 form hydrophobic interactions with sugar/non-sugar derivatives by holding the terminal glycosidic ring mimics. Molecular dynamic (MD) simulation studies were performed for protein alone and with chalcone derivative to prove its binding mechanism as shown by docking/Ligplot results. It would also help to substantiate the homology modeled structure stability. With the knowledge of the crucial interactions between ligand and protein from docking and MD simulation studies, features for pharmacophore model development were chosen. The CATALYST/HipHop was used to generate a five featured pharmacophore model with a training set of five non-sugar derivatives. As validation, all the crucial features of the model were perfectly mapped onto the 3D structures of the sugar derivatives as well as the newly tested non-sugar derivatives. Thus, it can be useful in virtual screening for finding new non-sugar derivatives as alpha-glucosidase inhibitors. PMID:18096420

  8. Binding mode analyses and pharmacophore model development for sulfonamide chalcone derivatives, a new class of alpha-glucosidase inhibitors.

    PubMed

    Bharatham, Kavitha; Bharatham, Nagakumar; Park, Ki Hun; Lee, Keun Woo

    2008-06-01

    Sulfonamide chalcone derivatives are a new class of non-saccharide compounds that effectively inhibit glucosidases which are the major targets in the treatment of Type 2 diabetes and HIV infection. Our aim is to explore their binding mode of interaction at the active site by comparing with the sugar derivatives and to develop a pharmacophore model which would represent the critical features responsible for alpha-glucosidase inhibitory activity. The homology modeled structure of Saccharomyces cerevisiae alpha-glucosidase was built and used for molecular docking of non-sugar/sugar derivatives. The validated docking results projected the crucial role of NH group in the binding of sugar/non-sugar derivatives to the active site. Ligplot analyses revealed that Tyr71, and Phe177 form hydrophobic interactions with sugar/non-sugar derivatives by holding the terminal glycosidic ring mimics. Molecular dynamic (MD) simulation studies were performed for protein alone and with chalcone derivative to prove its binding mechanism as shown by docking/Ligplot results. It would also help to substantiate the homology modeled structure stability. With the knowledge of the crucial interactions between ligand and protein from docking and MD simulation studies, features for pharmacophore model development were chosen. The CATALYST/HipHop was used to generate a five featured pharmacophore model with a training set of five non-sugar derivatives. As validation, all the crucial features of the model were perfectly mapped onto the 3D structures of the sugar derivatives as well as the newly tested non-sugar derivatives. Thus, it can be useful in virtual screening for finding new non-sugar derivatives as alpha-glucosidase inhibitors.

  9. Growth and characterization of an efficient nonlinear optical D π A π D type chalcone single crystal

    NASA Astrophysics Data System (ADS)

    Ravindra, H. J.; Kiran, A. John; Dharmaprakash, S. M.; Satheesh Rai, N.; Chandrasekharan, K.; Kalluraya, B.; Rotermund, F.

    2008-08-01

    A chalcone molecule, p-methoxy dibenzylideneacetone (PDBA), with molecular formula C 19H 18O 3 having D-π-A-π-D type, lambda (Λ)-shape structure has been synthesized by Claisen-Schmidt condensation reaction. High-quality single crystals of PDBA were grown by slow evaporation solution growth technique using acetone, methanol and dimethyl formamide (DMF) as solvents. PDBA easily crystallizes in orthorhombic system with noncentrosymmetric space group, Aba2, and the cell parameters are a=7.2756(9) Å, b=33.583(6) Å, c=6.132(5) Å and v=1498.3 Å 3. The powder second harmonic generation (SHG) efficiency of PDBA was determined to be 15.5 times that of urea. This large SHG efficiency of PDBA is due to (i) the Λ-shape of the molecule resulting in a head-to-tail molecular columns along the crystallographic c-direction where dipole moment of the individual molecule add up to establish a net macroscopic polarization and (ii) the C-H…π hydrogen bond interactions in PDBA crystal structure (which can extend molecular charge transfer into supramolecular realm in the exited state) which may partly contribute to the observed SHG. PDBA crystal is highly transparent in the visible to near infrared region and has lower optical cutoff of 440 nm. The thermal stability of PDBA is comparable with that of urea. High optical transparency down to blue region, better Vickers hardness value, higher powder SHG efficiency and laser damage resistance than that of urea, and the existence of phase-matching property in this chalcone make it a potential candidate for SHG applications.

  10. Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns

    PubMed Central

    König, Harald; Frank, Daniel; Heil, Reinhard; Coenen, Christopher

    2013-01-01

    New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications. PMID:23997647

  11. Synthetic Foveal Imaging Technology

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael; Monacos, Steve; Nikzad, Shouleh

    2009-01-01

    Synthetic Foveal imaging Technology (SyFT) is an emerging discipline of image capture and image-data processing that offers the prospect of greatly increased capabilities for real-time processing of large, high-resolution images (including mosaic images) for such purposes as automated recognition and tracking of moving objects of interest. SyFT offers a solution to the image-data processing problem arising from the proposed development of gigapixel mosaic focal-plane image-detector assemblies for very wide field-of-view imaging with high resolution for detecting and tracking sparse objects or events within narrow subfields of view. In order to identify and track the objects or events without the means of dynamic adaptation to be afforded by SyFT, it would be necessary to post-process data from an image-data space consisting of terabytes of data. Such post-processing would be time-consuming and, as a consequence, could result in missing significant events that could not be observed at all due to the time evolution of such events or could not be observed at required levels of fidelity without such real-time adaptations as adjusting focal-plane operating conditions or aiming of the focal plane in different directions to track such events. The basic concept of foveal imaging is straightforward: In imitation of a natural eye, a foveal-vision image sensor is designed to offer higher resolution in a small region of interest (ROI) within its field of view. Foveal vision reduces the amount of unwanted information that must be transferred from the image sensor to external image-data-processing circuitry. The aforementioned basic concept is not new in itself: indeed, image sensors based on these concepts have been described in several previous NASA Tech Briefs articles. Active-pixel integrated-circuit image sensors that can be programmed in real time to effect foveal artificial vision on demand are one such example. What is new in SyFT is a synergistic combination of recent

  12. Anti-HIV cytotoxicity enzyme inhibition and molecular docking studies of quinoline based chalcones as potential non-nucleoside reverse transcriptase inhibitors (NNRT).

    PubMed

    Hameed, Asima; Abdullah, Muhammad Imran; Ahmed, Ejaz; Sharif, Ahsan; Irfan, Ahmad; Masood, Sara

    2016-04-01

    A series of fourteen (A1 - A14) qunioline based chalcones were screened for reverse transcriptase inhibitors (RT) and found potentially active against RT. Bioassay, theoretical and dockings studies with RT (the enzyme required for reverse transcription of viral RNA) results showed that the type and positions of the substituents seemed to be critical for their inhibition against RT. The bromo and chloro substituted chalcone displayed high degree of inhibition against RT. The A4 andA6 showed high interaction with RT, contributing high free binding energy (ΔG -9.30 and -9.13kcal) and RT inhibition value (IC50 0.10μg/ml and 0.11μg/ml). PMID:26964017

  13. Inhibitory kinetics of novel 2,3-dihydro-1H-inden-1-one chalcone-like derivatives on mushroom tyrosinase.

    PubMed

    Radhakrishnan, Sini; Shimmon, Ronald; Conn, Costa; Baker, Anthony

    2015-12-01

    In this study, novel 2,3-dihydro-1H-inden-1-one chalcone-like compounds and their hydroxyl derivatives were synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. Two of the compounds synthesized inhibited the diphenolase activity of tyrosinase in a dose dependent manner and exhibited much higher tyrosinase inhibitory activities (IC50 values of 12.3 μM and 8.2 μM, respectively) than the positive control, kojic acid (IC50: 27.5 μM). Kinetic analysis showed that their inhibition was reversible. Both the novel compounds displayed competitive inhibition with their Ki values of 10.3 μM and 8.7 μM, respectively. This study suggests hydroxy substituted 2,3-dihydro-1H-inden-1-one chalcone-like compounds to serve as promising candidates for use as depigmentation agents.

  14. Distribution of Flavonoids and Cyclohexenyl Chalcone Derivatives in Conventional Propagated and In Vitro-Derived Field-Grown Boesenbergia rotunda (L.) Mansf.

    PubMed Central

    Tan, Siew Kiat; Ata, Nabeel; Rahman, Noorsaadah Abd.; Khalid, Norzulaani

    2015-01-01

    The distribution patterns of flavonoids and cyclohexenyl chalcone derivatives in conventional propagated (CP) and in vitro-derived (CPA) field-grown plants of an important medicinal ginger, Boesenbergia rotunda, are described. A total of eight compounds were extracted from six organs (rootlet, rhizome, shoot base, maroon stem, stalk, and leaf) of the CP and CPA plants. Five major chromatographic peaks, namely, alpinetin, pinocembrin, pinostrobin, 4-hydroxypanduratin A, and panduratin A, were consistently observed by high performance liquid chromatography. Nonaerial organs had higher levels of flavonoids than the aerial ones for all types of samples. Among the compounds detected, pinostrobin and 4-hydroxypanduratin A were the most abundant flavonoid and cyclohexenyl chalcone derivative, respectively. The distribution and abundance of the bioactive compounds suggested that the shoot base could be more potentially useful for medicinal application than other organs of the plant and may be the site of storage or occurrence of biosynthetic enzymatic activities. PMID:25883671

  15. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    PubMed

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-01-01

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma. PMID:27213317

  16. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    PubMed

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-05-19

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.

  17. Recent advances in synthetic biosafety.

    PubMed

    Simon, Anna J; Ellington, Andrew D

    2016-01-01

    Synthetically engineered organisms hold promise for a broad range of medical, environmental, and industrial applications. Organisms can potentially be designed, for example, for the inexpensive and environmentally benign synthesis of pharmaceuticals and industrial chemicals, for the cleanup of environmental pollutants, and potentially even for biomedical applications such as the targeting of specific diseases or tissues. However, the use of synthetically engineered organisms comes with several reasonable safety concerns, one of which is that the organisms or their genes could escape their intended habitats and cause environmental disruption. Here we review key recent developments in this emerging field of synthetic biocontainment and discuss further developments that might be necessary for the widespread use of synthetic organisms. Specifically, we discuss the history and modern development of three strategies for the containment of synthetic microbes: addiction to an exogenously supplied ligand; self-killing outside of a designated environment; and self-destroying encoded DNA circuitry outside of a designated environment. PMID:27635235

  18. Synthetic cannabis and respiratory depression.

    PubMed

    Jinwala, Felecia N; Gupta, Mayank

    2012-12-01

    In recent years, synthetic cannabis use has been increasing in appeal among adolescents, and its use is now at a 30 year peak among high school seniors. The constituents of synthetic cannabis are difficult to monitor, given the drug's easy accessibility. Currently, 40 U.S. states have banned the distribution and use of some known synthetic cannabinoids, and have included these drugs in the Schedule I category. The depressive respiratory effect in humans caused by synthetic cannabis inhalation has not been thoroughly investigated in the medical literature. We are the first to report, to our knowledge, two cases of self-reported synthetic cannabis use leading to respiratory depression and necessary intubation. PMID:23234589

  19. Recent advances in synthetic biosafety

    PubMed Central

    Simon, Anna J.; Ellington, Andrew D.

    2016-01-01

    Synthetically engineered organisms hold promise for a broad range of medical, environmental, and industrial applications. Organisms can potentially be designed, for example, for the inexpensive and environmentally benign synthesis of pharmaceuticals and industrial chemicals, for the cleanup of environmental pollutants, and potentially even for biomedical applications such as the targeting of specific diseases or tissues. However, the use of synthetically engineered organisms comes with several reasonable safety concerns, one of which is that the organisms or their genes could escape their intended habitats and cause environmental disruption. Here we review key recent developments in this emerging field of synthetic biocontainment and discuss further developments that might be necessary for the widespread use of synthetic organisms. Specifically, we discuss the history and modern development of three strategies for the containment of synthetic microbes: addiction to an exogenously supplied ligand; self-killing outside of a designated environment; and self-destroying encoded DNA circuitry outside of a designated environment.

  20. Recent advances in synthetic biosafety

    PubMed Central

    Simon, Anna J.; Ellington, Andrew D.

    2016-01-01

    Synthetically engineered organisms hold promise for a broad range of medical, environmental, and industrial applications. Organisms can potentially be designed, for example, for the inexpensive and environmentally benign synthesis of pharmaceuticals and industrial chemicals, for the cleanup of environmental pollutants, and potentially even for biomedical applications such as the targeting of specific diseases or tissues. However, the use of synthetically engineered organisms comes with several reasonable safety concerns, one of which is that the organisms or their genes could escape their intended habitats and cause environmental disruption. Here we review key recent developments in this emerging field of synthetic biocontainment and discuss further developments that might be necessary for the widespread use of synthetic organisms. Specifically, we discuss the history and modern development of three strategies for the containment of synthetic microbes: addiction to an exogenously supplied ligand; self-killing outside of a designated environment; and self-destroying encoded DNA circuitry outside of a designated environment. PMID:27635235

  1. Ecotoxicology of synthetic pyrethroids.

    PubMed

    Maund, S J; Campbell, P J; Giddings, J M; Hamer, M J; Henry, K; Pilling, E D; Warinton, J S; Wheeler, J R

    2012-01-01

    In this chapter we review the ecotoxicology of the synthetic pyrethroids (SPs). SPs are potent, broad-spectrum insecticides. Their effects on a wide range of nontarget species have been broadly studied, and there is an extensive database available to evaluate their effects. SPs are highly toxic to fish and aquatic invertebrates in the laboratory, but effects in the field are mitigated by rapid dissipation and degradation. Due to their highly lipophilic nature, SPs partition extensively into sediments. Recent studies have shown that toxicity in sediment can be predicted on the basis of equilibrium partitioning, and whilst other factors can influence this, organic carbon content is a key determining variable. At present for SPs, there is no clear evidence for adverse population-relevant effects with an underlying endocrine mode of action. SPs have been studied intensively in aquatic field studies, and their effects under field conditions are mitigated from those measured in the laboratory by their rapid dissipation and degradation. Studies with a range of test systems have shown consistent aquatic field endpoints across a variety of geographies and trophic states. SPs are also highly toxic to bees and other nontarget arthropods in the laboratory. These effects are mitigated in the field through repellency and dissipation of residues, and recovery from any adverse effects tends to be rapid.

  2. Synthetic retinoids in dermatology

    PubMed Central

    Heller, Elizabeth H.; Shiffman, Norman J.

    1985-01-01

    The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively nontoxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited. ImagesFig. 3 PMID:3158386

  3. Synthetic molecular walkers.

    PubMed

    Leigh, David A; Lewandowska, Urszula; Lewandowski, Bartosz; Wilson, Miriam R

    2014-01-01

    In biological systems, molecular motors have been developed to harness Brownian motion and perform specific tasks. Among the cytoskeletal motor proteins, kinesins ensure directional transport of cargoes to the periphery of the cell by taking discrete steps along microtubular tracks. In the past decade there has been an increasing interest in the development of molecules that mimic aspects of the dynamics of biological systems and can became a starting point for the creation of artificial transport systems.To date, both DNA-based and small-molecule walkers have been developed, each taking advantage of the different chemistries available to them. DNA strollers exploit orthogonal base pairing and utilize strand-displacement reactions to control the relative association of the component parts. Small-molecule walkers take advantage of the reversibility of weak noncovalent interactions as well as the robustness of dynamic covalent bonds in order to transport molecular fragments along surfaces and molecular tracks using both diffusional processes and ratchet mechanisms. Here we review both types of synthetic systems, including their designs, dynamics, and how they are being used to perform functions by controlled mechanical motion at the molecular level.

  4. Computing with synthetic protocells.

    PubMed

    Courbet, Alexis; Molina, Franck; Amar, Patrick

    2015-09-01

    In this article we present a new kind of computing device that uses biochemical reactions networks as building blocks to implement logic gates. The architecture of a computing machine relies on these generic and composable building blocks, computation units, that can be used in multiple instances to perform complex boolean functions. Standard logical operations are implemented by biochemical networks, encapsulated and insulated within synthetic vesicles called protocells. These protocells are capable of exchanging energy and information with each other through transmembrane electron transfer. In the paradigm of computation we propose, protoputing, a machine can solve only one problem and therefore has to be built specifically. Thus, the programming phase in the standard computing paradigm is represented in our approach by the set of assembly instructions (specific attachments) that directs the wiring of the protocells that constitute the machine itself. To demonstrate the computing power of protocellular machines, we apply it to solve a NP-complete problem, known to be very demanding in computing power, the 3-SAT problem. We show how to program the assembly of a machine that can verify the satisfiability of a given boolean formula. Then we show how to use the massive parallelism of these machines to verify in less than 20 min all the valuations of the input variables and output a fluorescent signal when the formula is satisfiable or no signal at all otherwise.

  5. SNP in Chalcone Synthase gene is associated with variation of 6-gingerol content in contrasting landraces of Zingiber officinale.Roscoe.

    PubMed

    Ghosh, Subhabrata; Mandi, Swati Sen

    2015-07-25

    Zingiber officinale, medicinally the most important species within Zingiber genus, contains 6-gingerol as the active principle. This compound obtained from rhizomes of Z.officinale, has immense medicinal importance and is used in various herbal drug formulations. Our record of variation in content of this active principle, viz. 6-gingerol, in land races of this drug plant collected from different locations correlated with our Gene expression studies exhibiting high Chalcone Synthase gene (Chalcone Synthase is the rate limiting enzyme of 6-gingerol biosynthesis pathway) expression in high 6-gingerol containing landraces than in the low 6-gingerol containing landraces. Sequencing of Chalcone Synthase cDNA and subsequent multiple sequence alignment revealed seven SNPs between these contrasting genotypes. Converting this nucleotide sequence to amino acid sequence, alteration of two amino acids becomes evident; one amino acid change (asparagine to serine at position 336) is associated with base change (A→G) and another change (serine to leucine at position 142) is associated with the base change (C→T). Since asparagine at position 336 is one of the critical amino acids of the catalytic triad of Chalcone Synthase enzyme, responsible for substrate binding, our study suggests that landraces with a specific amino acid change viz. Asparagine (found in high 6-gingerol containing landraces) to serine causes low 6-gingerol content. This is probably due to a weak enzyme substrate association caused by the absence of asparagine in the catalytic triad. Detailed study of this finding could also help to understand molecular mechanism associated with variation in 6-gingerol content in Z.officinale genotypes and thereby strategies for developing elite genotypes containing high 6-gingerol content.

  6. SNP in Chalcone Synthase gene is associated with variation of 6-gingerol content in contrasting landraces of Zingiber officinale.Roscoe.

    PubMed

    Ghosh, Subhabrata; Mandi, Swati Sen

    2015-07-25

    Zingiber officinale, medicinally the most important species within Zingiber genus, contains 6-gingerol as the active principle. This compound obtained from rhizomes of Z.officinale, has immense medicinal importance and is used in various herbal drug formulations. Our record of variation in content of this active principle, viz. 6-gingerol, in land races of this drug plant collected from different locations correlated with our Gene expression studies exhibiting high Chalcone Synthase gene (Chalcone Synthase is the rate limiting enzyme of 6-gingerol biosynthesis pathway) expression in high 6-gingerol containing landraces than in the low 6-gingerol containing landraces. Sequencing of Chalcone Synthase cDNA and subsequent multiple sequence alignment revealed seven SNPs between these contrasting genotypes. Converting this nucleotide sequence to amino acid sequence, alteration of two amino acids becomes evident; one amino acid change (asparagine to serine at position 336) is associated with base change (A→G) and another change (serine to leucine at position 142) is associated with the base change (C→T). Since asparagine at position 336 is one of the critical amino acids of the catalytic triad of Chalcone Synthase enzyme, responsible for substrate binding, our study suggests that landraces with a specific amino acid change viz. Asparagine (found in high 6-gingerol containing landraces) to serine causes low 6-gingerol content. This is probably due to a weak enzyme substrate association caused by the absence of asparagine in the catalytic triad. Detailed study of this finding could also help to understand molecular mechanism associated with variation in 6-gingerol content in Z.officinale genotypes and thereby strategies for developing elite genotypes containing high 6-gingerol content. PMID:25895474

  7. The impact of position and number of methoxy group(s) to tune the nonlinear optical properties of chalcone derivatives: a dual substitution strategy.

    PubMed

    Muhammad, Shabbir; Al-Sehemi, Abdullah G; Irfan, Ahmad; Chaudhry, Aijaz R; Gharni, Hamid; AlFaify, S; Shkir, Mohd; Asiri, Abdullah M

    2016-04-01

    Using the state-of-art computational techniques, we limelight a structure-property relationship for the position and number of methoxy group(s) to tune the optical and nonlinear optical (NLO) properties (first hyperpolarizability) of chalcone derivatives. Based on our previously synthesized chalcones [system 1 ((E)-1-(2,5-dimethylthiophen-3-yl)-3-(2-methoxyphenyl)prop-2-en-1-one and system 4 (E)-1-(2,5-dimethylthiophen-3-yl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one)], we systematically design several novel derivatives with tuned optical and NLO properties. For instance, the rotation of methoxy group substitutions at three different possible ortho, meta, and para positions on phenyl ring show significant changes in NLO properties of these chalcones derivatives. The system 3 has shown β tot amplitude of 1776 a.u. with terminal 4-methoxyphenyl group (para-methoxy substitution), which is ~2.2 and 2.4 times larger than that of ortho- and meta-methoxyphenyl systems 1 and 2, respectively. Additionally, systems 3a and 4a, which are cyano derivatives of the systems 3 and 4 show significantly large β tot amplitudes of 3280 and 4388 a.u., respectively, which are about 3 and 4 times larger than that of para-nitro aniline (PNA) molecule (a typical donor-acceptor molecule) at the same LC-wPBE/6-311G** level of theory. The origin of larger β tot amplitudes has been traced in lower transition energies and higher oscillator strengths for crucial transitions of designed derives. Thus, our investigation reveals that the chalcones derivatives with para-methoxyphenyl groups possess reasonably large amplitudes of their first hyperpolarizability and good optical transparency (3.0-4.7 eV), which can make them attractive candidates for nonlinear optical applications. PMID:26969679

  8. Synthetic biology: lessons from the history of synthetic organic chemistry.

    PubMed

    Yeh, Brian J; Lim, Wendell A

    2007-09-01

    The mid-nineteenth century saw the development of a radical new direction in chemistry: instead of simply analyzing existing molecules, chemists began to synthesize them--including molecules that did not exist in nature. The combination of this new synthetic approach with more traditional analytical approaches revolutionized chemistry, leading to a deep understanding of the fundamental principles of chemical structure and reactivity and to the emergence of the modern pharmaceutical and chemical industries. The history of synthetic chemistry offers a possible roadmap for the development and impact of synthetic biology, a nascent field in which the goal is to build novel biological systems. PMID:17710092

  9. Synthetic biology: Understanding biological design from synthetic circuits

    PubMed Central

    Mukherji, Shankar; van Oudenaarden, Alexander

    2011-01-01

    An important aim of synthetic biology is to uncover the design principles of natural biological systems through the rational design of gene and protein circuits. Here we highlight how the process of engineering biological systems — from synthetic promoters to the control of cell–cell interactions — has contributed to our understanding of how endogenous systems are put together and function. Synthetic biological devices allow us to intuitively grasp the ranges of behavior generated by simple biological circuits, such as linear cascades and interlocking feedback loops, as well as to exert control over natural processes such as gene expression and population dynamics. PMID:19898500

  10. Binary classification of chalcone derivatives with LDA or KNN based on their antileishmanial activity and molecular descriptors selected using the Successive Projections Algorithm feature-selection technique.

    PubMed

    Goodarzi, Mohammad; Saeys, Wouter; de Araujo, Mario Cesar Ugulino; Galvão, Roberto Kawakami Harrop; Vander Heyden, Yvan

    2014-01-23

    Chalcones are naturally occurring aromatic ketones, which consist of an α-, β-unsaturated carbonyl system joining two aryl rings. These compounds are reported to exhibit several pharmacological activities, including antiparasitic, antibacterial, antifungal, anticancer, immunomodulatory, nitric oxide inhibition and anti-inflammatory effects. In the present work, a Quantitative Structure-Activity Relationship (QSAR) study is carried out to classify chalcone derivatives with respect to their antileishmanial activity (active/inactive) on the basis of molecular descriptors. For this purpose, two techniques to select descriptors are employed, the Successive Projections Algorithm (SPA) and the Genetic Algorithm (GA). The selected descriptors are initially employed to build Linear Discriminant Analysis (LDA) models. An additional investigation is then carried out to determine whether the results can be improved by using a non-parametric classification technique (One Nearest Neighbour, 1NN). In a case study involving 100 chalcone derivatives, the 1NN models were found to provide better rates of correct classification than LDA, both in the training and test sets. The best result was achieved by a SPA-1NN model with six molecular descriptors, which provided correct classification rates of 97% and 84% for the training and test sets, respectively.

  11. Synergistic effect of iodide ions on the corrosion inhibition of steel in 0.5 M H 2SO 4 by new chalcone derivatives

    NASA Astrophysics Data System (ADS)

    Bouklah, M.; Hammouti, B.; Aouniti, A.; Benkaddour, M.; Bouyanzer, A.

    2006-07-01

    The effect of addition of 4',4-dihydroxychalcone (P 1), 4-aminochalcone (P 2) and 4-bromo, 4'-methoxychalcone (P 3) on the corrosion of steel in 0.5 M sulphuric acid has been studied by weight loss measurements, potentiodynamic and EIS measurements. We investigate the synergistic effect of iodide ions on the corrosion inhibition of steel in the presence of chalcone derivatives. The corrosion rates of the steel decrease with the increase of the chalcones concentration, while the inhibition efficiencies increase. The addition of iodide ions enhances the inhibition efficiency considerably. The presence of iodide ions increases the degree of surface coverage. The synergism parameters SΘ and SI, calculated from surface coverage and the values of inhibition efficiency, in the case of chalcone derivatives are found to be larger than unity. The enhanced inhibition efficiency in the presence of iodide ions is only due to synergism and there is a definite contribution from the inhibitors molecules. E (%) obtained from the various methods is in good agreement. Polarisation measurements show also that the compounds act as cathodic inhibitors.

  12. Bistatic synthetic aperture radar

    NASA Astrophysics Data System (ADS)

    Yates, Gillian

    Synthetic aperture radar (SAR) allows all-weather, day and night, surface surveillance and has the ability to detect, classify and geolocate objects at long stand-off ranges. Bistatic SAR, where the transmitter and the receiver are on separate platforms, is seen as a potential means of countering the vulnerability of conventional monostatic SAR to electronic countermeasures, particularly directional jamming, and avoiding physical attack of the imaging platform. As the receiving platform can be totally passive, it does not advertise its position by RF emissions. The transmitter is not susceptible to jamming and can, for example, operate at long stand-off ranges to reduce its vulnerability to physical attack. This thesis examines some of the complications involved in producing high-resolution bistatic SAR imagery. The effect of bistatic operation on resolution is examined from a theoretical viewpoint and analytical expressions for resolution are developed. These expressions are verified by simulation work using a simple 'point by point' processor. This work is extended to look at using modern practical processing engines for bistatic geometries. Adaptations of the polar format algorithm and range migration algorithm are considered. The principal achievement of this work is a fully airborne demonstration of bistatic SAR. The route taken in reaching this is given, along with some results. The bistatic SAR imagery is analysed and compared to the monostatic imagery collected at the same time. Demonstrating high-resolution bistatic SAR imagery using two airborne platforms represents what I believe to be a European first and is likely to be the first time that this has been achieved outside the US (the UK has very little insight into US work on this topic). Bistatic target characteristics are examined through the use of simulations. This also compares bistatic imagery with monostatic and gives further insight into the utility of bistatic SAR.

  13. Synthetic inhibitors of elastase.

    PubMed

    Edwards, P D; Bernstein, P R

    1994-03-01

    For more than two decades investigators around the world, in both academic and industrial institutions, have been developing inhibitors of human neutrophil elastase. A number of very elegant and insightful strategies have been reported. In the case of reversible peptidic inhibitors, this has resulted in the identification of some extremely potent compounds with dissociation constants in the 10(-11) M range. This is quite an accomplishment considering that these low molecular-weight inhibitors are only tri- and tetrapeptides. In the case of the heterocyclic-based inhibitors, the challenge of balancing the heterocycle's inherent reactivity and aqueous stability with the stability of the enzyme-inhibitor adduct has been meet by either using a latent, reactive functionality which is only activated within the enzyme, or by incorporating features which selectively obstruct deacylation but have little effect on the enzyme acylation step. The underlying goal of this research has been the identification of agents to treat diseases associated with HNE. Several animal models have been developed for evaluating the in vivo activity of elastase inhibitors, and compounds have been shown to be effective in all of these models by the intravenous, intratrachael or oral routes of administration. However, only a very small percentage of compounds have possessed all the necessary properties, including lack of toxicity, for progression into the clinic. The peptidyl TFMK ICI 200,880 (25-12) has many of the desired characteristics of a drug to treat the diseases associated with HNE: chemical stability, in vitro and in vivo activity, a long duration of action, and adequate metabolic stability. Currently ICI 200,880 is the only low molecular-weight HNE inhibitor known to be undergoing clinical trials, and may be the compound which finally demonstrates the clinical utility of a synthetic HNE inhibitor. PMID:8189835

  14. Spicing thing up: Synthetic cannabinoids

    PubMed Central

    Spaderna, Max; Addy, Peter H; D’Souza, Deepak Cyril

    2013-01-01

    Rationale Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. Objectives The availability, acute subjective effects—including self-reports posted on Erowid—laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed. Results Spice is sold under the guise of potpourri or incense. Unlike THC, the synthetic cannabinoids present in Spice are high-potency, high-efficacy, cannabinoid-receptor full agonists. Since standard urine toxicology does not test for the synthetic cannabinoids in Spice, it is often used by those who want to avoid detection of drug use. These compounds have not yet been subjected to rigorous testing in humans. Acute psychoactive effects include changes in mood, anxiety, perception, thinking, memory, and attention. Adverse effects include anxiety, agitation, panic, dysphoria, psychosis, and bizarre behavior. Psychosis outcomes associated with Spice provide additional data linking cannabinoids and psychosis. Adverse events necessitating intervention by Poison Control Centers, law enforcement, emergency responders, and hospitals are increasing. Despite statutes prohibiting the manufacture, distribution, and sale of Spice products, manufacturers are replacing banned compounds with newer synthetic cannabinoids that are not banned. Conclusions There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug-detection tests for synthetic cannabinoids need to become clinically available. PMID:23836028

  15. Approaches to chemical synthetic biology.

    PubMed

    Chiarabelli, Cristiano; Stano, Pasquale; Anella, Fabrizio; Carrara, Paolo; Luisi, Pier Luigi

    2012-07-16

    Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology.

  16. Is synthetic biology mechanical biology?

    PubMed

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  17. Synthetic Biology for Specialty Chemicals.

    PubMed

    Markham, Kelly A; Alper, Hal S

    2015-01-01

    In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

  18. Synthetic Turf Multiplies Stadium Use.

    ERIC Educational Resources Information Center

    Leach, Richard

    1979-01-01

    The high school stadium in Flint, Michigan, once was used only for varsity football games. After the installation of synthetic turf, an average of 332 events have been staged there each year. (Author/MLF)

  19. Programming languages for synthetic biology.

    PubMed

    Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

    2010-12-01

    In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented. PMID:22132053

  20. Programming languages for synthetic biology.

    PubMed

    Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

    2010-12-01

    In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented.

  1. SYNTHETIC SLING FAILURE - EVALUATIONS & RECOMMENDATIONS

    SciTech Connect

    MACKEY TC; HENDERSON CS

    2009-10-26

    The information and evaluations provided in this report were compiled to address the recurring problem of synthetic sling failure. As safety is the number one priority in all work aspects, a solution must be devised to prevent accidents from occurring. A total of thirteen cases regarding synthetic sling failure were evaluated in order to determine their causes, effects, and preventative measures. From the collected data, it was found that all cases in which the synthetic sling contacted the edge of its load resulted in sling failure. It is required that adequate synthetic sling protection devices be used to protect slings in any lift where the sling comes in direct contact with the edge or corner of its load. However, there are no consensus codes or standards stating the type, material, or purpose of the type of protective device used to protect the sling from being cut. Numerous industry standards and codes provide vague descriptions on how to protect synthetic slings. Without a clear, concise statement of how to protect synthetic slings, it is common for inadequate materials and sling protection devices to be used in an attempt to meet the intent of these requirements. The use of an inadequate sling protection device is the main cause of synthetic sling failure in all researched cases. Commercial sling protection devices come in many shapes and sizes, and have a variety of names, as well as advertised uses. 'Abrasion pads' and 'wear protectors' are two different names for products with the same intended purpose. There is no distinguishable way to determine the extent of sling protection which these devices will provide, or what specific scenarios they are made for. This creates room for error in a field where error is unacceptable. This report provides a recommended action for hoisting and rigging activities which require synthetic slings to contact a load, as well as recommended changes to industry standards which will benefit overall industry safety.

  2. Compounding in synthetic aperture imaging.

    PubMed

    Hansen, Jens Munk; Jensen, Jørgen Arendt

    2012-09-01

    A method for obtaining compound images using synthetic aperture data is investigated using a convex array transducer. The new approach allows spatial compounding to be performed for any number of angles without reducing the frame rate or temporal resolution. This important feature is an intrinsic property of how the compound images are constructed using synthetic aperture data and an improvement compared with how spatial compounding is obtained using conventional methods. The synthetic aperture compound images are created by exploiting the linearity of delay-and-sum beamformation for data collected from multiple spherical emissions to synthesize multiple transmit and receive apertures, corresponding to imaging the tissue from multiple directions. The many images are added incoherently, to produce a single compound image. Using a 192-element, 3.5-MHz, λ-pitch transducer, it is demonstrated from tissue-phantom measurements that the speckle is reduced and the contrast resolution improved when applying synthetic aperture compound imaging. At a depth of 4 cm, the size of the synthesized apertures is optimized for lesion detection based on the speckle information density. This is a performance measure for tissue contrast resolution which quantifies the tradeoff between resolution loss and speckle reduction. The speckle information density is improved by 25% when comparing synthetic aperture compounding to a similar setup for compounding using dynamic receive focusing. The cystic resolution and clutter levels are measured using a wire phantom setup and compared with conventional application of the array, as well as to synthetic aperture imaging without compounding. If the full aperture is used for synthetic aperture compounding, the cystic resolution is improved by 41% compared with conventional imaging, and is at least as good as what can be obtained using synthetic aperture imaging without compounding. PMID:23007781

  3. Superresolution and Synthetic Aperture Radar

    SciTech Connect

    DICKEY,FRED M.; ROMERO,LOUIS; DOERRY,ARMIN W.

    2001-05-01

    Superresolution concepts offer the potential of resolution beyond the classical limit. This great promise has not generally been realized. In this study we investigate the potential application of superresolution concepts to synthetic aperture radar. The analytical basis for superresolution theory is discussed. The application of the concept to synthetic aperture radar is investigated as an operator inversion problem. Generally, the operator inversion problem is ill posed. A criterion for judging superresolution processing of an image is presented.

  4. Tuning the push-pull configuration for efficient second-order nonlinear optical properties in some chalcone derivatives.

    PubMed

    Muhammad, Shabbir; Al-Sehemi, Abdullah G; Irfan, Ahmad; Chaudhry, Aijaz R

    2016-07-01

    Using the density functional theory methods, we effectively tune the second-order nonlinear optical (NLO) properties in some chalcone derivatives. Various unique push-pull configurations are used to efficiently enhance the intramolecular charge transfer process over the designed derivatives, which result in significantly larger amplitudes of the first hyperpolarizability as compared to their parent molecule. The ground state molecular geometries have been optimized using B3LYP/6-311G** level of theory. A variety of methods including B3LYP, CAM-B3LYP, PBE0, M06, BHandHLYP and MP2 are tested with 6-311G** basis set to calculate the first hyperpolarizability of parent system 1. The results of M06 are found closer to highly correlated MP2 method, which has been selected to calculate static and frequency dependent first hyperpolarizability amplitudes of all selected systems. At M06/6-311G** level of theory, the permanent electronic dipole moment (μtot), polarizability (α0) and static first hyperpolarizability (βtot) amplitudes for parent system 1 are found to be 5.139 Debye, 274a. u. and 24.22×10(-30)esu, respectively. These amplitudes have been significantly enhanced in designed derivatives 2 and 3. More importantly, the (βtot) amplitudes of systems 2 and 3 mount to 75.78×10(-30) and 128.51×10(-30)esu, respectively, which are about 3 times and 5 times larger than that of their parent system 1. Additionally, we have extended the structure-NLO property relationship to several newly synthesized chalcone derivatives. Interestingly, the amplitudes of dynamic frequency dependent hyperpolarizability μβω (SHG) are also significantly larger having values of 366.72×10(-48), 856.32×10(-48) and 1913.46×10(-48)esu for systems 1-3, respectively, at 1400nm of incident laser wavelength. The dispersion behavior over a wide range of change in wavelength has also been studied adopting a range of wavelength from 1907 to 544nm. Thus, the present work realizes the potential of

  5. Newly synthesized 'hidabeni' chalcone derivatives potently suppress LPS-induced NO production via inhibition of STAT1, but not NF-κB, JNK, and p38, pathways in microglia.

    PubMed

    Hara, Hirokazu; Ikeda, Ryoko; Ninomiya, Masayuki; Kamiya, Tetsuro; Koketsu, Mamoru; Adachi, Tetsuo

    2014-01-01

    Chalcones are open-chain flavonoids that are biosynthesized in various plants. Some of them possess anti-inflammatory activity. We previously found that chalcone glycosides from Brassica rapa L. 'hidabeni' suppress lipopolysaccharide (LPS)-induced nitric oxide (NO) production in rat microglia highly aggressively proliferating immortalized (HAPI) cells. In this study, to explore chalcone derivatives with potent NO inhibitory activity, we synthesized ten compounds based on 'hidabeni' chalcone and examined their effects on LPS-triggered inducible NO synthase (iNOS) expression and NO production. Compounds C4 and C10 potently inhibited NO production (IC50: 4.19, 2.88 µM, respectively). C4 and C10 suppressed LPS-induced iNOS expression via the inhibition of the signal transduction and activator of transcription 1 (STAT1), but not nuclear factor-kappa B (NF-κB), c-Jun N terminal kinase (JNK), and p38, pathways. C10, but not C4, inhibited activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. C4 and C10 also suppressed LPS-induced expression of interferon regulatory factor 1 (IRF-1), which is an important transcription factor involved in iNOS expression. Our findings indicate that these chalcone derivatives are candidate compounds for preventing microglia-mediated neuroinflammation.

  6. Synthetic biology as red herring.

    PubMed

    Preston, Beth

    2013-12-01

    It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice-agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy.

  7. Synthetic Eelgrass Oil Barrier

    NASA Astrophysics Data System (ADS)

    Curtis, T. G.

    2013-05-01

    Although surviving in situ micro-organisms eventually consume spilled oil, extensive inundation of shore biota by oil requires cleanup to enable ecological recovery within normal time scales. Although effective in calm seas and quiet waters, oil is advected over and under conventional curtain oil booms by wave actions and currents when seas are running. Most sorbent booms are not reusable, and are usually disposed of in landfills, creating excessive waste. A new concept is proposed for a floating oil barrier, to be positioned off vulnerable coasts, to interdict, contain, and sequester spilled oil, which can then be recovered and the barrier reused. While conventional oil boom designs rely principally on the immiscibility of oil in water and its relative buoyancy, the new concept barrier avoids the pitfalls of the former by taking advantage of the synergistic benefits of numerous fluid and material properties, including: density, buoyancy, elasticity, polarity, and surface area to volume ratio. Modeled after Zostera marina, commonly called eelgrass, the new barrier, referred to as synthetic eelgrass (SE), behaves analogously. Eelgrass has very long narrow, ribbon-like, leaves which support periphyton, a complex matrix of algae and heterotrophic microbes, which position themselves there to extract nutrients from the seawater flowing past them. In an analogous fashion, oil on, or in, seawater, which comes in contact with SE, is adsorbed on the surface and sequestered there. Secured to the bottom, in shoal waters, SE rises to the surface, and, if the tide is low enough, floats on the sea surface down wind, or down current to snare floating oil. The leaves of SE, called filaments, consist of intrinsically buoyant strips of ethylene methyl acrylate, aka EMA. EMA, made of long chain, saturated, hydrocarbon molecules with nearly homogeneous electron charge distributions, is a non-polar material which is oleophilic and hydrophobic. Oil must be in close proximity to the

  8. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

    PubMed

    Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

    2015-08-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. PMID:26272997

  9. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

    PubMed

    Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

    2015-08-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms.

  10. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

    PubMed Central

    Sliva, Anna; Yang, Huanming; Boeke, Jef D.; Mathews, Debra J. H.

    2015-01-01

    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 Project: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. PMID:26272997

  11. Development of new and selective Trypanosoma cruzi trans-sialidase inhibitors from sulfonamide chalcones and their derivatives.

    PubMed

    Kim, Jin Hyo; Ryu, Hyung Won; Shim, Jae Hoon; Park, Ki Hun; Withers, Stephen G

    2009-10-12

    A series of sulfonamide-containing hydroxylated chalcone (4-7) and quinolinone (8, 9) derivatives was synthesised and tested for inhibition of the trans-sialidase from Trypanosoma cruzi (TcTS). IC(50) values for these inhibitors ranged from 0.6 to 7.3 microM, with the dihydroxylated (catechol) derivatives being the tightest binders. Full kinetic analyses of inhibition were performed for these catechol derivatives, both for the transglycosylation reaction in the presence of lactose and for the hydrolysis reaction in its absence. Competitive inhibition was seen in each case with K(i) values for 5, 7 and 9 of 2.0, 2.2 and 0.2 microM, respectively, in the absence of lactose, and 4.6, 3.7 and 0.4 microM in its presence. None of the compounds tested showed any significant inhibition of the human sialidase Neu2, at concentrations up to 200 microM.

  12. Sequence variation of chalcone synthase gene in a spontaneous white-flower mutant of Chinese cabbage-pak-choi.

    PubMed

    Jiang, Ming; Cao, Jiashu

    2008-12-01

    A spontaneous white-flower mutant of Chinese cabbage-pak-choi (Brassica campestris ssp. chinenesis, syn. B. rapa ssp. chinenesis) was found in our test fields, and all the plant characters except flower color were identical with wild type ones. We hypothesized that a mutational event had occurred in the gene coding for chalcone synthase (CHS), the key enzyme of flavonoid biosynthesis pathway. Two genes, later designated BcCHS and BcCHS-wf, were isolated from wild type and mutant Chinese cabbage-pak-choi, respectively, using gene-specific primer pairs. Comparison of the genomic sequences revealed two mutations in BcCHS-wf, both with A to G transitions, one at position +37 bp and the other at +970 bp. Both nucleotide substitutions occurred in AGA codes for arginine into GGA for glycin at residue +13 and into AGC coding for serine at residue +229, respectively. Homologous genes of BcCHS were isolated from another four cruciferous plants, though there were some differences among the genomic and deduced amino acid sequences, the mutation locus of the mutant, as we called it, were identical to the wild type Chinese cabbage-pak-choi.

  13. RNA interference silencing of chalcone synthase, the first step in the flavonoid biosynthesis pathway, leads to parthenocarpic tomato fruits.

    PubMed

    Schijlen, Elio G W M; de Vos, C H Ric; Martens, Stefan; Jonker, Harry H; Rosin, Faye M; Molthoff, Jos W; Tikunov, Yury M; Angenent, Gerco C; van Tunen, Arjen J; Bovy, Arnaud G

    2007-07-01

    Parthenocarpy, the formation of seedless fruits in the absence of functional fertilization, is a desirable trait for several important crop plants, including tomato (Solanum lycopersicum). Seedless fruits can be of great value for consumers, the processing industry, and breeding companies. In this article, we propose a novel strategy to obtain parthenocarpic tomatoes by down-regulation of the flavonoid biosynthesis pathway using RNA interference (RNAi)-mediated suppression of chalcone synthase (CHS), the first gene in the flavonoid pathway. In CHS RNAi plants, total flavonoid levels, transcript levels of both Chs1 and Chs2, as well as CHS enzyme activity were reduced by up to a few percent of the corresponding wild-type values. Surprisingly, all strong Chs-silenced tomato lines developed parthenocarpic fruits. Although a relation between flavonoids and parthenocarpic fruit development has never been described, it is well known that flavonoids are essential for pollen development and pollen tube growth and, hence, play an essential role in plant reproduction. The observed parthenocarpic fruit development appeared to be pollination dependent, and Chs RNAi fruits displayed impaired pollen tube growth. Our results lead to novel insight in the mechanisms underlying parthenocarpic fruit development. The potential of this technology for applications in plant breeding and biotechnology will be discussed. PMID:17478633

  14. The Expression of Millettia pinnata Chalcone Isomerase in Saccharomyces cerevisiae Salt-Sensitive Mutants Enhances Salt-Tolerance

    PubMed Central

    Wang, Hui; Hu, Tangjin; Huang, Jianzi; Lu, Xiang; Huang, Baiqu; Zheng, Yizhi

    2013-01-01

    The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full length cDNA (666 bp) was obtained by 3′-end and 5′-end Rapid Amplification of cDNA Ends (RACE). The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%–86%). Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa), whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1) showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata. PMID:23615469

  15. The expression of Millettia pinnata chalcone isomerase in Saccharomyces cerevisiae salt-sensitive mutants enhances salt-tolerance.

    PubMed

    Wang, Hui; Hu, Tangjin; Huang, Jianzi; Lu, Xiang; Huang, Baiqu; Zheng, Yizhi

    2013-01-01

    The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full length cDNA (666 bp) was obtained by 3'-end and 5'-end Rapid Amplification of cDNA Ends (RACE). The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%-86%). Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa), whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1) showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata.

  16. Use of cyclodextrins in biotransformation reactions with cell cultures of Morus nigra: biosynthesis of prenylated chalcone isocordoin.

    PubMed

    Bolasco, Adriana; Fioravanti, Rossella; Rossi, Francesca; Rossi, Paola; Vitali, Alberto

    2010-06-16

    In vivo biotransformation experiments were performed by using a cell suspension culture of Morus nigra expressing a high PT (prenyltransferase) activity, fed with the target substrate 2',4'-dihydroxychalcone. In order to improve the reaction yields by enhancing the chalcone solubility, three different cyclodextrins have been used to host the substrate. The respective complexes have been studied by means of both spectroscopic and calorimetric techniques (Fourier-transform infrared, 1H-NMR and differential scanning calorimetry) and the solution behaviours have been characterized by solubility phase studies. The hydroxypropyl-beta-cyclodextrin complex was found to be the most suitable for biotransformation, and the reaction of prenylation resulted in a 6-fold higher yield of the final product when compared with the use of the free substrate. The reaction provided as the sole product the 3'-dimethylallyl derivative isocordoin, a biologically active plant compound. The results obtained allow the development of systems based on the use of biofermentors or the use of immobilized cells in order to enhance the biotransformation yields.

  17. Growth Inhibitory and Apoptosis-inducing Effects of Xanthohumol, a Prenylated Chalcone Present in Hops, in Human Prostate Cancer Cells

    PubMed Central

    DEEB, D.; GAO, X.; JIANG, H.; ARBAB, A.S.; DULCHAVSKY, S.A.; GAUTAM, S.C.

    2013-01-01

    Promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of hormone-refractory prostate cancer. Xanthohumol (XN), a prenylated chalcone-derived from hops, has shown strong antitumorigenic activity towards diverse types of cancer cells. In the present study, the growth-inhibitory and apoptosis-inducing activity of XN was tested in hormone-sensitive and hormone-refractory human prostate cancer cells lines. Cell growth/viability assay (MTS) demonstrated that prostate cancer cells are highly sensitive to XN at a concentration range of 20-40 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of annexin V-FITC, cleavage of PARP-1, activation of procaspases -3, -8, and -9, mitochondrial depolarization and release of cytochrome c from mitochondria. Induction of apoptosis by XN was associated with the inhibition of prosurvival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2 and survivin. These studies provide a rationale for clinical evaluation of XN for the treatment of hormone-refractory metastatic prostate cancer. PMID:20944105

  18. Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel.

    PubMed

    Fonseca, Joana; Marques, Sandra; Silva, Patrícia M A; Brandão, Pedro; Cidade, Honorina; Pinto, Madalena M; Bousbaa, Hassan

    2016-07-29

    We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination.

  19. Transient Silencing of CHALCONE SYNTHASE during Fruit Ripening Modifies Tomato Epidermal Cells and Cuticle Properties1[C][W

    PubMed Central

    España, Laura; Heredia-Guerrero, José A.; Reina-Pinto, José J.; Fernández-Muñoz, Rafael; Heredia, Antonio; Domínguez, Eva

    2014-01-01

    Tomato (Solanum lycopersicum) fruit ripening is accompanied by an increase in CHALCONE SYNTHASE (CHS) activity and flavonoid biosynthesis. Flavonoids accumulate in the cuticle, giving its characteristic orange color that contributes to the eventual red color of the ripe fruit. Using virus-induced gene silencing in fruits, we have down-regulated the expression of SlCHS during ripening and compared the cuticles derived from silenced and nonsilenced regions. Silenced regions showed a pink color due to the lack of flavonoids incorporated to the cuticle. This change in color was accompanied by several other changes in the cuticle and epidermis. The epidermal cells displayed a decreased tangential cell width; a decrease in the amount of cuticle and its main components, cutin and polysaccharides, was also observed. Flavonoids dramatically altered the cuticle biomechanical properties by stiffening the elastic and viscoelastic phase and by reducing the ability of the cuticle to deform. There seemed to be a negative relation between SlCHS expression and wax accumulation during ripening that could be related to the decreased cuticle permeability to water observed in the regions silencing SlCHS. A reduction in the overall number of ester linkages present in the cutin matrix was also dependent on the presence of flavonoids. PMID:25277718

  20. Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies.

    PubMed

    Mathew, Bijo; Mathew, Githa Elizabeth; Uçar, Gülberk; Baysal, Ipek; Suresh, Jerad; Vilapurathu, Jobin Kunjumon; Prakasan, Aneesh; Suresh, Jeethu Kuruppath; Thomas, Anjana

    2015-10-01

    A series of methoxylated chalcones with fluoro and trifluoromethyl derivatives were synthesized and investigated for their ability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been characterized by means of their (1)H NMR, (13)C NMR, Mass spectroscopic datas and elemental analysis. The results demonstrate that these compounds are reversible and selective MAO-B inhibitors with a competitive mode of inhibition. The most potent compound (2E)-1-(4-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl] prop-2-en-1-one showed the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.22±0.01μM and 0.05 comparable to that standard drug, Selegiline Ki and SI values were found as 0.33±0.03μM and 0.04, respectively. Molecular docking studies were carried out to further explain the in vitro results of the new compounds, and to identify the hypothetical binding mode for the compounds inside the inhibitor binding cavity of hMAO-B.

  1. Electrosynthesis, spectral and structural studies of a semi-conducting oligomer deriving from a methoxy-substituted chalcone

    NASA Astrophysics Data System (ADS)

    Aribi, Imen; Ghomrasni, Saber; Ayachi, Sahbi; Alimi, Kamel; Roudesli, Sadok; Said, Ayoub Haj

    2016-11-01

    The anodic oxidation of a substituted chalcone namely the (E)-1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl) prop-2-enone (TMC) was investigated by different electrochemical techniques using a platinum working electrode in acetonitrile. On the cyclic voltammetry time scale, the TMC exhibited a single irreversible anodic peak around 1.4 V vs. Ag/AgCl and the coupling of the radical cations, issued from the first electron transfer, was the governing reaction near the electrode. Electrolysis at a constant potential revealed that an oligo o-phenylenevinylene was the main product of the anodic oxidation of TMC. The chemical structure of the isolated oligomer was elucidated by 1H, 13C NMR, and IR spectroscopy. Gel permeation chromatography indicated that the average chain length was about 5 units. In addition, the obtained oligomer was thermally stable up to 220 °C and exhibited a light emission in the indigo-blue region. Finally, a mechanism for the TMC electro-oligomerization was proposed on the basis of the electrochemical data and the theoretical calculation of the spin densities distribution for the TMC radical cation.

  2. Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-01

    Hesperidin methyl chalcone (HMC) is a safe flavonoid used to treat chronic venous diseases, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress have never been described in vivo. Thus, the purpose of this study was to evaluate the effects of systemic administration of HMC in skin oxidative stress and inflammation induced by UVB irradiation. To induce skin damage, hairless mice were exposed to an acute UVB irradiation dose of 4.14 J/cm(2), and the dorsal skin samples were collected to evaluate oxidative stress and inflammatory response. The intraperitoneal treatment with HMC at the dose of 300 mg/kg inhibited UVB irradiation-induced skin edema, neutrophil recruitment, and matrix metalloproteinase-9 activity. HMC also protected the skin from UVB irradiation-induced oxidative stress by maintaining ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability and antioxidant levels (reduced glutathione and catalase). Corroborating, HMC inhibited UVB irradiation-induced superoxide anion generation and gp91phox (NADPH oxidase subunit) mRNA expression. Furthermore, the antioxidant effect of HMC resulted in lower production of inflammatory mediators, including lipid hydroperoxides and a wide range of cytokines. Taken together, these results unveil a novel applicability of HMC in the treatment of UVB irradiation-induced skin inflammation and oxidative stress.

  3. Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death.

    PubMed

    Robinson, Michael W; Overmeyer, Jean H; Young, Ashley M; Erhardt, Paul W; Maltese, William A

    2012-03-01

    Methuosis is a novel caspase-independent form of cell death in which massive accumulation of vacuoles derived from macropinosomes ultimately causes cells to detach from the substratum and rupture. We recently described a chalcone-like compound, 3-(2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e., MIPP), which can induce methuosis in glioblastoma and other types of cancer cells. Herein, we describe the synthesis and structure-activity relationships of a directed library of related compounds, providing insights into the contributions of the two aryl ring systems and highlighting a potent derivative, 3-(5-methoxy, 2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e., MOMIPP) that can induce methuosis at low micromolar concentrations. We have also generated biologically active azide derivatives that may be useful for future studies aimed at identifying the protein targets of MOMIPP by photoaffinity labeling techniques. The potential significance of these studies is underscored by the finding that MOMIPP effectively reduces the growth and viability of Temozolomide-resistant glioblastoma and doxorubicin-resistant breast cancer cells. Thus, it may serve as a prototype for drugs that could be used to trigger death by methuosis in cancers that are resistant to conventional forms of cell death (e.g., apoptosis).

  4. Synthesis, leishmanicidal and cytotoxic activity of triclosan-chalcone, triclosan-chromone and triclosan-coumarin hybrids.

    PubMed

    Otero, Elver; Vergara, Sebastián; Robledo, Sara M; Cardona, Wilson; Carda, Miguel; Vélez, Ivan D; Rojas, Carlos; Otálvaro, Felipe

    2014-08-28

    Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7-9 and 17, were active against Leishmania parasites (EC50=9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25-27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.

  5. The expression of Millettia pinnata chalcone isomerase in Saccharomyces cerevisiae salt-sensitive mutants enhances salt-tolerance.

    PubMed

    Wang, Hui; Hu, Tangjin; Huang, Jianzi; Lu, Xiang; Huang, Baiqu; Zheng, Yizhi

    2013-01-01

    The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full length cDNA (666 bp) was obtained by 3'-end and 5'-end Rapid Amplification of cDNA Ends (RACE). The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%-86%). Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa), whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1) showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata. PMID:23615469

  6. Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel.

    PubMed

    Fonseca, Joana; Marques, Sandra; Silva, Patrícia M A; Brandão, Pedro; Cidade, Honorina; Pinto, Madalena M; Bousbaa, Hassan

    2016-01-01

    We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination. PMID:27483224

  7. Crystal structure and nonlinear optical absorption of a new chalcone derivative: a promising candidate for optical switching

    NASA Astrophysics Data System (ADS)

    Chandra Shekhara Shetty, T.; Raghavendra, S.; Chidan Kumar, C. S.; Dharmaprakash, S. M.

    2016-07-01

    A new nonlinear optical material, 4-[(2 E)-3-(3-fluorophenyl) prop-2-enoyl] benzonitrile (3FPB), belonging to chalcone family was synthesized and characterized by FTIR and linear absorption spectroscopy. Single-crystal X-ray diffraction reveals that the new material crystallizes in monoclinic system with P21/c space group and lattice parameters a = 6.4841(2) Å, b = 13.6038(5) Å, c = 14.6418(6) Å, α = 90.00°, β = 94.552(2)° and γ = 90°. The crystallographic perfection of the synthesized material has been analyzed by X-ray powder diffraction. The X-ray powder diffraction peaks of the sample were indexed with hkl values. The UV-visible spectrum for 3FPB crystals showed the optical transmittance window and a lower cutoff wavelength of absorption at 343 nm. The direct transition band gap energy and indirect transition energy gap were determined using Tauc's plots. The thermal stability and melting point of the material have been investigated by thermogravimetric analysis/differential thermal analysis (TGA/DTA). The Thermogravimetric curve showed the absence of any phase transition before melting point. Third-order nonlinear absorption and optical limiting experiment were carried out using open-aperture Z-scan experiment with Nd:YAG laser nanosecond pulses at a wavelength of 532 nm.

  8. Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity.

    PubMed

    Gaur, Rashmi; Pathania, Anup Singh; Malik, Fayaz Ahmad; Bhakuni, Rajendra Singh; Verma, Ram Kishor

    2016-10-21

    A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 μM for 48 h whereas DHA has IC50 value of 2 μM at same time period. The most potent compounds 8 with IC50 = 0.3 μM (at par with doxorubicin (IC50 = 0.3 μM)) and 15 with IC50 = 0.4 μM, of the series, six and three times active than DHA (with IC50 = 2 μM) respectively were selected for further mechanistic work in human leukemia HL-60 cells. PMID:27371926

  9. In vivo phase II-enzymes inducers, as potential chemopreventive agents, based on the chalcone and furoxan skeletons.

    PubMed

    Cabrera, Mauricio; Mastandrea, Ignacio; Otero, Gabriel; Cerecetto, Hugo; González, Mercedes

    2016-04-15

    Cancer chemoprevention involves prevention/delay/reverse of the carcinogenic process through administration of cancer chemopreventive agents (CCA). Compounds which are able to induce detoxification-enzymes, especially monofunctional phase II enzymes, have become in excellent approaches for new CCA. Herein, we report the synthesis of new furoxanyl chalcone-like hybrid compounds as CCA. In vitro studies showed that phenylfuroxanyl derivatives 6 and 9 displayed the best activities being 9 the greatest monofunctional-inducer. Additionally, compounds were non-mutagenic against TA98 Salmonella typhimurium strain (Ames test) and could be used in the prevention of the progression of pre-malignant lesions for their cytotoxic activity against tumoral cells. In vivo proof of concept showed increment on phase II-enzymes activities in liver, colon and mammary gland having derivative 9 the best induction profiles. We probed Nrf2 nuclear translocation is operative for both compounds allowing to exert protective effects via expression of downstream phase-II enzymes. PMID:26970663

  10. Theoretical study of the asymmetric phase-transfer mediated epoxidation of chalcone catalyzed by chiral crown ethers derived from monosaccharides

    NASA Astrophysics Data System (ADS)

    Makó, Attila; Menyhárd, Dóra K.; Bakó, Péter; Keglevich, György; Tőke, László

    2008-12-01

    The synthesis of a novel, optically active crown ether derived from α- D-altropyranoside is described. A significantly different asymmetric induction was generated by the α- D-glucopyranoside-, α- D-mannopyranoside- and α- D-altropyranoside-based chiral crown catalysts in the epoxidation of trans-chalcone with tert-butyl hydroperoxide under phase-transfer catalytic conditions. It was shown that absolute configuration of the crown-ring fused carbon atoms of the monosaccharides has a great impact on the enantioselectivity. The asymmetric induction could be well explained by considering the possible mechanistic pathway. Molecular modeling (MCMM) and subsequent DFT calculations - in accordance with the experimental results - indicate that the use of glucopyranoside-based catalyst 1 and that of mannopyranoside-based crown ether 2 results in the preferred formation of the opposite antipodes (2 R,3 S and 2 S,3 R, respectively) of the corresponding epoxyketone. At the same time, practically no asymmetric induction was proved if altropyranoside-based crown 3 is applied as the catalyst. The computational results are in qualitative agreement with the experimental data.

  11. Control theory meets synthetic biology.

    PubMed

    Del Vecchio, Domitilla; Dy, Aaron J; Qian, Yili

    2016-07-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. PMID:27440256

  12. Control theory meets synthetic biology.

    PubMed

    Del Vecchio, Domitilla; Dy, Aaron J; Qian, Yili

    2016-07-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology.

  13. Control theory meets synthetic biology

    PubMed Central

    2016-01-01

    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. PMID:27440256

  14. Content metamorphosis in synthetic holography

    NASA Astrophysics Data System (ADS)

    Desbiens, Jacques

    2013-02-01

    A synthetic hologram is an optical system made of hundreds of images amalgamated in a structure of holographic cells. Each of these images represents a point of view on a three-dimensional space which makes us consider synthetic holography as a multiple points of view perspective system. In the composition of a computer graphics scene for a synthetic hologram, the field of view of the holographic image can be divided into several viewing zones. We can attribute these divisions to any object or image feature independently and operate different transformations on image content. In computer generated holography, we tend to consider content variations as a continuous animation much like a short movie. However, by composing sequential variations of image features in relation with spatial divisions, we can build new narrative forms distinct from linear cinematographic narration. When observers move freely and change their viewing positions, they travel from one field of view division to another. In synthetic holography, metamorphoses of image content are within the observer's path. In all imaging Medias, the transformation of image features in synchronisation with the observer's position is a rare occurrence. However, this is a predominant characteristic of synthetic holography. This paper describes some of my experimental works in the development of metamorphic holographic images.

  15. Meeting Report: Synthetic Biology Jamboree for Undergraduates

    ERIC Educational Resources Information Center

    Campbell, A. Malcolm

    2005-01-01

    The field of synthetic biology (the name is derived from an analogy to synthetic chemistry) has recognized itself as a "field" only since about 2002. Synthetic biology has gotten some high-profile attention recently, but most people are not aware the field even exists. Synthetic biologists apply engineering principles to genomic circuits to…

  16. Designer Drugs: A Synthetic Catastrophe

    PubMed Central

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    2016-01-01

    Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are “Not for Human Consumption”, therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance use disorder treatment centers. Urine Drug Testing is utilized as a clinical diagnostic tool in substance use disorder treatment centers, and the furious pace at which new synthetic stimulants are introduced to the black market are making the detection via urine increasingly difficult. This article will discuss the prevalence, pharmacology and difficulty developing laboratory assays to detect synthetic stimulants. PMID:27617301

  17. Synthetic Peptides as Protein Mimics

    PubMed Central

    Groß, Andrea; Hashimoto, Chie; Sticht, Heinrich; Eichler, Jutta

    2016-01-01

    The design and generation of molecules capable of mimicking the binding and/or functional sites of proteins represents a promising strategy for the exploration and modulation of protein function through controlled interference with the underlying molecular interactions. Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites because such peptides can be generated as exact copies of protein fragments, as well as in diverse chemical modifications, which includes the incorporation of a large range of non-proteinogenic amino acids as well as the modification of the peptide backbone. Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their utility for biological applications. This article reviews recent advances by this and other laboratories in the use of synthetic protein mimics to modulate protein function, as well as to provide building blocks for synthetic biology. PMID:26835447

  18. Differential Optical Synthetic Aperture Radar

    DOEpatents

    Stappaerts, Eddy A.

    2005-04-12

    A new differential technique for forming optical images using a synthetic aperture is introduced. This differential technique utilizes a single aperture to obtain unique (N) phases that can be processed to produce a synthetic aperture image at points along a trajectory. This is accomplished by dividing the aperture into two equal "subapertures", each having a width that is less than the actual aperture, along the direction of flight. As the platform flies along a given trajectory, a source illuminates objects and the two subapertures are configured to collect return signals. The techniques of the invention is designed to cancel common-mode errors, trajectory deviations from a straight line, and laser phase noise to provide the set of resultant (N) phases that can produce an image having a spatial resolution corresponding to a synthetic aperture.

  19. Synthetic neurosteroids on brain protection

    PubMed Central

    Rey, Mariana; Coirini, Héctor

    2015-01-01

    Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids administration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute promising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3α-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions. PMID:25788907

  20. US Competitiveness in Synthetic Biology.

    PubMed

    Gronvall, Gigi Kwik

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized. PMID:26690379

  1. US Competitiveness in Synthetic Biology.

    PubMed

    Gronvall, Gigi Kwik

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

  2. The design of synthetic genes.

    PubMed Central

    Presnell, S R; Benner, S A

    1988-01-01

    Computer programs are described that aid in the design of synthetic genes coding for proteins that are targets of a research program in site directed mutagenesis. These programs "reverse-translate" protein sequences into general nucleic acid sequences (those where codons have not yet been selected), map restriction sites into general DNA sequences, identify points in the synthetic gene where unique restriction sites can be introduced, and assist in the design of genes coding for hybrids and evolutionary intermediates between homologous proteins. Application of these programs therefore facilitates the use of modular mutagenesis to create variants of proteins, and the implementation of evolutionary guidance as a strategy for selecting mutants. PMID:2451218

  3. The Case for Synthetic Injectables.

    PubMed

    Joseph, John H

    2015-11-01

    There are several different classes of synthetic dermal fillers and volume enhancers including semipermanent and permanent products available in the United States. Based on clinical and scientific evidence, this article reviews the chemical and polymeric properties, clinical data, patient selection, indications for use, injection technique, and adverse event profiles of permanent synthetic injectables currently used in clinical practice in the United States: medical-grade liquid injectable silicone and polymethyl methacrylate. Understanding the unique characteristics of these two products reinforces the advantages and disadvantages of each, including under what circumstances they should be used and why they perform the way they do. PMID:26505540

  4. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  5. The Case for Synthetic Injectables.

    PubMed

    Joseph, John H

    2015-11-01

    There are several different classes of synthetic dermal fillers and volume enhancers including semipermanent and permanent products available in the United States. Based on clinical and scientific evidence, this article reviews the chemical and polymeric properties, clinical data, patient selection, indications for use, injection technique, and adverse event profiles of permanent synthetic injectables currently used in clinical practice in the United States: medical-grade liquid injectable silicone and polymethyl methacrylate. Understanding the unique characteristics of these two products reinforces the advantages and disadvantages of each, including under what circumstances they should be used and why they perform the way they do.

  6. Synthetic Phage for Tissue Regeneration

    PubMed Central

    Merzlyak, Anna; Lee, Seung-Wuk

    2014-01-01

    Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy. PMID:24991085

  7. Molecular docking based screening of novel designed chalcone series of compounds for their anti-cancer activity targeting EGFR kinase domain

    PubMed Central

    Rao, Chennu Maruthi Malya Prasada; Yejella, Rajendra Prasad; Rehman, Rehman Shaik Abdul; Basha, Syed Hussain

    2015-01-01

    Epidermal growth factor receptors (EGFR) are critical for the growth of many tumors and expressed at high levels in about one third of epithelial cancers. Hence, blockade of the binding sites for EGFR has been hypothesized as an effective anti-cancer therapy. Chalcone derivative compounds have been shown to be highly effective anti-cancer agents, however there are still so many novel derivatives possible, one of which might get us the best targeted EGFR inhibitor. In this effort directed towards the discovery of novel, potent anti-tumor agents for the treatment of cancer, in the present study a library of novel chalcone series of compounds has been designed and evaluated for their anti-cancer activity targeting EGFR kinase domain using various computational approaches. Among the twenty five novel designed chalcone series of compounds, all of them have found to be successfully docking inside the active binding domain of EGFR receptor target with a binding energy in a range of -6.10 to -9.25 Kcal/mol with predicted IC50 value range of 33.50 micor molar to 164.66 nano molar respectively. On the other hand, calculated 2DQSAR molecular descriptor properties of the compounds showed promising ADME parameters and found to be well in compliance with Lipinski׳s rule of five. Among all the twenty five compounds tested, compound 21 ((2E)-3-(anthracen-9-yl)-1-phenylprop-2-2n-1- one) was found to be the best lead like molecule with a binding energy of -9.25 kcal/mol with predicted IC50 value of 164.66 nano molar. Conclusively, novel designed compound 21 of the present study have shown promising anti-cancer potential worth considering for further evaluations. PMID:26339147

  8. Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

    NASA Astrophysics Data System (ADS)

    Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

    2015-08-01

    The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

  9. Methods for preparing synthetic freshwaters.

    PubMed

    Smith, E J; Davison, W; Hamilton-Taylor, J

    2002-03-01

    Synthetic solutions that emulate the major ion compositions of natural waters are useful in experiments aimed at understanding biogeochemical processes. Standard recipes exist for preparing synthetic analogues of seawater, with its relatively constant composition, but, due to the diversity of freshwaters, a range of compositions and recipes is required. Generic protocols are developed for preparing synthetic freshwaters of any desired composition. The major problems encountered in preparing hard and soft waters include dissolving sparingly soluble calcium carbonate, ensuring that the ionic components of each concentrated stock solution cannot form an insoluble salt and dealing with the supersaturation of calcium carbonate in many hard waters. For acidic waters the poor solubility of aluminium salts requires attention. These problems are overcome by preparing concentrated stock solutions according to carefully designed reaction paths that were tested using a combination of experiment and equilibrium modeling. These stock solutions must then be added in a prescribed order to prepare a final solution that is brought into equilibrium with the atmosphere. The example calculations for preparing hard, soft and acidic freshwater surrogates with major ion compositions the same as published analyses, are presented in a generalized fashion that should allow preparation of any synthetic freshwater according to its known analysis. PMID:11902783

  10. Where Synthetic Biology Meets ET

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.

    2016-01-01

    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  11. Digital 'faces' of synthetic biology.

    PubMed

    Friedrich, Kathrin

    2013-06-01

    In silicio design plays a fundamental role in the endeavour to synthesise biological systems. In particular, computer-aided design software enables users to manage the complexity of biological entities that is connected to their construction and reconfiguration. The software's graphical user interface bridges the gap between the machine-readable data on the algorithmic subface of the computer and its human-amenable surface represented by standardised diagrammatic elements. Notations like the Systems Biology Graphical Notation (SBGN), together with interactive operations such as drag & drop, allow the user to visually design and simulate synthetic systems as 'bio-algorithmic signs'. Finally, the digital programming process should be extended to the wet lab to manufacture the designed synthetic biological systems. By exploring the different 'faces' of synthetic biology, I argue that in particular computer-aided design (CAD) is pushing the idea to automatically produce de novo objects. Multifaceted software processes serve mutually aesthetic, epistemic and performative purposes by simultaneously black-boxing and bridging different data sources, experimental operations and community-wide standards. So far, synthetic biology is mainly a product of digital media technologies that structurally mimic the epistemological challenge to take both qualitative as well as quantitative aspects of biological systems into account in order to understand and produce new and functional entities.

  12. Synthetic Division and Matrix Factorization

    ERIC Educational Resources Information Center

    Barabe, Samuel; Dubeau, Franc

    2007-01-01

    Synthetic division is viewed as a change of basis for polynomials written under the Newton form. Then, the transition matrices obtained from a sequence of changes of basis are used to factorize the inverse of a bidiagonal matrix or a block bidiagonal matrix.

  13. Synthetic biology meets tissue engineering.

    PubMed

    Davies, Jamie A; Cachat, Elise

    2016-06-15

    Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. PMID:27284030

  14. SEASAT Synthetic Aperture Radar Data

    NASA Technical Reports Server (NTRS)

    Henderson, F. M.

    1981-01-01

    The potential of radar imagery from space altitudes is discussed and the advantages of radar over passive sensor systems are outlined. Specific reference is made to the SEASAT synthetic aperture radar. Possible applications include oil spill monitoring, snow and ice reconnaissance, mineral exploration, and monitoring phenomena in the urban environment.

  15. Synthetic substrates for enzyme analysis

    DOEpatents

    Bissell, E.R.; Mitchell, A.R.; Pearson, K.W.; Smith, R.E.

    1983-06-14

    Synthetic substrates are provided which may be represented as A-D. The A moiety includes an amino acid, polypeptide, or derivative. The D moiety includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons. No Drawings

  16. Synthetic substrates for enzyme analysis

    DOEpatents

    Bissell, Eugene R.; Mitchell, Alexander R.; Pearson, Karen W.; Smith, Robert E.

    1983-01-01

    Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.

  17. The synthetic biology open language.

    PubMed

    Myers, Chris; Clancy, Kevin; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline; Roehner, Nicholas; Sauro, Herbert M

    2015-01-01

    The design and construction of engineered organisms is an emerging new discipline called synthetic biology and holds considerable promise as a new technological platform. The design of biologically engineered systems is however nontrivial, requiring contributions from a wide array of disciplines. One particular issue that confronts synthetic biologists is the ability to unambiguously describe novel designs such that they can be reengineered by a third-party. For this reason, the synthetic biology open language (SBOL) was developed as a community wide standard for formally representing biological designs. A design created by one engineering team can be transmitted electronically to another who can then use this design to reproduce the experimental results. The development and the community of the SBOL standard started in 2008 and has since grown in use with now over 80 participants, including international, academic, and industrial interests. SBOL has stimulated the development of repositories and software tools to help synthetic biologists in their design efforts. This chapter summarizes the latest developments and future of the SBOL standard and its supporting infrastructure.

  18. Chemical aspects of synthetic biology.

    PubMed

    Luisi, Pier Luigi

    2007-04-01

    Synthetic biology as a broad and novel field has also a chemical branch: whereas synthetic biology generally has to do with bioengineering of new forms of life (generally bacteria) which do not exist in nature, 'chemical synthetic biology' is concerned with the synthesis of chemical structures such as proteins, nucleic acids, vesicular forms, and other which do not exist in nature. Three examples of this 'chemical synthetic biology' approach are given in this article. The first example deals with the synthesis of proteins that do not exist in nature, and dubbed as 'the never born proteins' (NBPs). This research is related to the question why and how the protein structures existing in our world have been selected out, with the underlying question whether they have something very particular from the structural or thermodynamic point of view (for example, the folding). The NBPs are produced in the laboratory by the modern molecular biology technique, the phage display, so as to produce a very large library of proteins having no homology with known proteins. The second example of chemical synthetic biology has also to do with the laboratory synthesis of proteins, but, this time, adopting a prebiotic synthetic procedure, the fragment condensation of short peptides, where short means that they have a length that can be obtained by prebiotic methods; for example, from the condensation of N-carboxy anhydrides. The scheme is illustrated and discussed, being based on the fragment condensation catalyzed by peptides endowed with proteolitic activity. Selection during chain growth is determined by solubility under the contingent environmental conditions, i.e., the peptides which result insoluble are eliminated from further growth. The scheme is tested preliminarily with a synthetic chemical fragment-condensation method and brings to the synthesis of a 44-residues-long protein, which has no homology with known proteins, and which has a stable tertiary folding. Finally, the third

  19. Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Pala, Danilo; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-04-01

    Skin exposure to ultraviolet B (UVB) irradiation has increased significantly in recent years due to ozone depletion, and it represents the main cause of many skin diseases. Hesperidin methyl chalcone (HMC) is a compound used to treat vascular diseases that has demonstrated anti-inflammatory activities in pre-clinical studies. Herein, we tested the antioxidant activity of HMC in cell free systems and the in vivo effects of a stable topical formulation containing HMC in a mouse model of skin oxidative stress and inflammation induced by UVB irradiation. HMC presented ferric reducing power, neutralized 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl free radicals, and inhibited lipid peroxidation. In hairless mice, a topical formulation containing HMC inhibited UVB irradiation-induced skin edema, depletion of antioxidant capacity (ferric and ABTS reducing abilities and catalase activity), lipid peroxidation, superoxide anion production and mRNA expression of gp91phox (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase 2 sub-unity). In addition, HMC inhibited UVB irradiation-induced depletion of reduced glutathione levels by maintaining glutathione peroxidase-1 and glutathione reductase mRNA expression, prevented down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression and increased heme oxygenase-1 mRNA expression. Finally, we demonstrated that topical application of the formulation containing HMC inhibited cytokine (TNF-α, IL-1β, IL-6, and IL-10) production induced by UVB irradiation. Therefore, this topical formulation containing HMC is a promising new therapeutic approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:27021784

  20. In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot)

    PubMed Central

    Isa, N.M.; Abdelwahab, S.I.; Mohan, S.; Abdul, A.B.; Sukari, M.A.; Taha, M.M.E.; Syam, S.; Narrima, P.; Cheah, S.Ch.; Ahmad, S.; Mustafa, M.R.

    2012-01-01

    The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µg/mL and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µg/mL. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract. PMID:22358425

  1. Modification of phenolic metabolism in soybean hairy roots through down regulation of chalcone synthase or isoflavone synthase.

    PubMed

    Lozovaya, Vera V; Lygin, Anatoliy V; Zernova, Olga V; Ulanov, Alexander V; Li, Shuxian; Hartman, Glen L; Widholm, Jack M

    2007-02-01

    Soybean hairy roots, transformed with the soybean chalcone synthase (CHS6) or isoflavone synthase (IFS2) genes, with dramatically decreased capacity to synthesize isoflavones were produced to determine what effects these changes would have on susceptibility to a fungal pathogen. The isoflavone and coumestrol concentrations were decreased by about 90% in most lines apparently due to gene silencing. The IFS2 transformed lines had very low IFS enzyme activity in microsomal fractions as measured by the conversion of naringenin to genistein. The CHS6 lines with decreased isoflavone concentrations had 5 to 20-fold lower CHS enzyme activities than the appropriate controls. Both IFS2 and CHS transformed lines accumulated higher concentrations of both soluble and cell wall bound phenolic acids compared to controls with higher levels found in the CHS6 lines indicating alterations in the lignin biosynthetic branch of the pathway. Induction of the soybean phytoalexin glyceollin, of which the precursor is the isoflavone daidzein, by the fungal pathogen Fusarium solani f. sp. glycines (FSG) that causes soybean sudden death syndrome (SDS) showed that the low isoflavone transformed lines did not accumulate glyceollin while the control lines did. The (iso)liquritigenin content increased upon FSG induction in the IFS2 transformed roots indicating that the pathway reactions before this point can control isoflavonoid synthesis. The lowest fungal growth rate on hairy roots was found on the FSG partially resistant control roots followed by the SDS sensitive control roots and the low isoflavone transformants. The results indicate the importance of phytoalexin synthesis in root resistance to the pathogen. PMID:16924535

  2. SAR studies of differently functionalized chalcones based hydrazones and their cyclized derivatives as inhibitors of mammalian cathepsin B and cathepsin H.

    PubMed

    Raghav, Neera; Singh, Mamta

    2014-08-01

    Cathepsins have emerged as potential drug targets for melanoma therapy and engrossed attention of researchers for development and evaluation of cysteine cathepsin inhibitors as cancer therapeutics. In this direction, we have designed, synthesized, and assayed in vitro a small library of 30 low molecular weight functionalized analogs of chalcone hydrazones for evaluating structure-activity relationship aspects and inhibitory potency against cathepsin B and H. The maximum inhibitory effect was exerted by chalcone hydrazones, which are open chain analogues followed by their cyclized derivatives, pyrazolines and pyrazoles. All the synthesized compounds were established as reversible inhibitors of these enzymes. Cathepsin B was selectively inhibited by the compounds in each series. Compounds 1d, 2d and 4d were recognized as most potent inhibitors of cathepsin B in this study with Ki values of 0.042 μM, 0.053 μM and 0.131 μM whereas 1b (Ki=1.111 μM), 2b (Ki=1.174 μM) and 4b (Ki=1.562 μM) inhibited cathepsin H activity effectively. And, preeminent cathepsin B inhibitors were -NO2 functionalized however, -Cl substituted moieties were the most persuasive inhibitors for cathepsin H among all the designed compounds. Molecular docking studies performed using iGemdock provided valuable insights. PMID:24913985

  3. The Plant-Derived Chalcone 2,2′,5′-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia

    PubMed Central

    Jiwrajka, Manasi; Phillips, Alexandra; Butler, Matt; Pocock, Jennifer M.

    2016-01-01

    Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2′,5′-trihydroxychalcone (225THC), a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2′,5′-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions. PMID:26798424

  4. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

    PubMed Central

    Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

    2016-01-01

    Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

  5. LAP5 and LAP6 Encode Anther-Specific Proteins with Similarity to Chalcone Synthase Essential for Pollen Exine Development in Arabidopsis1[W][OA

    PubMed Central

    Dobritsa, Anna A.; Lei, Zhentian; Nishikawa, Shuh-ichi; Urbanczyk-Wochniak, Ewa; Huhman, David V.; Preuss, Daphne; Sumner, Lloyd W.

    2010-01-01

    Pollen grains of land plants have evolved remarkably strong outer walls referred to as exine that protect pollen and interact with female stigma cells. Exine is composed of sporopollenin, and while the composition and synthesis of this biopolymer are not well understood, both fatty acids and phenolics are likely components. Here, we describe mutations in the Arabidopsis (Arabidopsis thaliana) LESS ADHESIVE POLLEN (LAP5) and LAP6 that affect exine development. Mutation of either gene results in abnormal exine patterning, whereas pollen of double mutants lacked exine deposition and subsequently collapsed, causing male sterility. LAP5 and LAP6 encode anther-specific proteins with homology to chalcone synthase, a key flavonoid biosynthesis enzyme. lap5 and lap6 mutations reduced the accumulation of flavonoid precursors and flavonoids in developing anthers, suggesting a role in the synthesis of phenolic constituents of sporopollenin. Our in vitro functional analysis of LAP5 and LAP6 using 4-coumaroyl-coenzyme A yielded bis-noryangonin (a commonly reported derailment product of chalcone synthase), while similar in vitro analyses using fatty acyl-coenzyme A as the substrate yielded medium-chain alkyl pyrones. Thus, in vitro assays indicate that LAP5 and LAP6 are multifunctional enzymes and may play a role in both the synthesis of pollen fatty acids and phenolics found in exine. Finally, the genetic interaction between LAP5 and an anther gene involved in fatty acid hydroxylation (CYP703A2) demonstrated that they act synergistically in exine production. PMID:20442277

  6. Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

    PubMed

    Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

    2016-08-21

    The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. PMID:27185536

  7. Preparation of highly ordered mesoporous AlSBA-15-SO 3H hybrid material for the catalytic synthesis of chalcone under solvent-free condition

    NASA Astrophysics Data System (ADS)

    Li, Wei; Xu, Kejin; Xu, Leilei; Hu, Jianglei; Ma, Fengyan; Guo, Yihang

    2010-03-01

    Single-step preparation of SBA-15 materials functionalized with both propylsulfonic acid groups and aluminum species (AlSBA-15-SO 3H) was carried out by hydrothermal treatment of a mixture of aluminum isopropoxide, 3-mercaptopropyltriethoxysilane, tetraethoxysilane, and triblock copolymer surfactant. At Si/Al molar ratio of 11-96, the materials exhibited well-ordered hexagonally arranged mesopores with pore diameter of ca. 9 nm, BET surface area of 546.9-666.0 m 2 g -1, and pore volume of 0.82-1.03 cm 3 g -1. As-prepared AlSBA-15-SO 3H was successfully used in the Claisen-Schmidt condensation reaction of benzaldehyde with acetophenone to produce chalcone under solvent-free condition, and the influence of the reaction parameters including temperatures, molar ratios of BZD to APN, and aluminum loadings were considered during the chalcone synthesis procedure. It showed that AlSBA-15-SO 3H exhibited significantly high catalytic activity and selectivity, outperforming the reference catalysts such as sulfuric acid, ZSM-5, and acidic MCM-49. In addition, the catalytic stability and regeneration of AlSBA-15-SO 3H was studied.

  8. The Plant-Derived Chalcone 2,2',5'-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia.

    PubMed

    Jiwrajka, Manasi; Phillips, Alexandra; Butler, Matt; Rossi, Miriam; Pocock, Jennifer M

    2016-01-01

    Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2',5'-trihydroxychalcone (225THC), a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2',5'-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions.

  9. Synthetic Metal-Containing Polymers

    NASA Astrophysics Data System (ADS)

    Manners, Ian

    2004-04-01

    The development of the field of synthetic metal-containing polymers - where metal atoms form an integral part of the main chain or side group structure of a polymer - aims to create new materials which combine the processability of organic polymers with the physical or chemical characteristics associated with the metallic element or complex. This book covers the major developments in the synthesis, properties, and applications of synthetic metal-containing macromolecules, and includes chapters on the preparation and characterization of metal-containing polymers, metallocene-based polymers, rigid-rod organometallic polymers, coordination polymers, polymers containing main group metals, and also covers dendritic and supramolecular systems. The book describes both polymeric materials with metals in the main chain or side group structure and covers the literature up to the end of 2002.

  10. Synthetic cannabinoids: analysis and metabolites.

    PubMed

    Elsohly, Mahmoud A; Gul, Waseem; Wanas, Amira S; Radwan, Mohamed M

    2014-02-27

    Cannabimimetics (commonly referred to as synthetic cannabinoids), a group of compounds encompassing a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors CB1 and CB2. The goal was to have compounds that could possess high therapeutic activity without many side effects. However, underground laboratories have used the information generated by the scientific community to develop these compounds for illicit use as marijuana substitutes. This chapter reviews the different classes of these "synthetic cannabinoids" with particular emphasis on the methods used for their identification in the herbal products with which they are mixed and identification of their metabolites in biological specimens.

  11. DNA recognition by synthetic constructs.

    PubMed

    Pazos, Elena; Mosquera, Jesús; Vázquez, M Eugenio; Mascareñas, José L

    2011-09-01

    The interaction of transcription factors with specific DNA sites is key for the regulation of gene expression. Despite the availability of a large body of structural data on protein-DNA complexes, we are still far from fully understanding the molecular and biophysical bases underlying such interactions. Therefore, the development of non-natural agents that can reproduce the DNA-recognition properties of natural transcription factors remains a major and challenging goal in chemical biology. In this review we summarize the basics of double-stranded DNA recognition by transcription factors, and describe recent developments in the design and preparation of synthetic DNA binders. We mainly focus on synthetic peptides that have been designed by following the DNA interaction of natural proteins, and we discuss how the tools of organic synthesis can be used to make artificial constructs equipped with functionalities that introduce additional properties to the recognition process, such as sensing and controllability.

  12. Synthetic microbial ecosystems for biotechnology.

    PubMed

    Pandhal, Jagroop; Noirel, Josselin

    2014-06-01

    Most highly controlled and specific applications of microorganisms in biotechnology involve pure cultures. Maintaining single strain cultures is important for industry as contaminants can reduce productivity and lead to longer "down-times" during sterilisation. However, microbes working together provide distinct advantages over pure cultures. They can undertake more metabolically complex tasks, improve efficiency and even expand applications to open systems. By combining rapidly advancing technologies with ecological theory, the use of microbial ecosystems in biotechnology will inevitably increase. This review provides insight into the use of synthetic microbial communities in biotechnology by applying the engineering paradigm of measure, model, manipulate and manufacture, and illustrate the emerging wider potential of the synthetic ecology field. Systems to improve biofuel production using microalgae are also discussed.

  13. Cell microencapsulation with synthetic polymers

    PubMed Central

    Olabisi, Ronke M

    2015-01-01

    The encapsulation of cells into polymeric microspheres or microcapsules has permitted the transplantation of cells into human and animal subjects without the need for immunosuppressants. Cell-based therapies use donor cells to provide sustained release of a therapeutic product, such as insulin, and have shown promise in treating a variety of diseases. Immunoisolation of these cells via microencapsulation is a hotly investigated field, and the preferred material of choice has been alginate, a natural polymer derived from seaweed due to its gelling conditions. Although many natural polymers tend to gel in conditions favorable to mammalian cell encapsulation, there remain challenges such as batch to batch variability and residual components from the original source that can lead to an immune response when implanted into a recipient. Synthetic materials have the potential to avoid these issues; however, historically they have required harsh polymerization conditions that are not favorable to mammalian cells. As research into microencapsulation grows, more investigators are exploring methods to microencapsulate cells into synthetic polymers. This review describes a variety of synthetic polymers used to microencapsulate cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 846–859, 2015. PMID:24771675

  14. Hydrogen speciation in synthetic quartz

    USGS Publications Warehouse

    Aines, R.D.; Kirby, S.H.; Rossman, G.R.

    1984-01-01

    The dominant hydrogen impurity in synthetic quartz is molecular H2O. H-OH groups also occur, but there is no direct evidence for the hydrolysis of Si-O-Si bonds to yield Si-OH HO-Si groups. Molecular H2O concentrations in the synthetic quartz crystals studied range from less than 10 to 3,300 ppm (H/Si), and decrease smoothly by up to an order of magnitude with distance away from the seed. OH- concentrations range from 96 to 715 ppm, and rise smoothly with distance away from the seed by up to a factor of three. The observed OH- is probably all associated with cationic impurities, as in natural quartz. Molecular H2O is the dominant initial hydrogen impurity in weak quartz. The hydrolytic weakening of quartz may be caused by the transformation H2O + Si-O-Si ??? 2SiOH, but this may be a transitory change with the SiOH groups recombining to form H2O, and the average SiOH concentration remaining very low. Synthetic quartz is strengthened when the H2O is accumulated into fluid inclusions and cannot react with the quartz framework. ?? 1984 Springer-Verlag.

  15. Nano-enabled synthetic biology

    PubMed Central

    Doktycz, Mitchel J; Simpson, Michael L

    2007-01-01

    Biological systems display a functional diversity, density and efficiency that make them a paradigm for synthetic systems. In natural systems, the cell is the elemental unit and efforts to emulate cells, their components, and organization have relied primarily on the use of bioorganic materials. Impressive advances have been made towards assembling simple genetic systems within cellular scale containers. These biological system assembly efforts are particularly instructive, as we gain command over the directed synthesis and assembly of synthetic nanoscale structures. Advances in nanoscale fabrication, assembly, and characterization are providing the tools and materials for characterizing and emulating the smallest scale features of biology. Further, they are revealing unique physical properties that emerge at the nanoscale. Realizing these properties in useful ways will require attention to the assembly of these nanoscale components. Attention to systems biology principles can lead to the practical development of nanoscale technologies with possible realization of synthetic systems with cell-like complexity. In turn, useful tools for interpreting biological complexity and for interfacing to biological processes will result. PMID:17625513

  16. Synthetic metabolons for metabolic engineering.

    PubMed

    Singleton, Chloe; Howard, Thomas P; Smirnoff, Nicholas

    2014-05-01

    It has been proposed that enzymes can associate into complexes (metabolons) that increase the efficiency of metabolic pathways by channelling substrates between enzymes. Metabolons may increase flux by increasing the local concentration of intermediates, decreasing the concentration of enzymes needed to maintain a given flux, directing the products of a pathway to a specific subcellular location or minimizing the escape of reactive intermediates. Metabolons can be formed by relatively loose non-covalent protein-protein interaction, anchorage to membranes, and (in bacteria) by encapsulation of enzymes in protein-coated microcompartments. Evidence that non-coated metabolons are effective at channelling substrates is scarce and difficult to obtain. In plants there is strong evidence that small proportions of glycolytic enzymes are associated with the outside of mitochondria and are effective in substrate channelling. More recently, synthetic metabolons, in which enzymes are scaffolded to synthetic proteins or nucleic acids, have been expressed in microorganisms and these provide evidence that scaffolded enzymes are more effective than free enzymes for metabolic engineering. This provides experimental evidence that metabolons may have a general advantage and opens the way to improving the outcome of metabolic engineering in plants by including synthetic metabolons in the toolbox.

  17. Synthetic biology with RNA motifs.

    PubMed

    Saito, Hirohide; Inoue, Tan

    2009-02-01

    Structural motifs in naturally occurring RNAs and RNPs can be employed as new molecular parts for synthetic biology to facilitate the development of novel devices and systems that modulate cellular functions. In this review, we focus on the following: (i) experimental evolution techniques of RNA molecules in vitro and (ii) their applications for regulating gene expression systems in vivo. For experimental evolution, new artificial RNA aptamers and RNA enzymes (ribozymes) have been selected in vitro. These functional RNA molecules are likely to be applicable in the reprogramming of existing gene regulatory systems. Furthermore, they may be used for designing hypothetical RNA-based living systems in the so-called RNA world. For the regulation of gene expressions in living cells, the development of new riboswitches allows us to modulate the target gene expression in a tailor-made manner. Moreover, recently RNA-based synthetic genetic circuits have been reported by employing functional RNA molecules, expanding the repertory of synthetic biology with RNA motifs. PMID:18775792

  18. Synthetic LDL as targeted drug delivery vehicle

    DOEpatents

    Forte, Trudy M.; Nikanjam, Mina

    2012-08-28

    The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

  19. 21 CFR 175.250 - Paraffin (synthetic).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Paraffin (synthetic). 175.250 Section 175.250 Food....250 Paraffin (synthetic). Synthetic paraffin may be safely used as an impregnant in, coating on, or... catalytically converted to a mixture of paraffin hydrocarbons. Lower molecular-weight fractions are removed...

  20. 21 CFR 175.250 - Paraffin (synthetic).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Paraffin (synthetic). 175.250 Section 175.250 Food... for Use as Components of Coatings § 175.250 Paraffin (synthetic). Synthetic paraffin may be safely... process from carbon monoxide and hydrogen, which are catalytically converted to a mixture of...

  1. 21 CFR 175.250 - Paraffin (synthetic).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Paraffin (synthetic). 175.250 Section 175.250 Food... for Use as Components of Coatings § 175.250 Paraffin (synthetic). Synthetic paraffin may be safely... process from carbon monoxide and hydrogen, which are catalytically converted to a mixture of...

  2. 21 CFR 175.250 - Paraffin (synthetic).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Paraffin (synthetic). 175.250 Section 175.250 Food... for Use as Components of Coatings § 175.250 Paraffin (synthetic). Synthetic paraffin may be safely... process from carbon monoxide and hydrogen, which are catalytically converted to a mixture of...

  3. Different lattice geometries with a synthetic dimension

    NASA Astrophysics Data System (ADS)

    Suszalski, Dominik; Zakrzewski, Jakub

    2016-09-01

    The possibility of creating different geometries with the help of an extra synthetic dimension in optical lattices is studied. The additional linear potential together with Raman-assisted tunnelings are used to engineer well-controlled tunnelings between available states. The great flexibility of the system allows us to obtain different geometries of synthetic lattices with the possibility for adding synthetic gauge fields.

  4. Synthetic thermoelectric materials comprising phononic crystals

    DOEpatents

    El-Kady, Ihab F; Olsson, Roy H; Hopkins, Patrick; Reinke, Charles; Kim, Bongsang

    2013-08-13

    Synthetic thermoelectric materials comprising phononic crystals can simultaneously have a large Seebeck coefficient, high electrical conductivity, and low thermal conductivity. Such synthetic thermoelectric materials can enable improved thermoelectric devices, such as thermoelectric generators and coolers, with improved performance. Such synthetic thermoelectric materials and devices can be fabricated using techniques that are compatible with standard microelectronics.

  5. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells

    PubMed Central

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3’,4’,5’-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development. PMID:27525972

  6. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells.

    PubMed

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3',4',5'-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development. PMID:27525972

  7. Synthetic Fuels Corporation's progress in aiding synthetic fuels development

    SciTech Connect

    Not Available

    1984-07-11

    It has been difficult for the Corporation to make progress toward the goals of the Energy Security Act of June 1980 because of the changing economic and energy conditions. Relative to the 1987 production goal of 500,000 barrels of crude oil equivalent per day, the Corporation had awarded contracts for two projects expected to have a total production equivalent of 9500 barrels of crude oil per day. Including these two projects, the Corporation has said that it plans to award by early 1985 up to $14.8 billion in financial assistance for about 12 projects representing a diverse range of technologies, which would have a combined total production of about 132,000 barrels of crude oil equivalent per day. These plans may be affected by a recent administration proposal to rescind $9 billion of the Corporation's remaining unobligated funds. Private industry officials said that synthetic fuels projects have been abandoned or postponed primarily because of an unfavorable economic climate, a world oil glut that has caused declines in crude oil prices, the uncertainty of future crude oil prices, and the large capital investment needed for project construction. These officials also said that 1982 tax legislation, by reducing the after-tax return on investment, has also caused industry to abandon or delay going forward with synthetic fuels projects.

  8. Interferometry with synthetic gauge fields

    SciTech Connect

    Anderson, Brandon M.; Taylor, Jacob M.; Galitski, Victor M.

    2011-03-15

    We propose a compact atom interferometry scheme for measuring weak, time-dependent accelerations. Our proposal uses an ensemble of dilute trapped bosons with two internal states that couple to a synthetic gauge field with opposite charges. The trapped gauge field couples spin to momentum to allow time-dependent accelerations to be continuously imparted on the internal states. We generalize this system to reduce noise and estimate the sensitivity of such a system to be S{approx}10{sup -7}(m/s{sup 2}/{radical}(Hz)).

  9. Synthetic Biology Guides Biofuel Production

    PubMed Central

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

  10. Synthetic magnetism for photon fluids

    NASA Astrophysics Data System (ADS)

    Westerberg, N.; Maitland, C.; Faccio, D.; Wilson, K.; Öhberg, P.; Wright, E. M.

    2016-08-01

    We develop a theory of artificial gauge fields in photon fluids for the cases of both second-order and third-order optical nonlinearities. This applies to weak excitations in the presence of pump fields carrying orbital angular momentum and is thus a type of Bogoliubov theory. The resulting artificial gauge fields experienced by the weak excitations are an interesting generalization of previous cases and reflect the PT-symmetry properties of the underlying non-Hermitian Hamiltonian. We illustrate the observable consequences of the resulting synthetic magnetic fields for examples involving both second-order and third-order nonlinearities.

  11. Synthetic Studies in Phytochrome Chemistry

    PubMed Central

    Jacobi, Peter A.; Adel Odeh, Imad M.; Buddhu, Subhas C.; Cai, Guolin; Rajeswari, Sundaramoorthi; Fry, Douglas; Zheng, Wanjun; DeSimone, Robert W.; Guo, Jiasheng; Coutts, Lisa D.; Hauck, Sheila I.; Leung, Sam H.; Ghosh, Indranath; Pippin., Douglas

    2008-01-01

    An account is given of the author’s several approaches to the synthesis of the parent chromophore of phytochrome (1), a protein-bound linear tetrapyrrole derivative that controls photomorphogenesis in higher plants. These studies culminated in enantioselective syntheses of both 2R- and 2S-phytochromobilin (4), as well as several 13C-labeled derivatives designed to probe the site of Z,E-isomerization during photoexcitation. When reacted in vitro, synthetic 2R-4 and recombinant-derived phytochrome apoprotein N-C produced a protein-bound chromophore with identical difference spectra to naturally occurring 1. PMID:18633455

  12. Synthetic carbonaceous fuels and feedstocks

    DOEpatents

    Steinberg, Meyer

    1980-01-01

    This invention relates to the use of a three compartment electrolytic cell in the production of synthetic carbonaceous fuels and chemical feedstocks such as gasoline, methane and methanol by electrolyzing an aqueous sodium carbonate/bicarbonate solution, obtained from scrubbing atmospheric carbon dioxide with an aqueous sodium hydroxide solution, whereby the hydrogen generated at the cathode and the carbon dioxide liberated in the center compartment are combined thermocatalytically into methanol and gasoline blends. The oxygen generated at the anode is preferably vented into the atmosphere, and the regenerated sodium hydroxide produced at the cathode is reused for scrubbing the CO.sub.2 from the atmosphere.

  13. Catalysts from synthetic genetic polymers.

    PubMed

    Taylor, Alexander I; Pinheiro, Vitor B; Smola, Matthew J; Morgunov, Alexey S; Peak-Chew, Sew; Cozens, Christopher; Weeks, Kevin M; Herdewijn, Piet; Holliger, Philipp

    2015-02-19

    The emergence of catalysis in early genetic polymers such as RNA is considered a key transition in the origin of life, pre-dating the appearance of protein enzymes. DNA also demonstrates the capacity to fold into three-dimensional structures and form catalysts in vitro. However, to what degree these natural biopolymers comprise functionally privileged chemical scaffolds for folding or the evolution of catalysis is not known. The ability of synthetic genetic polymers (XNAs) with alternative backbone chemistries not found in nature to fold into defined structures and bind ligands raises the possibility that these too might be capable of forming catalysts (XNAzymes). Here we report the discovery of such XNAzymes, elaborated in four different chemistries (arabino nucleic acids, ANA; 2'-fluoroarabino nucleic acids, FANA; hexitol nucleic acids, HNA; and cyclohexene nucleic acids, CeNA) directly from random XNA oligomer pools, exhibiting in trans RNA endonuclease and ligase activities. We also describe an XNA-XNA ligase metalloenzyme in the FANA framework, establishing catalysis in an entirely synthetic system and enabling the synthesis of FANA oligomers and an active RNA endonuclease FANAzyme from its constituent parts. These results extend catalysis beyond biopolymers and establish technologies for the discovery of catalysts in a wide range of polymer scaffolds not found in nature. Evolution of catalysis independent of any natural polymer has implications for the definition of chemical boundary conditions for the emergence of life on Earth and elsewhere in the Universe.

  14. Towards developing algal synthetic biology.

    PubMed

    Scaife, Mark Aden; Smith, Alison Gail

    2016-06-15

    The genetic, physiological and metabolic diversity of microalgae has driven fundamental research into photosynthesis, flagella structure and function, and eukaryotic evolution. Within the last 10 years these organisms have also been investigated as potential biotechnology platforms, for example to produce high value compounds such as long chain polyunsaturated fatty acids, pigments and antioxidants, and for biodiesel precursors, in particular triacylglycerols (TAGs). Transformation protocols, molecular tools and genome sequences are available for a number of model species including the green alga Chlamydomonas reinhardtii and the diatom Phaeodactylum tricornutum, although for both species there are bottlenecks to be overcome to allow rapid and predictable genetic manipulation. One approach to do this would be to apply the principles of synthetic biology to microalgae, namely the cycle of Design-Build-Test, which requires more robust, predictable and high throughput methods. In this mini-review we highlight recent progress in the areas of improving transgene expression, genome editing, identification and design of standard genetic elements (parts), and the use of microfluidics to increase throughput. We suggest that combining these approaches will provide the means to establish algal synthetic biology, and that application of standard parts and workflows will avoid parallel development and capitalize on lessons learned from other systems. PMID:27284033

  15. A Synthetic Multicellular Memory Device.

    PubMed

    Urrios, Arturo; Macia, Javier; Manzoni, Romilde; Conde, Núria; Bonforti, Adriano; de Nadal, Eulàlia; Posas, Francesc; Solé, Ricard

    2016-08-19

    Changing environments pose a challenge to living organisms. Cells need to gather and process incoming information, adapting to changes in predictable ways. This requires in particular the presence of memory, which allows different internal states to be stored. Biological memory can be stored by switches that retain information on past and present events. Synthetic biologists have implemented a number of memory devices for biological applications, mostly in single cells. It has been shown that the use of multicellular consortia provides interesting advantages to implement biological circuits. Here we show how to build a synthetic biological memory switch using an eukaryotic consortium. We engineered yeast cells that can communicate and retain memory of changes in the extracellular environment. These cells were able to produce and secrete a pheromone and sense a different pheromone following NOT logic. When the two strains were cocultured, they behaved as a double-negative-feedback motif with memory. In addition, we showed that memory can be effectively changed by the use of external inputs. Further optimization of these modules and addition of other cells could lead to new multicellular circuits that exhibit memory over a broad range of biological inputs. PMID:27439436

  16. The major synthetic evolutionary transitions.

    PubMed

    Solé, Ricard

    2016-08-19

    Evolution is marked by well-defined events involving profound innovations that are known as 'major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These 'synthetic' transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined.This article is part of the themed issue 'The major synthetic evolutionary transitions'. PMID:27431528

  17. Catalysts from synthetic genetic polymers

    PubMed Central

    Taylor, Alexander I.; Pinheiro, Vitor B.; Smola, Matthew J.; Morgunov, Alexey S.; Peak-Chew, Sew; Cozens, Christopher; Weeks, Kevin M.; Herdewijn, Piet; Holliger, Philipp

    2014-01-01

    The emergence of catalysis in early genetic polymers like RNA is considered a key transition in the origin of life1, predating the appearance of protein enzymes. DNA also demonstrates the capacity to fold into three-dimensional structures and form catalysts in vitro2. However, to what degree these natural biopolymers comprise functionally privileged chemical scaffolds3 for folding or the evolution of catalysis is not known. The ability of synthetic genetic polymers (XNAs) with alternative backbone chemistries not found in nature to fold into defined structures and bind ligands4 raises the possibility that these too might be capable of forming catalysts (XNAzymes). Here we report the discovery of such XNAzymes, elaborated in four different chemistries (ANA (arabino nucleic acids)5, FANA (2′-fluoroarabino nucleic acids)6, HNA (hexitol nucleic acids) and CeNA (cyclohexene nucleic acids)7 directly from random XNA oligomer pools, exhibiting in trans RNA endonuclease and ligase activities. We also describe an XNA-XNA ligase metalloenzyme in the FANA framework, establishing catalysis in an entirely synthetic system and enabling the synthesis of FANA oligomers and an active RNA endonuclease FANAzyme from its constituent parts. These results extend catalysis beyond biopolymers and establish technologies for the discovery of catalysts in a wide range of polymer scaffolds not found in nature8. Evolution of catalysis independent of any natural polymer has implications for the definition of chemical boundary conditions for the emergence of life on earth and elsewhere in the universe9. PMID:25470036

  18. The major synthetic evolutionary transitions.

    PubMed

    Solé, Ricard

    2016-08-19

    Evolution is marked by well-defined events involving profound innovations that are known as 'major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These 'synthetic' transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined.This article is part of the themed issue 'The major synthetic evolutionary transitions'.

  19. Vectoring of parallel synthetic jets

    NASA Astrophysics Data System (ADS)

    Berk, Tim; Ganapathisubramani, Bharathram; Gomit, Guillaume

    2015-11-01

    A pair of parallel synthetic jets can be vectored by applying a phase difference between the two driving signals. The resulting jet can be merged or bifurcated and either vectored towards the actuator leading in phase or the actuator lagging in phase. In the present study, the influence of phase difference and Strouhal number on the vectoring behaviour is examined experimentally. Phase-locked vorticity fields, measured using Particle Image Velocimetry (PIV), are used to track vortex pairs. The physical mechanisms that explain the diversity in vectoring behaviour are observed based on the vortex trajectories. For a fixed phase difference, the vectoring behaviour is shown to be primarily influenced by pinch-off time of vortex rings generated by the synthetic jets. Beyond a certain formation number, the pinch-off timescale becomes invariant. In this region, the vectoring behaviour is determined by the distance between subsequent vortex rings. We acknowledge the financial support from the European Research Council (ERC grant agreement no. 277472).

  20. Enzymatic biotransformation of synthetic dyes.

    PubMed

    Rodríguez-Couto, S

    2009-11-01

    Environmental pollution by discharge of dye-containing effluents represents a serious ecological concern in many countries. Public demands for colour-free discharges to receiving waters have made decolouration of a variety of industrial wastewater a top priority. The current existing techniques for dye removal have several drawbacks such as high cost, low efficiency, use of large amounts of chemicals and formation of toxic sub-products. This has impelled the search for alternative methods such as those based on oxidative enzymes. This approach is believed to be a promising technology since it is cost-effective, environmentally friendly and does not produce sludge. Enzymatic transformation of synthetic dyes can be described as the conversion of dye molecules by enzymes into simpler and generally colourless molecules. Detailed characterisation of the metabolites produced during enzymatic transformation of synthetic dyes as well as ecotoxicity studies is of great importance to assess the effectiveness of the biodegradation process. However, most reports on the biotreatment of dyes mainly deal with decolouration and there are few reports on the reduction in toxicity or on the identification of the biodegradation products. This implies a limitation to assess their true technical potential.

  1. Synthetic population system user guide

    SciTech Connect

    Roberts, D.J.

    1998-03-01

    The Los Alamos National Laboratory (LANL) TRansportation Analysis SIMulatiuon System (TRANSIMS) synthetic population system (SYN) is designed to produce populations (family households, non-family households, and group quarters) that are statistically equivalent to actual populations when compared at the level of block group or higher. The methodology used by this system is described in a report entitled Creating Synthetic Baseline Populations. The inputs to the system are US Census Bureau data (STF3A and PUMS) and MABLE/GEOCORR data. Census Bureau STF3A and PUMS data formats are commonly used and are available on CD-ROM from the Census Bureau. These data inputs will not be described in any detail in this guide. The primary function of MABLE/GEOCORR data is to cross-reference STF3 block group data to PUMS areas. The outputs of the system are files that contain family household, non-family household, and group quarters data in the form of household and person records. SYN will run on a variety of Unix platforms.

  2. Synthetic vision display evaluation studies

    NASA Technical Reports Server (NTRS)

    Regal, David M.; Whittington, David H.

    1994-01-01

    The goal of this research was to help us understand the display requirements for a synthetic vision system for the High Speed Civil Transport (HSCT). Four experiments were conducted to examine the effects of different levels of perceptual cue complexity in displays used by pilots in a flare and landing task. Increased levels of texture mapping of terrain and runway produced mixed results, including harder but shorter landings and a lower flare initiation altitude. Under higher workload conditions, increased texture resulted in an improvement in performance. An increase in familiar size cues did not result in improved performance. Only a small difference was found between displays using two patterns of high resolution texture mapping. The effects of increased perceptual cue complexity on performance was not as strong as would be predicted from the pilot's subjective reports or from related literature. A description of the role of a synthetic vision system in the High Speed Civil Transport is provide along with a literature review covering applied research related to perceptual cue usage in aircraft displays.

  3. CFIT prevention using synthetic vision

    NASA Astrophysics Data System (ADS)

    Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Kramer, Lynda J.; Bailey, Randall E.; Parrish, Russell V.

    2003-09-01

    In commercial aviation, over 30 percent of all fatal accidents worldwide are categorized as Controlled Flight Into Terrain (CFIT) accidents where a fully functioning airplane is inadvertently flown into the ground, water, or an obstacle. An experiment was conducted at NASA Langley Research Center investigating the presentation of a synthetic terrain database scene to the pilot on a Primary Flight Display (PFD). The major hypothesis for the experiment is that a synthetic vision system (SVS) will improve the pilot's ability to detect and avoid a potential CFIT compared to conventional flight instrumentation. All display conditions, including the baseline, contained a Terrain Awareness and Warning System (TAWS) and Vertical Situation Display (VSD) enhanced Navigation Display (ND). Sixteen pilots each flew 22 approach / departure maneuvers in Instrument Meteorological Conditions (IMC) to the terrain challenged Eagle County Regional Airport (EGE) in Colorado. For the final run, the flight guidance cues were altered such that the departure path went into the terrain. All pilots with a SVS enhanced PFD (12 of 16 pilots) noticed and avoided the potential CFIT situation. All of the pilots who flew the anomaly with the baseline display configuration (which included a TAWS and VSD enhanced ND) had a CFIT event.

  4. CFIT Prevention Using Synthetic Vision

    NASA Technical Reports Server (NTRS)

    Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Kramer, Lynda J.; Bailey, Randall E.; Parrish, Russell V.

    2003-01-01

    In commercial aviation, over 30-percent of all fatal accidents worldwide are categorized as Controlled Flight Into Terrain (CFIT) accidents where a fully functioning airplane is inadvertently flown into the ground, water, or an obstacle. An experiment was conducted at NASA Langley Research Center investigating the presentation of a synthetic terrain database scene to the pilot on a Primary Flight Display (PFD). The major hypothesis for the experiment is that a synthetic vision system (SVS) will improve the pilot s ability to detect and avoid a potential CFIT compared to conventional flight instrumentation. All display conditions, including the baseline, contained a Terrain Awareness and Warning System (TAWS) and Vertical Situation Display (VSD) enhanced Navigation Display (ND). Sixteen pilots each flew 22 approach - departure maneuvers in Instrument Meteorological Conditions (IMC) to the terrain challenged Eagle County Regional Airport (EGE) in Colorado. For the final run, the flight guidance cues were altered such that the departure path went into the terrain. All pilots with a SVS enhanced PFD (12 of 16 pilots) noticed and avoided the potential CFIT situation. All of the pilots who flew the anomaly with the baseline display configuration (which included a TAWS and VSD enhanced ND) had a CFIT event.

  5. Towards developing algal synthetic biology.

    PubMed

    Scaife, Mark Aden; Smith, Alison Gail

    2016-06-15

    The genetic, physiological and metabolic diversity of microalgae has driven fundamental research into photosynthesis, flagella structure and function, and eukaryotic evolution. Within the last 10 years these organisms have also been investigated as potential biotechnology platforms, for example to produce high value compounds such as long chain polyunsaturated fatty acids, pigments and antioxidants, and for biodiesel precursors, in particular triacylglycerols (TAGs). Transformation protocols, molecular tools and genome sequences are available for a number of model species including the green alga Chlamydomonas reinhardtii and the diatom Phaeodactylum tricornutum, although for both species there are bottlenecks to be overcome to allow rapid and predictable genetic manipulation. One approach to do this would be to apply the principles of synthetic biology to microalgae, namely the cycle of Design-Build-Test, which requires more robust, predictable and high throughput methods. In this mini-review we highlight recent progress in the areas of improving transgene expression, genome editing, identification and design of standard genetic elements (parts), and the use of microfluidics to increase throughput. We suggest that combining these approaches will provide the means to establish algal synthetic biology, and that application of standard parts and workflows will avoid parallel development and capitalize on lessons learned from other systems.

  6. Synthetic biology in Streptomyces bacteria.

    PubMed

    Medema, Marnix H; Breitling, Rainer; Takano, Eriko

    2011-01-01

    Actinomycete bacteria of the genus Streptomyces are major producers of bioactive compounds for the biotechnology industry. They are the source of most clinically used antibiotics, as well as of several widely used drugs against common diseases, including cancer . Genome sequencing has revealed that the potential of Streptomyces species for the production of valuable secondary metabolites is even larger than previously realized. Accessing this rich genomic resource to discover new compounds by activating "cryptic" pathways is an interesting challenge for synthetic biology. This approach is facilitated by the inherent natural modularity of secondary metabolite biosynthetic pathways, at the level of individual enzymes (such as modular polyketide synthases), but also of gene cassettes/operons and entire biosynthetic gene clusters. It also benefits from a long tradition of molecular biology in Streptomyces, which provides a number of specific tools, ranging from cloning vectors to inducible promoters and translational control elements. In this chapter, we first provide an overview of the synthetic biology challenges in Streptomyces and then present the existing toolbox of molecular methods that can be employed in this organism. PMID:21601100

  7. Enzymatic biotransformation of synthetic dyes.

    PubMed

    Rodríguez-Couto, S

    2009-11-01

    Environmental pollution by discharge of dye-containing effluents represents a serious ecological concern in many countries. Public demands for colour-free discharges to receiving waters have made decolouration of a variety of industrial wastewater a top priority. The current existing techniques for dye removal have several drawbacks such as high cost, low efficiency, use of large amounts of chemicals and formation of toxic sub-products. This has impelled the search for alternative methods such as those based on oxidative enzymes. This approach is believed to be a promising technology since it is cost-effective, environmentally friendly and does not produce sludge. Enzymatic transformation of synthetic dyes can be described as the conversion of dye molecules by enzymes into simpler and generally colourless molecules. Detailed characterisation of the metabolites produced during enzymatic transformation of synthetic dyes as well as ecotoxicity studies is of great importance to assess the effectiveness of the biodegradation process. However, most reports on the biotreatment of dyes mainly deal with decolouration and there are few reports on the reduction in toxicity or on the identification of the biodegradation products. This implies a limitation to assess their true technical potential. PMID:20214593

  8. Chalcone synthase localization in early stages of plant development. I. Immunohistochemical use of plasmolysis for localizing the enzyme in epidermal cell cytoplasm of illuminated buckwheat hypocotyls.

    PubMed

    Zobel, A M; Hrazdina, G

    1995-01-01

    Immunohistochemical methods combined with progressive plasmolysis were used to localize chalcone synthase (CHS), an important enzyme for plant metabolism of aromatics in hypocotyls of illuminated buckwheat (Fagopyrum esculentum M.) seedlings. Illumination of etiolated seedlings with white light results in anthocyanin synthesis in the epidermal layer of the hypocotyl. Anthocyanin-containing epidermal peels, after fixation for 30 min in 4% paraformaldehyde, 2.5% glutaraldehyde, 0.1% caffeine, were treated with a specific rabbit anti-buckwheat CHS antibody and a 20 nm goat anti-rabbit IgG gold conjugate. CHS is specifically shown in epidermal cells as pink to dark red deposits. Progressive plasmolysis combined with our immunohistochemical method showed that CHS was located exclusively in the cytoplasm of the epidermal cells of buckwheat hypocotyls except for the guard cells, which contained no detectable CHS.

  9. Synthesis and biological evaluation of beta-chloro vinyl chalcones as inhibitors of TNF-alpha and IL-6 with antimicrobial activity.

    PubMed

    Bandgar, Babasaheb P; Patil, Sachin A; Korbad, Balaji L; Nile, Shivraj H; Khobragade, Chandrahase N

    2010-06-01

    A series of beta-chloro vinyl chalcones have been synthesized by Claisen-Schmidt condensation. beta-chloro vinyl aldehyde has been synthesized by the Vilsmayer-Hack formylation reaction. The structures of the newly synthesized compounds were confirmed by 1H NMR, IR and Mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-alpha and IL-6) and antimicrobial (antibacterial and antifungal) activity. Compounds 5a, 5d, 5e, 5g and 5i exhibited promising activity against IL-6 with 58-83% inhibition at 10 microM concentration. None of the compound was found to be cytotoxic in CCK-8 cells at 10 microM concentration. Whereas compounds 5b, 5d, 5e and 5i showed very good antibacterial activity and compounds 5a, 5b, 5e and 5i showed good antifungal activity.

  10. Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents.

    PubMed

    Suwito, Hery; Jumina; Mustofa; Pudjiastuti, Pratiwi; Fanani, Much Zaenal; Kimata-Ariga, Yoko; Katahira, Ritsuko; Kawakami, Toru; Fujiwara, Toshimichi; Hase, Toshiharu; Sirat, Hasnah Mohd; Puspaningsih, Ni Nyoman Tri

    2014-01-01

    Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP+ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%-50%. The three strongest inhibition activities were shown by (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (50%), (E)-1-(4-aminophenyl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one (38.16%), and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one (31.58%). From the docking experiments we established that the amino group of the methoxyamino chlacone derivatives plays an important role in the inhibition activity by electrostatic interaction through salt bridges and that it forms more stable and better affinity complexes with FNR than with Fd.

  11. Analytical second derivatives for excited electronic states using the single excitation configuration interaction method: theory and application to benzo[a]pyrene and chalcone

    NASA Astrophysics Data System (ADS)

    Maurice, David; Head-Gordon, Martin

    A compact formulation and a semi-direct implementation are described of analytical second derivatives of the single excitation configuration interaction (CIS) energy. CPU time, memory usage and disc storage all scale with the same power of system size as the ground state Hartree-Fock (HF) method, with a coefficient only 2 to 3 times larger. Thus usually analytical excited state CIS frequencies are feasible when HF frequencies are feasible. As a computational example, analytical CIS/3-21G frequencies for benzo[a]pyrene are calculated more efficiently than with finite differences. As a chemical application, analytical CIS/6-31G* frequencies are used to investigate non-planarity in the lowest π→π* excited state of trans chalcone.

  12. Synthesis, characterization, and crystal structure of sulfonamide chalcone: ( E)-4-methoxy- N-(4-(3-(3,4,5-trimethoxyphenyl)acryloyl)phenyl)-benzenesulfonamide

    NASA Astrophysics Data System (ADS)

    Kobkeatthawin, T.; Chantrapromma, S.; Chidan Kumar, C. S.; Fun, H.-K.

    2015-12-01

    The title sulfonamide chalcone derivative was synthesized by condensation reaction of N-(4-acetylphenyl)-4-methoxybenzenesulfonamide and 3,4,5-trimethoxybenzaldehyde in basic solution. The structure was determined using FT-IR, 1H-NMR and UV-Vis spectroscopy. The crystal structure was characterized by single crystal X-ray structure analysis: triclinic system, sp. gr. P overline 1, Z = 2; a = 7.9273(5), b = 9.3159(6), c = 18.0174(12) Å, α = 94.6420(18)°, β = 93.0310(17)°, γ = 114.9200(15)°. In crystal packing, the molecules are linked by N-H···O hydrogen bonds into chains along the [100] direction. The crystal is further stabilized by weak C-H···O and C-H···π interactions.

  13. A synthetic zero air standard

    NASA Astrophysics Data System (ADS)

    Pearce, Ruth

    2016-04-01

    A Synthetic Zero Air Standard R. E. Hill-Pearce, K. V. Resner, D. R. Worton, P. J. Brewer The National Physical Laboratory Teddington, Middlesex TW11 0LW UK We present work towards providing traceability for measurements of high impact greenhouse gases identified by the World Meteorological Organisation (WMO) as critical for global monitoring. Standards for these components are required with challengingly low uncertainties to improve the quality assurance and control processes used for the global networks to better assess climate trends. Currently the WMO compatibility goals require reference standards with uncertainties of < 100 nmolmol-1 for CO2 (northern hemisphere) and < 2 nmolmol-1 for CH4 and CO. High purity zero gas is required for both the balance gas in the preparation of reference standards and for baseline calibrations of instrumentation. Quantification of the amount fraction of the target components in the zero gas is a significant contributor to the uncertainty and is challenging due to limited availability of reference standard at the amount fraction of the measurand and limited analytical techniques with sufficient detection limits. A novel dilutor was used to blend NPL Primary Reference Gas Mixtures containing CO2, CH4 and CO at atmospheric amount fractions with a zero gas under test. Several mixtures were generated with nominal dilution ratios ranging from 2000:1 to 350:1. The baseline of two cavity ring down spectrometers was calibrated using the zero gas under test after purification by oxidative removal of CO and hydrocarbons to < 1 nmolmol-1 (SAES PS15-GC50) followed by the removal of CO2 and water vapour to < 100 pmolmol-1 (SAES MC190). Using the standard addition method.[1] we have quantified the amount fraction of CO, CO2, and CH4 in scrubbed whole air (Scott Marrin) and NPL synthetic zero air. This is the first synthetic zero air standard with a matrix of N2, O2 and Ar closely matching ambient composition with gravimetrically assigned

  14. Word selection affects perceptions of synthetic biology.

    PubMed

    Pearson, Brianna; Snell, Sam; Bye-Nagel, Kyri; Tonidandel, Scott; Heyer, Laurie J; Campbell, A Malcolm

    2011-01-01

    Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008). Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create". PMID:21777466

  15. Nature's chemicals and synthetic chemicals: Comparative toxicology

    SciTech Connect

    Ames, B.N.; Profet, M.; Gold, L.S. )

    1990-10-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. The finding that in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30-50{percent} for each group) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests.

  16. Synthetic cannabinoids as drugs of abuse.

    PubMed

    Ashton, John C

    2012-06-01

    In the last decade a number of products have appeared in various countries that contain synthetic cannabinoids. This article reviews the history of the sale of these drugs, and the evidence that they contain synthetic cannabinoids. The biochemistry of the synthetic cannabinoids identified thus far is discussed, including a discussion of chemical structures and biochemical targets. The cannabinoid receptor targets for these drugs are discussed, as well as other possible targets such as serotonin receptors. Evidence for the abuse potential of these drugs is reviewed. The toxicity of synthetic cannabinoids and cannabinoid products is reviewed and compared to that of the phytocannabinoid Δ9- tetrahydrocannabinol (THC). As cannabinoids are a structurally diverse class of drugs, it is concluded that synthetic cannabinoids should be classified by biological activity rather than by structure, and that if this isn't done, novel synthetic cannabinoids will continue to emerge that fall outside of current regulatory classification models.

  17. Nature's chemicals and synthetic chemicals: comparative toxicology.

    PubMed Central

    Ames, B N; Profet, M; Gold, L S

    1990-01-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. The finding that in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30-50% for each group) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests. PMID:2217211

  18. A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

    SciTech Connect

    Fang, Qilu; Zhao, Leping; Wang, Yi; Zhang, Yali; Li, Zhaoyu; Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao; Li, Dan; Liang, Guang

    2015-01-15

    Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.

  19. Synthetic aperture radar target simulator

    NASA Technical Reports Server (NTRS)

    Zebker, H. A.; Held, D. N.; Goldstein, R. M.; Bickler, T. C.

    1984-01-01

    A simulator for simulating the radar return, or echo, from a target seen by a SAR antenna mounted on a platform moving with respect to the target is described. It includes a first-in first-out memory which has digital information clocked in at a rate related to the frequency of a transmitted radar signal and digital information clocked out with a fixed delay defining range between the SAR and the simulated target, and at a rate related to the frequency of the return signal. An RF input signal having a frequency similar to that utilized by a synthetic aperture array radar is mixed with a local oscillator signal to provide a first baseband signal having a frequency considerably lower than that of the RF input signal.

  20. [Mephedrone: a new synthetic drug].

    PubMed

    Petit, Aymeric; Karila, Laurent; Sananes, Michel; Lejoyeux, Michel

    2013-10-01

    Mephedrone is a synthetic psychostimulant derived from cathinone belonging to the family of phenylethylamines. Sold on the Internet, it has recently emerged in France in recreational settings, and is mostly consumed by young people from the gay community and festive environment. Identified in 2008 by the European Monitoring Centre for Drugs and Drug Addiction as a new drug on the market, the use of mephedrone has attracted media attention following the suspicious deaths of two young adults in Sweden and in England. Its legal aspect, ease of getting it on the Internet and cheap price coupled and an alternative-seeking to other psychostimulants make mephedrone a prime target for these populations and a source of abuse, with psychiatric and somatic complications. There is no curative pharmacological treatment approved by health authorities.

  1. Synthetic aperture interferometry: error analysis

    SciTech Connect

    Biswas, Amiya; Coupland, Jeremy

    2010-07-10

    Synthetic aperture interferometry (SAI) is a novel way of testing aspherics and has a potential for in-process measurement of aspherics [Appl. Opt.42, 701 (2003)].APOPAI0003-693510.1364/AO.42.000701 A method to measure steep aspherics using the SAI technique has been previously reported [Appl. Opt.47, 1705 (2008)].APOPAI0003-693510.1364/AO.47.001705 Here we investigate the computation of surface form using the SAI technique in different configurations and discuss the computational errors. A two-pass measurement strategy is proposed to reduce the computational errors, and a detailed investigation is carried out to determine the effect of alignment errors on the measurement process.

  2. Synthetic biology of antimicrobial discovery.

    PubMed

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

  3. Synthetic biology: a utilitarian perspective.

    PubMed

    Smith, Kevin

    2013-10-01

    I examine the positive and negative features of synthetic biology ('SynBio') from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a 'precautionary' approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio.

  4. Synthetic Jets in Quiescent Air

    NASA Technical Reports Server (NTRS)

    Yao, C. S.; Chen, F. J.; Neuhart, D.; Harris, J.

    2007-01-01

    An oscillatory jet with zero net mass flow is generated by a cavity-pumping actuator. Among the three test cases selected for the Langley CFD validation workshop to assess the current CFD capabilities to predict unsteady flow fields, this basic oscillating jet flow field is the least complex and is selected as the first test case. Increasing in complexity, two more cases studied include jet in cross flow boundary layer and unsteady flow induced by suction and oscillatory blowing with separation control geometries. In this experiment, velocity measurements from three different techniques, hot-wire anemometry, Laser Doppler Velocimetry (LDV) and Particle Image Velocimetry (PIV), documented the synthetic jet flow field. To provide boundary conditions for computations, the experiment also monitored the actuator operating parameters including diaphragm displacement, internal cavity pressure, and internal cavity temperature.

  5. Engineering life through Synthetic Biology.

    PubMed

    Chopra, Paras; Kamma, Akhil

    2006-01-01

    Synthetic Biology is a field involving synthesis of novel biological systems which are not generally found in nature. It has brought a new paradigm in science as it has enabled scientists to create life from the scratch, hence helping better understand the principles of biology. The viability of living organisms that use unnatural molecules is also being explored. Unconventional projects such as DNA playing tic-tac-toe, bacterial photographic film, etc. are taking biology to its extremes. The field holds a promise for mass production of cheap drugs and programming bacteria to seek-and-destroy tumors in the body. However, the complexity of biological systems make the field a challenging one. In addition to this, there are other major technical and ethical challenges which need to be addressed before the field realizes its true potential.

  6. Synthetically Simple, Highly Resilient Hydrogels

    PubMed Central

    Cui, Jun; Lackey, Melissa A.; Madkour, Ahmad E.; Saffer, Erika M.; Griffin, David M.; Bhatia, Surita R.; Crosby, Alfred J.; Tew, Gregory N.

    2014-01-01

    Highly resilient synthetic hydrogels were synthesized by using the efficient thiol-norbornene chemistry to cross-link hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polydimethylsiloxane (PDMS) polymer chains. The swelling and mechanical properties of the hydrogels were well-controlled by the relative amounts of PEG and PDMS. In addition, the mechanical energy storage efficiency (resilience) was more than 97% at strains up to 300%. This is comparable with one of the most resilient materials known: natural resilin, an elastic protein found in many insects, such as in the tendons of fleas and the wings of dragonflies. The high resilience of these hydrogels can be attributed to the well-defined network structure provided by the versatile chemistry, low cross-link density, and lack of secondary structure in the polymer chains. PMID:22372639

  7. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  8. Synthetic biology: a utilitarian perspective.

    PubMed

    Smith, Kevin

    2013-10-01

    I examine the positive and negative features of synthetic biology ('SynBio') from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a 'precautionary' approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio. PMID:24010857

  9. Synthetic chemistry with nitrous oxide.

    PubMed

    Severin, Kay

    2015-10-01

    This review article summarizes efforts to use nitrous oxide (N2O, 'laughing gas') as a reagent in synthetic chemistry. The focus will be on reactions which are carried out in homogeneous solution under (relatively) mild conditions. First, the utilization of N2O as an oxidant is discussed. Due to the low intrinsic reactivity of N2O, selective oxidation reactions of highly reactive compounds are possible. Furthermore, it is shown that transition metal complexes can be used to catalyze oxidation reactions, in some cases with high turnover numbers. In the final part of this overview, the utilization of N2O as a building block for more complex molecules is discussed. It is shown that N2O can be used as an N-atom donor for the synthesis of interesting organic molecules such as triazenes and azo dyes. PMID:26104268

  10. Microorganism Utilization for Synthetic Milk

    NASA Technical Reports Server (NTRS)

    Morford, Megan A.; Khodadad, Christina L.; Caro, Janicce I.; Spencer, LaShelle E.; Richards, Jeffery T.; Strayer, Richard F.; Birmele, Michele N.; Wheeler, Raymond M.

    2014-01-01

    A desired architecture for long duration spaceflight, like aboard the International Space Station or for future missions to Mars, is to provide a supply of fresh food crops for the astronauts. However, some crops can create a high proportion of inedible plant waste. The main goal of the Synthetic Biology project, Cow in a Column, was to produce the components of milk (sugar, lipid, protein) from inedible plant waste by utilizing microorganisms (fungi, yeast, bacteria). Of particular interest was utilizing the valuable polysaccharide, cellulose, found in plant waste, to naturally fuel-through microorganism cellular metabolism- the creation of sugar (glucose), lipid (milk fat), and protein (casein) in order to produce a synthetic edible food product. Environmental conditions such as pH, temperature, carbon source, aeration, and choice microorganisms were optimized in the laboratory and the desired end-products, sugars and lipids, were analyzed. Trichoderma reesei, a known cellulolytic fungus, was utilized to drive the production of glucose, with the intent that the produced glucose would serve as the carbon source for milk fat production and be a substitute for the milk sugar lactose. Lipid production would be carried out by Rhodosporidium toruloides, yeast known to accumulate those lipids that are typically found in milk fat. Results showed that glucose and total lipid content were below what was expected during this phase of experimentation. In addition, individual analysis of six fatty acids revealed that the percentage of each fatty acid was lower than naturally produced bovine milk. Overall, this research indicates that microorganisms could be utilized to breakdown inedible solid waste to produce useable products. For future work, the production of the casein protein for milk would require the development of a genetically modified organism, which was beyond the scope of the original project. Additional trials would be needed to further refine the required

  11. Opportunities for microfluidic technologies in synthetic biology

    PubMed Central

    Gulati, Shelly; Rouilly, Vincent; Niu, Xize; Chappell, James; Kitney, Richard I.; Edel, Joshua B.; Freemont, Paul S.; deMello, Andrew J.

    2009-01-01

    We introduce microfluidics technologies as a key foundational technology for synthetic biology experimentation. Recent advances in the field of microfluidics are reviewed and the potential of such a technological platform to support the rapid development of synthetic biology solutions is discussed. PMID:19474079

  12. 78 FR 22209 - Additional Synthetic Drug Testing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... COMMISSION 10 CFR Part 26 Additional Synthetic Drug Testing AGENCY: Nuclear Regulatory Commission. ACTION... NRC amend its Fitness for Duty program regulations to amend drug testing requirements to test for additional synthetic drugs currently not included in the regulations. The NRC determined that the...

  13. Synthetic diagnostics platform for fusion plasmas (invited)

    NASA Astrophysics Data System (ADS)

    Shi, L.; Valeo, E. J.; Tobias, B. J.; Kramer, G. J.; Hausammann, L.; Tang, W. M.; Chen, M.

    2016-11-01

    A Synthetic Diagnostics Platform (SDP) for fusion plasmas has been developed which provides state of the art synthetic reflectometry, beam emission spectroscopy, and Electron Cyclotron Emission (ECE) diagnostics. Interfaces to the plasma simulation codes GTC, XGC-1, GTS, and M3D-C1 are provided, enabling detailed validation of these codes. In this paper, we give an overview of SDP's capabilities, and introduce the synthetic diagnostic modules. A recently developed synthetic ECE Imaging module which self-consistently includes refraction, diffraction, emission, and absorption effects is discussed in detail. Its capabilities are demonstrated on two model plasmas. The importance of synthetic diagnostics in validation is shown by applying the SDP to M3D-C1 output and comparing it with measurements from an edge harmonic oscillation mode on DIII-D.

  14. Synthetic therapeutic gene circuits in mammalian cells.

    PubMed

    Ye, Haifeng; Fussenegger, Martin

    2014-08-01

    In the emerging field of synthetic biology, scientists are focusing on designing and creating functional devices, systems, and organisms with novel functions by engineering and assembling standardised biological building blocks. The progress of synthetic biology has significantly advanced the design of functional gene networks that can reprogram metabolic activities in mammalian cells and provide new therapeutic opportunities for future gene- and cell-based therapies. In this review, we describe the most recent advances in synthetic mammalian gene networks designed for biomedical applications, including how these synthetic therapeutic gene circuits can be assembled to control signalling networks and applied to treat metabolic disorders, cancer, and immune diseases. We conclude by discussing the various challenges and future prospects of using synthetic mammalian gene networks for disease therapy.

  15. Mammalian synthetic biology: emerging medical applications

    PubMed Central

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

    2015-01-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

  16. Development of synthetic lethality anticancer therapeutics.

    PubMed

    Fang, Bingliang

    2014-10-01

    The concept of synthetic lethality (the creation of a lethal phenotype from the combined effects of mutations in two or more genes) has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics. These efforts include screening for novel anticancer agents, identifying novel therapeutic targets, characterizing mechanisms of resistance to targeted therapy, and improving efficacies through the rational design of combination therapy. This review discusses recent developments in synthetic lethality anticancer therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small molecule agents targeting RAS gene mutant cancers. Because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene or oncogene is likely cell context-dependent. Delineation of the mechanisms underlying synthetic lethality and identification of treatment response biomarkers will be critical for the success of synthetic lethality anticancer therapy.

  17. Mammalian synthetic biology: emerging medical applications.

    PubMed

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

  18. Synthetic biology: an emerging engineering discipline.

    PubMed

    Cheng, Allen A; Lu, Timothy K

    2012-01-01

    Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

  19. Synthetic mammalian gene circuits for biomedical applications.

    PubMed

    Ye, Haifeng; Aubel, Dominique; Fussenegger, Martin

    2013-12-01

    Synthetic biology is the science of reassembling cataloged and standardized biological items in a systematic and rational manner to create and engineer functional biological designer devices, systems and organisms with novel and useful, preferably therapeutic functions. Synthetic biology has significantly advanced the design of complex genetic networks that can reprogram metabolic activities in mammalian cells and provide novel therapeutic strategies for future gene-based and cell-based therapies. Synthetic biology-inspired therapeutic strategies provide new opportunities for improving human health in the 21st century. This review covers the most recent synthetic mammalian circuits designed for therapy of diseases such as metabolic disorders, cancer, and immune disorders. We conclude by discussing current challenges and future perspectives for biomedical applications of synthetic mammalian gene networks.

  20. Synthetic Landau levels for photons.

    PubMed

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-06-30

    Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock–Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen–Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons.

  1. Nanostructures from Synthetic Genetic Polymers

    PubMed Central

    Beuron, Fabienne; Peak‐Chew, Sew‐Yeu; Morris, Edward P.; Herdewijn, Piet

    2016-01-01

    Abstract Nanoscale objects of increasing complexity can be constructed from DNA or RNA. However, the scope of potential applications could be enhanced by expanding beyond the moderate chemical diversity of natural nucleic acids. Here, we explore the construction of nano‐objects made entirely from alternative building blocks: synthetic genetic polymers not found in nature, also called xeno nucleic acids (XNAs). Specifically, we describe assembly of 70 kDa tetrahedra elaborated in four different XNA chemistries (2′‐fluro‐2′‐deoxy‐ribofuranose nucleic acid (2′F‐RNA), 2′‐fluoroarabino nucleic acids (FANA), hexitol nucleic acids (HNA), and cyclohexene nucleic acids (CeNA)), as well as mixed designs, and a ∼600 kDa all‐FANA octahedron, visualised by electron microscopy. Our results extend the chemical scope for programmable nanostructure assembly, with implications for the design of nano‐objects and materials with an expanded range of structural and physicochemical properties, including enhanced biostability. PMID:26992063

  2. Synthetic Landau levels for photons

    NASA Astrophysics Data System (ADS)

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-06-01

    Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock–Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen–Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons.

  3. Electrospun Synthetic Polypeptide Nanofibrous Biomaterials

    NASA Astrophysics Data System (ADS)

    Khadka, Dhan; Haynie, Donald

    2011-03-01

    Water-insoluble nanofiber mats of synthetic polypeptides of defined composition have been prepared from fibers electrospun from aqueous solution in the absence of organic co-solvents. 20-50 kDa poly(L-glutamate, L-tyrosine) 4:1 (PLGY) but not 15-50 kDa or 50-100 kDa poly(L-glutamate) was spinnable at 20-55% (w/v) polymer in water. Applied voltage and needle-collector distance were crucial for spinnability. Attractive fibers were obtained at 50% polymer. Fiber diameter and mat morphology have been characterized by electron microscopy. Exposure of spun fiber mats to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), which reacts with carboxylate, decreased fiber solubility. Fluorescein-conjugated poly(L-lysine) (FITC-PLL) but not the fluorophore alone was able bind PLGY fiber mats electrostatically, judging by fluorescence microscopy. Key advances of this work are the avoidance of an animal source of peptides and of an inorganic co-solvent to achieve polypeptide spinnability. Polypeptide fiber mats are a promising type of nano-structured biomaterial for applications in biomedicine and biotechnology.

  4. Disease, dysfunction, and synthetic biology.

    PubMed

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs.

  5. Synthetic polymers for solar harvesting.

    PubMed

    Ghiggino, Kenneth P; Bell, Toby D M; Hooley, Emma N

    2012-01-01

    Synthetic polymers incorporating appropriate chromophores can act as light harvesting antennae for artificial photosynthetic systems. The photophysical processes occurring in a polymer based on phenylene vinylene have been investigated at the single chain level and in bulk solution to study energy transfer processes. Most single chains of an alternating copolymer of 2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene and 1,4-phenylene vinylene (alt-co-MEH-PPV) dispersed in a transparent polymer matrix act as single chromophore emitters demonstrating that energy transfer is an efficient process in these polymers. However for individual polymer chains there are fluctuations in emission intensity ('blinking') and shifts in emission spectra, decay lifetimes and emission dipole orientation occurring on a time-scale of tens of seconds. Fluorescence blinking also occurs on a sub-millisecond time-scale and follows exponential kinetics, whereas the longer blinking is better described by a power law. These observations can be interpreted as arising from environmental relaxation processes and/or changes in the emitter and demonstrate the wide distribution of photophysical behaviours that can be observed among the individual molecules of a polymer sample. The relevance of these studies to the application of polymer materials for solar harvesting is highlighted.

  6. Synthetic Landau levels for photons

    NASA Astrophysics Data System (ADS)

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-06-01

    Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock-Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen-Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons.

  7. The major synthetic evolutionary transitions

    PubMed Central

    Solé, Ricard

    2016-01-01

    Evolution is marked by well-defined events involving profound innovations that are known as ‘major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These ‘synthetic’ transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431528

  8. Synthetic Landau levels for photons.

    PubMed

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-06-30

    Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock–Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen–Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons. PMID:27281214

  9. Effects of the Synthetic Neurosteroid

    PubMed Central

    Parésys, Lucie; Hoffmann, Kerstin; Bianchi, Massimiliano; Villey, Isabelle; Baulieu, Etienne-Emile; Fuchs, Eberhard

    2016-01-01

    Background: Most currently available active antidepressant drugs are selective serotonin/noradrenaline reuptake inhibitors. However, as their clinical efficacy is not immediate, long-term administration is often accompanied by substantial side effects, and numerous patients remain non- or partial responders. We have recently found that the synthetic neurosteroid derivative 3β-methoxypregnenolone, which binds to the microtubule-associated protein-2, can provide a novel therapeutic approach in experimental model of depressive disorders in rats. To further validate the antidepressant-like efficacy of 3β-methoxypregnenolone, we investigated effects of a longer treatment (4-week oral administration; 50mg/kg/d) in a nonrodent species, the tree shrew, exposed to psychosocial stress that elicits close-to-human alterations observed in patients with depressive disorders. Methods: During the experimental period, physiological parameters were registered, including core body temperature and electroencephalogram, while animals were videotaped to analyze their avoidance behavior. Morning urine samples were collected for measurements of cortisol and noradrenaline levels. Results: We found that treatment with 3β-methoxypregnenolone abolished stress-triggered avoidance behavior and prevented hormone hypersecretion, hypothermia, and sleep disturbances, further suggesting its antidepressant-like efficacy. Comparative treatment with fluoxetine also prevented some of the physiological alterations, while the hypersecretion of cortisol and sleep disturbances were not or partially restored by fluoxetine, suggesting a better efficacy of 3β-methoxypregnenolone. Alpha-tubulin isoforms were measured in hippocampi: we found that 3β-methoxypregnenolone reversed the specific decrease in acetylation of α-tubulin induced by psychosocial stress, while it did not modify the psychosocial stress-elicited reduction of tyrosinated α-tubulin. Conclusions: Taken together, these data strongly suggest

  10. New synthetic drugs in addictovigilance.

    PubMed

    Chavant, François; Boucher, Alexandra; Le Boisselier, Reynald; Deheul, Sylvie; Debruyne, Danièle

    2015-01-01

    New substances, also known as "designer drugs" or "legal highs" are increasingly available to drug users. Two hundred and fifteen hitherto unlisted substances have been notified by European Union member states since 2005. These synthetic drugs, which have been developed to side-step the legislation on drugs, are analogues or derivatives of existing drugs and medications. The availability of these "legal highs", sold on Internet under various denominations such as bath salt, plant fertilizer, chemical not intended for human use, or spice, is unlimited. The effects felt by users vary, and the substances may be stimulant, entactogenic, hallucinogenic, psychedelic or dissociative. The pharmacological targets also vary, and may be either the increase of extracellular levels of neurotransmitters via different mechanisms (reuptake inhibition, stimulation of intracellular release) or else fixation on specific receptors. Several chemical classes, themselves divided into sub-classes, are involved: phenethylamines, tryptamines, piperazines, cathinones, cannabinoids etc. The toxicity of the main members of these categories is increasingly well known, the most deleterious being behavioural effects, physical manifestations, and cardiovascular consequences. However, small variations in their chemical structure can generate effects that are quantitatively different, thus enhancing their toxicity or addictive potential, and much remains to be achieved in terms of knowledge about these new drugs. These substances are indeed present on the French territory, as shown by data provided by the Observatoire Français des Drogues et Toxicomanies, and notifications by the French Addictovigilance network. Screening in clinical toxicology laboratories is not widespread, since these molecules are not detected by the standard screening tests, so that there is probably an under-estimation of the use of these new drugs. The legislation on these substances changes regularly, with more and more

  11. Bacterial Adhesion at Synthetic Surfaces

    PubMed Central

    Cunliffe, D.; Smart, C. A.; Alexander, C.; Vulfson, E. N.

    1999-01-01

    A systematic investigation into the effect of surface chemistry on bacterial adhesion was carried out. In particular, a number of physicochemical factors important in defining the surface at the molecular level were assessed for their effect on the adhesion of Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus, and Escherichia coli. The primary experiments involved the grafting of groups varying in hydrophilicity, hydrophobicity, chain length, and chemical functionality onto glass substrates such that the surfaces were homogeneous and densely packed with functional groups. All of the surfaces were found to be chemically well defined, and their measured surface energies varied from 15 to 41 mJ · m−2. Protein adsorption experiments were performed with 3H-labelled bovine serum albumin and cytochrome c prior to bacterial attachment studies. Hydrophilic uncharged surfaces showed the greatest resistance to protein adsorption; however, our studies also showed that the effectiveness of poly(ethyleneoxide) (PEO) polymers was not simply a result of its hydrophilicity and molecular weight alone. The adsorption of the two proteins approximately correlated with short-term cell adhesion, and bacterial attachment for L. monocytogenes and E. coli also correlated with the chemistry of the underlying substrate. However, for S. aureus and S. typhimurium a different pattern of attachment occurred, suggesting a dissimilar mechanism of cell attachment, although high-molecular-weight PEO was still the least-cell-adsorbing surface. The implications of this for in vivo attachment of cells suggest that hydrophilic passivating groups may be the best method for preventing cell adsorption to synthetic substrates provided they can be grafted uniformly and in sufficient density at the surface. PMID:10543814

  12. Synthetic biology: mapping the scientific landscape.

    PubMed

    Oldham, Paul; Hall, Stephen; Burton, Geoff

    2012-01-01

    This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.

  13. Synthetic Biology: Mapping the Scientific Landscape

    PubMed Central

    Oldham, Paul; Hall, Stephen; Burton, Geoff

    2012-01-01

    This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves. PMID:22539946

  14. Grand challenges in space synthetic biology

    PubMed Central

    Montague, Michael G.; Cumbers, John; Hogan, John A.

    2015-01-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

  15. Synthetic Cathinones: Chemical Phylogeny, Physiology, and Neuropharmacology

    PubMed Central

    De Felice, Louis J; Glennon, Richard A; Negus, Sidney S

    2014-01-01

    This mini-review summarizes the history of cathinone and its synthesized derivatives from early records to the present day, including the appearance of synthetic cathinones in the drug combination known as bath salts. Bath salts may consist of one compound (MDPV) or combinations of MDPV and one or more other synthetic cathinones, which may also appear alone without MDPV. We briefly review recent in vitro studies of bath salts components alone or in combination, focusing on pharmacological and biophysical studies. Finally we summarize new data from in vivo procedures that characterize the abuse-related neurochemical and behavioral effects of synthetic cathinones in rats. PMID:24231923

  16. Grand challenges in space synthetic biology.

    PubMed

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

  17. Synthetic promoter design for new microbial chassis

    PubMed Central

    Gilman, James; Love, John

    2016-01-01

    The judicious choice of promoter to drive gene expression remains one of the most important considerations for synthetic biology applications. Constitutive promoter sequences isolated from nature are often used in laboratory settings or small-scale commercial production streams, but unconventional microbial chassis for new synthetic biology applications require well-characterized, robust and orthogonal promoters. This review provides an overview of the opportunities and challenges for synthetic promoter discovery and design, including molecular methodologies, such as saturation mutagenesis of flanking regions and mutagenesis by error-prone PCR, as well as the less familiar use of computational and statistical analyses for de novo promoter design. PMID:27284035

  18. Grand challenges in space synthetic biology.

    PubMed

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth.

  19. Involvement of Salicylic Acid on Antioxidant and Anticancer Properties, Anthocyanin Production and Chalcone Synthase Activity in Ginger (Zingiber officinale Roscoe) Varieties

    PubMed Central

    Ghasemzadeh, Ali; Jaafar, Hawa Z. E.; Karimi, Ehsan

    2012-01-01

    The effect of foliar application of salicylic acid (SA) at different concentrations (10−3 M and 10−5 M) was investigated on the production of secondary metabolites (flavonoids), chalcone synthase (CHS) activity, antioxidant activity and anticancer activity (against breast cancer cell lines MCF-7 and MDA-MB-231) in two varieties of Malaysian ginger, namely Halia Bentong and Halia Bara. The results of high performance liquid chromatography (HPLC) analysis showed that application of SA induced the synthesis of anthocyanin and fisetin in both varieties. Anthocyanin and fisetin were not detected in the control plants. Accordingly, the concentrations of some flavonoids (rutin and apigenin) decreased significantly in plants treated with different concentrations of SA. The present study showed that SA enhanced the chalcone synthase (CHS) enzyme activity (involving flavonoid synthesis) and recorded the highest activity value of 5.77 nkat /mg protein in Halia Bara with the 10−5 M SA treatment. As the SA concentration was decreased from 10−3 M to 10−5 M, the free radical scavenging power (FRAP) increased about 23% in Halia Bentong and 10.6% in Halia Bara. At a concentration of 350 μg mL−1, the DPPH antioxidant activity recorded the highest value of 58.30%–72.90% with the 10−5 M SA treatment followed by the 10−3 M SA (52.14%–63.66%) treatment. The lowest value was recorded in the untreated control plants (42.5%–46.7%). These results indicate that SA can act not only as an inducer but also as an inhibitor of secondary metabolites. Meanwhile, the highest anticancer activity against MCF-7 and MDA-MB-231 cell lines was observed for H. Bara extracts treated with 10−5 M SA with values of 61.53 and 59.88%, respectively. The results suggest that the high anticancer activity in these varieties may be related to the high concentration of potent anticancer components including fisetin and anthocyanin. The results thus indicate that the synthesis of flavonoids in

  20. Involvement of salicylic acid on antioxidant and anticancer properties, anthocyanin production and chalcone synthase activity in ginger (Zingiber officinale Roscoe) varieties.

    PubMed

    Ghasemzadeh, Ali; Jaafar, Hawa Z E; Karimi, Ehsan

    2012-01-01

    The effect of foliar application of salicylic acid (SA) at different concentrations (10-3 M and 10-5 M) was investigated on the production of secondary metabolites (flavonoids), chalcone synthase (CHS) activity, antioxidant activity and anticancer activity (against breast cancer cell lines MCF-7 and MDA-MB-231) in two varieties of Malaysian ginger, namely Halia Bentong and Halia Bara. The results of high performance liquid chromatography (HPLC) analysis showed that application of SA induced the synthesis of anthocyanin and fisetin in both varieties. Anthocyanin and fisetin were not detected in the control plants. Accordingly, the concentrations of some flavonoids (rutin and apigenin) decreased significantly in plants treated with different concentrations of SA. The present study showed that SA enhanced the chalcone synthase (CHS) enzyme activity (involving flavonoid synthesis) and recorded the highest activity value of 5.77 nkat /mg protein in Halia Bara with the 10-5 M SA treatment. As the SA concentration was decreased from 10-3 M to 10-5 M, the free radical scavenging power (FRAP) increased about 23% in Halia Bentong and 10.6% in Halia Bara. At a concentration of 350 μg mL-1, the DPPH antioxidant activity recorded the highest value of 58.30%-72.90% with the 10-5 M SA treatment followed by the 10-3 M SA (52.14%-63.66%) treatment. The lowest value was recorded in the untreated control plants (42.5%-46.7%). These results indicate that SA can act not only as an inducer but also as an inhibitor of secondary metabolites. Meanwhile, the highest anticancer activity against MCF-7 and MDA-MB-231 cell lines was observed for H. Bara extracts treated with 10-5 M SA with values of 61.53 and 59.88%, respectively. The results suggest that the high anticancer activity in these varieties may be related to the high concentration of potent anticancer components including fisetin and anthocyanin. The results thus indicate that the synthesis of flavonoids in ginger can be increased