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Sample records for fully active derivative

  1. Development of Low Energy Gap and Fully Regioregular Polythienylenevinylene Derivative

    DOE PAGES

    David, Tanya M. S.; Zhang, Cheng; Sun, Sam-Shajing

    2014-01-01

    Low energy gap and fully regioregular conjugated polymers find its wide use in solar energy conversion applications. This paper will first briefly review this type of polymers and also report synthesis and characterization of a specific example new polymer, a low energy gap, fully regioregular, terminal functionalized, and processable conjugated polymer poly-(3-dodecyloxy-2,5-thienylene vinylene) or PDDTV. The polymer exhibited an optical energy gap of 1.46 eV based on the UV-vis-NIR absorption spectrum. The electrochemically measured highest occupied molecular orbital (HOMO) level is −4.79 eV, resulting in the lowest unoccupied molecular orbital (LUMO) level of −3.33 eV based on optical energy gap. The polymer wasmore » synthesized via Horner-Emmons condensation and is fairly soluble in common organic solvents such as tetrahydrofuran and chloroform with gentle heating. DSC showed two endothermic peaks at 67°C and 227°C that can be attributed to transitions between crystalline and liquid states. The polymer is thermally stable up to about 300°C. This polymer appears very promising for cost-effective solar cell applications.« less

  2. Analytical First and Second Derivatives for a Fully Polarizable QM/Classical Hamiltonian.

    PubMed

    Lipparini, Filippo; Cappelli, Chiara; Scalmani, Giovanni; De Mitri, Nicola; Barone, Vincenzo

    2012-11-13

    In this work, we present the derivation and implementation of analytical first and second derivatives for a fully polarizable QM/MM/PCM energy functional. First derivatives with respect to both QM- and MM-described nuclear coordinates and electric perturbations are derived and implemented, and some preliminary application is shown. Analytical second derivatives with respect to nuclear and electric perturbations are then derived, and some numerical test is presented both for a solvated system and for a cromophore embedded in a biological matrix.

  3. Derivation of electrostatic Korteweg-deVries equation in fully relativistic two-fluid plasmas

    SciTech Connect

    Lee, Nam C.

    2008-08-15

    A second order Korteweg-deVries (KdV) equation that describes the evolution of nonlinear electrostatic waves in fully relativistic two-fluid plasmas is derived without any assumptions restricting the magnitudes of the flow velocity and the temperatures of each species. In the derivation, the positive and negative species of plasmas are treated with equal footings, not making any species specific assumptions. Thus, the resulting equation, which is expressed in transparent form symmetric in particle species, can be applied to any two-fluid plasmas having arbitrarily large flow velocity and ultrarelativistically high temperatures. The phase velocity of the nonlinear electrostatic waves found in this paper is shown to be related to the flow velocity and the acoustic wave velocity through the Lorentz addition law of velocities, revealing the relativistic nature of the formulation in the present study. The derived KdV equation is applied to some limiting cases, and it is shown that it can be reduced to existing results in nonrelativistic plasmas, while there are some discrepancies from the results in the weak relativistic approximations.

  4. Producing fully ES cell-derived mice from eight-cell stage embryo injections.

    PubMed

    DeChiara, Thomas M; Poueymirou, William T; Auerbach, Wojtek; Frendewey, David; Yancopoulos, George D; Valenzuela, David M

    2010-01-01

    In conventional methods for the generation of genetically modified mice, gene-targeted embryonic stem (ES) cells are injected into blastocyst-stage embryos or are aggregated with morula-stage embryos, which are then transferred to the uterus of a surrogate mother. F0 generation mice born from the embryos are chimeras composed of genetic contributions from both the modified ES cells and the recipient embryos. Obtaining a mouse strain that carries the gene-targeted mutation requires breeding the chimeras to transmit the ES cell genetic component through the germ line to the next (F1) generation (germ line transmission, GLT). To skip the chimera stage, we developed the VelociMouse method, in which injection of genetically modified ES cells into eight-cell embryos followed by maturation to the blastocyst stage and transfer to a surrogate mother produces F0 generation mice that are fully derived from the injected ES cells and exhibit a 100% GLT efficiency. The method is simple and flexible. Both male and female ES cells can be introduced into the eight-cell embryo by any method of injection or aggregation and using all ES cell and host embryo combinations from inbred, hybrid, and outbred genetic backgrounds. The VelociMouse method provides several unique opportunities for shortening project timelines and reducing mouse husbandry costs. First, as VelociMice exhibit 100% GLT, there is no need to test cross chimeras to establish GLT. Second, because the VelociMouse method permits efficient production of ES cell-derived mice from female ES cells, XO ES cell subclones, identified by screening for spontaneous loss of the Y chromosome, can be used to generate F0 females that can be bred with isogenic F0 males derived from the original targeted ES cell clone to obtain homozygous mutant mice in the F1 generation. Third, as VelociMice are genetically identical to the ES cells from which they were derived, the VelociMouse method opens up myriad possibilities for creating mice with

  5. Endomorphins fully activate a cloned human mu opioid receptor.

    PubMed

    Gong, J; Strong, J A; Zhang, S; Yue, X; DeHaven, R N; Daubert, J D; Cassel, J A; Yu, G; Mansson, E; Yu, L

    1998-11-13

    Endomorphins were recently identified as endogenous ligands with high selectivity for mu opioid receptors. We have characterized the ability of endomorphins to bind to and functionally activate the cloned human mu opioid receptor. Both endomorphin-1 and endomorphin-2 exhibited binding selectivity for the mu opioid receptor over the delta and kappa opioid receptors. Both agonists inhibited forskolin-stimulated increase of cAMP in a dose-dependent fashion. When the mu opioid receptor was coexpressed in Xenopus oocytes with G protein-activated K+ channels, application of either endomorphin activated an inward K+ current. This activation was dose-dependent and blocked by naloxone. Both endomorphins acted as full agonists with efficacy similar to that of [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO). These data indicate that endomorphins act as full agonists at the human mu opioid receptor, capable of stimulating the receptor to inhibit the cAMP/adenylyl cyclase pathway and activate G-protein-activated inwardly rectifying potassium (GIRK) channels.

  6. Maize Bronze 1:Dspm Insertion Mutations That Are Not Fully Suppressed by an Active Spm

    PubMed Central

    Bunkers, G.; Nelson-Jr., O. E.; Raboy, V.

    1993-01-01

    The Suppressor-mutator (Spm) family of maize transposable elements consists of autonomous Spm elements and nonautonomous defective Spm (dSpm) elements. One characteristic of this family is that the insertion of dSpm elements into a structural gene often permits some level of structural gene expression in the absence of Spm activity, and this structural gene expression is suppressed in trans by Spm activity. The Spm's subterminal repetitive regions (SRRs) contain several iterations of a 12-bp repeat motif. It had been proposed that binding of an Spm-encoded protein to these repeat motifs blocks structural gene transcriptional readthrough, thus suppressing gene expression. The bz-m13 allele of the bronze 1 locus contains a 2.24-kb dSpm insertion in the second exon of a Bz allele. In the absence of Spm activity, bz-m13 displays substantial Bz expression, and this expression is fully suppressed by Spm. Four intra-dSpm deletion derivatives are described in which this Bz expression is only partially suppressed by Spm. Each of these derivatives retains at least 12 SRR repeat motifs. Thus the presence of these repeat motifs is not sufficient to guarantee complete suppression by Spm. Some other property such as secondary structure or element size must play a role. PMID:8397136

  7. An extension to chaos control via Lie derivatives: Fully linearizable systems.

    PubMed

    Femat, Ricardo

    2002-12-01

    The technique of using Lie derivatives to control chaos introduced by Kocarev et al. [Chaos, Solitons Fractals 9, 1359-1366 (1998)] is extended in this contribution. Here, by using Lie derivatives in an extended space state, it is proved that chaos can be practically suppressed via feedback in spite of the Lie derivative being ill-posed at the reference. The main idea is to construct a dynamically equivalent system. In this way, the chaotic system can be practically stabilized around any point of singularity x(0). The Lorenz equation is used as an illustrative example to show the application in the chaos control context. (c) 2002 American Institute of Physics.

  8. Derivation of gender and age-specific reference intervals from fully normal Japanese individuals and the implications for health screening.

    PubMed

    Yamakado, Minoru; Ichihara, Kiyoshi; Matsumoto, Yoshiyuki; Ishikawa, Yoshiki; Kato, Kiminori; Komatsubara, Yusuke; Takaya, Norihide; Tomita, Shohken; Kawano, Reo; Takada, Keisuke; Watanabe, Kiyoaki

    2015-07-20

    With nationwide standardization of laboratory tests among institutions for health screening in Japan, common reference intervals (RIs) were derived from records of 1,500,000 health check attendees. Targets were 20 basic laboratory tests including body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling the following strict criteria were chosen: SBP<130, DBP<85mmHg, BMI<25kg/m(2), non-smoking, ethanol consumption<20g/day and under no mediation with no remarkable current/past illnesses. The latent abnormal values exclusion (LAVE) method was applied to ensure fully normal results. RIs were derived by parametric method using modified Box-Cox power transformation. Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40%-50%. Age-related charts of test results differed greatly between genders in almost all tests. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to gender and age. Implementation of gender and age-specific RIs derived from individuals with fully normal health attributes will (1) enable appropriate interpretation of test results in health screening and (2) promote judicious application of CDLs for therapeutic intervention, taking into account gender, age and other health attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses.

    PubMed

    Poueymirou, William T; Auerbach, Wojtek; Frendewey, David; Hickey, Joseph F; Escaravage, Jennifer M; Esau, Lakeisha; Doré, Anthony T; Stevens, Sean; Adams, Niels C; Dominguez, Melissa G; Gale, Nicholas W; Yancopoulos, George D; DeChiara, Thomas M; Valenzuela, David M

    2007-01-01

    A useful approach for exploring gene function involves generating mutant mice from genetically modified embryonic stem (ES) cells. Recent advances in genetic engineering of ES cells have shifted the bottleneck in this process to the generation of mice. Conventional injections of ES cells into blastocyst hosts produce F0 generation chimeras that are only partially derived from ES cells, requiring additional breeding to obtain mutant mice that can be phenotyped. The tetraploid complementation approach directly yields mice that are almost entirely derived from ES cells, but it is inefficient, works only with certain hybrid ES cell lines and suffers from nonspecific lethality and abnormalities, complicating phenotypic analyses. Here we show that laser-assisted injection of either inbred or hybrid ES cells into eight cell-stage embryos efficiently yields F0 generation mice that are fully ES cell-derived and healthy, exhibit 100% germline transmission and allow immediate phenotypic analysis, greatly accelerating gene function assignment.

  10. Dynamics of G-band bright points derived using two fully automated algorithms

    NASA Astrophysics Data System (ADS)

    Bodnárová, M.; Utz, D.; Rybák, J.; Hanslmeier, A.

    Small-scale magnetic field concentrations (˜ 1 kG) in the solar photosphere can be identified in the G-band of the solar spectrum as bright points. Study of the G-band bright points (GBPs) dynamics can help us in solving several questions related also to the coronal heating problem. Here a set of 142 G-band speckled images obtained using the Dutch Open Telescope (DOT) on October 19, 2005 are used to compare identification of the GBPs by two different fully automated identification algorithms: an algorithm developed by Utz et al. (2009a, 2009b) and an algorithm developed according to papers of Berger et al. (1995, 1998). Temporal and spatial tracking of the GBPs identified by both algorithms was performed resulting in distributions of lifetimes, sizes and velocities of the GBPs. The obtained results show that both algorithms give very similar values in the case of lifetime and velocity estimation of the GBPs, but they differ significantly in case of estimation of the GBPs sizes. This difference is caused by the fact that we have applied no additional exclusive criteria on the GBPs identified by the algorithm based on the work of Berger et al. (1995, 1998). Therefore we conclude that in a future study of the GBPs dynamics we will prefer to use the Utz's algorithm to perform identification and tracking of the GBPs in G-band images.

  11. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

    PubMed Central

    Scott, Charlotte L.; Zheng, Fang; De Baetselier, Patrick; Martens, Liesbet; Saeys, Yvan; De Prijck, Sofie; Lippens, Saskia; Abels, Chloé; Schoonooghe, Steve; Raes, Geert; Devoogdt, Nick; Lambrecht, Bart N.; Beschin, Alain; Guilliams, Martin

    2016-01-01

    Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them. PMID:26813785

  12. Characterization of complexes formed in fully hydrated dispersions of dipalmitoyl derivatives of phosphatidylcholine and diacylglycerol.

    PubMed

    Quinn, P J; Takahashi, H; Hatta, I

    1995-04-01

    The phase diagram of fully hydrated binary mixtures of dipalmitoylphosphatidylcholine (DPPC) with 1,2-dipalmitoylglycerol (DPG) published recently by López-García et al. identifies regions where stoichiometric complexes of 1:1 and 1:2 DPPC:DPG, respectively, are formed. In this study, the structural parameters of the 1:1 complex in the presence of pure DPPC was characterized by synchrotron low angle and static x-ray diffraction methods. Structural changes upon transitions through phase boundaries were correlated with enthalpy changes observed by differential scanning calorimetry in mixtures of DPPC with 5, 7.5, 10, and 20 mol% DPG dispersed in excess water. Phase separation of a complex in gel phase could be detected by calorimetry in the mixture containing 5 mol% DPG but was not detectable by synchrotron low angle x-ray diffraction. Static x-ray measurements show evidence of phase separation, particularly in the reflections indexing chain packing. In the mixture containing 7.5 mol% DPG, two distinct lamellar repeat spacings could be seen in the temperature range from 25 to 34 degrees C. The lamellar spacing of about 6.6 nm was assigned to pure gel phase DPPC because the change in the spacing corresponds with thermal transition of the pure phospholipid, and a longer repeat spacing of about 7.2 nm was assigned to domains of the 1:1 complex of DPPC-DPG. In the temperature range from 34 to 420C, i.e., in the region of coexistence of the ripple phase of DPPC and the gel phase of the complex, a single, rather broad lamellar reflection appears because of superposition of two reflections of DPPC and the complex; the lamellar spacing of DPPC in the ripple phase is similar to that of the gel phase of complex. In the coexistence region of the liquid-crystalline phase of DPPC and the gel phase of complex (-42-480C), the lamellar reflections of the both phases are present. The fluidus boundary lies between the coexistence region and the fluid region.In the fluid region (-48

  13. Generation of “LYmph Node Derived Antibody Libraries” (LYNDAL) for selecting fully human antibody fragments with therapeutic potential

    PubMed Central

    Diebolder, Philipp; Keller, Armin; Haase, Stephanie; Schlegelmilch, Anne; Kiefer, Jonathan D; Karimi, Tamana; Weber, Tobias; Moldenhauer, Gerhard; Kehm, Roland; Eis-Hübinger, Anna M; Jäger, Dirk; Federspil, Philippe A; Herold-Mende, Christel; Dyckhoff, Gerhard; Kontermann, Roland E; Arndt, Michaela AE; Krauss, Jürgen

    2014-01-01

    The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro, the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential. PMID:24256717

  14. The Operating Principle of a Fully Solid State Active Magnetic Regenerator

    SciTech Connect

    Abdelaziz, Omar

    2016-01-01

    As an alternative refrigeration technology, magnetocaloric refrigeration has the potential to be safer, quieter, more efficient, and more environmentally friendly than the conventional vapor compression refrigeration technology. Most of the reported active magnetic regenerator (AMR) systems that operate based on the magnetocaloric effect use heat transfer fluid to exchange heat, which results in complicated mechanical subsystems and components such as rotating valves and hydraulic pumps. This paper presents an operating principle of a fully solid state AMR, in which an alternative mechanism for heat transfer between the AMR and the heat source/sink is proposed. The operating principle of the fully solid state AMR is based on moving rods/sheets (e.g. copper, brass, iron or aluminum), which are employed to replace the heat transfer fluid. Such fully solid state AMR would provide a significantly higher heat transfer rate than a conventional AMR because the conductivity of moving solid rods/plates is high and it enables the increase in the machine operating frequency hence the cooling capacity. The details of operating principle are presented and discussed here. One of the key enabling features for this technology is the contact between the moving rods/sheets and magnetocaloric material, and heat exchange mechanism at the heat source/sink. This paper provides an overview of the design for a fully solid state magnetocaloric refrigeration system along with guidelines for their optimal design.

  15. The effect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling

    NASA Astrophysics Data System (ADS)

    Sulistyo, Bambang

    2016-11-01

    The research was aimed at studying the efect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling of The USLE using remote sensing data and GIS technique. Methods applied was by analysing all factors affecting erosion such that all data were in the form of raster. Those data were R, K, LS, C and P factors. Monthly R factor was evaluated based on formula developed by Abdurachman. K factor was determined using modified formula used by Ministry of Forestry based on soil samples taken in the field. LS factor was derived from Digital Elevation Model. Three C factors used were all derived from NDVI and developed by Suriyaprasit (non-linear) and by Sulistyo (linear and non-linear). P factor was derived from the combination between slope data and landcover classification interpreted from Landsat 7 ETM+. Another analysis was the creation of map of Bulk Density used to convert erosion unit. To know the model accuracy, model validation was done by applying statistical analysis and by comparing Emodel with Eactual. A threshold value of ≥ 0.80 or ≥ 80% was chosen to justify. The research result showed that all Emodel using three formulae of C factors have coeeficient of correlation value of > 0.8. The results of analysis of variance showed that there was significantly difference between Emodel and Eactual when using C factor formula developed by Suriyaprasit and Sulistyo (non-linear). Among the three formulae, only Emodel using C factor formula developed by Sulistyo (linear) reached the accuracy of 81.13% while the other only 56.02% as developed by Sulistyo (nonlinear) and 4.70% as developed by Suriyaprasit, respectively.

  16. In vitro interaction of artemisinin derivatives or the fully synthetic peroxidic anti-malarial OZ277 with thapsigargin in Plasmodium falciparum strains

    PubMed Central

    2013-01-01

    Background Semi-synthetic artemisinin derivatives are powerful peroxidic drugs in artemisinin-based combination therapy (ACT) recommended as first-line treatment of Plasmodium falciparum malaria in disease-endemic countries. Studies by Eckstein-Ludwig and co-workers showed both thapsigargin and artemisinin specifically inhibit the sarcoplasmic reticulum Ca2+−ATPase of Plasmodium falciparum (PfATP6). In the present study the type of interaction between thapsigargin and artemisinin derivatives as well as the ozonide OZ277 (RBx11160 or arterolane) was evaluated in parasite cultures. The latter compound is an adamantane-based peroxide and the first fully synthetic clinical candidate recently registered in India by Ranbaxy Laboratories Ltd. for anti-malarial combination therapy. Methods Drug interaction studies were performed using a previously described fixed ratio method and anti-malarial activity measured using the [3H] hypoxanthine incorporation assay. Results The sum 50% and 90% fractional inhibitory concentration (∑FIC50, 90) of the interaction of thapsigargin with OZ277, artemether or artesunate, against NF54 and K1 strains of P. falciparum ranged from 0.9 to 1.4. Conclusion The interaction of thapsigargin with OZ277, artesunate or artemether was additive, data consistent with previous observations indicating that activity of anti-malarial peroxides does not derive from reversible interactions with parasite targets. PMID:23368889

  17. Phosphorus-nitrogen compounds. Part 20: Fully substituted spiro-cyclotriphosphazenic lariat (PNP-pivot) ether derivatives

    NASA Astrophysics Data System (ADS)

    Okumuş, Aytuğ; Bilge, Selen; Kılıç, Zeynel; Öztürk, Aslı; Hökelek, Tuncer; Yılmaz, Filiz

    2010-08-01

    The condensation reactions of partly substituted spiro-cyclotriphosphazenic lariat (PNP-pivot) ethers, N 3P 3[( o-NHPhO) 2R]Cl 4 [where R = -CH 2CH 2- ( 1) and -CH 2CH 2OCH 2CH 2- ( 2)] with morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) produce fully substituted morpholino ( 3 and 4) and 1,4-dioxa-8-azaspiro[4,5]deca ( 5 and 6) phosphazenes. These are the new examples of the spiro-cyclophosphazenic lariat ether derivatives with N 2O x ( x = 2 and 3) donor type containing 11- and 14-membered macrocycles. The solid state structures of 3, 5 and 6 have been determined by X-ray diffraction techniques. Compound 3 has intermolecular N-H…O hydrogen bond, compound 5 has intra- and intermolecular N-H…O hydrogen bonds, while compound 6 has intramolecular N-H…O and O-H…N and intermolecular N-H…O and O-H…O hydrogen bonds. The correlations of the endocyclic ( α) and exocyclic ( α') NPN bond angles with δP spiro values are investigated. The structural investigations of 3- 6 have been verified by elemental analyses, MS, FTIR, 1H, 13C and 31P NMR, DEPT and HETCOR techniques.

  18. Dynamic Surface Activity of a Fully Synthetic Phospholipase-Resistant Lipid/Peptide Lung Surfactant

    PubMed Central

    Walther, Frans J.; Waring, Alan J.; Hernandez-Juviel, Jose M.; Gordon, Larry M.; Schwan, Adrian L.; Jung, Chun-Ling; Chang, Yusuo; Wang, Zhengdong; Notter, Robert H.

    2007-01-01

    Background This study examines the surface activity and resistance to phospholipase degradation of a fully-synthetic lung surfactant containing a novel diether phosphonolipid (DEPN-8) plus a 34 amino acid peptide (Mini-B) related to native surfactant protein (SP)-B. Activity studies used adsorption, pulsating bubble, and captive bubble methods to assess a range of surface behaviors, supplemented by molecular studies using Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD), and plasmon resonance. Calf lung surfactant extract (CLSE) was used as a positive control. Results DEPN-8+1.5% (by wt.) Mini-B was fully resistant to degradation by phospholipase A2 (PLA2) in vitro, while CLSE was severely degraded by this enzyme. Mini-B interacted with DEPN-8 at the molecular level based on FTIR spectroscopy, and had significant plasmon resonance binding affinity for DEPN-8. DEPN-8+1.5% Mini-B had greatly increased adsorption compared to DEPN-8 alone, but did not fully equal the very high adsorption of CLSE. In pulsating bubble studies at a low phospholipid concentration of 0.5 mg/ml, DEPN-8+1.5% Mini-B and CLSE both reached minimum surface tensions <1 mN/m after 10 min of cycling. DEPN-8 (2.5 mg/ml)+1.5% Mini-B and CLSE (2.5 mg/ml) also reached minimum surface tensions <1 mN/m at 10 min of pulsation in the presence of serum albumin (3 mg/ml) on the pulsating bubble. In captive bubble studies, DEPN-8+1.5% Mini-B and CLSE both generated minimum surface tensions <1 mN/m on 10 successive cycles of compression/expansion at quasi-static and dynamic rates. Conclusions These results show that DEPN-8 and 1.5% Mini-B form an interactive binary molecular mixture with very high surface activity and the ability to resist degradation by phospholipases in inflammatory lung injury. These characteristics are promising for the development of related fully-synthetic lipid/peptide exogenous surfactants for treating diseases of surfactant deficiency or dysfunction. PMID

  19. Depth heterogeneity of fully aromatic polyamide active layers in reverse osmosis and nanofiltration membranes.

    PubMed

    Coronell, Orlando; Mariñas, Benito J; Cahill, David G

    2011-05-15

    We studied the depth heterogeneity of fully aromatic polyamide (PA) active layers in commercial reverse osmosis (RO) and nanofiltration (NF) membranes by quantifying near-surface (i.e., top 6 nm) and volume-averaged properties of the active layers using X-ray photoelectron spectrometry (XPS) and Rutherford backscattering spectrometry (RBS), respectively. Some membranes (e.g., ESPA3 RO) had active layers that were depth homogeneous with respect to the concentration and pK(a) distribution of carboxylic groups, degree of polymer cross-linking, concentration of barium ion probe that associated with ionized carboxylic groups, and steric effects experienced by barium ion. Other membranes (e.g., NF90 NF) had active layers that were depth heterogeneous with respect to the same properties. Our results therefore support the existence of both depth-homogeneous and depth-heterogeneous active layers. It remains to be assessed whether the depth heterogeneity consists of gradually changing properties throughout the active layer depth or of distinct sublayers with different properties.

  20. A fully human chimeric antigen receptor with potent activity against cancer cells but reduced risk for off-tumor toxicity

    PubMed Central

    Song, De-Gang; Ye, Qunrui; Poussin, Mathilde; Liu, Lin; Figini, Mariangela; Powell, Daniel J.

    2015-01-01

    Chimeric antigen receptors (CARs) can redirect T cells against antigen-expressing tumors in an HLA-independent manner. To date, various CARs have been constructed using mouse single chain antibody variable fragments (scFvs) of high affinity that are immunogenic in humans and have the potential to mediate “on-target” toxicity. Here, we developed and evaluated a fully human CAR comprised of the human C4 folate receptor-alpha (αFR)-specific scFv coupled to intracellular T cell signaling domains. Human T cells transduced to express the C4 CAR specifically secreted proinflammatory cytokine and exerted cytolytic functions when cultured with αFR-expressing tumors in vitro. Adoptive transfer of C4 CAR T cells mediated the regression of large, established human ovarian cancer in a xenogeneic mouse model. Relative to a murine MOv19 scFv-based αFR CAR, C4 CAR T cells mediated comparable cytotoxic tumor activity in vitro and in vivo but had lower affinity for αFR protein and exhibited reduced recognition of normal cells expressing low levels of αFR. Thus, T cells expressing a fully human CAR of intermediate affinity can efficiently kill antigen-expressing tumors in vitro and in vivo and may overcome issues of transgene immunogenicity and “on-target off-tumor” toxicity that plague trials utilizing CARs containing mouse-derived, high affinity scFvs. PMID:26101914

  1. A fully resolved fluid-structure-muscle-activation model for esophageal transport

    NASA Astrophysics Data System (ADS)

    Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

    2013-11-01

    Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

  2. A fully resolved active musculo-mechanical model for esophageal transport.

    PubMed

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E; Pandolfino, John E; Kahrilas, Peter J; Patankar, Neelesh A

    2015-10-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

  3. A fully resolved active musculo-mechanical model for esophageal transport

    NASA Astrophysics Data System (ADS)

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

    2015-10-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

  4. A fully resolved active musculo-mechanical model for esophageal transport

    PubMed Central

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

    2015-01-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function. PMID:26190859

  5. Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice

    PubMed Central

    Robert, Jérôme; Veziris, Nicolas; Aubry, Alexandra; Jarlier, Vincent

    2016-01-01

    Background The treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field. Methodology/Principal findings The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks. The bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens, i.e. RFP-CLR 5/7 or RIF-STR 5/7. A single mouse from the RFP-MFX 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 RFP-CLR 2/7, 39 RFP-CLR 3/7, 39 RFP-MXF 2/7, 39 RFP-BDQ 2/7). Conclusions/Significance These results open the door for a fully intermittent oral drug regimen for BU treatment avoiding intramuscular injections and facilitating supervision by health care workers. PMID:27755552

  6. Antimicrobial activity of a food-grade fully dilutable microemulsion against Escherichia coli and Staphylococcus aureus.

    PubMed

    Zhang, Hui; Shen, Yan; Weng, Peifang; Zhao, Guoqun; Feng, Fengqin; Zheng, Xiaodong

    2009-11-15

    Microemulsions are colloidal nanodispersions of oil and water stabilized by an interfacial film of surfactant molecules, typically in conjunction with a cosurfactant. There is a limited number of reports in the literature on microemulsion use for antimicrobial purposes. The physicochemical characterization of a food-grade fully dilutable microemulsion system with glycerol monolaurate (GML) as oil, organic acids as cosurfactant, Tween 80 as surfactant, and the antimicrobial activities against Escherichia coli and Staphylococcus aureus have been studied in this paper. The influence of organic acids on oil solubilization was clearly reflected in the phase behavior of these systems. Propionic acid demonstrated the greatest capability to improve the oil solubilization among the tested linear and nonlinear chain organic acids and contributed to the formation of U-type microemulsion systems. One microemulsion formulation with an average particle size of 8nm was selected, the composition is GML/propionic acid/Tween 80/water=3:9:8:12. The kinetics of killing experiments demonstrated that the undiluted microemulsion caused a complete loss of viability of E. coli or S. aureus cells in 1min and still had effective bactericidal effects even when diluted, more than 99% viable E. coli cells were killed within 15min and a complete loss of viability was achieved at 45min while more than 99% viable S. aureus cells were killed within 30min and a complete loss of viability was achieved at 60min in the presence of the 10-fold diluted microemulsion. The fast killing kinetics of the ten-fold serial dilutions of microemulsions were in good agreement with the mode of action studies, indicating that the interaction between the antimicrobial microemulsions and bacterial membranes significantly decreased the bacterial cell surface hydrophobicity and induced the quick release of 260nm absorbing materials. This work suggests the potential use of food-grade fully dilutable microemulsions for

  7. Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment.

    PubMed

    Mei, Baisong; Pan, Clark; Jiang, Haiyan; Tjandra, Hendri; Strauss, Jonathan; Chen, Yaoqi; Liu, Tongyao; Zhang, Xin; Severs, Joanne; Newgren, Jim; Chen, Jianmin; Gu, Jian-Ming; Subramanyam, Babu; Fournel, Michael A; Pierce, Glenn F; Murphy, John E

    2010-07-15

    A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A. To develop a FVIII with an extended circulating half-life, but without a reduction in activity, we have engineered 23 FVIII variants with introduced surface-exposed cysteines to which a polyethylene glycol (PEG) polymer was specifically conjugated. Screening of variant expression level, PEGylation yield, and functional assay identified several conjugates retaining full in vitro coagulation activity and von Willebrand factor (VWF) binding.PEGylated FVIII variants exhibited improved pharmacokinetics in hemophilic mice and rabbits. In addition, pharmacokinetic studies in VWF knockout mice indicated that larger molecular weight PEG may substitute for VWF in protecting PEGylated FVIII from clearance in vivo. In bleeding models of hemophilic mice, PEGylated FVIII not only exhibited prolonged efficacy that is consistent with the improved pharmacokinetics but also showed efficacy in stopping acute bleeds comparable with that of unmodified rFVIII. In summary site-specifically PEGylated FVIII has the potential to be a long-acting prophylactic treatment while being fully efficacious for on-demand treatment for patients with hemophilia A.

  8. Antifungal activity of ajoene derived from garlic.

    PubMed Central

    Yoshida, S; Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H; Nakagawa, S

    1987-01-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml. Images PMID:3555334

  9. Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet-derived growth factor receptor alpha.

    PubMed

    Shah, Gaurav D; Loizos, Nick; Youssoufian, Hagop; Schwartz, Jonathan D; Rowinsky, Eric K

    2010-02-15

    A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor alpha (PDGFRalpha) with high affinity and blocks PDGF ligand binding and PDGFRalpha activation. The results of preclinical studies and the frequent expression of PDGFRalpha in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies.

  10. Perspectives on Biologically Active Camptothecin Derivatives

    PubMed Central

    Liu, Ying-Qian; Li, Wen-Qun; Morris-Natschke, Susan L.; Qian, Keduo; Yang, Liu; Zhu, Gao-Xiang; Wu, Xiao-Bing; Chen, An-Liang; Zhang, Shao-Yong; Song, Zi-Long; Lee, Kuo-Hsiung

    2015-01-01

    Camptothecins (CPTs) are cytotoxic natural alkaloids that specifically target DNA topoisomerase I. Research on CPTs has undergone a significant evolution from the initial discovery of CPT in the late 1960s through the study of synthetic small molecule derivatives to investigation of macromolecular constructs and formulations. Over the past years, intensive medicinal chemistry efforts have generated numerous CPT derivatives. Three derivatives, topotecan, irinotecan, and belotecan, are currently prescribed as anticancer drugs, and several related compounds are now in clinical trials. Interest in other biological effects, besides anticancer activity, of CPTs is also growing exponentially, as indicated by the large number of publications on the subject during the last decades. Therefore, the main focus of the present review is to provide an ample but condensed overview on various biological activities of CPT derivatives, in addition to continued up-to-date coverage of anticancer effects. PMID:25808858

  11. Recovering planet radial velocity signals in the presence of starspot activity in fully convective stars

    NASA Astrophysics Data System (ADS)

    Barnes, J. R.; Jeffers, S. V.; Anglada-Escudé, G.; Haswell, C. A.; Jones, H. R. A.; Tuomi, M.; Feng, F.; Jenkins, J. S.; Petit, P.

    2017-04-01

    Accounting for stellar activity is a crucial component of the search for ever-smaller planets orbiting stars of all spectral types. We use Doppler imaging methods to demonstrate that starspot-induced radial velocity variability can be effectively reduced for moderately rotating, fully convective stars. Using starspot distributions extrapolated from sunspot observations, we adopt typical M dwarf starspot distributions with low contrast spots to synthesize line profile distortions. The distortions are recovered using maximum entropy regularized fitting and the corresponding stellar radial velocities are measured. The procedure is demonstrated that for a late-M star harbouring an orbiting planet in the habitable zone. The technique is effective for stars with v sin i = 1-10km s-1, reducing the stellar noise contribution by factors of nearly an order of magnitude. With a carefully chosen observing strategy, the technique can be used to determine the stellar rotation period and is robust to uncertainties such as unknown stellar inclination. While demonstrated for late-type M stars, the procedure is applicable to all spectral types.

  12. Antiretroviral (HIV-1) activity of azulene derivatives.

    PubMed

    Peet, Julia; Selyutina, Anastasia; Bredihhin, Aleksei

    2016-04-15

    The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2-10 and 8-20 μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents.

  13. Activities and Prevalence of Proteobacteria Members Colonizing Echinacea purpurea Fully Account for Macrophage Activation Exhibited by Extracts of this Botanical

    PubMed Central

    Haron, Mona H.; Tyler, Heather L.; Pugh, Nirmal D.; Moraes, Rita M.; Maddox, Victor L.; Jackson, Colin R.; Pasco, David S.

    2017-01-01

    Evidence supports the theory that bacterial communities colonizing Echinacea purpurea contribute to the innate immune enhancing activity of this botanical. Previously we reported that only about half of the variation in in vitro monocyte stimulating activity exhibited by E. purpurea extracts could be accounted for by total bacterial load within the plant material. In the current study we test the hypothesis that the type of bacteria, in addition to bacterial load, is necessary to fully account for extract activity. Bacterial community composition within commercial and freshly harvested (wild and cultivated) E. purpurea aerial samples was determined using high-throughput 16S rRNA gene pyrosequencing. Bacterial isolates representing 38 different taxa identified to be present within E. purpurea were acquired and the activity exhibited by extracts of these isolates varied by over 8,000-fold. Members of the Proteobacteria exhibited the highest potency for in vitro macrophage activation and were the most predominant taxa. Furthermore, the mean activity exhibited by the Echinacea extracts could be solely accounted for by the activities and prevalence of Proteobacteria members comprising the plant-associated bacterial community. The efficacy of E. purpurea material for use against respiratory infections may be determined by the Proteobacterial community composition of this plant, since ingestion of bacteria (probiotics) is reported to have a protective effect against this health condition. PMID:27286330

  14. Activities and Prevalence of Proteobacteria Members Colonizing Echinacea purpurea Fully Account for Macrophage Activation Exhibited by Extracts of This Botanical.

    PubMed

    Haron, Mona H; Tyler, Heather L; Pugh, Nirmal D; Moraes, Rita M; Maddox, Victor L; Jackson, Colin R; Pasco, David S

    2016-09-01

    Evidence supports the theory that bacterial communities colonizing Echinacea purpurea contribute to the innate immune enhancing activity of this botanical. Previously, we reported that only about half of the variation in in vitro monocyte stimulating activity exhibited by E. purpurea extracts could be accounted for by total bacterial load within the plant material. In the current study, we test the hypothesis that the type of bacteria, in addition to bacterial load, is necessary to fully account for extract activity. Bacterial community composition within commercial and freshly harvested (wild and cultivated) E. purpurea aerial samples was determined using high-throughput 16S rRNA gene pyrosequencing. Bacterial isolates representing 38 different taxa identified to be present within E. purpurea were acquired, and the activity exhibited by the extracts of these isolates varied by over 8000-fold. Members of the Proteobacteria exhibited the highest potency for in vitro macrophage activation and were the most predominant taxa. Furthermore, the mean activity exhibited by the Echinacea extracts could be solely accounted for by the activities and prevalence of Proteobacteria members comprising the plant-associated bacterial community. The efficacy of E. purpurea material for use against respiratory infections may be determined by the Proteobacterial community composition of this plant, since ingestion of bacteria (probiotics) is reported to have a protective effect against this health condition. Georg Thieme Verlag KG Stuttgart · New York.

  15. New steroid derivative with hypoglycemic activity

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

    2014-01-01

    Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative. PMID:25550906

  16. New steroid derivative with hypoglycemic activity.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

    2014-01-01

    Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative.

  17. The cytotoxic activity of ursolic acid derivatives.

    PubMed

    Ma, Chao-Mei; Cai, Shao-Qing; Cui, Jing-Rong; Wang, Rui-Qing; Tu, Peng-Fei; Hattori, Masao; Daneshtalab, Mohsen

    2005-06-01

    Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.

  18. Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei

    PubMed Central

    Graça, Nuno A. G.; Gaspar, Luis; Costa, David M.; Loureiro, Inês; Thoo-Lin, Paul Kong; Ramos, Isbaal; Roura, Meritxell; Pruvost, Alain; Pemberton, Ian K.; Loukil, Hadjer; MacDougall, Jane

    2016-01-01

    Current treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives against Trypanosoma brucei. BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showed in vitro inhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite load in BNIPDabut-treated mice was observed. However, cure was not achieved. BNIPDabut constitutes a new scaffold for antitrypanosomal drugs that deserves further consideration. PMID:26787703

  19. Nonclassical biological activities of quinolone derivatives.

    PubMed

    Ahmed, Abeer; Daneshtalab, Mohsen

    2012-01-01

    Quinolones are considered as a big family of multi-faceted drugs; their chemical synthesis is flexible and can be easily adapted to prepare new congeners with rationally devised structures. This is shown by the description of many thousands of derivatives in the literature. Scientists could accurately describe their QSAR, which is essential for effective drug design. This also gave them the chance to discover new and unprecedented activities, which makes quinolones an endless source of hope and enables further development of new clinically useful drugs. Quinolones are among the most common frameworks present in the bioactive molecules that have dominated the market for more than four decades. Since 1962, 4(1H)-quinolone-3-carboxylic acid derivatives are widely used as antibacterial agents. Quinolones have a broad and potent spectrum of activity and are also used as second-line drugs to treat tuberculosis (TB). Recently, quinolones have been reported to display "nonclassical" biological activities, such as antitumor, anti-HIV-1 integrase, anti-HCV-NS3 helicase and -NS5B-polymerase activities. The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent and/or an antiviral agent. Indeed, quinolones' antimicrobial action is distinguishable among antibacterial agents, because they target different type II topoisomerase enzymes. Many derivatives of this family show high activity against bacterial topoisomerases and eukaryotic topoisomerases, and are also toxic to cultured mammalian cells and in vivo tumor models. Moreover, quinolones have shown antiviral activity against HIV and HCV viruses. In this context the quinolones family of drugs seem to link three different biological activities (antibacterial, anticancer, and the antiviral profiles) and the review will also provide an insight into the different mechanisms responsible for these activities among different species.

  20. A sensitive radioimmunoassay for corticotropin using a fully biologically active 125I-labeled ligand

    SciTech Connect

    Buckley, D.I.; Hagman, J.; Ramachandran, J.

    1981-07-01

    The human corticotropin (ACTH) analog, Phe2,Nle4-ACTH-(1-38) was iodinated by the chloramine-T procedure and the product was purified by reverse phase high performance liquid chromatography. The specific radioactivity of (/sup 125/I)Tyr23,Phe2,Nle4-ACTH-(1-38) was determined by comparing the antiserum binding curves of the iodinated peptide and (3H)ACTH of known specific activity. This method gave a value of 1800 +/- 75 Ci/mmol, which is close to the theoretical radioactivity expected for the introduction of a single /sup 125/I atom into the peptide. (/sup 125/I)Tyr23,Phe2,Nle4-ACTH-(1-38) was as potent as ACTH in stimulating corticosterone production in isolated rat adrenocortical cells. The concentrations for half-maximal steroidogenesis were 36.5 +/- 6.1 pM for the /sup 125/I derivative and 37.6 +/- 6.7 pM for ACTH. By the use of this /sup 125/I-labeled ligand, a highly sensitive RIA capable of detecting 1 pg ACTH was developed.l The antiserum employed in this study appeared to be directed against residues 11-13 of ACTH.

  1. Thermally activated delayed fluorescence OLEDs with fully solution processed organic layers exhibiting nearly 10% external quantum efficiency.

    PubMed

    Albrecht, Ken; Matsuoka, Kenichi; Yokoyama, Daisuke; Sakai, Yoshiya; Nakayama, Akira; Fujita, Katsuhiko; Yamamoto, Kimihisa

    2017-02-21

    New solution processable and laminatable terminally modified carbazole-triazine thermally activated delayed fluorescence (TADF) dendrimers are reported. An OLED device with fully solution processed organic layers exhibited an external quantum efficiency of up to 9.4% at 100 cd m(-2).

  2. Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform

    PubMed Central

    Adil, Maroof M.; Rodrigues, Gonçalo M. C.; Kulkarni, Rishikesh U.; Rao, Antara T.; Chernavsky, Nicole E.; Miller, Evan W.; Schaffer, David V.

    2017-01-01

    Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson’s Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior). Importantly, mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. A defined, scalable, and resource-efficient cell culture platform can thus rapidly generate high quality differentiated cells, both neurons and potentially other cell types, with strong potential to accelerate both basic and translational research. PMID:28091566

  3. Carbon nanomaterials: Biologically active fullerene derivatives.

    PubMed

    Bogdanović, Gordana; Djordjević, Aleksandar

    2016-01-01

    Since their discovery, fullerenes, carbon nanotubes, and graphene attract significant attention of researches in various scientific fields including biomedicine. Nano-scale size and a possibility for diverse surface modifications allow carbon nanoallotropes to become an indispensable nanostructured material in nanotechnologies, including nanomedicine. Manipulation of surface chemistry has created diverse populations of water-soluble derivatives of fullerenes, which exhibit different behaviors. Both non-derivatized and derivatized fullerenes show various biological activities. Cellular processes that underline their toxicity are oxidative, genotoxic, and cytotoxic responses.The antioxidant/cytoprotective properties of fullerenes and derivatives have been considered in the prevention of organ oxidative damage and treatment. The same unique physiochemical properties of nanomaterials may also be associated with potential health hazards. Non-biodegradability and toxicity of carbon nanoparticles still remain a great concern in the area of biomedical application. In this review, we report on basic physical and chemical properties of carbon nano-clusters--fullerenes, nanotubes, and grapheme--their specificities, activities, and potential application in biological systems. Special emphasis is given to our most important results obtained in vitro and in vivo using polyhydroxylated fullerene derivative C₆₀(OH)₂₄.

  4. Structure activity relationships of selected naphthalene derivatives

    SciTech Connect

    Schultz, T.W.; Dumont, J.N.; Sankey, F.D.; Schmoyer, R.L. Jr.

    1983-01-01

    Twenty-two derivatives of naphthalene were assayed under an acute static regime with biological activity being monitored as population growth of Tetrahymena pyriformis. Activity varied over one log unit. Substituent constant structure-activity analyses revealed the model, log BR = 0.282Ha + 0.352..pi.. + 0.692F + 0.334/sup 1/X/sub sub//sup v/ - 0.326R + 0.027, to be best and to account for 85% of the variation in log BR (BR, biological response; Ha, hydrogen acceptance; ..pi.., hydrophobic substituent constant; F, polar electronic substituent constant, /sup 1/X/sub sub//sup v/, substituent molar connectivity index; R, resonance electronic substituent constant). The Ha and ..pi.. parameters are the most important, accounting for 71% of the log BR variability. 21 references, 1 figure, 7 tables.

  5. Antimicrobial activity of chemically modified dextran derivatives.

    PubMed

    Tuchilus, Cristina G; Nichifor, Marieta; Mocanu, Georgeta; Stanciu, Magdalena C

    2017-04-01

    Cationic amphiphilic dextran derivatives with a long alkyl group attached to the reductive end of the polysaccharide chain and quaternary ammonium groups attached as pendent groups to the main dextran backbone were synthesized and tested for their antimicrobial properties against several bacteria and fungi strains. Dependence of antimicrobial activity on both polymer chemical composition (dextran molar mass, length of end alkyl group and chemical structure of ammonium groups) and type of microbes was highlighted by disc-diffusion method (diameter of inhibition zone) and broth microdilution method (minimum inhibitory concentrations). Polymers had antimicrobial activity for all strains studied, except for Pseudomonas aeruginosa ATCC 27853. The best activity against Staphylococcus aureus (Minimun Inhibitory Concentration 60μg/mL) was provided by polymers obtained from dextran with lower molecular mass (Mn=4500), C12H25 or C18H37 end groups, and N,N-dimethyl-N-benzylammonium pendent groups.

  6. Antioxidant Activities of 4-Methylumbelliferone Derivatives

    PubMed Central

    Al-Majedy, Yasameen K.; Al-Amiery, Ahmed A.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2016-01-01

    The synthesis of derivatives of 4-Methylumbelliferone (4-MUs), which are structurally interesting antioxidants, was performed in this study. The modification of 4-Methylumbelliferone (4-MU) by different reaction steps was performed to yield the target compounds, the 4-MUs. The 4-MUs were characterized by different spectroscopic techniques (Fourier transform infrared; FT-IR and Nuclear magnetic resonance; NMR) and micro-elemental analysis (CHNS). The in vitro antioxidant activity of the 4-MUs was evaluated in terms of their free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH), Nitric oxide radical scavenging activity assay, chelating activity and their (FRAP) ferric-reducing antioxidant power, which were compared with a standard antioxidant. Our results reveal that the 4-MUs exhibit excellent radical scavenging activities. The antioxidant mechanisms of the 4-MUs were also studied. Density Function Theory (DFT)-based quantum chemical studies were performed with the basis set at 3-21G. Molecular models of the synthesized compounds were studied to understand the antioxidant activity. The electron levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), for these synthesized antioxidants were also studied. PMID:27243231

  7. Anticancer Activity of Stilbene-based Derivatives.

    PubMed

    De Filippis, Barbara; Ammazzalorso, Alessandra; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Amoroso, Rosa

    2017-03-07

    Anticancer Activity of Stilbene-based Derivatives Barbara De Filippis,* Alessandra Ammazzalorso, Marialuigia Fantacuzzi, Letizia Giampietro, Cristina Maccallini, Rosa Amoroso Dipartimento di Farmacia, Università "G. d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy; * E-mail: barbara.defilippis@unich.it Stilbene is a very present structural scaffold in nature and stilbene-based compounds are largely described for their biological activity such as cardioprotective, potent antioxidant, anti-inflammatory, and anticancer agents. Starting from their potent chemotherapeutic activity against a wide variety of cancers, stilbene scaffold of resveratrol has been subjected to synthetic manipulations with the aim to obtaining new resveratrol analogues with improved anticancer activity and better bioavailability. In the last decade, majority of new synthetic stilbenoids demonstrated significant anticancer activity against a large number of cancer cell lines employed, depending on the type and position of substituents on stilbene skeleton. Given the importance of this topic and the vast therapeutic potential, especially in the field of cancer research, in the last years, some reviews have been published focusing on general pharmacological activity or, more recently, on the usefulness of hybrid molecule containing stilbene scaffold. The present review article focuses on the pharmacological profile of the key compounds containing stilbene scaffold and classify them on the type of structural modifications in stilbene skeleton.

  8. Antimalarial Activities of Dermaseptin S4 Derivatives

    PubMed Central

    Krugliak, Miriam; Feder, Rina; Zolotarev, Vadim Y.; Gaidukov, Leonid; Dagan, Arie; Ginsburg, Hagai; Mor, Amram

    2000-01-01

    The hemolytic antimicrobial peptide dermaseptin S4 was recently shown to exert antimalarial activity. In this study, we attempted to understand the underlying mechanism(s) and identify derivatives with improved antimalarial activity. A number of dermaseptin S4 derivatives inhibited parasite growth with a 50% inhibitory concentration (IC50) in the micromolar range. Among these, the substituted S4 analog K4K20-S4 was the most potent (IC50 = 0.2 μM), while its shorter version, K4-S4(1–13)a, retained a considerable potency (IC50 = 6 μM). Both K4K20-S4 and K4-S4(1–13)a inhibited growth of the parasites more at the trophozoite stage than at the ring stage. Significant growth inhibition was observed after as little as 1 min of exposure to peptides and proceeded with nearly linear kinetics. The peptides selectively lysed infected red blood cells (RBC) while having a weaker effect on noninfected RBC. Thus, K4K20-S4 lysed trophozoites at concentrations similar to those that inhibited their proliferation, but trophozoites were >30-fold more susceptible than normal RBC to the lytic effect of K4K20-S4, the most hemolytic dermaseptin. The same trend was observed with K4-S4(1–13)a. The d isomers of K4K20-S4 or K4-S4(1–13)a were as active as the l counterparts, indicating that antimalarial activity of these peptides, like their membrane-lytic activity, is not mediated by specific interactions with a chiral center. Moreover, dissipation of transmembrane potential experiments with infected cells indicated that the peptides induce damage in the parasite's plasma membrane. Fluorescence confocal microscopy analysis of treated infected cells also indicated that the peptide is able to find its way through the complex series of membranes and interact directly with the intracellular parasite. Overall, the data showed that dermaseptins exert antimalarial activity by lysis of infected cells. Dermaseptin derivatives are also able to disrupt the parasite plasma membrane without

  9. Directed differentiation and long-term maintenance of epicardial cells derived from human pluripotent stem cells under fully defined conditions.

    PubMed

    Bao, Xiaoping; Lian, Xiaojun; Qian, Tongcheng; Bhute, Vijesh J; Han, Tianxiao; Palecek, Sean P

    2017-09-01

    Here, we describe how to efficiently direct human pluripotent stem cells (hPSCs) differentiation into self-renewing epicardial cells in a completely defined, xeno-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate differentiation-stage-specific application of Gsk3 inhibitor, Wnt inhibitor, and Gsk3 inhibitor (GiWiGi) is sufficient to produce cells expressing epicardial markers and exhibiting epicardial phenotypes with a high yield and purity from multiple hPSC lines in 16 d. Characterization of differentiated cells is performed via flow cytometry and immunostaining to assess quantitative expression and localization of epicardial cell-specific proteins. In vitro differentiation into fibroblasts and smooth muscle cells (SMCs) is also described. In addition, culture in the presence of transforming growth factor (TGF)-β inhibitors allows long-term expansion of hPSC-derived epicardial cells (for at least 25 population doublings). Functional human epicardial cells differentiated via this protocol may constitute a potential cell source for heart disease modeling, drug screening, and cell-based therapeutic applications.

  10. Note: Fully integrated active quenching circuit achieving 100 MHz count rate with custom technology single photon avalanche diodes

    NASA Astrophysics Data System (ADS)

    Acconcia, G.; Labanca, I.; Rech, I.; Gulinatti, A.; Ghioni, M.

    2017-02-01

    The minimization of Single Photon Avalanche Diodes (SPADs) dead time is a key factor to speed up photon counting and timing measurements. We present a fully integrated Active Quenching Circuit (AQC) able to provide a count rate as high as 100 MHz with custom technology SPAD detectors. The AQC can also operate the new red enhanced SPAD and provide the timing information with a timing jitter Full Width at Half Maximum (FWHM) as low as 160 ps.

  11. Note: Fully integrated active quenching circuit achieving 100 MHz count rate with custom technology single photon avalanche diodes.

    PubMed

    Acconcia, G; Labanca, I; Rech, I; Gulinatti, A; Ghioni, M

    2017-02-01

    The minimization of Single Photon Avalanche Diodes (SPADs) dead time is a key factor to speed up photon counting and timing measurements. We present a fully integrated Active Quenching Circuit (AQC) able to provide a count rate as high as 100 MHz with custom technology SPAD detectors. The AQC can also operate the new red enhanced SPAD and provide the timing information with a timing jitter Full Width at Half Maximum (FWHM) as low as 160 ps.

  12. Antifeedant and cytotoxic activity of longipinane derivatives.

    PubMed

    Cerda-García-Rojas, Carlos M; Burgueño-Tapia, Eleuterio; Román-Marín, Luisa U; Hernández-Hernández, Juan D; Agulló-Ortuño, Teresa; González-Coloma, Azucena; Joseph-Nathan, Pedro

    2010-02-01

    The polyoxygenated longipinane derivatives 1- 8 were tested as antifeedant compounds against the herbivorous insects Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae. Compounds 1-3 and 8 exhibited significant antifeedant activity against S. littoralis and M. persicae. The antifeedant activity against S. littoralis increased moderately after the C-8 hydroxy group in 3 was removed to afford 1 and increased strongly after the remaining two hydroxy groups were acetylated to afford 2. Compound 1 was active on M. persicae. Compounds 1, 3, and 4, with an unsaturated six-membered ring, exhibited an increase in post-ingestive effects on S. littoralis ranging from antifeedant in the case of 1 to toxic for compounds 3 and 4. These compounds did not have any phytotoxic effect on Lactuca sativa. When tested on a panel of tumoral cells, compounds 2 and 6 exhibited moderate selective cytotoxic effects on the p53 null lung carcinoma cells H1299, which were not affected by the drug paclitaxel. In addition, vibrational circular dichroism (VCD) was applied to the representative longipinene derivative 2 to verify its absolute configuration, and the sensitivity of the VCD methodology was evaluated by comparing spectra of the three diastereoisomers (4 R,5 S,7 R,9 R,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one (2), (4 R,5 S,7 S,9 R,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one, and (4 R,5 S,7 R,9 S,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one. Georg Thieme Verlag KG Stuttgart-New York.

  13. Shoulder and elbow muscle activity during fully supported trajectory tracking in neurologically intact older people.

    PubMed

    Hughes, A M; Freeman, C T; Burridge, J H; Chappell, P H; Lewin, P L; Pickering, R M; Rogers, E

    2009-12-01

    An inability to perform tasks involving reaching is a common problem for stroke patients. Knowledge of normal muscle activation patterns during these tasks is essential to the identification of abnormal patterns in post-stroke hemiplegia. Findings will provide insight into changes in muscle activation patterns associated with recovery of upper limb function. In this study with neurologically intact participants the co-ordination of shoulder and elbow muscle activity during two dimensional reaching tasks is explored. Eight participants undertook nine tracking tasks in which trajectory (orientation and length), duration, speed and resistance to movement were varied. The participants' forearm was supported using a hinged arm-holder, which constrained their hand to move in a two dimensional plane. EMG signals were recorded from triceps, biceps, anterior deltoid, upper, middle and lower trapezius and pectoralis major. A wide variation in muscle activation patterns, in terms of timing and amplitude, was observed between participants performing the same task. EMG amplitude increased significantly with length, duration and resistance of the task for all muscles except anterior deltoid. Co-activation between biceps and triceps was significantly dependent on both task and trajectory orientation. Activation pattern of pectoralis major was dependent on trajectory. Neither trajectory orientation nor task condition affected the activation pattern of anterior deltoid. Normal ranges of timing of muscle activity during the tasks were identified.

  14. Effect of (1-->3)- and (1-->4)-linkages of fully sulfated polysaccharides on their anticoagulant activity.

    PubMed

    Chaidedgumjorn, Amornrut; Toyoda, Hidenao; Woo, Eun Rhan; Lee, Kyung Bok; Kim, Yeong Shik; Toida, Toshihiko; Imanari, Toshio

    2002-05-13

    Chemically fully sulfated polysaccharides including xylan (-->4Xylbeta-(1-->4)Xylbeta1-->), amylose (-->4Glcalpha-(1-->4)Glcalpha1-->), cellulose (-->4Glcbeta-(1-->4)Glcbeta1-->), curdlan (-->3Glcbeta-(1-->3)Glcbeta1-->) and galactan (-->3Galbeta-(1-->3)Galbeta1-->), which have been isolated from Korean clam, were prepared, and their anticoagulant activity was investigated. The results strongly suggest that the activity might not be depending on anomeric configuration (alpha or beta) or monosaccharide species but on the glycosidic linkage, either (1-->3) or (1-->4). 1H NMR studies of these modified polysaccharides show that the neighboring sulfate groups at the C-2 and C-3 positions might have caused the conformational changes of each monosaccharide from 4C(1) to 1C(4). Furthermore, the effect of 6-sulfate residues on the anticoagulant activity was investigated using a specific desulfated reaction for the chemically fully sulfated polysaccharides. The 6-sulfate group is very important in determining anticoagulant activity of (1-->3)-linked polysaccharides, whereas the activity is not affected by presence or absence of the 6-sulfate group in (1-->4)-linked polysaccharides.

  15. Antibacterial and antioxidant activities in extracts of fully grown cladodes of 8 cultivars of cactus pear.

    PubMed

    Sánchez, E; Dávila-Aviña, J; Castillo, S L; Heredia, N; Vázquez-Alvarado, R; García, S

    2014-04-01

    The antimicrobial and antioxidant activities of some cultivars of the nopal cactus have not been determined. In this study, 8 cultivars of nopal cacti from Mexico were assayed for phenolic content, antioxidant activities, and antimicrobial activities against Campylobacter Jejuni, Vibrio cholera, and Clostridium Perfringens. Plant material was washed, dried, and macerated in methanol. Minimum bactericidal concentrations (MBCs) were determined using the broth microdilution method. Antioxidant activities were quantitatively determined using spectrophotometric methods. The MCBs of the nopal cacti ranged from 1.1 to 12.5 mg/mL for c. jejuni, 4.4 to 30 mg/mL for V. cholera, and 0.8 to 16 mg/mL for C. perfringens in the cultivars Cardon Blanco, Real de Catorce, and Jalpa, respectively. High quantities of total phenols and total flavonoids were found in the Jalpa cacti (3.80 mg of gallic acid equivalent GAE/g dry weight [DW] and 36.64 mg of quercetin equivalents [QE]/g DW, respectively). 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities (RSA) were correlated to bioactive compound contents. The Villanueva cacti had the highest %RSA at 42.31%, and the lowest activity was recorded in Copena V1 at 19.98%. In conclusion, we found that some of the 8 cactus pear cultivars studied may be used for their antioxidant compounds or antimicrobials to control or prevent the contamination of foods. © 2014 Institute of Food Technologists®

  16. "Oh, Chute??" A Fully Illustrated Booklet of Parachute Activities for Fun and Fitness.

    ERIC Educational Resources Information Center

    Evans, Doug

    Exercise and games performed with a parachute are outlined in this booklet. At school the parachute can be used on the playground or in the gymnasium. It may be used to teach locomotor and fundamental movements; to develop rhythm, coordination, and physical fitness; and encourage creative play. This activity is designed for groups, enhancing…

  17. "Oh, Chute??" A Fully Illustrated Booklet of Parachute Activities for Fun and Fitness.

    ERIC Educational Resources Information Center

    Evans, Doug

    Exercise and games performed with a parachute are outlined in this booklet. At school the parachute can be used on the playground or in the gymnasium. It may be used to teach locomotor and fundamental movements; to develop rhythm, coordination, and physical fitness; and encourage creative play. This activity is designed for groups, enhancing…

  18. Versatile strategy to access fully functionalized benzodifurans: redox-active chromophores for the construction of extended pi-conjugated materials.

    PubMed

    Yi, Chenyi; Blum, Carmen; Lehmann, Mario; Keller, Stephan; Liu, Shi-Xia; Frei, Gabriela; Neels, Antonia; Hauser, Jürg; Schürch, Stefan; Decurtins, Silvio

    2010-05-21

    An efficient synthetic approach to construct a fully substituted benzo[1,2-b:4,5-b']difuran (BDF) 2a via base-catalyzed double annulations is presented. Compound 2a can readily undergo Suzuki, Heck, and Sonogashira coupling reactions to afford in good yields a manifold of extended pi-conjugated BDF derivatives, e.g., with pyridine termini (4-6) and with different spacers. These are highly luminescent materials that undergo two reversible one-electron oxidations. Remarkably, their photophysical and electrochemical properties can be largely tuned by methylation or protonation. Consequently, they can function as pH-dependent fluorescence switches. Finally, the observed electronic properties are explained on the basis of density functional theory.

  19. NASA's Advanced Propulsion Technology Activities for Third Generation Fully Reusable Launch Vehicle Applications

    NASA Technical Reports Server (NTRS)

    Hueter, Uwe

    2000-01-01

    NASA's Office of Aeronautics and Space Transportation Technology (OASTT) established the following three major goals, referred to as "The Three Pillars for Success": Global Civil Aviation, Revolutionary Technology Leaps, and Access to Space. The Advanced Space Transportation Program Office (ASTP) at the NASA's Marshall Space Flight Center in Huntsville, Ala. focuses on future space transportation technologies under the "Access to Space" pillar. The Propulsion Projects within ASTP under the investment area of Spaceliner100, focus on the earth-to-orbit (ETO) third generation reusable launch vehicle technologies. The goals of Spaceliner 100 is to reduce cost by a factor of 100 and improve safety by a factor of 10,000 over current conditions. The ETO Propulsion Projects in ASTP, are actively developing combination/combined-cycle propulsion technologies that utilized airbreathing propulsion during a major portion of the trajectory. System integration, components, materials and advanced rocket technologies are also being pursued. Over the last several years, one of the main thrusts has been to develop rocket-based combined cycle (RBCC) technologies. The focus has been on conducting ground tests of several engine designs to establish the RBCC flowpaths performance. Flowpath testing of three different RBCC engine designs is progressing. Additionally, vehicle system studies are being conducted to assess potential operational space access vehicles utilizing combined-cycle propulsion systems. The design, manufacturing, and ground testing of a scale flight-type engine are planned. The first flight demonstration of an airbreathing combined cycle propulsion system is envisioned around 2005. The paper will describe the advanced propulsion technologies that are being being developed under the ETO activities in the ASTP program. Progress, findings, and future activities for the propulsion technologies will be discussed.

  20. Fully characterization of an active optical filter based on an equivalent-phase-shifted DFB-SOA

    NASA Astrophysics Data System (ADS)

    Deng, Ye; Li, Ming; Shi, Nuannuan; Tang, Jian; Sun, Shuqian; Zhang, Lihong; Li, Wei; Zhu, Ninghua

    2016-10-01

    A fully characterization of an active optical filter based on an equivalent-phase-shifted DFB-SOA has been theoretically analyzed and experimentally demonstrated in this paper. By employing an optical vector network analyzer (OVNA), transmission characteristics of the equivalent-phase-shifted DFB-SOA are obtained. The influences of driven current on transmission characteristics of the equivalent-phase-shifted DFB-SOA are also investigated. In addition to the advantage of integration, the proposed equivalent-phase-shifted DFB-SOA also shows significant application in design of photonic devices for all-optical signal processing and computing.

  1. Fully automated hybrid diode laser assembly using high precision active alignment

    NASA Astrophysics Data System (ADS)

    Böttger, Gunnar; Weber, Daniel; Scholz, Friedemann; Schröder, Henning; Schneider-Ramelow, Martin; Lang, Klaus-Dieter

    2016-03-01

    Fraunhofer IZM, Technische Universität Berlin and eagleyard Photonics present various implementations of current micro-optical assemblies for high quality free space laser beam forming and efficient fiber coupling. The laser modules shown are optimized for fast and automated assembly in small form factor packages via state-of-the-art active alignment machinery, using alignment and joining processes that have been developed and established in various industrial research projects. Operational wavelengths and optical powers ranging from 600 to 1600 nm and from 1 mW to several W respectively are addressed, for application in high-resolution laser spectroscopy, telecom and optical sensors, up to the optical powers needed in industrial and medical laser treatment.

  2. Q2122-444: A NAKED ACTIVE GALACTIC NUCLEUS FULLY DRESSED

    SciTech Connect

    Gliozzi, M.; Satyapal, S.; Panessa, F.; Franca, F. La; Saviane, I.; Monaco, L.; Foschini, L.; Kedziora-Chudczer, L.; Sambruna, R. M.

    2010-12-20

    Based on previous spectral and temporal optical studies, Q2122-444 has been classified as a naked active galactic nucleus (AGN) or true type 2 AGN, that is, an AGN that genuinely lacks a broad-line region (BLR). Its optical spectrum seemed to possess only narrow forbidden emission lines that are typical of type 2 (obscured) AGNs, but the long-term optical light curve, obtained from a monitoring campaign over more than two decades, showed strong variability, apparently ruling out the presence of heavy obscuration. Here we present the results from a {approx}40 ks XMM-Newton observation of Q2122-444 carried out to shed light on the energetics of this enigmatic AGN. The X-ray analysis was complemented with Australia Telescope Compact Array radio data to assess the possible presence of a jet, and with new NTT/EFOSC2 optical spectroscopic data to verify the actual absence of a BLR. The higher-quality optical data revealed the presence of strong and broad Balmer lines that are at odds with the previous spectral classification of this AGN. The lack of detection of radio emission rules out the presence of a jet. The X-ray data combined with simultaneous UV observations carried out by the Optical Monitor (OM) aboard XMM-Newton confirm that Q2122-444 is a typical type 1 AGN without any significant intrinsic absorption. New estimates of the black hole mass independently obtained from the broad Balmer lines and from a new scaling technique based on X-ray spectral data suggest that Q2122-444 is accreting at a relatively high rate in Eddington units.

  3. Synthesis of (-)-arctigenin derivatives and their anticancer activity.

    PubMed

    Gui-Rong, Chen; Li-Ping, Cai; De-Qiang, Dou; Ting-Guo, Kang; Hong-Fu, Li; Fu-Rui, Li; Ning, Jiang

    2012-01-01

    The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin, which was prepared from fructus arctii, showed obvious anticancer activity. The synthesis of four new (-)-arctigenin derivatives and their anticancer bioactivities were examined. The structures of the four new synthetic derivatives were elucidated.

  4. Deriving stellar inclination of slow rotators using stellar activity signal

    NASA Astrophysics Data System (ADS)

    Dumusque, Xavier

    2015-01-01

    Stellar inclination is an important parameter for many astrophysical studies. In the context of exoplanets, this allows us to derive the true obliquity of a system if the projected stellar spin-planetary orbit angle can measured via the Rossiter-Mclaughlin effect. Although different techniques allow us to estimate stellar inclination for fast rotators, it becomes much more difficult when stars are rotating slower than 2-2.5 km.s-1. By using the new activity simulation SOAP 2.0 that can reproduce the photometric and spectroscopic variations induced by stellar activity, we are able to fit the activity variation of solar-type stars and derive their inclination. The case of the equator-on star HD189733 will be presented, as well as the case of Alpha Centauri B, which present an inclination of 45+9-19 degrees, implying that the earth-mass orbiting planet is not transiting if aligned with its host star. Other exemples will also demonstrate the power of the technique, that can infer a stellar inclination, even for slow rotators like Alpha Centauri B, that present a projected rotational velocity smaller than 1.15 km.s-1. In addition, the SOAP 2.0 simulation can be used to correct for the effect of activity when one major active region is dominating the RV signal. This could enhance the detection of small mass exoplanets orbiting slightly active stars.This project is funded by ETAEARTH (European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement n. 313014), a transnational collaboration between European countries and the US (the Swiss Space Office, the Harvard Origin of Life Initiative, the Scottish Universities Physics Alliance, the University of Geneva, the Smithsonian Astrophysical Observatory, the Italian National Astrophysical Institute, the University of St. Andrews, Queens University Belfast, and the University of Edinburgh) setup to optimize the synergy between space-and ground-based data whose scientific potential for the characterization of

  5. Synthesis and antibacterial activity of 9-substituted minocycline derivatives.

    PubMed

    Sum, Phaik-Eng; Ross, Adma T; Petersen, Peter J; Testa, Raymond T

    2006-01-15

    A number of 9-acylamino and 9-sulfonylamino derivatives of minocycline have been synthesized for structure-activity relationship studies. These compounds showed activity against both tetracycline-susceptible and tetracycline-resistant strains. Many of the 9-sulfonylamino derivatives exhibited improved antibacterial activity against a number of tetracycline- and minocycline-resistant Gram-positive pathogens.

  6. Fully activated MEK1 exhibits compromised affinity for binding of allosteric inhibitors U0126 and PD0325901.

    PubMed

    Sheth, Payal R; Liu, Yuqi; Hesson, Thomas; Zhao, Jia; Vilenchik, Lev; Liu, Yan-Hui; Mayhood, Todd W; Le, Hung V

    2011-09-20

    Kinases catalyze the transfer of γ-phosphate from ATP to substrate protein residues triggering signaling pathways responsible for a plethora of cellular events. Isolation and production of homogeneous preparations of kinases in their fully active forms is important for accurate in vitro measurements of activity, stability, and ligand binding properties of these proteins. Previous studies have shown that MEK1 can be produced in its active phosphorylated form by coexpression with RAF1 in insect cells. In this study, using activated MEK1 produced by in vitro activation by RAF1 (pMEK1(in vitro)), we demonstrate that the simultaneous expression of RAF1 for production of activated MEK1 does not result in stoichiometric phosphorylation of MEK1. The pMEK1(in vitro) showed higher specific activity toward ERK2 protein substrate compared to the pMEK1 that was activated via coexpression with RAF1 (pMEK1(in situ)). The two pMEK1 preparations showed quantitative differences in the phosphorylation of T-loop residue serine 222 by Western blotting and mass spectrometry. Finally, pMEK1(in vitro) showed marked differences in the ligand binding properties compared to pMEK1(in situ). Contrary to previous findings, pMEK1(in vitro) bound allosteric inhibitors U0126 and PD0325901 with a significantly lower affinity than pMEK1(in situ) as well as its unphosphorylated counterpart (npMEK1) as demonstrated by thermal-shift, AS-MS, and calorimetric studies. The differences in inhibitor binding affinity provide direct evidence that unphosphorylated and RAF1-phosphorylated MEK1 form distinct inhibitor sites.

  7. Disconnecting the Yin and Yang Relation of Epidermal Growth Factor Receptor (EGFR)-Mediated Delivery: A Fully Synthetic, EGFR-Targeted Gene Transfer System Avoiding Receptor Activation

    PubMed Central

    Schäfer, A.; Pahnke, A.; Schaffert, D.; van Weerden, W.M.; de Ridder, C.M.A.; Rödl, W.; Vetter, A.; Spitzweg, C.; Kraaij, R.; Wagner, E.

    2011-01-01

    Abstract The epidermal growth factor receptor (EGFR) is upregulated within a high percentage of solid tumors and hence is an attractive target for tumor-targeted therapies including gene therapy. The natural EGFR ligand epidermal growth factor (EGF) has been used for this purpose, despite the risk of mitogenic effects due to EGFR activation. We have developed a fully synthetic, EGFR-targeted gene delivery system based on PEGylated linear polyethylenimine (LPEI), allowing evaluation of different EGFR-binding peptides in terms of transfection efficiency and EGFR activation. Peptide sequences directly derived from the human EGF molecule enhanced transfection efficiency with concomitant EGFR activation. Only the EGFR-binding peptide GE11, which has been identified by phage display technique, showed specific enhancement of transfection on EGFR-overexpressing tumor cells including glioblastoma and hepatoma, but without EGFR activation. EGFR targeting led to high levels of cell association of fluorescently labeled polyplexes after only 30 min of incubation. EGF pretreatment of cells induced enhanced cellular internalization of all polyplex types tested, pointing at generally enhanced macropinocytosis. EGF polyplexes diminished cell surface expression of EGFR for up to 4 hr, whereas GE11 polyplexes did not. In a clinically relevant orthotopic prostate cancer model, intratumorally injected GE11 polyplexes were superior in inducing transgene expression when compared with untargeted polyplexes. PMID:21644815

  8. Derivation of nonlinear Schroedinger equation for electrostatic and electromagnetic waves in fully relativistic two-fluid plasmas by the reductive perturbation method

    SciTech Connect

    Lee, Nam C.

    2012-08-15

    The reductive perturbation method is used to derive a generic form of nonlinear Schroedinger equation (NLSE) that describes the nonlinear evolution of electrostatic (ES)/electromagnetic (EM) waves in fully relativistic two-fluid plasmas. The matrix eigenvector analysis shows that there are two mutually exclusive modes of waves, each mode involving only either one of two electric potentials, A and {phi}. The general result is applied to the electromagnetic mode in electron-ion plasmas with relativistically high electron temperature (T{sub e} Much-Greater-Than m{sub e}c{sup 2}). In the limit of high frequency (ck Much-Greater-Than {omega}{sub e}), the NLSE predicts bump type electromagnetic soliton structures having width scaling as {approx}kT{sub e}{sup 5/2}. It is shown that, in electron-positron pair plasmas with high temperature, dip type electromagnetic solitons can exist. The NLSE is also applied to electrostatic (Langmuir) wave and it is shown that dip type solitons can exist if k{lambda}{sub D} Much-Less-Than 1, where {lambda}{sub D} is the electron's Debye length. For the k{lambda}{sub D} Much-Greater-Than 1, however, the solution is of bump type soliton with width scaling as {approx}1/(k{sup 5}T{sub e}). It is also shown that dip type solitons can exist in cold plasmas having relativistically high streaming speed.

  9. A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents

    PubMed Central

    Zheng, Weimin; Ycu, Edgar A.

    2012-01-01

    We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be investigated in a single task sequence. The unique feature of this system is a custom-made, acoustically transparent chamber that eliminates many of the issues associated with auditory cue control in most commercially available chambers. The ease with which operant devices can be added or replaced makes this system quite versatile, allowing for the implementation of a variety of auditory, visual, and olfactory behavioral tasks. Automation of the system allows fine temporal (10 ms) control and precise time-stamping of each event in a predesigned behavioral sequence. When combined with a multi-channel electrophysiology recording system, multiple cognitive brain functions, such as motivation, attention, decision-making, patience, and rewards, can be examined sequentially or independently. PMID:22588124

  10. Genotoxic activity of halogenated phenylglycine derivatives.

    PubMed

    Boto, Alicia; Gallardo, Juan A; Hernández, Rosendo; Ledo, Francisco; Muñoz, Ana; Murguía, José R; Menacho-Márquez, Mauricio; Orjales, Aurelio; Saavedra, Carlos J

    2006-12-01

    The discovery of genotoxic amino acids derived from phenylglycine, and possessing halogen substituents, is described. The utility of hypervalent iodine reagents in the synthesis of this class of compounds is highlighted. The mechanism of action of the (haloaryl)glycines was studied in Saccharomyces cerevisiae.

  11. Antiprotozoal activity of betulinic acid derivatives.

    PubMed

    Domínguez-Carmona, D B; Escalante-Erosa, F; García-Sosa, K; Ruiz-Pinell, G; Gutierrez-Yapu, D; Chan-Bacab, M J; Giménez-Turba, A; Peña-Rodríguez, L M

    2010-04-01

    Betulinic acid (1), isolated from the crude extract of the leaves of Pentalinon andrieuxii (Apocynaceae), together with betulinic acid acetate (2), betulonic acid (3), betulinic acid methyl ester (4), and betulin (5) were evaluated for their antiprotozoal activity. The results showed that modifying the C-3 position increases leishmanicidal activity while modification of the C-3 and C-28 positions decreases trypanocidal activity.

  12. Biological activities of water-soluble fullerene derivatives

    NASA Astrophysics Data System (ADS)

    Nakamura, S.; Mashino, T.

    2009-04-01

    Three types of water-soluble fullerene derivatives were synthesized and their biological activities were investigated. C60-dimalonic acid, an anionic fullerene derivative, showed antioxidant activity such as quenching of superoxide and relief from growth inhibition of E. coli by paraquat. C60-bis(7V,7V-dimethylpyrrolidinium iodide), a cationic fullerene derivative, has antibacterial activity and antiproliferative effect on cancer cell lines. The mechanism is suggested to be respiratory chain inhibition by reactive oxygen species produced by the cationic fullerene derivative. Proline-type fullerene derivatives showed strong inhibition activities on HIV-reverse transcriptase. The IC50 values were remarkably lower than nevirapine, a clinically used anti-HIV drug. Fullerene derivatives have a big potential for a new type of lead compound to be used as medicine.

  13. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    PubMed Central

    Hébert, Martin J. G.; Flewelling, Andrew J.; Clark, Trevor N.; Jean-François, Jacques; Surette, Marc E.; Gray, Christopher A.; Vogels, Christopher M.; Touaibia, Mohamed; Westcott, Stephen A.

    2015-01-01

    Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE. PMID:25834744

  14. Synthesis and biological activity of arylspiroborate salts derived from caffeic Acid phenethyl ester.

    PubMed

    Hébert, Martin J G; Flewelling, Andrew J; Clark, Trevor N; Levesque, Natalie A; Jean-François, Jacques; Surette, Marc E; Gray, Christopher A; Vogels, Christopher M; Touaibia, Mohamed; Westcott, Stephen A

    2015-01-01

    Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  15. Is the catalytic activity of triosephosphate isomerase fully optimized? An investigation based on maximization of entropy production.

    PubMed

    Bonačić Lošić, Željana; Donđivić, Tomislav; Juretić, Davor

    2017-03-01

    Triosephosphate isomerase (TIM) is often described as a fully evolved housekeeping enzyme with near-maximal possible reaction rate. The assumption that an enzyme is perfectly evolved has not been easy to confirm or refute. In this paper, we use maximization of entropy production within known constraints to examine this assumption by calculating steady-state cyclic flux, corresponding entropy production, and catalytic activity in a reversible four-state scheme of TIM functional states. The maximal entropy production (MaxEP) requirement for any of the first three transitions between TIM functional states leads to decreased total entropy production. Only the MaxEP requirement for the product (R-glyceraldehyde-3-phosphate) release step led to a 30% increase in enzyme activity, specificity constant kcat/KM, and overall entropy production. The product release step, due to the TIM molecular machine working in the physiological direction of glycolysis, has not been identified before as the rate-limiting step by using irreversible thermodynamics. Together with structural studies, our results open the possibility for finding amino acid substitutions leading to an increased frequency of loop six opening and product release.

  16. Influence of muscle activation and mucosal material property on esophageal transport: study based on a fully-resolved computational model

    NASA Astrophysics Data System (ADS)

    Kou, Wenjun; Pandolfino, John; Kahrilas, Peter; Patankar, Neelesh

    2014-11-01

    Esophageal transport involves interactions between food (bolus), the esophageal walls (composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers), and neurally coordinated muscle activation including CM contraction and LM shortening. Due to the complexity of these interactions, few studies have been conducted on the mechanical role of the mucosal layer in esophageal transport. Also poorly understood are the collaborative roles of CM contraction and LM shortening and the influence of their synchronization. Here, based on a fully-resolved computational model that we developed, we investigated the individual roles of CM contraction and LM shortening, compared bolus transport with various levels of discoordination between CM and LM activation, and studied the role of the mucosa and how its stiffening influenced transport. These preliminary findings should help understand the synergy between LM, CM, and the mucosal layer in facilitating bolus transport, thereby providing insight into related physiology and pathophysiology. The support of Grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

  17. Gene networks of fully connected triads with complete auto-activation enable multistability and stepwise stochastic transitions.

    PubMed

    Faucon, Philippe C; Pardee, Keith; Kumar, Roshan M; Li, Hu; Loh, Yuin-Han; Wang, Xiao

    2014-01-01

    Fully-connected triads (FCTs), such as the Oct4-Sox2-Nanog triad, have been implicated as recurring transcriptional motifs embedded within the regulatory networks that specify and maintain cellular states. To explore the possible connections between FCT topologies and cell fate determinations, we employed computational network screening to search all possible FCT topologies for multistability, a dynamic property that allows the rise of alternate regulatory states from the same transcriptional network. The search yielded a hierarchy of FCTs with various potentials for multistability, including several topologies capable of reaching eight distinct stable states. Our analyses suggested that complete auto-activation is an effective indicator for multistability, and, when gene expression noise was incorporated into the model, the networks were able to transit multiple states spontaneously. Different levels of stochasticity were found to either induce or disrupt random state transitioning with some transitions requiring layovers at one or more intermediate states. Using this framework we simulated a simplified model of induced pluripotency by including constitutive overexpression terms. The corresponding FCT showed random state transitioning from a terminal state to the pluripotent state, with the temporal distribution of this transition matching published experimental data. This work establishes a potential theoretical framework for understanding cell fate determinations by connecting conserved regulatory modules with network dynamics. Our results could also be employed experimentally, using established developmental transcription factors as seeds, to locate cell lineage specification networks by using auto-activation as a cipher.

  18. Gene Networks of Fully Connected Triads with Complete Auto-Activation Enable Multistability and Stepwise Stochastic Transitions

    PubMed Central

    Faucon, Philippe C.; Pardee, Keith; Kumar, Roshan M.; Li, Hu; Loh, Yuin-Han; Wang, Xiao

    2014-01-01

    Fully-connected triads (FCTs), such as the Oct4-Sox2-Nanog triad, have been implicated as recurring transcriptional motifs embedded within the regulatory networks that specify and maintain cellular states. To explore the possible connections between FCT topologies and cell fate determinations, we employed computational network screening to search all possible FCT topologies for multistability, a dynamic property that allows the rise of alternate regulatory states from the same transcriptional network. The search yielded a hierarchy of FCTs with various potentials for multistability, including several topologies capable of reaching eight distinct stable states. Our analyses suggested that complete auto-activation is an effective indicator for multistability, and, when gene expression noise was incorporated into the model, the networks were able to transit multiple states spontaneously. Different levels of stochasticity were found to either induce or disrupt random state transitioning with some transitions requiring layovers at one or more intermediate states. Using this framework we simulated a simplified model of induced pluripotency by including constitutive overexpression terms. The corresponding FCT showed random state transitioning from a terminal state to the pluripotent state, with the temporal distribution of this transition matching published experimental data. This work establishes a potential theoretical framework for understanding cell fate determinations by connecting conserved regulatory modules with network dynamics. Our results could also be employed experimentally, using established developmental transcription factors as seeds, to locate cell lineage specification networks by using auto-activation as a cipher. PMID:25057990

  19. Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2

    SciTech Connect

    Miao, H.-Q. . E-mail: hua-quan.miao@imclone.com; Hu, Kun; Jimenez, Xenia; Navarro, Elizabeth; Zhang, Haifan; Lu Dan; Ludwig, Dale L.; Balderes, Paul; Zhu Zhenping . E-mail: zhenping.zhu@imclone.com

    2006-06-23

    Compelling evidence suggest that vascular endothelial growth factor (VEGF) and its receptors, especially receptor 2 (VEGFR2, or kinase insert domain-containing receptor, KDR), play a critical role in angiogenesis under both physiological and pathological conditions, including cancer and angiogenic retinopathies such as age-related macular degeneration (AMD). To this end, inhibition of angiogenesis with antagonists to either VEGF or KDR has yielded significant therapeutic efficacy both in preclinical studies in animal models and in clinical trials in patients with cancer and AMD. We previously reported the identification of a high affinity, fully human anti-KDR antibody fragment, 1121B Fab, through a highly stringent affinity maturation process with a Fab originally isolated from a naive human antibody phage display library. In this study, we demonstrate that 1121B Fab is able to strongly block KDR/VEGF interaction, resulting in potent inhibition of an array of biological activities of VEGF, including activation of the receptor and its signaling pathway, intracellular calcium mobilization, and migration and proliferation of endothelial cells. Taken together, our data lend strong support to the further development of 1121B Fab fragment as an anti-angiogenesis agent in both cancer and angiogenic retinopathies.

  20. The fully synthetic MAG-Tn3 therapeutic vaccine containing the tetanus toxoid-derived TT830-844 universal epitope provides anti-tumor immunity.

    PubMed

    Laubreton, Daphné; Bay, Sylvie; Sedlik, Christine; Artaud, Cécile; Ganneau, Christelle; Dériaud, Edith; Viel, Sophie; Puaux, Anne-Laure; Amigorena, Sebastian; Gérard, Catherine; Lo-Man, Richard; Leclerc, Claude

    2016-03-01

    Malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. Of these carbohydrate antigens, the Tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. We designed MAG-Tn3, a fully synthetic vaccine based on three consecutive Tn moieties that are O-linked to a CD4+ T cell epitope, to induce anti-Tn antibody responses that could be helpful for therapeutic vaccination against cancer. To ensure broad coverage within the human population, the tetanus toxoid-derived peptide TT830-844 was selected as a T-helper epitope because it can bind to various HLA-DRB molecules. We showed that the MAG-Tn3 vaccine, which was formulated with the GSK proprietary immunostimulant AS15 and designed for human cancer therapy, is able to induce an anti-Tn antibody response in mice of various H-2 haplotypes, and this response correlates with the ability to induce a specific T cell response against the TT830-844 peptide. The universality of the TT830-844 peptide was extended to new H-2 and HLA-DRB molecules that were capable of binding this T cell epitope. Finally, the MAG-Tn3 vaccine was able to induce anti-Tn antibody responses in cynomolgus monkeys, which targeted Tn-expressing tumor cells and mediated tumor cell death both in vitro and in vivo. Thus, MAG-Tn3 is a highly promising anticancer vaccine that is currently under evaluation in a phase I clinical trial.

  1. Postbiotic activities of lactobacilli-derived factors.

    PubMed

    Cicenia, Alessia; Scirocco, Annunziata; Carabotti, Marilia; Pallotta, Lucia; Marignani, Massimo; Severi, Carola

    2014-01-01

    Probiotics are alive nonpathogenic microorganisms present in the gut microbiota that confer benefits to the host for his health. They act through molecular and cellular mechanisms that contrast pathogen bacteria adhesion, enhance innate immunity, decrease pathogen-induced inflammation, and promote intestinal epithelial cell survival, barrier function, and protective responses. Some of these beneficial effects result to be determined by secreted probiotic-derived factors that recently have been identified as "postbiotic" mediators. They have been reported for several probiotic strains but most available literature concerns Lactobacilli. In this review, we focus on the reported actions of several secretory products of different Lactobacillus species highlighting the available mechanistic data. The identification of soluble factors mediating the beneficial effects of probiotics may present an opportunity not only to understand their fine mechanisms of action, but also to develop effective pharmacological strategies that could integrate the action of treatments with live bacteria.

  2. Benzimidazole derivatives with atypical antiinflammatory activity.

    PubMed

    Lazer, E S; Matteo, M R; Possanza, G J

    1987-04-01

    A number of substituted 2-[(2,2,2-trifluoroethyl)sulfonyl]-1H-benzimidazoles (4) have demonstrated antiinflammatory activity that appears to have a mechanism distinct from typical cyclooxygenase inhibiting nonsteroidal antiinflammatory drugs. Several of these compounds inhibit adjuvant-induced arthritis in rats at 25 mg/kg while showing no activity in the carrageenan paw edema model at up to 100 mg/kg. Two compounds, 4a and 4b, showed no significant inhibition of cyclooxygenase in vitro at concentrations as high as 5 X 10(-5) M. All compounds 4 active in adjuvant-induced arthritis were also found to inhibit release of lysosomal enzymes from neutrophils, raising the possibility that their antiinflammatory effect is at least partially mediated by an effect on neutrophil function.

  3. The biomass derived activated carbon for supercapacitor

    NASA Astrophysics Data System (ADS)

    Senthilkumar, S. T.; Selvan, R. Kalai; Melo, J. S.

    2013-06-01

    In this work, the activated carbon was prepared from biowaste of Eichhornia crassipes by chemical activation method using KOH as the activating agent at various carbonization temperatures (600 °C, 700 °C and 800 °C). The disordered nature, morphology and surface functional groups of ACs were examined by XRD, SEM and FT-IR. The electrochemical properties of AC electrodes were studied in 1M H2SO4 in the potential range of -0.2 to 0.8 V using cyclic voltammetry (CV), galvanostatic charge-discharge and electrochemical impedance spectroscopy (EIS) techniques in a three electrode system. Subsequently, the fabricated supercapacitor using AC electrode delivered the higher specific capacitance and energy density of 509 F/g at current density of 1 mA/cm2 and 17 Wh/kg at power density of 0.416 W/g.

  4. Silica nanoparticles for the layer-by-layer assembly of fully electro-active cytochrome c multilayers

    PubMed Central

    2011-01-01

    discussed. Conclusions This study demonstrates the ability to construct fully electro-active cyt c multilayer assemblies by using carboxy-modified silica nanoparticles. Thus it can be shown that functional, artificial systems can be build up following natural examples of protein arrangements. The absence of any conductive properties in the second building block clearly demonstrates that mechanisms for electron transfer through such protein multilayer assemblies is based on interprotein electron exchange, rather than on wiring of the protein to the electrode. The construction strategy of this multilayer system provides a new controllable route to immobilize proteins in multiple layers featuring direct electrochemistry without mediating shuttle molecules and controlling the electro-active amount by the number of deposition steps. PMID:22208693

  5. A fully roll-to-roll gravure-printed carbon nanotube-based active matrix for multi-touch sensors

    NASA Astrophysics Data System (ADS)

    Lee, Wookyu; Koo, Hyunmo; Sun, Junfeng; Noh, Jinsoo; Kwon, Kye-Si; Yeom, Chiseon; Choi, Younchang; Chen, Kevin; Javey, Ali; Cho, Gyoujin

    2015-12-01

    Roll-to-roll (R2R) printing has been pursued as a commercially viable high-throughput technology to manufacture flexible, disposable, and inexpensive printed electronic devices. However, in recent years, pessimism has prevailed because of the barriers faced when attempting to fabricate and integrate thin film transistors (TFTs) using an R2R printing method. In this paper, we report 20 × 20 active matrices (AMs) based on single-walled carbon nanotubes (SWCNTs) with a resolution of 9.3 points per inch (ppi) resolution, obtained using a fully R2R gravure printing process. By using SWCNTs as the semiconducting layer and poly(ethylene terephthalate) (PET) as the substrate, we have obtained a device yield above 98%, and extracted the key scalability factors required for a feasible R2R gravure manufacturing process. Multi-touch sensor arrays were achieved by laminating a pressure sensitive rubber onto the SWCNT-TFT AM. This R2R gravure printing system overcomes the barriers associated with the registration accuracy of printing each layer and the variation of the threshold voltage (Vth). By overcoming these barriers, the R2R gravure printing method can be viable as an advanced manufacturing technology, thus enabling the high-throughput production of flexible, disposable, and human-interactive cutting-edge electronic devices based on SWCNT-TFT AMs.

  6. A Combined Random Forests and Active Contour Model Approach for Fully Automatic Segmentation of the Left Atrium in Volumetric MRI

    PubMed Central

    Luo, Gongning

    2017-01-01

    Segmentation of the left atrium (LA) from cardiac magnetic resonance imaging (MRI) datasets is of great importance for image guided atrial fibrillation ablation, LA fibrosis quantification, and cardiac biophysical modelling. However, automated LA segmentation from cardiac MRI is challenging due to limited image resolution, considerable variability in anatomical structures across subjects, and dynamic motion of the heart. In this work, we propose a combined random forests (RFs) and active contour model (ACM) approach for fully automatic segmentation of the LA from cardiac volumetric MRI. Specifically, we employ the RFs within an autocontext scheme to effectively integrate contextual and appearance information from multisource images together for LA shape inferring. The inferred shape is then incorporated into a volume-scalable ACM for further improving the segmentation accuracy. We validated the proposed method on the cardiac volumetric MRI datasets from the STACOM 2013 and HVSMR 2016 databases and showed that it outperforms other latest automated LA segmentation methods. Validation metrics, average Dice coefficient (DC) and average surface-to-surface distance (S2S), were computed as 0.9227 ± 0.0598 and 1.14 ± 1.205 mm, versus those of 0.6222–0.878 and 1.34–8.72 mm, obtained by other methods, respectively. PMID:28316992

  7. A fully roll-to-roll gravure-printed carbon nanotube-based active matrix for multi-touch sensors

    PubMed Central

    Lee, Wookyu; Koo, Hyunmo; Sun, Junfeng; Noh, Jinsoo; Kwon, Kye-Si; Yeom, Chiseon; Choi, Younchang; Chen, Kevin; Javey, Ali; Cho, Gyoujin

    2015-01-01

    Roll-to-roll (R2R) printing has been pursued as a commercially viable high-throughput technology to manufacture flexible, disposable, and inexpensive printed electronic devices. However, in recent years, pessimism has prevailed because of the barriers faced when attempting to fabricate and integrate thin film transistors (TFTs) using an R2R printing method. In this paper, we report 20 × 20 active matrices (AMs) based on single-walled carbon nanotubes (SWCNTs) with a resolution of 9.3 points per inch (ppi) resolution, obtained using a fully R2R gravure printing process. By using SWCNTs as the semiconducting layer and poly(ethylene terephthalate) (PET) as the substrate, we have obtained a device yield above 98%, and extracted the key scalability factors required for a feasible R2R gravure manufacturing process. Multi-touch sensor arrays were achieved by laminating a pressure sensitive rubber onto the SWCNT-TFT AM. This R2R gravure printing system overcomes the barriers associated with the registration accuracy of printing each layer and the variation of the threshold voltage (Vth). By overcoming these barriers, the R2R gravure printing method can be viable as an advanced manufacturing technology, thus enabling the high-throughput production of flexible, disposable, and human-interactive cutting-edge electronic devices based on SWCNT-TFT AMs. PMID:26635237

  8. Barbiturate bearing aroylhydrazine derivatives: Synthesis, NMR investigations, single crystal X-ray studies and biological activity

    NASA Astrophysics Data System (ADS)

    Giziroglu, Emrah; Sarikurkcu, Cengiz; Aygün, Muhittin; Basbulbul, Gamze; Soyleyici, H. Can; Firinci, Erkan; Kirkan, Bulent; Alkis, Ayse; Saylica, Tayfur; Biyik, Halil

    2016-03-01

    A series of barbituric acid aroylhydrazine derivatives have been prepared from their corresponding 1,3-dimethyl-5-acetyl barbituric acid and aroylhydrazines. All compounds have been fully characterized by using FT-IR, multinuclear NMR (1H, 13C) and Mass (MS) spectrometry. We also describe the X-ray crystal structure of 3a, which crystallizes in the monoclinic P21/n space group. The crystal structure is stabilized with infinite linear chains of dimeric units. Furthermore, all compounds were investigated for their tyrosinase inhibition, antioxidative and antimicrobial activies. The results from biological activity assays have shown that all of compounds have excellent antioxidant, significant tyrosinase inhibition and moderate antimicrobial activity.

  9. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.

    PubMed

    Guzman, Juan David

    2014-11-25

    Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  10. Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives.

    PubMed

    Yi, Yunpeng; Fu, Yunxing; Dong, Pengcheng; Qin, Wenwen; Liu, Yu; Liang, Jiangping; Shang, Ruofeng

    2017-06-15

    A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR), and High Resolution Mass Spectrometer (HRMS). Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus (VRE) in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, 3a, 3b, and 3f, displayed modest antibacterial activities. Compound 3a, the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of tiamulin fumarate. Moreover, molecular docking studies of 3a and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives.

  11. Evaluation of Drag Reduction via Superhydrophobic Surfaces and Active Gas Replenishment in a Fully-developed Turbulent Flow

    NASA Astrophysics Data System (ADS)

    Gose, James W.; Golovin, Kevin; Ceccio, Steven L.; Perlin, Marc; Tuteja, Anish

    2014-11-01

    The development of superhydrophobic surfaces (SHS) for skin-friction drag reduction in the laminar regime has shown great promise. A team led by the University of Michigan is examining the potential of similar SHS in high-speed naval applications. Specifically, we have developed a recirculating facility to investigate the reduction of drag along robustly engineered SHS in a fully-developed turbulent boundary layer flow. The facility can accommodate both small and large SHS samples in a test section 7 mm (depth) × 100 mm (span) × 1200 mm (length). Coupled with an 11.2 kilowatt pump and a 30:1 contraction, the facility is capable of producing an average flow velocity of 20 m/s, yielding a height based (7 mm) Reynolds number of 140,000. The SHS tested were designed for large-scale application. The present investigation shows skin-friction drag reduction for various sprayable and chemically developed SHS that were applied over a 100 mm (span) × 1100 mm (length) area. The drag measurement methods include pressure drop across the test specimen and PIV measured boundary layers. Additional SHS investigations include the implementation of active gas replenishment, providing an opportunity to replace gas-pockets that would otherwise be disrupted in traditional passive SHS due to high shear stress and turbulent pressure fluctuations. Gas is evenly distributed through a 90 mm (span) × 600 mm (length) sintered porous media with pore sizes of 10 to 100 microns. The impact of the active gas replenishment is being evaluated with and without SHS.

  12. Discovery of Fully Human Anti-MET Monoclonal Antibodies with Antitumor Activity against Colon Cancer Tumor Models In Vivo1

    PubMed Central

    van der Horst, Edward Htun; Chinn, Lawrence; Wang, Min; Velilla, Timothy; Tran, Hoang; Madrona, Yarrow; Lam, Andrew; Ji, May; Hoey, Timothy C; Sato, Aaron K

    2009-01-01

    The receptor tyrosine kinase MET is a major component controlling the invasive growth program in embryonic development and in invasive malignancies. The discovery of therapeutic antibodies against MET has been difficult, and antibodies that compete with hepatocyte growth factor (HGF) act as agonists. By applying phage technology and cell-based panning strategies, we discovered two fully human antibodies against MET (R13 and R28), which synergistically inhibit HGF binding to MET and elicit antibody-dependent cellular cytotoxicity. Cell-based phosphorylation assays demonstrate that R13 and R28 abrogate HGF-induced activation of MET, AKT1, ERK1/2, and HGF-induced migration and proliferation. FACS experiments suggest that the inhibitory effect is mediated by “locking” MET receptor in a state with R13, which then increases avidity of R28 for the extracellular domain of MET, thus blocking HGF binding without activating the receptor. In vivo studies demonstrate that the combination of R13/28 significantly inhibited tumor growth in various colon tumor xenograft models. Inhibition of tumor growth was associated with induction of hypoxia. Global gene expression analysis shows that inhibition of HGF/MET pathway significantly upregulated the tumor suppressors KLF6, CEACAM1, and BMP2, the negative regulator of phosphatidylinositol-3-OH-kinase PIK3IP1, and significantly suppressed SCF and SERPINE2, both enhancers of proliferation and invasiveness. Moreover, in an experimental metastasis model, R13/28 increased survival by preventing the recurrence of otherwise lethal lung metastases. Taken together, these results underscore the utility of a dual-antibody approach for targeting MET and possibly other receptor tyrosine kinases. Our approach could be expanded to drug discovery efforts against other cell surface proteins. PMID:19308290

  13. New pyridazinone derivatives with vasorelaxant and platelet antiaggregatory activities.

    PubMed

    Costas, Tamara; Besada, Pedro; Piras, Alessandro; Acevedo, Laura; Yañez, Matilde; Orallo, Francisco; Laguna, Reyes; Terán, Carmen

    2010-11-15

    New 6-substituted and 2,6-disubstituted pyridazinone derivatives were obtained starting from easily accessible alkyl furans by using oxidation with singlet oxygen to give 4-methoxy or 4-hydroxybutenolides, key intermediates of this synthetic strategy. The new pyridazinone derivatives have been studied as vasorelaxant and antiplatelet agents. Analysis of biological data revealed the silyl ethers (4a-i) and N,O-dibenzyl derivatives (6g-i) as the most active compounds.

  14. Synthesis and anti-inflammatory activities of novel dihydropyranoaurone derivatives.

    PubMed

    Wang, Zheng; Bae, Eun Ju; Han, Young Taek

    2017-04-10

    A novel series of dihydropyranoaurone derivatives were synthesized and evaluated as potential anti-inflammatory agents. Late-stage derivatization by versatile piperazine-catalyzed aldol reaction between dihydropyanobenzofuran intermediate 2 and diverse aldehydes readily afforded the novel dihydropyranoaurone analogs. Evaluation of the synthesized dihydropyranoaurone derivatives and related compounds regarding their inhibiting inducible nitric oxide synthase and nitrite production of lipopolysaccaride-stimulated RAW 264.7 cells provided insight into the structure-activity relationship of aurone derivatives.

  15. Synthesis of active nitroguaiacol ether derivatives of streptomycin.

    PubMed Central

    Abad, J P; Amils, R

    1990-01-01

    The synthesis, purification, and biological properties of nitroguaiacol ether derivatives of streptomycin and their corresponding radioactive reduced products were examined. These derivatives are biologically active against gram-positive and gram-negative eubacteria and they are also photoreactive because of the presence of the nitroguaiacol group in the molecule. We demonstrated that these derivatives can be used as streptomycin analogs in photoaffinity labeling of the macromolecular structures related to the mode of action of the antibiotic. Images PMID:2127172

  16. Assessment of antiprotease activity of some carbamate derivatives.

    PubMed

    Shinogi, M; Agha, B J; Tsuji, K; Digenis, G A

    1985-04-01

    Six carbamate derivatives were tested for inhibitory activity towards porcine pancreatic elastase, trypsin, and chymotrypsin. Only three esters that are isatoic anhydride derivatives were found to inhibit elastase competitively but nonspecifically. KI values for the best two inhibitors were determined from Dixon plots.

  17. Dehydroepiandrosterone Derivatives as Potent Antiandrogens With Marginal Agonist Activity

    DTIC Science & Technology

    2011-07-01

    physiological metabolite from dehydroepiandrosterone ( DHEA ) and a precursor of testosterone, has an intrinsic androgenic activity which was not...antiandrogenic compounds with marginal androgenic activities need to be identified. Our hypothesis in the current project was that DHEA metabolites or their...ones. We previously screened DHEA derivatives/metabolites for their androgenic and antiandrogenic activities and found that three compounds, 3β

  18. Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

    DTIC Science & Technology

    2012-07-01

    a physiological metabolite from dehydroepiandrosterone ( DHEA ) and a precursor of testosterone, has an intrinsic androgenic activity which was not...antiandrogenic compounds with marginal androgenic activities need to be identified. Our hypothesis in the current project was that DHEA metabolites or...available ones. We previously screened DHEA derivatives/metabolites for their androgenic and antiandrogenic activities and found that three compounds, 3β

  19. Phosphorus Determination by Derivative Activation Analysis: A Multifaceted Radiochemical Application.

    ERIC Educational Resources Information Center

    Kleppinger, E. W.; And Others

    1984-01-01

    Although determination of phosphorus is important in biology, physiology, and environmental science, traditional gravimetric and colorimetric methods are cumbersome and lack the requisite sensitivity. Therefore, a derivative activation analysis method is suggested. Background information, procedures, and results are provided. (JN)

  20. Phosphorus Determination by Derivative Activation Analysis: A Multifaceted Radiochemical Application.

    ERIC Educational Resources Information Center

    Kleppinger, E. W.; And Others

    1984-01-01

    Although determination of phosphorus is important in biology, physiology, and environmental science, traditional gravimetric and colorimetric methods are cumbersome and lack the requisite sensitivity. Therefore, a derivative activation analysis method is suggested. Background information, procedures, and results are provided. (JN)

  1. Antioxidant and antimicrobial activities of cinnamic acid derivatives.

    PubMed

    Sova, M

    2012-07-01

    Cinnamic acid is an organic acid occurring naturally in plants that has low toxicity and a broad spectrum of biological activities. In the search for novel pharmacologically active compounds, cinnamic acid derivatives are important and promising compounds with high potential for development into drugs. Many cinnamic acid derivatives, especially those with the phenolic hydroxyl group, are well-known antioxidants and are supposed to have several health benefits due to their strong free radical scavenging properties. It is also well known that cinnamic acid has antimicrobial activity. Cinnamic acid derivatives, both isolated from plant material and synthesized, have been reported to have antibacterial, antiviral and antifungal properties. Acids, esters, amides, hydrazides and related derivatives of cinnamic acid with such activities are here reviewed.

  2. Synthesis and in vitro antiproliferative activities of quinoline derivatives.

    PubMed

    Broch, Sidonie; Aboab, Bettina; Anizon, Fabrice; Moreau, Pascale

    2010-04-01

    The synthesis of new di- and trimeric quinoline derivatives is described as well as their in vitro antiproliferative activities toward a human fibroblast primary culture and two human solid cancer cell lines (MCF-7 and PA 1).

  3. 20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... War II active military or naval service. We consider that a person, who was not otherwise fully... States during World War II; (b) The person died within three years after separation from service...

  4. 20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... War II active military or naval service. We consider that a person, who was not otherwise fully... States during World War II; (b) The person died within three years after separation from service...

  5. 20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... War II active military or naval service. We consider that a person, who was not otherwise fully... States during World War II; (b) The person died within three years after separation from service...

  6. 20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... War II active military or naval service. We consider that a person, who was not otherwise fully... States during World War II; (b) The person died within three years after separation from service...

  7. 20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... War II active military or naval service. We consider that a person, who was not otherwise fully... States during World War II; (b) The person died within three years after separation from service...

  8. The Antioxidant Activity of New Coumarin Derivatives

    PubMed Central

    Kadhum, Abdul Amir H.; Al-Amiery, Ahmed A.; Musa, Ahmed Y.; Mohamad, Abu Bakar

    2011-01-01

    The antioxidant activity of two synthesized coumarins namely, N-(4,7-dioxo-2- phenyl-1,3-oxazepin-3(2H,4H,7H)-yl)-2-(2-oxo-2H-chromen-4-yloxy)acetamide 5 and N-(4-oxo-2-phenylthiazolidin-3-yl)-2-(2-oxo-2H-chromen-4-yloxy)acetamide 6 were studied with the DPPH, hydrogen peroxide and nitric oxide radical methods and compared with the known antioxidant ascorbic acid. Compounds 5 and 6 were synthesized in a good yield from the addition reaction of maleic anhydride or mercaptoacetic acid to compound 4, namely N′-benzylidene-2-(2-oxo-2H-chromen-4-yloxy)acetohydrazide. Compound 4 was synthesized by the condensation of compound 3, namely 2-(2-oxo-2H-chromen-4-yloxy) acetohydrazide, with benzaldehyde. Compound 3, however, was synthesized from the addition of hydrazine to compound 2, namely ethyl 2-(2-oxo-2H-chromen-4-yloxy)acetate, which was synthesized from the reaction of ethyl bromoacetate with 4-hydroxycoumarin 1. Structures for the synthesized coumarins 2–6 are proposed on the basis of spectroscopic evidence. PMID:22016624

  9. In vitro antioxidant activity study of novel chromone derivatives.

    PubMed

    Phosrithong, Narumol; Samee, Weerasak; Nunthanavanit, Patcharawee; Ungwitayatorn, Jiraporn

    2012-06-01

    Forty-eight chromone derivatives were evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, ferrous ions (Fe(2+) ) chelating activity test, total antioxidant activity test (Ferric thiocyanate and Thiobarbituric acid methods), and total reductive capability (potassium ferricyanide reduction). 7,8-Dihydroxy-2-(3'-trifluoromethylphenyl)-3-(3″-trifluoromethylbenzoyl) chromone 32 showed stronger radical scavenging and metal chelating activities than butylated hydroxytoluene, vitamin E, and trolox. Chromone derivatives that exhibited good radical scavenging and metal chelating also displayed strong total antioxidant and reductive power activities. The results obtained from this study indicated that the synthesized chromone derivatives have remarkable antioxidant activity. © 2012 John Wiley & Sons A/S.

  10. Synthesis of 13-amino telekin derivatives and their cytotoxic activity.

    PubMed

    Wang, Xiujie; Zhang, Xiumei; Zheng, Beibei; Hu, Nan; Xie, Weidong; Row, Kyungho

    2015-01-01

    Telekin is a eudesmane sesquiterpene-lactone naturally occurring in many medicinal plants with antitumour and anti-inflammatory activity. In this study, a series of 13-amino derivatives of telekin have been synthesised through Michael addition reaction, and their relative configurations were exemplified by the single crystal X-ray diffraction of the dimethylamine adduct. The in vitro cytotoxicity against three tumour cell lines of these amine derivatives was evaluated. The piperidine and 4-hydroxypiperidine adducts displayed stronger cytotoxic activity than telekin.

  11. JAK3/STAT6 Stimulates Bone Marrow-Derived Fibroblast Activation in Renal Fibrosis.

    PubMed

    Yan, Jingyin; Zhang, Zhengmao; Yang, Jun; Mitch, William E; Wang, Yanlin

    2015-12-01

    Renal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow-derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow-derived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of α-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6(+/+) bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow-derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development.

  12. Cytotoxic activities of some benzothiazole-piperazine derivatives.

    PubMed

    Gurdal, Enise Ece; Durmaz, Irem; Cetin-Atalay, Rengul; Yarim, Mine

    2015-01-01

    Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Compound 1d is highly cytotoxic against all tested cancer cell lines. Further investigation of compound 1d by Hoechst Staining and Fluorescence-Activated Cell Sorting Analysis (FACS) revealed that this compound causes apoptosis by cell cycle arrest at subG1 phase.

  13. Synthesis and hypoglycemic activity of some new theophylline derivatives.

    PubMed

    Alafeefy, Ahmed M; Alqasoumi, Saleh I; Abdel Hamid, Sami G; El-Tahir, Kamal E H; Mohamed, Menshawy; Zain, Mohamed E; Awaad, Amani S

    2014-06-01

    Thirty-one new theophylline derivatives have been synthesized and evaluated for their hypoglycemic activity. Compounds 24 (56% reduction) and 31 (57% reduction) showed better hypoglycemic activity than the standard drug glibenclamide which showed 52% reduction in serum glucose level. Compound 27 remarkably reduced serum glucose level by 53%. Ten compounds showed varying degrees of hypoglycemic activity ranging from 20 to 37% reduction in serum glucose level compared to the standard drug. The aromatic amide functionality is the common feature of these theophylline hypoglycemic derivatives. However, anthranilamide and or aliphatic amides proved to be the least active compounds in the present series.

  14. Fully Internally Contracted Multireference Configuration Interaction Theory Using Density Matrix Renormalization Group: A Reduced-Scaling Implementation Derived by Computer-Aided Tensor Factorization.

    PubMed

    Saitow, Masaaki; Kurashige, Yuki; Yanai, Takeshi

    2015-11-10

    We present an extended implementation of the multireference configuration interaction (MRCI) method combined with the quantum-chemical density matrix renormalization group (DMRG). In the previous study, we introduced the combined theory, referred to as DMRGMRCI, as a method to calculate high-level dynamic electron correlation on top of the DMRG wave function that accounts for active-space (or strong) correlation using a large number of active orbitals. The DMRG-MRCI method is built on the full internal-contraction scheme for the compact reference treatment and on the cumulant approximation for the treatment of the four-particle rank reduced density matrix (4-RDM). The previous implementation achieved the MRCI calculations with the active space (24e,24o), which are deemed the record largest, whereas the inherent Nact 8 × N complexity of computation was found a hindrance to using further large active space. In this study, an extended optimization of the tensor contractions is developed by explicitly incorporating the rank reduction of the decomposed form of the cumulant-approximated 4-RDM into the factorization. It reduces the computational scaling (to Nact7 × N) as well as the cache-miss penalty associated with direct evaluation of complex cumulant reconstruction. The present scheme, however, faces the increased complexity of factorization patterns for optimally implementing the tensor contraction terms involving the decomposed 4-RDM objects. We address this complexity using the enhanced symbolic manipulation computer program for deriving and coding programmable equations. The new DMRG-MRCI implementation is applied to the determination of the stability of the iron(IV)-oxo porphyrin relative to the iron(V) electronic isomer (electromer) using the active space (29e,29o) (including four second d-shell orbitals of iron) with triple-ζ-quality atomic orbital basis sets. The DMRG-cu(4)-MRCI+Q model is shown to favor the triradicaloid iron(IV)-oxo state as the lowest

  15. Design, synthesis and insecticidal activity of novel phenylurea derivatives.

    PubMed

    Sun, Jialong; Zhou, Yuanming

    2015-03-19

    A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and 1H-NMR spectral data. All of the compounds were evaluated for the insecticidal activity against the third instars larvae of Spodoptera exigua Hiibner, Plutella xyllostella Linnaeus, Helicoverpa armigera Hubner and Pieris rapae Linne respectively, at the concentration of 10 mg/L. The results showed that all of the derivatives displayed strong insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, chlorbenzuron and metaflumizone. Among the synthesized compounds, 3b, 3d, 3f, 4b and 4g displayed broad spectrum insecticidal activity.

  16. Anticancer activities of bovine and human lactoferricin-derived peptides.

    PubMed

    Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

    2017-02-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

  17. Modulating rheological and degradation properties of temperature-responsive gelling systems composed of blends of PCLA-PEG-PCLA triblock copolymers and their fully hexanoyl-capped derivatives.

    PubMed

    Petit, Audrey; Müller, Benno; Bruin, Peter; Meyboom, Ronald; Piest, Martin; Kroon-Batenburg, Loes M J; de Leede, Leo G J; Hennink, Wim E; Vermonden, Tina

    2012-12-01

    In this study, the ability to modulate rheological and degradation properties of temperature-responsive gelling systems composed of aqueous blends of poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) triblock copolymers (i.e. uncapped) and their fully capped derivatives was investigated. Uncapped and capped PCLA-PEG-PCLA triblock copolymers, abbreviated as degree of modification 0 and 2 (DM0 and DM2, respectively), were composed of identical PCLA and PEG blocks but different end groups: namely hydroxyl and hexanoyl end groups. DM0 was synthesized by ring opening polymerization of l-lactide and ε-caprolactone in toluene using PEG as initiator and tin(II) 2-ethylhexanoate as the catalyst. A portion of DM0 was subsequently reacted with an excess of hexanoyl chloride in solution to yield DM2. The cloud point and phase behaviour of DM0 and DM2 in buffer as well as that of their blends were determined by light scattering in a diluted state and by vial tilting and rheological measurements in a concentrated state. Degradation/dissolution properties of temperature-responsive gelling systems were studied in vitro at pH 7.4 and 37°C. The cloud points of DM0/DM2 blends were ratio-dependent and could be tailored from 15 to 40°C for blends containing 15 to 100wt.% DM0. Vial tilting and rheological experiments showed that, with solid contents between 20 and 30wt.%, DM0/DM2 blends (15/85 to 25/75w/w) had a sol-to-gel transition temperature at 10-20°C, whereas blends with less than 15wt.% DM0 formed gels below 4°C and the ones with more than 25wt.% DM0 did not show a sol-to-gel transition up to 50°C. Complete degradation of temperature-responsive gelling systems took ∼100days, independent of the DM0 fraction and the initial solid content. Analysis of residual gels in time by GPC and (1)H-NMR showed no chemical polymer degradation, but indicated gel degradation by dissolution. Preferential dissolution of lactoyl

  18. The antibacterial activity of honey derived from Australian flora.

    PubMed

    Irish, Julie; Blair, Shona; Carter, Dee A

    2011-03-28

    Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57%) of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla), jarrah (Eucalyptus marginata) and jellybush (Leptospermum polygalifolium). In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8%) samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4 °C than at 25 °C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25 °C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted.

  19. The Antibacterial Activity of Honey Derived from Australian Flora

    PubMed Central

    Irish, Julie; Blair, Shona; Carter, Dee A.

    2011-01-01

    Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57%) of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla), jarrah (Eucalyptus marginata) and jellybush (Leptospermum polygalifolium). In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8%) samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4°C than at 25°C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25°C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted. PMID:21464891

  20. Urea and carbamate derivatives of primaquine: synthesis, cytostatic and antioxidant activities.

    PubMed

    Simunović, M; Perković, I; Zorc, B; Ester, K; Kralj, M; Hadjipavlou-Litina, D; Pontiki, E

    2009-08-01

    The novel urea primaquine derivatives 3 were prepared by aminolysis of primaquine benzotriazolide 2 with several hydroxyamines and ethylendiamine, while carbamates 4 were synthesized from the same precursor 2 and alcohols. All compounds are fully chemically characterized and evaluated for their cytostatic and antioxidant activities. The most prominent antiproliferative activity was obtained by compounds 3c, 3d, 3g, and 5b (IC(50)=9-40 microM). 1-(5-Hydroxypentyl)-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]urea (3c) showed extreme selectivity toward SW 620 colon cancer cells (IC(50)=0.2 microM) and a bit less toward lung cancer cells H 460. Hydroxyurea 3h showed the highest interaction with DPPH. Primaquine twin drug 3g showed very significant inhibition on LOX soybean (IC(50)=62 microM). Almost all the tested derivatives highly inhibited lipid peroxidation, significantly stronger than primaquine phosphate.

  1. Novel pleuromutilin derivatives with excellent antibacterial activity against Staphylococcus aureus.

    PubMed

    Xu, Peng; Zhang, Yuan-Yuan; Sun, Yong-Xue; Liu, Jian-Hua; Yang, Bing; Wang, Yu-Zhong; Wang, Yu-Liang

    2009-06-01

    Ten novel pleuromutilin derivatives with thioether moiety and heterocyclic carboxamide or chloroformate group in the side chain were synthesized and confirmed by (1)H NMR, IR and HRMS. The results of the antibacterial activity showed that the title compounds had excellent antibacterial activity against Staphylococcus aureus, among which the MIC of 5f reached 0.03125 microg/mL.

  2. Surface active properties of chitosan and its derivatives.

    PubMed

    Elsabee, Maher Z; Morsi, Rania Elsayed; Al-Sabagh, A M

    2009-11-01

    This review discusses the definition of surface active agents and specifically natural polymeric surface active agents. Chitosan by itself was found to have weak surface activity since it has no hydrophobic segments. Chemical modifications of chitosan could improve such surface activity. This is achieved by introducing hydrophobic substituents in its glucosidic group. Several examples of chitosan derivatives with surfactant activity have been surveyed. The surface active polymers form micelles and aggregates which have enormous importance in the entrapment of water-insoluble drugs and consequently applications in the controlled drug delivery and many biomedical fields. Chitosan also interacts with several substrates by electrostatic and hydrophobic interactions with considerable biomedical applications.

  3. A fully Bayesian approach to the parcel-based detection-estimation of brain activity in fMRI.

    PubMed

    Makni, Salima; Idier, Jérôme; Vincent, Thomas; Thirion, Bertrand; Dehaene-Lambertz, Ghislaine; Ciuciu, Philippe

    2008-07-01

    Within-subject analysis in fMRI essentially addresses two problems, i.e., the detection of activated brain regions in response to an experimental task and the estimation of the underlying dynamics, also known as the characterisation of Hemodynamic response function (HRF). So far, both issues have been treated sequentially while it is known that the HRF model has a dramatic impact on the localisation of activations and that the HRF shape may vary from one region to another. In this paper, we conciliate both issues in a region-based joint detection-estimation framework that we develop in the Bayesian formalism. Instead of considering function basis to account for spatial variability, spatially adaptive General Linear Models are built upon region-based non-parametric estimation of brain dynamics. Regions are first identified as functionally homogeneous parcels in the mask of the grey matter using a specific procedure [Thirion, B., Flandin, G., Pinel, P., Roche, A., Ciuciu, P., Poline, J.-B., August 2006. Dealing with the shortcomings of spatial normalization: Multi-subject parcellation of fMRI datasets. Hum. Brain Mapp. 27 (8), 678-693.]. Then, in each parcel, prior information is embedded to constrain this estimation. Detection is achieved by modelling activating, deactivating and non-activating voxels through mixture models within each parcel. From the posterior distribution, we infer upon the model parameters using Markov Chain Monte Carlo (MCMC) techniques. Bayesian model comparison allows us to emphasize on artificial datasets first that inhomogeneous gamma-Gaussian mixture models outperform Gaussian mixtures in terms of sensitivity/specificity trade-off and second that it is worthwhile modelling serial correlation through an AR(1) noise process at low signal-to-noise (SNR) ratio. Our approach is then validated on an fMRI experiment that studies habituation to auditory sentence repetition. This phenomenon is clearly recovered as well as the hierarchical temporal

  4. West Nile virus-infected human dendritic cells fail to fully activate invariant natural killer T cells.

    PubMed

    Kovats, S; Turner, S; Simmons, A; Powe, T; Chakravarty, E; Alberola-Ila, J

    2016-11-01

    West Nile virus (WNV) infection is a mosquito-borne zoonosis with increasing prevalence in the United States. WNV infection begins in the skin, and the virus replicates initially in keratinocytes and dendritic cells (DCs). In the skin and cutaneous lymph nodes, infected DCs are likely to interact with invariant natural killer T cells (iNKTs). Bidirectional interactions between DCs and iNKTs amplify the innate immune response to viral infections, thus controlling viral load and regulating adaptive immunity. iNKTs are stimulated by CD1d-bound lipid antigens or activated indirectly by inflammatory cytokines. We exposed human monocyte-derived DCs to WNV Kunjin and determined their ability to activate isolated blood iNKTs. DCs became infected as judged by synthesis of viral mRNA and Envelope and NS-1 proteins, but did not undergo significant apoptosis. Infected DCs up-regulated the co-stimulatory molecules CD86 and CD40, but showed decreased expression of CD1d. WNV infection induced DC secretion of type I interferon (IFN), but no or minimal interleukin (IL)-12, IL-23, IL-18 or IL-10. Unexpectedly, we found that the WNV-infected DCs stimulated human iNKTs to up-regulate CD69 and produce low amounts of IL-10, but not proinflammatory cytokines such as IFN-γ or tumour necrosis factor (TNF)-α. Both CD1d and IFNAR blockade partially abrogated this iNKT response, suggesting involvement of a T cell receptor (TCR)-CD1d interaction and type I interferon receptor (IFNAR) signalling. Thus, WNV infection interferes with DC-iNKT interactions by preventing the production of proinflammatory cytokines. iNKTs may be a source of IL-10 observed in human flavivirus infections and initiate an anti-inflammatory innate response that limits adaptive immunity and immune pathology upon WNV infection. © 2016 British Society for Immunology.

  5. Synthesis and antibacterial activity evaluation of two androgen derivatives.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer

    2015-01-01

    In this study two androgen derivatives were synthesized using several strategies; the first stage an aza-steroid derivative (3) was developed by the reaction of a testosterone derivative (1) with thiourea (2) in presence of hydrogen chloride. The second step, involves the synthesis of an amino-steroid derivative (4) by the reaction of 1 with 2 using boric acid as catalyst. The third stage was achieved by the preparation of an aminoaza-androgen derivative (6) by the reaction of 3 with ethylenediamine using boric acid as catalyst. In addition, the compound 6 was made reacting with dihydrotestosterone to form a new androgen derivative (7) in presence of boric acid. The following step was achieved by the reaction of 7 with chloroacetyl chloride to synthesize an azetidinone-androgen derivative (8) using triethylamine as catalyst. Additionally, a thiourea-androgen derivative (9) was synthetized by the reaction of 4 with dihydrotestosterone using boric acid as catalyst. Finally, the compound 9 was made reacting with chloroacetyl chloride in presence of triethylamine to synthesize a new azetidinone-androgen derivative (10). On the other hand, antibacterial activity of compounds synthesized was evaluated on Gram negative (Escherichia coli and Vibrio cholerae) and Gram positive (Staphylococos aureus) bacteria. The results indicate that only the compound 3 and 8 decrease the growth bacterial of E. coli and V. cholerae. Nevertheless, growth bacterial of S. aureus was not inhibited by these compounds. These data indicate that antibacterial activity exerted by the compounds 3 and 8 depend of their structure chemical in comparison with the controls and other androgen derivatives that are involved in this study.

  6. Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

    PubMed Central

    Sikora, Karol; Woziwodzka, Anna; Piosik, Jacek; Podgórska, Beata

    2016-01-01

    Summary This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyranosides with an elongated hydrophobic hydrocarbon chain. The new N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides and their O-acetyl derivatives were analyzed via 1H and 13C NMR spectroscopy. The mutagenic activity of the newly synthesized QAS was investigated using two different techniques: The Vibrio harveyi luminescence assay and the Ames test. The obtained results support previous findings contesting QAS safety and indicate that QAS, specifically pyridinium derivatives, might be mutagenic. PMID:27559394

  7. Preparation Methods and Antioxidant Activities of Polysaccharides and Their Derivatives.

    PubMed

    Mei, Xinya; Yi, Chengkun; Huang, Gangliang

    2017-01-01

    In recent years, the antioxidant effects of polysaccharides have become a hot spot in the field of polysaccharide research. Herein, the action mechanisms of polysaccharide antioxidation and scavenging free radicals were analyzed. The research progresses on the preparation methods and antioxidant properties of polysaccharides and their derivatives were summarized. Investigating the antioxidant activities of polysaccharides and their derivatives can find useful polysaccharides and their derivatives, which have great potential as natural antioxidants used in functional foods or medicines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Ultrasonics in isocyanide-based multicomponent reactions: a new, efficient and fast method for the synthesis of fully substituted 1,3,4-oxadiazole derivatives under ultrasound irradiation.

    PubMed

    Rouhani, Morteza; Ramazani, Ali; Joo, Sang Woo

    2015-01-01

    A fast and convenient approach to the synthesis of fully substituted 1,3,4-oxadiazoles via three-component reaction of aromatic carboxylic acids, acenaphthoquinone, and (N-isocyanimino)triphenylphosphorane under ultrasound irradiation is described. Furthermore, a series of compounds were synthesized and characterized by melting point, IR, NMR and MS. Utilization of easy reaction conditions, very high to excellent yields, and short reaction times makes this manipulation potentially very useful.

  9. Praziquantel derivatives with antischistosomal activity: aromatic ring modification.

    PubMed

    Wang, Zhi-xia; Chen, Jing-lei; Qiao, Chunhua

    2013-08-01

    A series of aromatic ring-modified praziquantel derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin. Several analogs comparable in activity to the drug praziquantel have been identified based on in vitro and in vivo japonuicum schistosomes worm viability assay. Structure and activity relationship of these praziquantel aromatic ring-modified compounds was revealed. Specifically, a compound in which a bromine has been introduced in the aromatic ring of praziquantel demonstrated close antischistosomal activity to praziquantel in vivo.

  10. Anti-Trichomonas vaginalis activity of betulinic acid derivatives.

    PubMed

    Hübner, Dariana Pimentel Gomes; de Brum Vieira, Patrícia; Frasson, Amanda Piccoli; Menezes, Camila Braz; Senger, Franciane Rios; Santos da Silva, Gloria Narjara; Baggio Gnoatto, Simone Cristina; Tasca, Tiana

    2016-12-01

    Caused by Trichomonas vaginalis, trichomoniasis is the most common non-viral STD worldwide. Currently, metronidazole and tinidazole are the only drugs approved for treatment of the condition. However, problems such as metronidazole-resistant T. vaginalis isolates and allergic reactions have been reported. Based on data previously published by our group, structural changes in betulinic acid (1) were performed, generating three new compounds that were tested for in vitro anti-T.vaginalis activity in this study. Whereas derivative 2 did not demonstrate anti-T. vaginalis activity, derivatives 3 and 4 reduced trophozoite viability by 100%, with MIC values of 50μM. The structural difference of two compounds was performed only on the C-28 position. Derivative 3 showed low cytotoxicity against Vero cells in 24h; however, derivative 4 was highly cytotoxic, but efficient when associated with metronidazole in the synergism assay. ROS production by neutrophils was reduced, and derivative 3 showed anti-inflammatory effect. Collectively, the results of this study provide in vitro evidence that betulinic acid derivatives 3 and 4 are potential compounds with anti-T. vaginalis activity.

  11. Synthesis and anticancer activity of novel fluorinated asiatic acid derivatives.

    PubMed

    Gonçalves, Bruno M F; Salvador, Jorge A R; Marín, Silvia; Cascante, Marta

    2016-05-23

    A series of novel fluorinated Asiatic Acid (AA) derivatives were successfully synthesized, tested for their antiproliferative activity against HeLa and HT-29 cell lines, and their structure activity relationships were evaluated. The great majority of fluorinated derivatives showed stronger antiproliferative activity than AA in a concentration dependent manner. The most active compounds have a pentameric A-ring containing an α,β-unsaturated carbonyl group. The compounds with better cytotoxic activity were then evaluated against MCF-7, Jurkat, PC-3, A375, MIA PaCa-2 and BJ cell lines. Derivative 14 proved to be the most active compound among all tested derivatives and its mechanism of action was further investigated in HeLa cell line. The results showed that compound 14 induced cell cycle arrest in G0/G1 stage as a consequence of up-regulation of p21(cip1/waf1) and p27(kip1) and down-regulation of cyclin D3 and Cyclin E. Furthermore, compound 14 was found to induce caspase driven-apoptosis with activation of caspases-8 and caspase-3 and the cleavage of PARP. The cleavage of Bid into t-Bid, the up-regulation of Bax and the down-regulation of Bcl-2 were also observed after treatment of HeLa cells with compound 14. Taken together, these mechanistic studies revealed the involvement of extrinsic and intrinsic pathways in the apoptotic process induced by compound 14. Importantly, the antiproliferative activity of this compound on the non-tumor BJ human fibroblast cell line is weaker than in the tested cancer cell lines. The enhanced potency (between 45 and 90-fold more active than AA in a panel of cancer cell lines) and selectivity of this new AA derivative warrant further preclinical evaluation.

  12. Design, synthesis and potent cytotoxic activity of novel podophyllotoxin derivatives.

    PubMed

    Li, Wen-Qun; Wang, Xu-Li; Qian, Keduo; Liu, Ying-Qian; Wang, Chih-Ya; Yang, Liu; Tian, Jin; Morris-Natschke, Susan L; Zhou, Xing-Wen; Lee, Kuo-Hsiung

    2013-04-15

    Twenty new acyl thiourea derivatives of podophyllotoxin and 4'-demethylepipodophyllotoxin were prepared and screened for their cytotoxicity against four human tumor cell lines, A-549, DU-145, KB, and KBvin. With IC50 values of 0.098-1.13 μM, compounds 13b, 13c, and 13o displayed much better cytotoxic activity than the control etoposide. Most importantly, 13b and 13o exhibited promising cytotoxicity against the drug resistant tumor cell line KBvin with IC50 values of 0.098 and 0.13 μM, respectively, while etoposide lost activity completely. Structure-activity relationship (SAR) correlations of the new derivatives have been established. Compounds 13b and 13o merit further development as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidates.

  13. Synthesis and antitumor activity of natural compound aloe emodin derivatives.

    PubMed

    Thimmegowda, Naraganahalli R; Park, Chanmi; Shwetha, Bettaswamigowda; Sakchaisri, Krisada; Liu, Kangdong; Hwang, Joonsung; Lee, Sangku; Jeong, Sook J; Soung, Nak K; Jang, Jae H; Ryoo, In-Ja; Ahn, Jong S; Erikson, Raymond L; Kim, Bo Y

    2015-05-01

    In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a-j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure-activity relationships. The structures of the compounds were determined by (1) H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI-H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations.

  14. Synthesis and antitumour activity of 4-aminoquinazoline derivatives

    NASA Astrophysics Data System (ADS)

    Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

    2016-07-01

    Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

  15. Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

    PubMed

    Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

    2016-11-22

    Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm(2) V(-1) s(-1), on-off current ratio Ion/Ioff ∼ 10(4), and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

  16. Anticerebral Ischemia-Reperfusion Injury Activity of Synthesized Puerarin Derivatives

    PubMed Central

    Ji, Yubin; Yan, Xinjia

    2016-01-01

    When cerebral ischemia-reperfusion injury happened in patients, multiple pathological processes occur, such as leukocyte infiltration, platelet, and complement activation, which would result in cognitive dysfunction and inflammation. Puerarin has shown protective effect on injury of neural cell. In order to enhance this protective effect of puerarin, puerarin derivatives with different log⁡P values were designed and synthesized. The original phenolic hydroxyl in the puerarin molecules was substituted in order to change the blood-brain barrier permeability and thus enhance the efficacy for preventing cerebral ischemia/reperfusion injury. And the structure of the newly synthesized molecules was confirmed by 1H NMR spectroscopy and mass spectrometry. The mouse model of cerebral artery ischemia/reperfusion injury was established to test the anticerebral ischemia-reperfusion injury activity of the puerarin derivatives. The assays of the water maze, Y maze, brain cortex Ca2+-Mg2+-ATP enzyme, and iNOS enzyme activity were performed in this mouse model. The results showed that puerarin derivative P1-EA and P2-EA were resulting in an increased lipophilicity that enabled the derivatives to pass more efficiently through the blood-brain barrier, thus, improving the protective effects against cerebral ischemia/reperfusion injury. Therefore, derivatives of puerarin may serve as promising approach to improve neuron function in ischemia-reperfusion brain injury-related disorders. PMID:27807543

  17. [Synthesis and antidepressant activities of aryl alkanol piperidine derivatives].

    PubMed

    Zheng, Yong-yong; Gao, Kai; Weng, Zhi-jie; Li, Jian-qi

    2010-03-01

    To explore novel monoamine reuptake inhibitor with antidepressant activity, a series of substituted aryl alkanol piperidine derivatives were designed and synthesized. All of them were new compounds, and their structures were confirmed with 1H NMR and HR-MS. The results showed that compounds 4, 5 and 8 displayed strong 5-HT, NA and DA reuptake inhibiting activities in vitro. Among the tested compounds, 4, 5 and 13 exhibited potent antidepressant activities in the mice forced swimming test. Compounds 4 and 5 have potent antidepressant activities and are worth further development.

  18. Antiglycation activity of lipophilized epigallocatechin gallate (EGCG) derivatives.

    PubMed

    Wang, Mingfu; Zhang, Xinchen; Zhong, Ying Joy; Perera, Nishani; Shahidi, Fereidoon

    2016-01-01

    Lipophilized EGCG derivatives were synthesized by esterification of EGCG with aliphatic fatty acids and demonstrated to possess many advantages, such as higher lipophilicity and apparent health benefits over the parent EGCG. This study used a total of seven lipophilized EGCG derivatives with fatty acids of different chain lengths attached and examined the impact of lipophilization on EGCG's antiglycation activity in vitro. The length of fatty acid chain was found to be an important factor, which positively correlated with ABTS radical scavenging capacity but long chain bulky substitutes prevented methylglyoxal (MGO) trapping. Except docosahexaenoic acid (DHA), lipophilization generally showed no interference with EGCG's in vitro inhibitory activity of advanced glycation endproducts (AGEs) formation. Therefore, the lipophilized EGCG derivatives are promising candidates worthy of further exploration for preventing AGEs accumulation in vivo and hence treating AGEs-associated diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Synthesis and Antibacterial Activity of Novel Hydroxy Semicarbazone Derivatives

    PubMed Central

    Hariri, Elham; Mahboubi, Arash; Fathi, Mohammad; Rahmani, Parisa; Haj Mohammad Ebrahim Tehrani, Kamaleddin; Babaeian, Mohammad; Mashayekhi, Vida; Kobarfard, Farzad

    2016-01-01

    A series of hydroxyl semicarbazone derivatives of substituted diaryl ketones and acetophenones were synthesized and their structures were confirmed by analytical and spectroscopic methods including elemental analysis, infrared and nuclear magnetic resonance spectroscopy. The derivatives were prepared by a condensation reaction between N-hydroxy semicarbazide and substituted diaryl ketones or acetophenones leading to the desired hydroxysemicarbazones with excellent purity. The synthesized hydrazones were then evaluated for their inhibitory activity against bacterial strains including S. aureus, E. Coli, P. aeruginosa, K. pneumonia and M. luteus. Among the tested derivatives, compounds 2, 6 and 7 exhibited the highest bioactivity. Analysis of the activity data suggests that hydrophilicity is an important factor for the bioactivity of compounds 2 and 6 and also their selectivity over the gram-negative bacteria. PMID:28228801

  20. Semisynthetic derivatives of madurahydroxylactone and their antibacterial activities.

    PubMed

    Heinisch, L; Roemer, E; Jütten, P; Haas, W; Werner, W; Möllmann, U

    1999-11-01

    Madurahydroxylactone is a secondary metabolite from Nonomuria rubra (former Actinomadura rubra) with in vitro activity against gram-positive bacteria and belongs to the family of benzo[a]naphthacenequinones. A series of derivatives of madurahydroxylactone were synthesized to investigate the effect on the antibacterial activity. Reaction with alcohols and amines gave cyclic acetals or aminals derived from the lactone form, whereas other amino reagents like hydroxylamines and acyl or sulfonyl hydrazides led to the corresponding imine derivatives of the aldehyde. Hydrazine, alkyl and aryl hydrazines react with madurahydroxylactone under cyclization to give compounds of the new heterocyclic basic structure naphthaceno[1,2-g]phthalazine. Some new compounds strongly inhibit gram-positive bacteria, in part stronger than the parent compound.

  1. A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.

    PubMed

    Rodríguez-Berna, Guillermo; Mangas-Sanjuán, Víctor; Gonzalez-Alvarez, Marta; Gonzalez-Alvarez, Isabel; García-Giménez, José Luis; Díaz Cabañas, María José; Bermejo, Marival; Corma, Avelino

    2014-08-18

    Oral administration of camptothecin (CPT) derivatives and other antitumoral agents is being actively developed in order to improve the quality of life of patients with cancer. Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration. Semisynthesis, antitumor activity, biological inhibition mechanism, and in situ intestinal permeability of 9, 10-[1,3]-Dioxinocamptothecin (CDiox), an unexplored CPT derivative, have been studied in this paper. The hexacyclic analog was as effective as Topotecan and CPT in different tumor cell lines, showing an expected similar apoptosis cell mechanism and high ability to inhibit DNA synthesis in HeLa, Caco-2, A375 and MDA-MB-231 cell lines. Furthermore, in vitro and in situ pharmacokinetics transport values obtained for CDiox displayed more favorable absorption profile than CPT and Topotecan.

  2. Potential Biosignificant Interest and Surface Activity of Efficient Heterocyclic Derivatives.

    PubMed

    El-Sayed, Refat; Althagafi, Ismail

    2016-01-01

    Some functionalized pyridine and fused system derivatives were synthesized using enaminonitrile derivative 5 as a starting material for the reaction, with various reagents under different conditions. Propoxylation of these compounds using different moles of propylene oxide (3, 5 and 7 moles) leads to a novel group of surface active agents. The antimicrobial and surface activities of the synthesized compounds were investigated. Most of the evaluated compounds proved to be active as antibacterial and antifungal agents and showed good surface activity, which makes them suitable for diverse applications such as the manufacturing of emulsifiers, cosmetics, drugs, pesticides, etc. Additionally, biodegradation testing exhibits significant breakdown within six to seven days, and hence, lowers the toxicity to human beings and becomes environmentally friendly.

  3. Synthesis and Biological Activities of Camphor Hydrazone and Imine Derivatives

    PubMed Central

    da Silva, Emerson T.; da Silva Araújo, Adriele; Moraes, Adriana M.; de Souza, Leidiane A.; Silva Lourenço, Maria Cristina; de Souza, Marcus V. N.; Wardell, James L.; Wardell, Solange M. S. V.

    2015-01-01

    Both sonochemical and classical methodologies have been employed to convert camphor, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one, C9H16C=O, into a number of derivatives including hydrazones, C9H16C=N-NHAr 3, imines, C9H16C=N-R 7, and the key intermediate nitroimine, C9H16C=N-NO2 6. Reactions of nitroamine 6 with nucleophiles by classical methods provided the desired compounds in a range of yields. In evaluations of activity against Mycobacterium tuberculosis, compound 7j exhibited the best activity (minimal inhibitory concentration (MIC) = 3.12 µg/mL), comparable to that of the antitubercular drug ethambutol. The other derivatives displayed modest antimycobacterial activities at 25–50 µg/mL. In in vitro tests against cancer cell lines, none of the synthesized camphor compounds exhibited cytotoxic activities. PMID:28117313

  4. An analytical derivative procedure for the calculation of vibrational Raman optical activity spectra

    NASA Astrophysics Data System (ADS)

    Liégeois, Vincent; Ruud, Kenneth; Champagne, Benoît

    2007-11-01

    We present an analytical time-dependent Hartree-Fock algorithm for the calculation of the derivatives of the electric dipole-magnetic dipole polarizability with respect to atomic Cartesian coordinates. Combined with analogous procedures to determine the derivatives of the electric dipole-electric dipole and electric dipole-electric quadrupole polarizabilities, it enables a fully analytical evaluation of the three frequency-dependent vibrational Raman optical activity (VROA) invariants within the harmonic approximation. The procedure employs traditional non-London atomic orbitals, and the gauge-origin dependence of the VROA intensities has, therefore, been assessed for the commonly used aug-cc-pVDZ and rDPS:3-21G basis sets.

  5. Novel pyrazolyl-s-triazine derivatives, molecular structure and antimicrobial activity

    NASA Astrophysics Data System (ADS)

    Sharma, Anamika; Ghabbour, Hazem; Khan, Shams Tabrez; de la Torre, Beatriz G.; Albericio, Fernando; El-Faham, Ayman

    2017-10-01

    A new series of pyrazole-containing s-triazine derivatives were synthesized by reaction of the corresponding s-triazinyl hydrazine derivatives with acetylacetone in the presence of HClO4 or DMF/TEA. The former method allowed the preparation of the target products with higher yields. All compounds were fully characterized. X-ray single crystal diffraction for two representative compounds (4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine and N-benzyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine) was studied and the molecular structures were optimized using the DFT/B3LYP method. The structures were found to be in agreement with X-ray structures. The antimicrobial and antifungal activity of the prepared compounds were tested against the growth of several microorganisms.

  6. Synthesis and radioprotective activity of new cysteamine and cystamine derivatives

    SciTech Connect

    Oiry, J.; Pue, J.Y.; Imbach, J.L.; Fatome, M.; Sentenac-Roumanou, H.; Lion, C.

    1986-11-01

    A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting compounds of this series was N-glycyl-S-acetylcysteamine trifluoroacetate (16, I 102). Structure-activity relationships are discussed.

  7. Synthesis and radioprotective activity of dipeptide cysteamine and cystamine derivatives

    SciTech Connect

    Oiry, J.; Pue, J.Y.; Imbach, J.L.; Fatome, M.; Sentenac-Roumanou, H.

    1989-02-01

    Some N-(dipeptidyl)-S-acetylcysteamine and N,N'-(dipeptidyl)cystamine salt derivatives were synthesized and evaluated as candidate radioprotector agents. Toxicity and radioprotective activity as the dose reduction factor (DRF) were determined in vivo on mice and compared to N-glycyl-S-acetylcysteamine trifluoroacetate. One of the most interesting compounds of this series was N-glycylglycyl-S-acetylcysteamine trifluoroacetate (8).

  8. Synthesis and antimicrobial activities of some sulphur containing chromene derivatives.

    PubMed

    Serbetçi, Tuba; Birteksöz, Seher; Prado, Soizic; Michel, Sylvie; Tillequin, François

    2012-07-01

    A series of 3,3-dimethyl-3Hbenzothieno[3,2-f][1]-benzopyran analogues modified at the pyran 1,2-double bond were synthesized. The corresponding dihydro and (+/-)-cis-diol derivatives were converted into diacetate and cyclic carbonate upon acylation. The title compounds were characterized by spectroscopic analysis and screened for their antimicrobial activity in vitro.

  9. Preparation and antimalarial activity of semisynthetic lycorenine derivatives.

    PubMed

    Cedrón, Juan C; Gutiérrez, David; Flores, Ninoska; Ravelo, Ángel G; Estévez-Braun, Ana

    2013-05-01

    A set of twenty one lycorenine derivatives has been prepared from the alkaloid hippeastrine (1). The modifications performed on hippeastrine included some functional group transformations, structural simplification and preparation of dimers. All alkaloids were tested as potential antimalarial agents, being the hippeastrine dimers the most active compounds.

  10. An amphiphilic, catalytically active, vitamin B12 derivative.

    PubMed

    Giedyk, M; Fedosov, S N; Gryko, D

    2014-05-11

    We performed the reaction of vitamin B12 with N,N-dimethylformamide dimethyl acetal for primary amide activation, and added MeOH as a nucleophile, to afford cobalester, the first amphiphilic cobalamin derivative. The unique combination of redox properties and solubility represents an asset for its use as a catalyst in C-C bond forming reactions.

  11. Syntheses and insulin-like activity of phosphorylated galactose derivatives.

    PubMed

    Caro, H N; Martín-Lomas, M; Bernabé, M

    1993-02-24

    The syntheses of the poly-phosphorylated galactosides 6, 8, 10, 13, 16, and 20, isolated as sodium salts, have been performed. The non-phosphorylated disaccharide 17 and trisaccharide 21 have been prepared via glycosylation of the 2-(trimethylsilyl)ethyl galactosides 3 and 2, respectively, and subsequent complete deprotection. Preliminary insulin-like activity of the phosphorylated derivatives is reported.

  12. Synthesis and antibacterial activity of novel enolphosphate derivatives.

    PubMed

    Grison, Claude; Barthes, Nicolas; Finance, Chantal; Duval, Raphael E

    2010-10-01

    A new class of enolphosphates derivatives, the 1-alkenyldiphosphates, was designed and a rapid and efficient synthesis for these compounds was developed. These new molecules showed interesting in vitro antibacterial activities (MIC) against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative pathogens including Pseudomonas aeruginosa and Escherichia coli. 2010 Elsevier Inc. All rights reserved.

  13. Syntheses and In Vitro Biological Activity of Some Derivatives of C-9154 Antibiotic

    PubMed Central

    Bello, Isaac Asusheyi; Ndukwe, George Iloegbulam; Amupitan, Joseph Olorunju; Ayo, Rachael Gbekele; Shode, Francis Oluwole

    2012-01-01

    In our continued attempts at designing new antibiotics based on the structure of the C-9154 antibiotic, to simultaneously improve activity and lower toxicity, an analogue to the C-9154 antibiotic and six derivatives of this analogue were synthesized. The approach was to significantly reduce the polarity of the synthesized analogue in the derivatives to achieve increased permeability across cell membranes by conversion of the highly polar carboxylic group to an ester functional group. The compounds were synthesized using a two-step reaction which involved an additional reaction between benzyl amine and maleic anhydride and then conversion of the terminal carboxylic acid functional group to an ester functional group using a thionyl chloride mediated esterification reaction. The compounds were fully characterized using Infrared, GC-MS, and 1D and 2D NMR experiments. The in vitro biological activity of the compounds showed that the derivatives were more active than the analogues as was anticipated with minimum inhibitory concentration in the range 0.625–5 μg/mL. The analogue had minimum inhibitory concentration in the range 2.5–10 μg/mL. These values are significantly better than that obtained for the original C-9154 antibiotic which had activity in the range 10–>100 μg/mL. PMID:25374687

  14. Syntheses and Biological Activity of Some Derivatives of C-9154 Antibiotic

    PubMed Central

    Bello, Isaac Asusheyi; Ndukwe, George Iloegbulam; Amupitan, Joseph Olorunju; Ayo, Rachael Gbekele; Shode, Francis Oluwole

    2012-01-01

    This research was undertaken to design several new antibiotics, by structurally modifying the C-9154 antibiotic, simultaneously improving its activity and lowering toxicity. This was achieved by synthesizing an analogue to the C-9154 antibiotic and seven derivatives of this analogue. The approach was to significantly reduce the polarity of the synthesized analogue in the derivatives to achieve increased permeability across cell membranes by conversion of the highly polar carboxylic group to an ester functional group. The compounds were fully characterized using infrared, GC-MS, and 1D and 2D NMR experiments. The in vitro biological activity of the compounds showed that the derivatives were more active than the analogue as was anticipated and both were more active than the standard drugs used for comparison. Work is ongoing to establish applications for the compounds as antiplasmodials, antivirals, anticancers/tumours, antitrypanosomiasis, anthelminthic, and as general antibiotics for human, veterinary, and even agricultural use as they had marked effect on both Gram-positive and Gram-negative bacteria and some fungi. PMID:25374681

  15. Preparation and antitussive, expectorant, and antiasthmatic activities of verticinone's derivatives.

    PubMed

    Zhang, Yong-Hui; Ruan, Han-Li; Pi, Hui-Fang; Wu, Ji-Zhou; Sun, Han-Dong; Fujita, Tetsuro

    2008-01-01

    To prepare verticinone derivatives with significant antitussive, expectorant, and antiasthmatic activities, the compounds 3beta-acetylverticinone (1), 3-ketoverticinone (2), 3beta-benzoylverticinone (3), 3beta-propionylverticinone (4), 3beta-butyrylverticinone (5), and 3beta-butoxycarbonylverticinone (6) have been prepared. All of these are new compounds. Among them, 1-6 exhibited potent antitussive and expectorant activities; 1 and 3-6 displayed various antiasthmatic activities. The antitussive activity of 1-6, the expectorant activity of 1-2 and 4-6, and the antiasthmatic activity of 1 are higher than those of verticinone. The results demonstrated that 1 had dominant biological activities, suggesting that it would be a potential antitussive, expectorant, and antiasthmatic agent.

  16. Structure, toxicity and antibiotic activity of gramicidin S and derivatives.

    PubMed

    Swierstra, J; Kapoerchan, V; Knijnenburg, A; van Belkum, A; Overhand, M

    2016-05-01

    Development of new antibiotics is declining whereas antibiotic resistance is rising, heralding a post-antibiotic era. Antimicrobial peptides such as gramicidin S (GS), exclusively topically used due to its hemolytic side-effect, could still be interesting as therapeutic compounds. By modifying the amino-acid composition of GS, we synthesized GS analogues. We now show that derivative VK7 has a lower MIC (7.8-31.2 μg/ml, median 15.6 μg/ml) against strains of multi-drug resistant (MDR) Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa than GS has (3.9-62.5 μg/ml, median 31.3 μg/ml). Low MICs for both VK7 and GS were observed for Staphylococcus aureus and Enterococcus faecium. VK7 showed reduced haemolysis and less lactate dehydrogenase release. All compounds were fully bactericidal at MIC values. Modification of GS enables production of novel derivatives potentially useful for systemic treatment of human infections.

  17. Production and characterization of lignocellulosic biomass-derived activated carbon.

    PubMed

    Namazi, A B; Jia, C Q; Allen, D G

    2010-01-01

    The goal of this work is to establish the technical feasibility of producing activated carbon from pulp mill sludges. KOH chemical activation of four lignocellulosic biomass materials, two sludges from pulp mills, one sludge for a linerboard mill, and cow manure, were investigated experimentally, with a focus on the effects of KOH/biomass ratio (1/1, 1.5/1 and 2/1), activation temperature (400-600 °C) and activation time (1 to 2 h) on the development of porosity. The activation products were characterized for their physical and chemical properties using a surface area analyzer, scanning electron microscopy and Fourier transform infrared spectroscopy. Experiments were carried out to establish the effectiveness of the lignocellulosic biomass-derived activated carbon in removing methylene blue (MB), a surrogate of large organic molecules. The results show that the activated carbon are highly porous with specific surface area greater than 500 m²/g. The yield of activated carbon was greater than the percent of fixed carbon in the dry sludge, suggesting that the activation process was able to capture a substantial amount of carbon from the organic matter in the sludge. While 400 °C was too low, 600 °C was high enough to sustain a substantial rate of activation for linerboard sludge. The KOH/biomass ratio, activation temperature and time all play important roles in pore development and yield control, allowing optimization of the activation process. MB adsorption followed a Langmuir isotherm for all four activated carbon, although the adsorption capacity of NK-primary sludge-derived activated carbon was considerably lower than the rest, consistent with its lower specific surface area.

  18. (E)- and (Z)-stereodefined enol phosphonates derived from β-ketoesters: stereocomplementary synthesis of fully-substituted α,β-unsaturated esters.

    PubMed

    Nakatsuji, Hidefumi; Ashida, Yuichiro; Hori, Hiroshi; Sato, Yuka; Honda, Atsushi; Taira, Mayu; Tanabe, Yoo

    2015-08-14

    A versatile, robust, and stereocomplementary synthesis of fully-substituted (E)- and (Z)-stereodefined α,β-unsaturated esters 3 from accessible α-substituted β-ketoesters 1via (E)- and (Z)-enol phosphonates was achieved. The present method involves two accessible reaction sequences: (i) (E)- and (Z)-stereocomplementary enol phosphorylations of a wide variety of β-ketoesters 1 (24 examples; 71–99% yield, each >95: 5 ds), and (ii) (E)- and (Z)-stereoretentive Suzuki–Miyaura cross-coupling (16 examples; 71–91% yield, >81/19 ds) and Negishi cross-coupling (32 examples; 65–96% yield, >95 : 5 ds) using (E)- and (Z)-enol phosphonates 2. 1H-NMR monitoring for a key reactive N-phosphorylammonium (imidazolium) intermediate I and an application in the synthesis of both (E)- and (Z)-tamoxifen precursors 6 are described.

  19. Fully Automated Gis-Based Individual Tree Crown Delineation Based on Curvature Values from a LIDAR Derived Canopy Height Model in a Coniferous Plantation

    NASA Astrophysics Data System (ADS)

    Argamosa, R. J. L.; Paringit, E. C.; Quinton, K. R.; Tandoc, F. A. M.; Faelga, R. A. G.; Ibañez, C. A. G.; Posilero, M. A. V.; Zaragosa, G. P.

    2016-06-01

    The generation of high resolution canopy height model (CHM) from LiDAR makes it possible to delineate individual tree crown by means of a fully-automated method using the CHM's curvature through its slope. The local maxima are obtained by taking the maximum raster value in a 3 m x 3 m cell. These values are assumed as tree tops and therefore considered as individual trees. Based on the assumptions, thiessen polygons were generated to serve as buffers for the canopy extent. The negative profile curvature is then measured from the slope of the CHM. The results show that the aggregated points from a negative profile curvature raster provide the most realistic crown shape. The absence of field data regarding tree crown dimensions require accurate visual assessment after the appended delineated tree crown polygon was superimposed to the hill shaded CHM.

  20. Insecticidal and Nematicidal Activities of Novel Mimosine Derivatives.

    PubMed

    Nguyen, Binh Cao Quan; Chompoo, Jamnian; Tawata, Shinkichi

    2015-09-14

    Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal and nematicidal activities of novel mimosine derivatives. Interestingly, mimosinol and deuterated mimosinol (D-mimosinol) from mimosine had strong insecticidal activity which could be a result of tyrosinase inhibition (IC50 = 31.4 and 46.1 μM, respectively). Of synthesized phosphoramidothionate derivatives from two these amino alcohols, two compounds (1a and 1b) showed high insecticidal activity (LD50 = 0.5 and 0.7 μg/insect, respectively) with 50%-60% mortality at 50 μg/mL which may be attributed to acetylcholinesterase inhibition. Compounds 1a and 1b also had strong nematicidal activity with IC50 = 31.8 and 50.2 μM, respectively. Our results suggest that the length of the alkyl chain and the functional group at the C₅-position of phosphoramidothionates derived from mimosinol and d-mimosinol are essential for the insecticidal and nematicidal activities. These results reveal an unexplored scaffold as new insecticide and nematicide.

  1. Pathogen-derived biomarkers for active tuberculosis diagnosis.

    PubMed

    Tucci, Paula; González-Sapienza, Gualberto; Marin, Monica

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by members of Mycobacterium tuberculosis complex. Despite the availability of effective treatments, TB remains a major public health concern in most low and middle-income countries, representing worldwide the second leading cause of death from an infectious disease. Inadequate case detection and failures to classify the disease status hamper proper TB control. The limitations of the conventional diagnostic methods have encouraged much research activities in this field, but there is still an urgent need for an accurate point of care test for active TB diagnosis. A rapid, precise, and inexpensive TB diagnostic test would allow an earlier implementation of an appropriate treatment and the reduction of disease transmission. Pathogen-derived molecules present in clinical specimens of affected patients are being validated for that purpose. This short review aims to summarize the available data regarding biomarkers derived from M. tuberculosis, and their current usage in active TB diagnosis.

  2. Anti-Influenza Activity of C60 Fullerene Derivatives

    PubMed Central

    Shoji, Masaki; Takahashi, Etsuhisa; Hatakeyama, Dai; Iwai, Yuma; Morita, Yuka; Shirayama, Riku; Echigo, Noriko; Kido, Hiroshi; Nakamura, Shigeo; Mashino, Tadahiko; Okutani, Takeshi; Kuzuhara, Takashi

    2013-01-01

    The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs. PMID:23785493

  3. Synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.

    PubMed

    Abada, Zahra; Cojean, Sandrine; Pomel, Sébastien; Ferrié, Laurent; Akagah, Bernardin; Lormier, Anh Tuan; Loiseau, Philippe M; Figadère, Bruno

    2013-09-01

    Importance of heme in African trypanosomes, Leishmania sp. and Plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. Consequently, twenty-four porphyrin precursors and derivatives were evaluated against Leishmania donovani, Trypanosoma brucei and Plasmodium sp. The best active compound against Trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, with a MEC value of 6.25 μM justifying further in vivo evaluation. Whereas these compounds were not active against intramacrophage amastigotes of L. donovani, another new porphyrin derivative, compound 4f was active in vitro against Plasmodium falciparum at 20 nM and a slight delay of mice survival was observed on the Plasmodium berghei/Swiss mice model at 50 μmol/kg/day × 4. Pharmacomodulations should be further developed relying on a better knowledge on the porphyrin behaviour into the parasites comparatively to host cells.

  4. Anti-influenza activity of c60 fullerene derivatives.

    PubMed

    Shoji, Masaki; Takahashi, Etsuhisa; Hatakeyama, Dai; Iwai, Yuma; Morita, Yuka; Shirayama, Riku; Echigo, Noriko; Kido, Hiroshi; Nakamura, Shigeo; Mashino, Tadahiko; Okutani, Takeshi; Kuzuhara, Takashi

    2013-01-01

    The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs.

  5. Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives.

    PubMed

    Khunnawutmanotham, Nisachon; Chimnoi, Nitirat; Saparpakorn, Patchreenart; Techasakul, Supanna

    2016-04-01

    A series of scopoletin derivatives incorporated with the pyridinium moiety was synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity by the colorimetric Ellman's method. A 2-fluorobenzylpyridinium derivative was the most potent among the tested compounds, with an IC50 value of 0.215±0.015μM, which was greatly improved from that of scopoletin. Docking studies revealed that the scopoletin portion of the mentioned compound was bound to the peripheral anionic site of the AChE, whereas the N-benzylpyridinium residue to the catalytic anionic site. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. [S-Acyl derivatives of thiosalicylamides having antifungal activity. II].

    PubMed

    Mazza, M; Modena, T; Montanari, L; Pavanetto, F

    1978-07-01

    Some S-acyl derivatives of N-alkylthiosalicylamides [Table I: substances (I leads to XXXI)] were prepared and tested for antifungal activity. The substances, most of which had not been previously reported, were prepared by condensation of 2-mercapto-N-alkylbenzamides with suitable acylating agents. The antifungal activity of the compounds was tested in vitro against Candida albicans and Trichophyton mentagrophytes. For some compounds the was tested activity against the above strains fungicidal, Candida tropicalis and Saccharomyces cerevisiae. Many of the compounds proved to have high antifungal activity comparable with that of Clotrimazol. The results extended knowledge on the structure-antifungal activity relationships of this class of compounds. The compounds with the highest antifungal activity were: 2-acetylmercapto-N,n-heptylbenzamide (XXVIII); 2-acetylmercapto-5-Cl-N,n-propylbenzamide (XIV); 2-acetylmercapto-N,n-octylbenzamide (XXXI); 2-acetylmercapto-N,n-pentylbenzamide (XXV); 2-acetylmercapto-N,n-hexylbenzamide (XXVII).

  7. Biological Activities of 2-Mercaptobenzothiazole Derivatives: A Review

    PubMed Central

    Azam, Mohammed Afzal; Suresh, Bhojraj

    2012-01-01

    2-Mercaptobenzothiazoles are an important class of bioactive and industrially important organic compounds. These compounds are reported for their antimicrobial and antifungal activities, and are subsequently highlighted as a potent mechanism-based inhibitor of several enzymes like acyl coenzyme A cholesterol acyltransferase, monoamine oxidase, heat shock protein 90, cathepsin D, and c-Jun N-terminal kinases. These derivatives are also known to possess antitubercular, anti-inflammatory, antitumor, amoebic, antiparkinsonian, anthelmintic, antihypertensive, antihyperlipidemic, antiulcer, chemoprotective, and selective CCR3 receptor antagonist activity. This present review article focuses on the pharmacological profile of 2-mercaptobenzothiazoles with their potential activities. PMID:23264933

  8. Hydrogen bonds and antiviral activity of benzaldehyde derivatives

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Skornyakov, I. V.; Belkov, M. V.; Shadyro, O. I.; Brinkevich, S. D.; Samovich, S. N.

    2012-09-01

    We have obtained the Fourier transform IR spectra of solutions of benzaldehyde derivatives having different antiviral activities against a herpes virus. We observe a correlation between the presence of hydrogen bonds in the benzaldehyde molecules and the appearance of antiviral properties in the compounds. For compounds having antiviral activity, we have obtained spectral data suggesting the existence of hydrogen bonds of the type C=OṡṡṡH-O and O-HṡṡṡO in the molecules. When the hydrogen atom in the hydroxyl groups are replaced by a methyl group, no intramolecular hydrogen bonds are formed and the compounds lose their antiviral activity.

  9. Synthesis and trypanocidal activity of novel benzimidazole derivatives.

    PubMed

    Velázquez-López, José Miguel; Hernández-Campos, Alicia; Yépez-Mulia, Lilián; Téllez-Valencia, Alfredo; Flores-Carrillo, Paulina; Nieto-Meneses, Rocío; Castillo, Rafael

    2016-09-01

    The present work reports the synthesis and biological activity of a series of 14 benzimidazole derivatives designed to act on the enzyme triosephosphate isomerase of Trypanosoma cruzi (TcTIM). This enzyme is involved in the metabolism of glucose, the only source of energy for the parasite. In this study, we found four compounds that inhibit TcTIM moderately and lack inhibitory activity against human TIM (HsTIM). In vitro studies against T. cruzi epimastigotes showed two compounds that were more active than the reference drug nifurtimox, and these presented a low cytotoxic effect in mouse macrophages (J744 cell line).

  10. Antioxidant Activity of Novel Fused Heterocyclic Compounds Derived from Tetrahydropyrimidine Derivative.

    PubMed

    Salem, Marwa Sayed; Farhat, Mahmoud; Errayes, Asma Omar; Madkour, Hassan Mohamed Fawzy

    2015-01-01

    6-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile has been utilized for synthesis of the fused heterocyclic compounds namely thiazolopyrimidines, tetrazolopyrimidine, pyrimidoquinazoline, pyrimidothiazolopyrimidine, pyrimidothiazolotriazine and pyrrolothiazolopyrimidine derivatives. The newly synthesized compounds were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. Antioxidant activities of all synthesized compounds were investigated.

  11. SrCl2 Derived Perovskite Facilitating a High Efficiency of 16% in Hole-Conductor-Free Fully Printable Mesoscopic Perovskite Solar Cells.

    PubMed

    Zhang, Hua; Wang, Huan; Williams, Spencer T; Xiong, Dehua; Zhang, Wenjun; Chueh, Chu-Chen; Chen, Wei; Jen, Alex K-Y

    2017-02-07

    Despite the breakthrough of over 22% power conversion efficiency demonstrated in organic-inorganic hybrid perovskite solar cells (PVSCs), critical concerns pertaining to the instability and toxicity still remain that may potentially hinder their commercialization. In this study, a new chemical approach using environmentally friendly strontium chloride (SrCl2 ) as a precursor for perovskite preparation is demonstrated to result in enhanced device performance and stability of the derived hole-conductor-free printable mesoscopic PVSCs. The CH3 NH3 PbI3 perovskite is chemically modified by introducing SrCl2 in the precursor solution. The results from structural, elemental, and morphological analyses show that the incorporation of SrCl2 affords the formation of CH3 NH3 PbI3 (SrCl2 ) x perovskites endowed with lower defect concentration and better pore filling in the derived mesoscopic PVSCs. The optimized compositional CH3 NH3 PbI3 (SrCl2 )0.1 perovskite can substantially enhance the photovoltaic performance of the derived hole-conductor-free device to 15.9%, outperforming the value (13.0%) of the pristine CH3 NH3 PbI3 device. More importantly, the stability of the device in ambient air under illumination is also improved.

  12. Quality of poultry litter-derived granular activated carbon.

    PubMed

    Qiu, Guannan; Guo, Mingxin

    2010-01-01

    Utilization of poultry litter as a source material for generating activated carbon is a value-added and environmentally beneficial approach to recycling organic waste. In this study, the overall quality of poultry litter-derived granular activated carbon was systematically evaluated based on its various physical and chemical properties. Granular activated carbon generated from pelletized poultry litter following a typical steam-activation procedure possessed numerous micropores in the matrix. The product exhibited a mean particle diameter of 2.59 mm, an apparent density of 0.45 g cm(-3), a ball-pan hardness of 91.0, an iodine number of 454 mg g(-1), and a BET surface area of 403 m(2) g(-1). It contained high ash, nitrogen, phosphorus contents and the trace elements Cu, Zn, and As. Most of the nutrients and toxic elements were solidified and solution-unextractable. In general, poultry litter-based activated carbon demonstrated overall quality comparable to that of low-grade commercial activated carbon derived from coconut shell and bituminous coal. It is promising to use poultry litter as a feedstock to manufacture activated carbon for wastewater treatment.

  13. Ergosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone.

    PubMed

    Lardy, H; Kneer, N; Wei, Y; Partridge, B; Marwah, P

    1998-03-01

    An improved procedure for the synthesis of 3 beta-hydroxyandrost-5-ene-7,17-dione, a natural metabolite of dehydroepiandrosterone (DHEA) is described. The synthesis and magnetic resonance spectra of several other related steroids are presented. Feeding dehydroepiandrosterone to rats induces enhanced formation of several liver enzymes among which are mitochondrial sn-glycerol 3-phosphate dehydrogenase (GPDH) and cytosolic malic enzyme. The induction of these two enzymes, that complete a thermogenic system in rat liver, was used as an assay to search for derivatives of DHEA that might be more active than the parent steroid. Activity is retained in steroids that are reduced to the corresponding 17 beta-hydroxy derivative, or hydroxylated at 7 alpha or 7 beta, and is considerably enhanced when the 17-hydroxy or 17-carbonyl steroid is converted to the 7-oxo derivative. Several derivatives of DHEA did not induce the thermogenic enzymes whereas the corresponding 7-oxo compounds did. Both short and long chain acyl esters of DHEA and of 7-oxo-DHEA are active inducers of the liver enzymes when fed to rats. 7-Oxo-DHEA-3-sulfate is as active as 7-oxo-DHEA or its 3-acetyl ester, whereas DHEA-3-sulfate is much less active than DHEA. Among many steroids tested, those possessing a carbonyl group at position 3, a methyl group at 7, a hydroxyl group at positions 1, 2, 4, 11, or 19, or a saturated B ring, with or without a 4-5 double bond, were inactive.

  14. Synthesis, characterization, in vitro antimicrobial, and U2OS tumoricidal activities of different coumarin derivatives

    PubMed Central

    2013-01-01

    Background Coumarin and its derivatives are biologically very active. It was found that the enhanced activities are dependent on the coumarin nucleus. Biological significance of these compounds include anti-bacterial, anti-thrombotic and vasodilatory, anti-mutagenic, lipoxygenase and cyclooxygenase inhibition, scavenging of reactive oxygen species, and anti-tumourigenic. Our interest in medicinal chemistry of dicoumarol compounds have been developed by keeping in view the importance of coumarins along with its derivatives in medicinal chemistry. All the synthesized compounds were fully characterized by spectroscopic and analytical techniques and were screened for antimicrobial and U2OS bone cancer activities. Results 4-hydroxycoumarin was derivatized by condensing with different aldehydes yielding the dicoumarol and translactonized products. Elemental analyses, ESI(+,−) MS, 1H and 13C{1H}-NMR, infrared spectroscopy and conductance studies were used to characterize the synthesized compounds which revealed the dicoumarol and dichromone structures for the compounds. The compounds were screened against U2OS cancerous cells and pathogenic micro organisms. The compounds with intermolecular H-bonding were found more active revealing a possible relationship among hydrogen bonding, cytotoxicity and antimicrobial activities. Conclusion Coumarin based drugs can be designed for the possible treatment of U2OS leukemia. PMID:23587363

  15. Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives.

    PubMed

    Fernandez-Pastor, Ignacio; Fernandez-Hernandez, Antonia; Rivas, Francisco; Martinez, Antonio; Garcia-Granados, Andres; Parra, Andres

    2016-07-22

    Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.

  16. Quantitative Structure-Antifungal Activity Relationships for cinnamate derivatives.

    PubMed

    Saavedra, Laura M; Ruiz, Diego; Romanelli, Gustavo P; Duchowicz, Pablo R

    2015-12-01

    Quantitative Structure-Activity Relationships (QSAR) are established with the aim of analyzing the fungicidal activities of a set of 27 active cinnamate derivatives. The exploration of more than a thousand of constitutional, topological, geometrical and electronic molecular descriptors, which are calculated with Dragon software, leads to predictions of the growth inhibition on Pythium sp and Corticium rolfsii fungi species, in close agreement to the experimental values extracted from the literature. A set containing 21 new structurally related cinnamate compounds is prepared. The developed QSAR models are applied to predict the unknown fungicidal activity of this set, showing that cinnamates like 38, 28 and 42 are expected to be highly active for Pythium sp, while this is also predicted for 28 and 34 in C. rolfsii.

  17. Antiprotozoal Activity of 1-Phenethyl-4-Aminopiperidine Derivatives

    PubMed Central

    Dardonville, Christophe; Fernández-Fernández, Cristina; Gibbons, Sarah-Louise; Jagerovic, Nadine; Nieto, Lidia; Ryan, Gary; Kaiser, Marcel; Brun, Reto

    2009-01-01

    A series of 44 4-aminopiperidine derivatives was screened in vitro against four protozoan parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum). This screening identified 29 molecules selectively active against bloodstream-form T. b. rhodesiense trypomastigotes, with 50% inhibitory concentrations (IC50) ranging from 0.12 to 10 μM, and 33 compounds active against the chloroquine- and pyrimethamine-resistant K1 strain of P. falciparum (IC50 range, 0.17 to 5 μM). In addition, seven compounds displayed activity against intracellular T. cruzi amastigotes in the same range as the reference drug benznidazole (IC50, 1.97 μM) but were also cytotoxic to L-6 cells, showing little selectivity for T. cruzi. None of the molecules tested showed interesting antileishmanial activity against axenic amastigotes of L. donovani. To our knowledge, this is the first report of the antitrypanosomal activity of molecules bearing the 4-aminopiperidine skeleton. PMID:19564359

  18. Synthesis and herbicidal activity of N-oxide derivatives.

    PubMed

    Cerecetto, H; Dias, E; Di Maio, R; González, M; Pacce, S; Saenz, P; Seoane, G; Suescun, L; Mombrú, A; Fernández, G; Lema, M; Villalba, J

    2000-07-01

    As part of an ongoing program on the chemistry and biological activity of N-oxide-containing molecules, a number of novel 1,2, 5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were synthesized and evaluated for their herbicidal activity. Many of these compounds exhibited moderate to good herbicidal pre-emergence activity against Triticum aestivum. Dose-response studies were done on the more representative compounds (12, 20, and 26). The most active compound, butylcarbamoylbenzo[1,2-c]1,2,5-oxadiazole N-oxide, 26, displayed herbicidal activity at concentrations as low as 24 g/ha.

  19. Adsorption Properties of Lignin-derived Activated Carbon Fibers (LACF)

    SciTech Connect

    Contescu, Cristian I.; Gallego, Nidia C.; Thibaud-Erkey, Catherine; Karra, Reddy

    2016-04-01

    The object of this CRADA project between Oak Ridge National Laboratory (ORNL) and United Technologies Research Center (UTRC) is the characterization of lignin-derived activated carbon fibers (LACF) and determination of their adsorption properties for volatile organic compounds (VOC). Carbon fibers from lignin raw materials were manufactured at Oak Ridge National Laboratory (ORNL) using the technology previously developed at ORNL. These fibers were physically activated at ORNL using various activation conditions, and their surface area and pore-size distribution were characterized by gas adsorption. Based on these properties, ORNL did down-select five differently activated LACF materials that were delivered to UTRC for measurement of VOC adsorption properties. UTRC used standard techniques based on breakthrough curves to measure and determine the adsorption properties of indoor air pollutants (IAP) - namely formaldehyde and carbon dioxide - and to verify the extent of saturated fiber regenerability by thermal treatments. The results are summarized as follows: (1) ORNL demonstrated that physical activation of lignin-derived carbon fibers can be tailored to obtain LACF with surface areas and pore size distributions matching the properties of activated carbon fibers obtained from more expensive, fossil-fuel precursors; (2) UTRC investigated the LACF potential for use in air cleaning applications currently pursued by UTRC, such as building ventilation, and demonstrated their regenerability for CO2 and formaldehyde, (3) Both partners agree that LACF have potential for possible use in air cleaning applications.

  20. Antimicrobial and Immunomodulatory Activities of PR-39 Derived Peptides

    PubMed Central

    Veldhuizen, Edwin J. A.; Schneider, Viktoria A. F.; Agustiandari, Herfita; van Dijk, Albert; Tjeerdsma-van Bokhoven, Johanna L. M.; Bikker, Floris J.; Haagsman, Henk P.

    2014-01-01

    The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics. PMID:24755622

  1. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives.

  2. Cytotoxic and Antifungal Activities of Diverse α-Naphthylamine Derivatives

    PubMed Central

    Kouznetsov, Vladímir V.; Zacchino, Susana A.; Sortino, Maximiliano; Vargas Méndez, Leonor Y.; Gupta, Mahabir P.

    2012-01-01

    Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were active (IC50 < 10 μg/mL) against breast (MCF-7), non-small cell lung (H-460), and central nervous system (SF-268) human cancer cell lines, while N-(pyridinylmethyl)-naphthalen-1-amines resulted in activity against (MIC 25–32 μg/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes. PMID:23264936

  3. Synthesis, antifungal activities and qualitative structure activity relationship of carabrone hydrazone derivatives as potential antifungal agents.

    PubMed

    Wang, Hao; Ren, Shuang-Xi; He, Ze-Yu; Wang, De-Long; Yan, Xiao-Nan; Feng, Jun-Tao; Zhang, Xing

    2014-03-11

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents.

  4. Assay of Flippase Activity in Proteoliposomes Using Fluorescent Lipid Derivatives.

    PubMed

    Marek, Magdalena; Günther-Pomorski, Thomas

    2016-01-01

    Specific membrane proteins, termed lipid flippases, play a central role in facilitating the movement of lipids across cellular membranes. In this protocol, we describe the reconstitution of ATP-driven lipid flippases in liposomes and the analysis of their in vitro flippase activity based on the use of fluorescent lipid derivatives. Working with purified and reconstituted systems provides a well-defined experimental setup and allows to directly characterize these membrane proteins at the molecular level.

  5. Synthesis and pharmacological activity of 1,4-benzodiazepine derivatives.

    PubMed

    Osman, A N; el-Gendy, A A; Omar, R H; Wagdy, L; Omar, A H

    2002-01-01

    2-Aminobenzamides (3a-g) were prepared starting with isatoic anhydride. These compounds reacted with chloroacetic acid to give (4a-g), which were cyclized by dicyclohexylcorbodiimide to afford (5a-g). The preliminary pharmacological screening revealed that some of the new 2H-1,4-benzodiazepin-3,5(1H,4H)-dione derivatives (5) exhibited CNS-depressant and anticonvulsant activities.

  6. [Functional activity of bone marrow-derived peptides (myelopeptides)].

    PubMed

    Mikhaĭlova, A A; Petrov, R V

    2009-12-01

    The review describes structure and functions of bone marrow-derived peptides (myelopeptides). The final biological effects of these endogenous bioregulators (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their immunocorrecting and differentiating activity. Myelopeptides are the integral parts of the immune homeostasis maintenance system. Nowadays, medical preparations with no side effects and natural mechanisms of action are being developed on the basis of synthesized myelopeptides.

  7. Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics

    NASA Technical Reports Server (NTRS)

    Ho, K. K.; Moody, G. B.; Peng, C. K.; Mietus, J. E.; Larson, M. G.; Levy, D.; Goldberger, A. L.

    1997-01-01

    BACKGROUND: Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. METHODS AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.

  8. Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics

    NASA Technical Reports Server (NTRS)

    Ho, K. K.; Moody, G. B.; Peng, C. K.; Mietus, J. E.; Larson, M. G.; Levy, D.; Goldberger, A. L.

    1997-01-01

    BACKGROUND: Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. METHODS AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.

  9. Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities.

    PubMed

    Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

    2016-03-25

    Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi's productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances.

  10. Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

    PubMed Central

    Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

    2016-01-01

    Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances. PMID:27023571

  11. Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity

    PubMed Central

    Lei, Liang; Xue, Yong-bo; Liu, Zhong; Peng, Si-si; He, Yan; Zhang, Yang; Fang, Rong; Wang, Jian-ping; Luo, Zeng-wei; Yao, Guang-min; Zhang, Jin-wen; Zhang, Geng; Song, Hong-ping; Zhang, Yong-hui

    2015-01-01

    Coumarin derivatives are an important class of C6–C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4–8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting. PMID:26315062

  12. Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity.

    PubMed

    Lei, Liang; Xue, Yong-bo; Liu, Zhong; Peng, Si-si; He, Yan; Zhang, Yang; Fang, Rong; Wang, Jian-ping; Luo, Zeng-wei; Yao, Guang-min; Zhang, Jin-wen; Zhang, Geng; Song, Hong-ping; Zhang, Yong-hui

    2015-08-28

    Coumarin derivatives are an important class of C6-C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4-8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting.

  13. Antimicrobial activity of rhodanine-3-acetic acid derivatives.

    PubMed

    Krátký, Martin; Vinšová, Jarmila; Stolaříková, Jiřina

    2017-03-15

    Twenty-four 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine-3-acetic acid)-based amides, esters and 5-arylalkylidene derivatives were synthesized, characterized and evaluated as potential antimicrobial agents against a panel of bacteria, mycobacteria and fungi. All of the derivatives were active against mycobacteria. N-(4-Chlorophenyl)-2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetamide demonstrated the highest activity against Mycobacterium tuberculosis with minimum inhibitory concentrations (MIC) of 8-16μM. Non-tuberculous mycobacteria were the most susceptible to 2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetic acids (MIC values ⩾32μM). The highest antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus exhibited 4-(trifluoromethyl)phenyl 2-(4-oxo-2-thioxothiazolidin-3-yl)acetate (MIC⩾15.62μM). Several structure-activity relationships were identified. The activity against Gram-negative and fungal pathogens was marginal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Activity of dehydroabietic acid derivatives against wood contaminant fungi.

    PubMed

    Savluchinske-Feio, Sonia; Nunes, Lina; Pereira, Pablo Tavares; Silva, Ana M; Roseiro, José C; Gigante, Bárbara; Marcelo Curto, Maria João

    2007-09-01

    The antifungal activity of 10 dehydroabietic acid derivatives with different configuration in A and B rings (cis/trans A/B junction) and different substituents and/or functionalities was evaluated in bioassays in vitro and in situ (pine wood blocks). The test compounds dissolved in acetone were assayed at several concentrations w/w (test compound/culture medium) against the fungi. The Relative Inhibition (RI) was determined by measuring the radial growth of colonies of the fungi treated with the test compounds by comparison with those of control cultures; the results are expressed as EC(50). The results of bioassays in vitro have shown that hydroxyl and aldehyde functions are required for antifungal activity in this group of compounds and deisopropylation can increase the activity. Our assay of antifungal activity in situ (in pine wood blocks) provides a means to investigate the preservative activities of these antifungal compounds under actual conditions of use. The dehydroabietic acid derivative cis-deisopropyldehydroabietanol (10) inhibited the growth of several of the fungi tested, in vitro and in situ. The results obtained in situ with the test compound (10) at 6% and 8% were not significantly different from the reference products and a good level of protection of the wood against the organisms tested was achieved. The results in wood bioassays present new possibilities in the search for natural new compounds in the wood protection, as an alternative to conventional fungicides.

  15. Surface photoisomerization activity vs. functionalization of azobenzene derivatives

    NASA Astrophysics Data System (ADS)

    Berbil-Bautista, Luis; Cho, Jongweon; Levy, Niv; Comstock, Matthew J.; Poulsen, Dan; Frechet, Jean M. J.; Crommie, Michael F.

    2008-03-01

    Azobenzene and its derivatives can be reversibly photoisomerized between their cis and trans conformations in solution. The photoisomerization process is wavelength selective and results in a large length change. Hence, it is ideally suited to actuating molecular nanomachines on surfaces. However, it has recently been shown [1] that to recover photoisomerization activity on a metallic surface molecules must be functionalized with bulky spacing groups to decouple the optically active part of the molecule from the surface. This results in various trade-offs between molecular optical activity and overall flexibility/functionality. We have explored the photoisomerization activity of different azobenzene derivatives on metallic surfaces using a scanning tunneling microscope (STM) with optical access to the sample. The effects on molecular photo-activity and self-assembly for different substituent groups has been studied. [1] Matthew J. Comstock, Niv Levy, Armen Kirakosian, Jongweon Cho, Frank Lauterwasser, Jessica H. Harvey, David A. Strubbe, Jean M. J. Fr'echet, Dirk Trauner, Steven G. Louie, and Michael F. Crommie Phys. Rev. Lett. 99, 038301 (2007)

  16. Synthesis and pharmacological activity evaluation of arctigenin monoester derivatives.

    PubMed

    Chen, Qiulian; Yang, Limin; Han, Mei; Cai, Enbo; Zhao, Yan

    2016-12-01

    Arctigenin (ARG), a nature medicine with many pharmacological activities, was poorly soluble in water and placed restriction on practical usage. Six novel arctigenin monoester derivatives were obtained from the reflux reaction with arctigenin, carboxylic acids (crotonic acid, furoic acid, 2-naphthalene acid and indol-3-acetic acid), EDCI and DMAP in dichloromethane at 60°C for 4-6h and their properties on nitrite scavenging assay were investigated in vitro. Based on the results, the one of the most effective derivatives, arctigenin β-indolylacetate (ARG6), was selected to study anti-tumor activity in vivo at doses of 20 and 40mg/kg. The results showed that comparison with ARG group, ARG6 exhibited more anti-tumor activity in H22 tumor-bearing mice. Furthermore, ARG6 exhibited less damage to the liver, kidney, spleen and thymus when compared with those in positive group. Biochemical parameters of ALT, AST, BUN and Cre showed ARG6 had little toxicity to mice as well. ARG6 significantly improved serum cytokine levels of IL-2, IL-6, IFN-γ and TNF-α, and decreased VEGF compared with ARG. Moreover, H & E staining, TUNEL assay and immunohistochemical of tumor issues also indicated that ARG6 exhibited anti-tumor activity in vivo. In brief, the present study provide a method to improve ARG anti-tumor activity and provide a reference for new anti-tumor agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives

    PubMed Central

    Shtyrlin, Nikita V.; Sapozhnikov, Sergey V.; Galiullina, Albina S.; Kayumov, Airat R.; Bondar, Oksana V.; Mirchink, Elena P.; Isakova, Elena B.; Firsov, Alexander A.; Balakin, Konstantin V.

    2016-01-01

    A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistant S. aureus strains with MICs in the range of 0.5–2 μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negative E. coli and P. aeruginosa strains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest in S. typhimurium showed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies. PMID:27800491

  18. Factors affecting antibacterial activity of hop compounds and their derivatives.

    PubMed

    Simpson, W J; Smith, A R

    1992-04-01

    The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone.

  19. Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives.

    PubMed

    Shtyrlin, Nikita V; Sapozhnikov, Sergey V; Galiullina, Albina S; Kayumov, Airat R; Bondar, Oksana V; Mirchink, Elena P; Isakova, Elena B; Firsov, Alexander A; Balakin, Konstantin V; Shtyrlin, Yurii G

    2016-01-01

    A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistant S. aureus strains with MICs in the range of 0.5-2 μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negative E. coli and P. aeruginosa strains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest in S. typhimurium showed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies.

  20. Design, Synthesis, and Antibacterial Activities of Novel Heterocyclic Arylsulphonamide Derivatives.

    PubMed

    Singh, Anuradha; Srivastava, Ritika; Singh, Ramendra K

    2017-02-13

    Design, synthesis, and antibacterial activities of a series of arylsulphonamide derivatives as probable peptide deformylase (PDF) inhibitors have been discussed. Compounds have been designed following Lipinski's rule and after docking into the active site of PDF protein (PDB code: 1G2A) synthesized later on. Furthermore, to assess their antibacterial activity, screening of the compound was done in vitro conditions against Gram-positive and Gram-negative bacterial strains. In silico, studies revealed these compounds as potential antibacterial agents and this fact was also supported by their prominent scoring functions. Antibacterial results indicated that these molecules possessed a significant activity against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli with MIC values ranging from 0.06 to 0.29 μM. TOPKAT results showed that high LD50 values and the compounds were assumed non-carcinogenic when various animal models were studied computationally.

  1. [Bio-active substances derived from marine microorganisms].

    PubMed

    Liu, Quanyong; Hu, Jiangchun; Xue, Delin; Ma, Chengxin; Wang, Shujin

    2002-07-01

    Marine microorganisms, which are taxonomically diverse and genetically special, have powerful potential in producing novel bio-active substances. This article summarized research progress in this respect. The results showed that marine bacteria which are main marine microorganism flora can produce rich kinds of bio-active substances and that even though marine actinomycetes and marine fungi are not as many as marine bacteria in species and quantity, they should be paid no less attention about their bio-active substances. Besides, present research are limited to those marine microorganisms which are easily cultured. One of the future research trends will be focused on bio-active substances derived from non-culturable marine microorganisms.

  2. Synthesis, topoisomerase I inhibitory and cytotoxic activities of chromone derivatives.

    PubMed

    Maicheen, Chirattikan; Jittikoon, Jiraphun; Vajragupta, Opa; Ungwitayatorn, Jiraporn

    2013-05-01

    A series of chromone derivatives were designed as potential topoisomerase I (Top I) inhibitors based on the docking simulation study. Sixteen synthesized compounds were evaluated for Top I inhibitory activity and some compounds were further tested for in vitro cytotoxic activity. The most potent inhibitor, chromone 11b showed greater inhibitory activity (IC50 = 1.46 μM) than the known Top I inhibitors, i.e., camptothecin, fisetin and morin, but inactive against breast cancer cell (MCF-7), oral cavity cancer cell (KB) and small cell lung cancer (NCI-H187). Chromone 11c, another potent inhibitor (IC50 = 6.16 μM), exhibited cytotoxic activity against KB (IC50 = 73.32 μM) and NCI-H187 (IC50 = 36.79 μM).

  3. Antimalarial activity of new water-soluble dihydroartemisinin derivatives.

    PubMed

    Lin, A J; Klayman, D L; Milhous, W K

    1987-11-01

    The usefulness of sodium artesunate (3), a water-soluble derivative of artemisinin (1), is impaired by its poor stability in aqueous solution. To overcome the ease of hydrolysis of the ester group in 3, a new series of derivatives of dihydroartemisinin (2) was prepared in which the solubilizing moiety, which contains a carboxylate group, is joined to dihydroartemisinin by an ether rather than an ester linkage. The new derivatives were prepared in good yield by treatment of dihydroartemisinin with an appropriate alcohol under boron trifluoride etherate catalysis at room temperature. All major condensation products are the beta isomer. Hydrolysis of the esters with 2.5% KOH/MeOH gave the corresponding potassium salts, which were converted to free acids (8b-d) by acidification. The derivatives were tested in vitro against two clones of human malaria, Plasmodium falciparum D-6 (Sierra Leone clone) and W-2 (Indochina clone). No cross-resistance to the antimalarial agents mefloquine, chloroquine, pyrimethamine, sulfadoxine, and quinine was observed. In general, the new compounds are more effective against the W-2 than the D-6 strain. Esters (5a-d) possess activity comparable to that of the parent compounds 1 and 2; however, conversion of the esters to their corresponding carboxylates (7a-d) or acids (8b-d), with the exception of artelinic acid (8d), drastically decreases the antimalarial activities in both cell lines. Artelinic acid, which is both soluble and stable in 2.5% K2CO3 solution, possesses superior in vivo activity against Plasmodium berghei than artemisinin or artesunic acid.

  4. Structure-activity relationship studies of microbiologically active thiosemicarbazides derived from hydroxybenzoic acid hydrazides.

    PubMed

    Plech, Tomasz; Paneth, Agata; Kaproń, Barbara; Kosikowska, Urszula; Malm, Anna; Strzelczyk, Aleksandra; Stączek, Paweł

    2015-03-01

    Forty-five derivatives of thiosemicarbazide were synthesized, and their antibacterial activity against Gram-positive and Gram-negative bacteria was evaluated. Some of the described compounds exhibited interesting activity against reference strains of Gram-positive bacteria, whereas only two derivatives had the ability to inhibit the growth of Gram-negative species (Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453). The most potent antimicrobial activity was observed in the cases of salicylic acid hydrazide derivatives. The differences in activity inspired us to conduct conformational analysis using molecular mechanics level. The obtained results suggest that the molecule geometry, especially at the N4-terminus of thiosemicarbazide skeleton, determines the antibacterial activity. Unfortunately, in opposition to what we expected, only one of the tested compounds inhibited the activity of the topoIV enzyme, and none of them was active against DNA gyrase. © 2014 John Wiley & Sons A/S.

  5. Lead sorption performance on active silica derived from fly ash.

    PubMed

    Zhang, Xizhu; Zhu, Zhibao

    2015-01-01

    The object of this study was to estimate the sorption property of active silica derived from fly ash after separation of silica and aluminum. The specific surface area of active silica enlarged to 115 m(2)/g was compared with the original fly ash (4 m(2)/g). Field emission scanning electron microscopy displayed the active silica, which looked like a honeycomb or curly layer with many lamellae that formed many mesopores. The uptake kinetics indicated that the residual concentration of Pb(2+) in the aqueous solution decreased rapidly from the initial 1.25 mg/L to less than 10 μg/L within 45 min. The removal efficiency of Pb(2+) on active silica was pH dependent. The increase in pH value promoted Pb(2+) removal because the negative surface provided more electrostatic attraction sites. A stepwise non-linear isotherm was obtained because the lamellae of active silica provided a heterogeneous surface with various kinds of active sites. The maximum sorption amount of Pb on active silica was more than 90 mg/g, which was better than some pristine-activated carbon.

  6. Investigation of membrane active properties and antiradical activity of gossypol and its derivatives

    USDA-ARS?s Scientific Manuscript database

    New asymmetrical derivatives of gossypol were synthesized. The antioxidant activity of gossypol and these derivatives was studied. The interaction of these compounds with modeled lipid membranes was also studied. It was found that the antioxidant effects and ability to interact with membranes was...

  7. Membrane-Active Properties and Antiradical Activity of Gossypol and Its Derivatives

    USDA-ARS?s Scientific Manuscript database

    New asymmetrical derivatives of gossypol were synthesized. The antioxidant activity of gossypol and these derivatives was studied. The interaction of these compounds with modeled lipid membranes was also studied. It was found that the antioxidant effects and ability to interact with membranes was...

  8. Some characteristics of activity of potential chemotherapeutics--benzimidazole derivatives.

    PubMed

    Błaszczak-Świątkiewicz, Katarzyna; Mikiciuk-Olasik, Elżbieta

    2015-03-01

    In this work, the biological activity of some benzimidazoles and benzimidazole-4,7-diones was compared. These two groups of compounds were evaluated as potential chemotherapeutics and their characteristic relationship structure to biological activity was discussed. The authors compared their effect into the cytotoxic, apoptosis and DNA destruction approach. Their cytotoxic effect on the human lung adenocarcinoma A549 cells line was determined by WST-1 test. Next the cytotoxic way of tumor cells death was determined by caspase 3/7 test. The last point referred to the DNA destruction of A549 cells and test in situ DNA Assay Kit was applied. Two of the examined compounds (B2 and D2) show a very good correlation of the cytotoxic effect normoxia to hypoxia and they have been found as the potential agents of the DNA damage. The most cytotoxic feature possesses N-oxide benzimidazole derivatives (D and B groups). The screening test of the DNA damage established that N-oxide benzimidazole derivatives (D and B groups) can be more potent as the hypoxia-selective agents for tumor cells than benzimidazole derivatives (A and C groups). Additionally, the test of the caspase-dependent apoptosis proved that the exposure of benzimidazole-4,7-diones against A549 cells, especially in hypoxia, promotes apoptotic cell death.

  9. [Design, synthesis and activities of novel benzothiazole derivatives containing arylpiperazine].

    PubMed

    Liu, Wen-Hu; Chang, Jin-Xia; Liu, Yi; Luo, Jie-Wei; Zhang, Jian-Wu

    2013-08-01

    Twenty-four novel benzothiazole derivatives containing arylpiperazine were designed and synthesized by bioisosterism principle. Anti-proliferative effect of these synthesized compounds against four cancer cell and two normal cell lines were evaluated in vitro by the standard MTT assay. Pharmacological test showed that most of the compounds exhibited potent antitumor activity. Some of the compounds (II2, II3, II6, II7) showed strong anti-proliferation activities against HepG2 and HeLa229 cell lines with the IC 50 values of 1.6-4.5 micromol x L(-1) and 2.5-5.3 micromol x L(-1), respectively, and compounds having cyan in p-substituted benzene ring (I4, I8, I12, II4, II8 and II12) were found to have better antitumor activities against AsPC-1 cell lines with the IC50 values of 5.2-11.3 micromol x L(-1). The structure-activity relationship of benzothiazole derivatives containing arylpiperazine was also discussed preliminarily.

  10. Phosphine derivatives of sparfloxacin - Synthesis, structures and in vitro activity

    NASA Astrophysics Data System (ADS)

    Komarnicka, Urszula K.; Starosta, Radosław; Guz-Regner, Katarzyna; Bugla-Płoskońska, Gabriela; Kyzioł, Agnieszka; Jeżowska-Bojczuk, Małgorzata

    2015-09-01

    We synthesized two derivatives of sparfloxacin (HSf): aminomethyl(diphenyl)phosphine (PSf) and its oxide (OPSf). The compounds were characterized by NMR spectroscopy, MS and elemental analysis. In addition, the molecular structures of the compounds were determined using DFT and X-ray (OPSf) analysis. The antibacterial activity of HSf and both derivatives was tested against four reference and fifteen clinical Gram-positive and Gram-negative strains of bacteria (sensitive or resistant to fluoroquinolones). The results showed that the activity of PSf was similar to or higher than the activity of HSf, while OPSf was found significantly less active. The compounds were also tested in vitro toward the following cancer cell lines: mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). Regardless of the cancer cell line, derivatization of HSf resulted in the gradual increase of cytotoxicity. OPSf exhibited the highest one (4 h - incubation time: IC50(CT26) = 51.0 ± 1.2; IC50(A549) = 74.9 ± 1.4 and 24 h: IC50(CT26) = 109.2 ± 8.8; IC50(A549) = 52.7 ± 9.2).

  11. Synthesis and evaluation of the antiplasmodial activity of tryptanthrin derivatives

    PubMed Central

    Onambele, Liliane Abodo; Riepl, Herbert; Fischer, Rainer; Pradel, Gabriele; Prokop, Aram; Aminake, Makoah Nigel

    2015-01-01

    Malaria remains one of the most deadly diseases threatening humankind and is still affecting a significant proportion of the world population, especially in Africa. Chemotherapy is a vital component of the fight against the disease and new antimalarial agents are urgently needed to curb the spread of malaria parasites that are resistant to existing drugs. The natural product tryptanthrin is known for its wide range of activities, including antiplasmodial activity, but its poor solubility has undermined its development as potent antimicrobial and antiprotozoan agent. The aim of this work was to synthesize analogues of tryptanthrin and to evaluate their antiplasmodial activity against the asexual and sexual blood stages of Plasmodium falciparum. Our results suggest that most tryptanthrin analogues retained their antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30–100 nM). The antiplasmodial activity of the most active compound NT1 (IC50: 30 nM; SI: 155.9) was similar in both strains and close to that of chloroquine (IC50: 20 nM) on the sensitive strain. The antiplasmodial activity was improved with derivatization, thus pointing out the necessity to explore tryptanthrin using medicinal chemistry approaches. Ten (10) of the tested derivatives met the criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 < 100 nM. In addition to their activity on the asexual stages, tryptanthrin and two selected derivatives (NT1 and T8) prevented the maturation of gametocytes at their IC90 concentrations, indicating a transmission-blocking potential. Moreover, NT1 was able to impair gametogenesis by reducing the exflagellation of microgametes by 20% at IC90, while tryptanthrin and T8 had no influence on exflagellation. The results of this study confirm that tryptanthrin and its derivatives are potential antimalarial candidates with abilities to kill the intraerythrocytic

  12. Synthesis and cytostatic activity of purine nucleosides derivatives of allofuranose.

    PubMed

    Besada, Pedro; Costas, Tamara; Teijeira, Marta; Terán, Carmen

    2010-12-01

    Several new purine nucleosides derivatives of allofuranose were prepared according to Vorbrüggen method, starting from 1,2,5,6-di-O-isopropylidene-α-D-allofuranose and using 1,2,3,5,6-pentaacetoxy-β-D-allofuranose as key intermediate. The synthesized allofuranosyl nucleosides, as well as some acetyl derivatives, were evaluated for their cytotoxicity in vitro in three human cancer cell lines (MCF-7, Hela-229 and HL-60). Among the studied compounds the 9-(2,3,5,6-tetra-O-acetyl-β-D-allofuranosyl)-2,6-dichloropurine (9) was the most potent one on the three cell lines evaluated, being its activity against HL-60 cells similar to cisplatin.

  13. Synthesis and DPPH radical scavenging activity of prenylated phenol derivatives.

    PubMed

    Osorio, Mauricio; Aravena, Jacqueline; Vergara, Alejandra; Taborga, Lautaro; Baeza, Evelyn; Catalán, Karen; González, Cesar; Carvajal, Marcela; Carrasco, Héctor; Espinoza, Luis

    2012-01-06

    The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF(3)×OEt(2). Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho position occurred with some phenols. All the synthesized compounds were evaluated as antioxidants according to a DPPH radical scavenging activity assay. IC(50) values of five synthesized compounds indicated they were as good antioxidants as Trolox™.

  14. Structure and antimicrobial activity of phloroglucinol derivatives from Achyrocline satureioides.

    PubMed

    Casero, Carina; Machín, Félix; Méndez-Álvarez, Sebastián; Demo, Mirta; Ravelo, Ángel G; Pérez-Hernández, Nury; Joseph-Nathan, Pedro; Estévez-Braun, Ana

    2015-01-23

    The new prenylated phloroglucinol α-pyrones 1-3 and the new dibenzofuran 4, together with the known 23-methyl-6-O-demethylauricepyrone (5), achyrofuran (6), and 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphaliin A), were isolated from the aerial parts of Achyrocline satureioides. Their structures were determined by 1D and 2D NMR spectroscopic studies, while the absolute configuration of the sole stereogenic center of 1 was established by vibrational circular dichroism measurements in comparison to density functional theory calculated data. The same (S) absolute configuration of the α-methylbutyryl chain attached to the phloroglucinol nucleus was assumed for compounds 2-6 based on biogenetic considerations. Derivatives 7-16 were prepared from 1 and 5, and the antimicrobial activities of the isolated metabolites and some of the semisynthetic derivatives against a selected panel of Gram-positive and Gram-negative bacteria, as well as a set of yeast molds, were determined.

  15. Synthesis of chitosan derivative with diethyldithiocarbamate and its antifungal activity.

    PubMed

    Qin, Yukun; Xing, Ronge; Liu, Song; Li, Kecheng; Hu, Linfeng; Yu, Huahua; Chen, Xiaolin; Li, Pengcheng

    2014-04-01

    With an aim to discover novel chitosan derivatives with enhanced antifungal properties compared with chitosan. Diethyl dithiocarbamate chitosan (EtDTCCS) was investigated and its structure was well identified. The antifungal activity of EtDTCCS against Alternaria porri (A. porri), Gloeosporium theae sinensis Miyake (G. theae sinensis), and Stemphylium solani Weber (S. solani) was tested at 0.25, 0.5, and 1.0 mg/mL, respectively. Compared with plain chitosan, EtDTCCS shows better inhibitory effect with 93.2% inhibitory index on G. theae sinensis at 1.0 mg/mL, even stronger than for polyoxin (82.5%). It was inferred derivatives of this kind may find potential applications for the treatment of various crop-threatening diseases.

  16. Antifungal activity of the allylamine derivative terbinafine in vitro.

    PubMed Central

    Petranyi, G; Meingassner, J G; Mieth, H

    1987-01-01

    Terbinafine, an allylamine derivative, represents the most effective of this new chemical class of antimycotic compounds. Under in vitro conditions, terbinafine proved to be highly active against dermatophytes (MIC range, 0.001 to 0.01 microgram/ml), aspergilli (MIC range, 0.05 to 1.56 micrograms/ml), and Sporothrix schenckii (MIC range, 0.1 to 0.4 microgram/ml) and also exerted good activity against yeasts (MIC range, 0.1 to greater than 100 micrograms/ml). The growth of Malassezia furfur was inhibited also (MIC range, 0.2 to 0.8 microgram/ml). Terbinafine displays a primary fungicidal action against dermatophytes, other filamentous fungi, and S. schenckii. The type of action against yeasts is species dependent and can be primarily fungicidal (Candida parapsilosis) or fungistatic (Candida albicans). The in vitro activity of terbinafine is pH dependent and rises with increasing pH value. PMID:3674847

  17. meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

    PubMed

    Reyes-Melo, Karen; García, Abraham; Romo-Mancillas, Antonio; Garza-González, Elvira; Rivas-Galindo, Verónica M; Miranda, Luis D; Vargas-Villarreal, Javier; Favela-Hernández, Juan Manuel J; Camacho-Corona, María Del Rayo

    2017-10-15

    Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Fast and Fully Automatic Left Ventricular Segmentation and Tracking in Echocardiography Using Shape-Based B-Spline Explicit Active Surfaces.

    PubMed

    Pedrosa, Joao; Queiros, Sandro; Bernard, Olivier; Engvall, Jan; Edvardsen, Thor; Nagel, Eike; Dhooge, Jan

    2017-08-02

    Cardiac volume/function assessment remains a critical step in daily cardiology and 3D ultrasound plays an increasingly important role. Fully automatic left ventricular segmentation is, however, a challenging task due to the artifacts and low contrast-to-noise ratio of ultrasound imaging. In the present work, a fast and fully automatic framework for full cycle endocardial left ventricle segmentation is proposed. This approach couples the advantages of the B-spline explicit active surfaces framework, a purely image information approach, to those of statistical shape models to give prior information about the expected shape for an accurate segmentation. The segmentation is propagated throughout the heart cycle using a localized anatomical affine optical flow. It is shown that this approach not only outperforms other state-of-the-art methods in terms of distance metrics with mean average distances of 1.81±0.59 mm and 1.98±0.66 mm at end-diastole and end-systole respectively but is computationally efficient (in average 11 seconds per 4D image) and fully automatic.

  19. In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa

    NASA Astrophysics Data System (ADS)

    Verchère, Alice; Dezi, Manuela; Adrien, Vladimir; Broutin, Isabelle; Picard, Martin

    2015-04-01

    Antibiotic resistance is a major public health issue and many bacteria responsible for human infections have now developed a variety of antibiotic resistance mechanisms. For instance, Pseudomonas aeruginosa, a disease-causing Gram-negative bacteria, is now resistant to almost every class of antibiotics. Much of this resistance is attributable to multidrug efflux pumps, which are tripartite membrane protein complexes that span both membranes and actively expel antibiotics. Here we report an in vitro procedure to monitor transport by the tripartite MexAB-OprM pump. By combining proteoliposomes containing the MexAB and OprM portions of the complex, we are able to assay energy-dependent substrate translocation in a system that mimics the dual-membrane architecture of Gram-negative bacteria. This assay facilitates the study of pump transport dynamics and could be used to screen pump inhibitors with potential clinical use in restoring therapeutic activity of old antibiotics.

  20. [Condition setting for the measurement of blood coagulation factor XIII activity using a fully automated blood coagulation analyzer, COAGTRON-350].

    PubMed

    Kanno, Nobuko; Kaneko, Makoto; Tanabe, Kumiko; Jyona, Masahiro; Yokota, Hiromitsu; Yatomi, Yutaka

    2012-12-01

    The automated laboratory analyzer COAGTRON-350 (Trinity Biotech) is used for routine and specific coagulation testing for the detection of fibrin formation utilizing either mechanical principles (ball method) or photo-optical principles, chromogenic kinetic enzyme analysis, and immune-turbidimetric detection systems in one benchtop unit. In this study, we demonstrated and established a parameter for the measurement of factor XIII (FXIII) activity using Berichrom FXIII reagent and the COAGTRON-350 analyzer. The usual protocol used for this reagent, based on the handling method, was slightly modified for this device. The analysis showed that fundamental study for the measurement of FXIII activity under our condition setting was favorable in terms of reproducibility, linearity, and correlation with another assays. Since FXIII is the key enzyme that plays important roles in hemostasis by stabilizing fibrin formation, the measurement of FXIII is essential for the diagnosis of bleeding disorders. Therefore, FXIII activity assessment as well as a routine coagulation testing can be conducted simultaneously with one instrument, which is useful in coagulopathy assessment.

  1. Antifungal activity of topical microemulsion containing a thiophene derivative

    PubMed Central

    Guimarães, Geovani Pereira; de Freitas Araújo Reis, Mysrayn Yargo; da Silva, Dayanne Tomaz Casimiro; Junior, Francisco Jaime Bezerra Mendonça; Converti, Attílio; Pessoa, Adalberto; de Lima Damasceno, Bolívar Ponciano Goulart; da Silva, José Alexsandro

    2014-01-01

    Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270–540 μg.mL−1) and good activity against C. neoformans (MIC = 17 μg.mL−1). Candida species were susceptible to ME-5CN05 (70–140 μg.mL−1), but C. neoformans was much more, presenting a MIC value of 2.2 μg.mL−1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans. PMID:25242940

  2. Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives.

    PubMed

    Demir Özkay, Ümide; Kaya, Ceren; Acar Çevik, Ulviye; Can, Özgür Devrim

    2017-09-07

    Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a-3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f-3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f-3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a-3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

  3. Synthesis and biological activity of alkynoic acids derivatives against mycobacteria

    PubMed Central

    Vilchèze, Catherine; Leung, Lawrence W.; Bittman, Robert; Jacobs, William R.

    2015-01-01

    2-alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2- alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development. PMID:26256431

  4. Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity.

    PubMed

    Can, Nafiz Öncü; Osmaniye, Derya; Levent, Serkan; Sağlık, Begüm Nurpelin; İnci, Beril; Ilgın, Sinem; Özkay, Yusuf; Kaplancıklı, Zafer Asım

    2017-08-20

    In the present work, 14 new 1-substituted-2-phenylhydrazone derivatives were synthesized to evaluate their inhibitory activity against hMAO enzymes. The structures of the newly synthesized hydrazones 2a-2n were characterized by IR, 1H-NMR, 13C-NMR, HR-MS spectroscopic methods. The inhibitory activity of compounds 2a-2n against hMAO-A and hMAO-B enzymes was elucidated by using an in-vitro Amplex Red® reagent assay based on fluorometric methods. According to the activity studies, 2a and 2b were found to be the most active compounds against hMAO-A enzyme, with IC50 values of 0.342 µM and 0.028 µM, respectively. The most active compounds 2a-2b were evaluated by means of enzyme kinetics and docking studies. Moreover, these compounds were subjected to cytotoxicity and genotoxicity tests to establish their preliminary toxicological profiles and were found to be non-cytotoxic and non-genotoxic. Consequently, the findings of this study display the biological importance of compounds 2a, 2b as selective, irreversible and competitive inhibitors of hMAO-A. Docking studies revealed that there is a strong interaction between hMAO-A and the most active compound 2b.

  5. Asymmetric synthesis and cytotoxic activity of isomeric phytosphingosine derivatives.

    PubMed

    Rives, Arnaud; Baudoin-Dehoux, Cécile; Saffon, Nathalie; Andrieu-Abadie, Nathalie; Génisson, Yves

    2011-12-07

    New phytosphingosine analogues have been conceived, synthesised and their cytotoxicity in B16 murine melanoma cells tested. These compounds embed an isomeric substitution pattern resulting from a formal permutation of the C-2 and C-4 substituents along the aliphatic skeleton of the original sphingoid base. Five different stereoisomers have been accessed through regio- and stereocontrolled opening of the oxirane of long chain epoxyamine precursors. The corresponding N-hexyl and N-octanoyl derivatives have also been prepared. In cell viability experiments all the primary amines were found to be more active than the natural phytosphingosine with IC(50) in the low μM range for the most potent compounds.

  6. Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

    DTIC Science & Technology

    2014-07-01

    Summary 3. DATES COVERED 1 JUL 2013 - 30 JUN 2014 4 . TITLE AND SUBTITLE Dehydroepiandrosterone Derivatives as Potent Antiandrogens with... 4 Conclusion…………………………………………………………………………… 5 References……………………………………………………………………………. 6 Appendices...metabolite from dehydroepiandrosterone ( DHEA ) and a precursor of testosterone, has an intrinsic androgenic activity which was not completely antagonized by

  7. Synthesis of novel chromene derivatives of expected antitumor activity.

    PubMed

    Kandeel, Manal M; Kamal, Aliaa M; Abdelall, Eman K A; Elshemy, Heba A H

    2013-01-01

    Inhibition of tubulin polymerization is one of the important tactics in cancer therapy. Since 4-aryl-4H-chromene derivatives are found to be microtubule-binding agents via interfering with tubulin polymerization so we decide to concentrate our exploration efforts on the combination of this nucleus with 5-, 6-, and/or 7-memebered heterocyclic moieties in a novel series of compounds to explore the effect that might result from this combination. Ten novel compounds were selected for anticancer screening assay against MCF-7 breast cancer cell line in comparison to colchicine as positive control and most of them showed excellent activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. Synthesis and biological activity of novel deoxycholic acid derivatives.

    PubMed

    Popadyuk, Irina I; Markov, Andrey V; Salomatina, Oksana V; Logashenko, Evgeniya B; Shernyukov, Andrey V; Zenkova, Marina A; Salakhutdinov, Nariman F

    2015-08-01

    We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Antiplatelet effect of active components derived from Chinese herbal medicine.

    PubMed

    Zhang, Ying; Ma, Xiao-Juan; Shi, Da-Zhuo

    2015-10-10

    Atherothrombosis is the major cause of acute coronary syndromes and cardiovascular deaths. Platelets participate in the processes of forming and extending atherosclerotic plaques. Therefore, antiplatelet therapy is a milestone in the primary and second prevention of atherothrombotic diseases. Along with the longterm use of antiplatelet agents, the safety and drug resistance has become a big concern in clinic and new drugs possessing higher effectiveness and fewer adverse effects are needed. Abundant recent data support that traditional Chinese herbs may be a good alternative and complementary choice of new antiplatelet drugs. This review highlights the progress of antiplatelet effect of active components derived from traditional Chinese herbs based on their chemical structures.

  10. Exploring the phosphoproteome profiles during Xenopus egg activation by calcium stimulation using a fully automated phosphopeptide purification system

    PubMed Central

    Kanno, Takuma; Furukawa, Kazuhiro; Horigome, Tsuneyoshi

    2016-01-01

    To explore the phosphoproteome profiles during Xenopus egg activation by Ca2+-stimulation, an automated phosphopeptide purification system involving a titania column was improved by introducing 4-step elution with phosphate buffers. The number of detected phosphopeptides in the tryptic digest of a Xenopus egg cytosol fraction on mass spectrometry (MS) was increased 1.5-fold and the percentage of multiply phosphorylated peptides increased from 17 to 24% with introduction of the 4-step elution method. Phosphopeptides were purified by the improved method from tryptic digests of cytosol fractions of Xenopus eggs without and with a Ca2+-stimulus, and then, analysed by MS. One thousand three hundred and seventy-five and 994 phosphopeptides were reproducibly detected on duplicate MS, respectively. They included 818 and 437 phosphopeptides specific to each digest, respectively. A method involving isobaric tags for relative and absolute quantitation (iTRAQ) was also applied to compare the phosphorylation levels in Xenopus eggs without and with a Ca2+-stimulus, the ratios for 112 phosphopeptides in tryptic digests of these egg cytosol fractions being obtained. It was suggested from all the results that the phosphorylation sites and levels change during Xenopus egg activation for many known and unknown sites on structural proteins, signalling related proteins, cell cycle-related proteins and others. PMID:26530081

  11. Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives.

    PubMed

    Alakurtti, Sami; Heiska, Tuomo; Kiriazis, Alexandros; Sacerdoti-Sierra, Nina; Jaffe, Charles L; Yli-Kauhaluoma, Jari

    2010-02-15

    Betulin, a naturally occurring abundant triterpene is converted in four steps to 3,28-di-O-acetyllupa-12,18-diene. When various 4-substituted urazoles were oxidized to the corresponding urazines with iodobenzene diacetate in the presence of 3,28-di-O-acetyllupa-12,18-diene, new heterocyclic betulin derivatives were produced. These betulin derivatives were examined in a microplate assay at 50 microM for their ability to inhibit the growth of Leishmania donovani axenic amastigotes, a species that causes the fatal visceral leishmaniasis. GI(50) (concentration for 50% growth inhibition) values of the most effective compounds were determined and their cytotoxicity on the human macrophage cell line THP-1 evaluated. The anti-leishmanial activity on L. donovani amastigotes growing in macrophages was also examined. The heterocycloadduct between 3,28-di-O-acetyllupa-12,18-diene and 4-methylurazine was the most effective derivative with an GI(50)=8.9 microM against L. donovani amastigotes.

  12. Fully relativistic complete active space self-consistent field for large molecules: Quasi-second-order minimax optimization

    NASA Astrophysics Data System (ADS)

    Bates, Jefferson E.; Shiozaki, Toru

    2015-01-01

    We develop an efficient algorithm for four-component complete active space self-consistent field (CASSCF) methods on the basis of the Dirac equation that takes into account spin-orbit and other relativistic effects self-consistently. Orbitals are optimized using a trust-region quasi-Newton method with Hessian updates so that energies are minimized with respect to rotations among electronic orbitals and maximized with respect to rotations between electronic and positronic orbitals. Utilizing density fitting and parallel computation, we demonstrate that Dirac-Coulomb CASSCF calculations can be routinely performed on systems with 100 atoms and a few heavy-elements. The convergence behavior and wall times for octachloridodirhenate(III) and a tungsten methylidene complex are presented. In addition, the excitation energies of octachloridodirhenate(III) are reported using a state-averaged variant.

  13. Fully relativistic complete active space self-consistent field for large molecules: quasi-second-order minimax optimization.

    PubMed

    Bates, Jefferson E; Shiozaki, Toru

    2015-01-28

    We develop an efficient algorithm for four-component complete active space self-consistent field (CASSCF) methods on the basis of the Dirac equation that takes into account spin-orbit and other relativistic effects self-consistently. Orbitals are optimized using a trust-region quasi-Newton method with Hessian updates so that energies are minimized with respect to rotations among electronic orbitals and maximized with respect to rotations between electronic and positronic orbitals. Utilizing density fitting and parallel computation, we demonstrate that Dirac-Coulomb CASSCF calculations can be routinely performed on systems with 100 atoms and a few heavy-elements. The convergence behavior and wall times for octachloridodirhenate(III) and a tungsten methylidene complex are presented. In addition, the excitation energies of octachloridodirhenate(III) are reported using a state-averaged variant.

  14. Fully relativistic complete active space self-consistent field for large molecules: Quasi-second-order minimax optimization

    SciTech Connect

    Bates, Jefferson E.; Shiozaki, Toru

    2015-01-28

    We develop an efficient algorithm for four-component complete active space self-consistent field (CASSCF) methods on the basis of the Dirac equation that takes into account spin–orbit and other relativistic effects self-consistently. Orbitals are optimized using a trust-region quasi-Newton method with Hessian updates so that energies are minimized with respect to rotations among electronic orbitals and maximized with respect to rotations between electronic and positronic orbitals. Utilizing density fitting and parallel computation, we demonstrate that Dirac–Coulomb CASSCF calculations can be routinely performed on systems with 100 atoms and a few heavy-elements. The convergence behavior and wall times for octachloridodirhenate(III) and a tungsten methylidene complex are presented. In addition, the excitation energies of octachloridodirhenate(III) are reported using a state-averaged variant.

  15. Structure-activity relationship studies of phencyclidine derivatives in rats.

    PubMed

    Cone, E J; McQuinn, R L; Shannon, H E

    1984-01-01

    Phencyclidine (PCP), a semirigid molecule containing a cyclohexane ring with vicinally attached aromatic and piperidine rings, produces characteristic discriminative stimulus properties and pupillary miosis in rats. The effectiveness of a series of aromatic and nitrogen substituted analogs of PCP in producing PCP-like discriminative stimuli and changes in pupil diameter was determined in rats trained to discriminate between saline and 3.0 mg/kg of PCP. Dexoxadrol and its optical isomer levoxadrol were also evaluated for purposes of comparison. Analogs in which the electron-density of the aromatic ring was increased (3NH2-PCP) or only slightly reduced (3F-PCP) retained PCP-like activity. A loss of PCP-like activity occurred with analogs in which the electron-density of the aromatic ring was greatly reduced (3NO2-PCP) or extended to a larger system (1NCP and 2NCP). PCP-like activity also was abolished in analogs in which the distance between the aromatic ring and the remainder of the molecule was systematically increased by one, two or three methylene units. In contrast, substitutions on the nitrogen atom altered the potency, but not the efficacy, of such analogs. Dexoxadrol produced PCP-like activity whereas its optical enantiomer levoxadrol was devoid of such activity. These findings suggest a drug receptor surface with multiple domains or subsites which recognize regions of structural overlap among the phencyclidines, dioxolanes and psychotomimetic benzomorphan derivatives.

  16. Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.

    PubMed

    Shiraki, Hiroaki; Kozar, Michael P; Melendez, Victor; Hudson, Thomas H; Ohrt, Colin; Magill, Alan J; Lin, Ai J

    2011-01-13

    In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth. The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone. Analogues with electron donating groups showed better activity than those with electron withdrawing substituents. Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC(50) data. The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests.

  17. Synthesis and Herbicidal Activity of New Hydrazide and Hydrazonoyl Derivatives

    PubMed Central

    Šeršeň, František; Gregáň, Fridrich; Peško, Matúš; Dvoranová, Dana; Král’ová, Katarína; Matkovičová, Zuzana; Gregáň, Juraj; Donovalová, Jana

    2016-01-01

    Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and growth of the green algae Chlorella vulgaris. IC50 values of these compounds varied in wide range, from a strong to no inhibitory effect. EPR spectroscopy showed that the active compounds interfered with intermediates Z•/D•, which are localized on the donor side of photosystem II. Fluorescence spectroscopy suggested that the mechanism of inhibitory action of the prepared compounds possibly involves interactions with aromatic amino acids present in photosynthetic proteins. PMID:26248070

  18. Some heterocyclic thione derivatives exhibit anticoccidial activity by inhibiting glycosidases.

    PubMed

    Balbaa, Mahmoud; Abd El-Hady, Neama; Taha, Nabil; El Ashry, El Sayed H

    2012-01-01

    Coccidiosis is one of the most common parasitic diseases affecting many species of domestic animals. This disease has a major economic significance and the search for new compounds having anticoccidial activity is of great importance. In this article, different levels of protection from coccidian infection by Eimeria stiedae were developed in rabbits by treatment with compounds incorporating the skeleton of thiourea. These compounds include 4,5-diphenylimidazole-2-thione (1), 4,5-Diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-Hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) compared to the anticoccidial drug toltrazuril as a reference compound. Compounds 1-3 inhibit coccidiosis-induced activity of α-glucosidase. The protection from coccidial infection by compound 1 was higher than that shown for compounds 2 and 3. These data suggest that diazole and triazole thione derivatives have a mimetic effect for anticoccidial drugs through their inhibition of glycosidases.

  19. Synthesis and in vitro antitumor activity of novel scopoletin derivatives.

    PubMed

    Liu, Wukun; Hua, Jie; Zhou, Jinpei; Zhang, Huibin; Zhu, Haiyang; Cheng, Yanhua; Gust, Ronald

    2012-08-01

    Twenty scopoletin derivatives were developed by a systematic combinatorial chemical approach and their chemical structures were confirmed by MS, IR, (1)H NMR spectra and elemental analysis. Primary screening against mammary (MCF-7 and MDA-MB 231) and colon (HT-29) carcinoma cells indicated that five compounds (8d, 8g, 8j, 11b and 11g) displayed high antitumor potencies with IC(50) values below 20 μM whereas scopoletin showed IC(50) values above 100 μM. Moreover, the most promising compound 11g was more active than 5-fluorouracil. These results clearly indicated that the modification of the scopoletin structure could greatly increase its antitumor activity in vitro. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Plant growth regulation activity of steviol and derivatives.

    PubMed

    de Oliveira, Brás Heleno; Stiirmer, Júlio César; de Souza Filho, José D; Ayub, Ricardo Antonio

    2008-05-01

    This work describes the preparation of tetracyclic diterpenoids and determination of their plant growth regulator properties. Stevioside (2) was used as starting material and the derivatives 13-hydroxy-ent-kaur-16-en-19-oic acid (steviol, 3), ent-7alpha,13-dihydroxy-kaur-16-en-19-oic acid (4), 13-hydroxy, ent-kaur-16,17-epoxi-19-oic acid (steviol epoxide, 5), 17-hydroxy-16-ketobayeran-19-oic acid (17-hydroxyisosteviol, 6), 17-hydroxy-16-hydroxyiminobayeran-19-oic acid (7), 16-ketobayeran-19-oic acid (isosteviol, 9), 16,17-dihydroxybeyeran-19-oic acid (8), and 16-hydroxyiminobayeran-19-oic acid (isosteviol oxime, 10) were obtained by simple chemical procedures. Another derivative, ent-7alpha,13-dihydroxycaur-15-en-19-oic acid (4), was obtained by biotransformation of steviol (3) by Penicillium citrinum. In order to determine the plant growth regulator activity the compounds were submitted to the lettuce hypocotyl and barley aleurone bioassays. All compounds showed significant activities in both bioassays. Steviol (3) and isosteviol (9) were also tested in field-grown grapes resulting in an increase in berry weight and size.

  1. Synthesis and antimicrobial activity of some new diphenylamine derivatives

    PubMed Central

    Kumar, Arvind; Mishra, Arun K.

    2015-01-01

    In search of new leads toward potent antimicrobial agent, an array of novel derivatives of 2-hydrazinyl–N-N, diphenyl acetamide has been synthesized from the chloroacetylation reaction of diphenylamine (DPA). For this, a series of DPA derivatives were prepared by replacing chlorine with hydrazine hydrate in alcoholic medium and 2-hydrazino-N, N-diphenylacetamide was synthesized. The 2-hydrazino-N, N-diphenylacetamide was further subjected to reaction with various aromatic aldehydes in presence of glacial acetic acid in methanol. The synthesized compounds were characterized by their IR, 1HNMR spectral data and elemental analysis. The compounds were screened for antibacterial and antifungal activity by cup plate method. 2-(2-Benzylidenehydrazinyl)-N, N-diphenylacetamide (A1); 2-(2-(3-methylbenzylidene) hydrazinyl)-N, N-diphenyl-acetamide (A5) and 2-(2-(2-nitrobenzylidine) hydrazinyl)-N, N-diphenyl-acetamide compounds (A7) showed significant antimicrobial as well as antifungal activity. Diphenylamine compounds may be explored as potent antimicrobial and antifungal compounds. PMID:25709343

  2. Deriving stellar inclination of slow rotators using stellar activity

    SciTech Connect

    Dumusque, X.

    2014-12-01

    Stellar inclination is an important parameter for many astrophysical studies. Although different techniques allow us to estimate stellar inclination for fast rotators, it becomes much more difficult when stars are rotating slower than ∼2-2.5 km s{sup –1}. By using the new activity simulation SOAP 2.0 which can reproduce the photometric and spectroscopic variations induced by stellar activity, we are able to fit observations of solar-type stars and derive their inclination. For HD 189733, we estimate the stellar inclination to be i=84{sub −20}{sup +6} deg, which implies a star-planet obliquity of ψ=4{sub −4}{sup +18} considering previous measurements of the spin-orbit angle. For α Cen B, we derive an inclination of i=45{sub −19}{sup +9}, which implies that the rotational spin of the star is not aligned with the orbital spin of the α Cen binary system. In addition, assuming that α Cen Bb is aligned with its host star, no transit would occur. The inclination of α Cen B can be measured using 40 radial-velocity measurements, which is remarkable given that the projected rotational velocity of the star is smaller than 1.15 km s{sup –1}.

  3. Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives.

    PubMed

    Nasr, Tamer; Bondock, Samir; Youns, Mahmoud

    2014-04-09

    Drug resistance is a major impediment for cancer treatment, to overcome it we designed and synthesized sixteen coumarins bearing hydrazide-hydrazone moiety and evaluated them against human drug-resistant pancreatic carcinoma (Panc-1) cells and drug-sensitive (hepatic carcinoma; Hep-G2 and leukemia; CCRF) cell lines in vitro. The 6-brominated coumarin hydrazide-hydrazone derivatives (BCHHD) 7c, 8c and 10c were more potent than doxorubicin (DOX) against resistant Panc-1 cells. BCHHD 7c showed significant cytotoxicity against all tested cells (IC50: 3.60-6.50 μM) on comparison with all other coumarin hydrazide-hydrazone derivatives (CHHD), whereas BCHHD's 8c and 10c showed significant antiproliferative activity only against resistant Panc-1 cells with IC50 of 2.02 μM and 2.15 μM, respectively. All the investigated BCHHD's were able to activate caspases 3/7 and they could induce apoptosis in resistant Panc-1 cells. Microarray analysis showed that BCHHD 7c induced the expression of apoptotic- and cell cycle arrest (G2/M)- genes in resistant Panc-1 cells. Moreover, BCHHD 7c induced the up-regulation of CDKN1A, DDIT4, GDF-15 and down-regulation of CDC2, CDC20, CDK2 genes. Based on our results, we conclude that 7c could be a potent anticancer drug to overcome drug resistance in cancer and it could be highly beneficial for patients in the clinic.

  4. Construction, expression, and characterization of a novel fully activated recombinant single-chain hepatitis C virus protease.

    PubMed Central

    Taremi, S. S.; Beyer, B.; Maher, M.; Yao, N.; Prosise, W.; Weber, P. C.; Malcolm, B. A.

    1998-01-01

    Efficient proteolytic processing of essential junctions of the hepatitis C virus (HCV) polyprotein requires a heterodimeric complex of the NS3 bifunctional protease/helicase and the NS4A accessory protein. A single-chain recombinant form of the protease has been constructed in which NS4A residues 21-32 (GSVVIVGRIILS) were fused in frame to the amino terminus of the NS3 protease domain (residues 3-181) through a tetrapeptide linker. The single-chain recombinant protease has been overexpressed as a soluble protein in E. coli and purified to homogeneity by a combination of metal chelate and size-exclusion chromatography. The single-chain recombinant protease domain shows full proteolytic activity cleaving the NS5A-5B synthetic peptide substrate, DTEDVVCCSMSYTWTGK with a Km and k(cat) of 20.0 +/- 2.0 microM and 9.6 +/- 2.0 min(-1), respectively; parameters identical to those of the authentic NS3(1-631)/NS4A(1-54) protein complex generated in eukaryotic cells (Sali DL et al., 1998, Biochemistry 37:3392-3401). PMID:9792101

  5. A fully parallel in time and space algorithm for simulating the electrical activity of a neural tissue.

    PubMed

    Bedez, Mathieu; Belhachmi, Zakaria; Haeberlé, Olivier; Greget, Renaud; Moussaoui, Saliha; Bouteiller, Jean-Marie; Bischoff, Serge

    2016-01-15

    The resolution of a model describing the electrical activity of neural tissue and its propagation within this tissue is highly consuming in term of computing time and requires strong computing power to achieve good results. In this study, we present a method to solve a model describing the electrical propagation in neuronal tissue, using parareal algorithm, coupling with parallelization space using CUDA in graphical processing unit (GPU). We applied the method of resolution to different dimensions of the geometry of our model (1-D, 2-D and 3-D). The GPU results are compared with simulations from a multi-core processor cluster, using message-passing interface (MPI), where the spatial scale was parallelized in order to reach a comparable calculation time than that of the presented method using GPU. A gain of a factor 100 in term of computational time between sequential results and those obtained using the GPU has been obtained, in the case of 3-D geometry. Given the structure of the GPU, this factor increases according to the fineness of the geometry used in the computation. To the best of our knowledge, it is the first time such a method is used, even in the case of neuroscience. Parallelization time coupled with GPU parallelization space allows for drastically reducing computational time with a fine resolution of the model describing the propagation of the electrical signal in a neuronal tissue. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Human Relaxin Receptor Is Fully Functional in Humanized Mice and Is Activated by Small Molecule Agonist ML290

    PubMed Central

    Kaftanovskaya, Elena M.; Soula, Mariluz; Myhr, Courtney; Ho, Brian A.; Moore, Stefanie N.; Yoo, Changwon; Cervantes, Briana; How, Javier; Marugan, Juan; Agoulnik, Irina U.; Agoulnik, Alexander I.

    2017-01-01

    Relaxin, a small peptide hormone of the insulin/relaxin family, demonstrated antifibrotic, organ protective, vasodilatory, and proangiogenic properties in clinical trials and several animal models of human diseases. Relaxin family peptide receptor 1 (RXFP1) is the relaxin cognate G protein-coupled receptor. We have identified a series of small molecule agonists of human RXFP1. The lead compound ML290 demonstrated preferred absorption, distribution, metabolism, and excretion profiles, is easy to synthesize, and has high stability in vivo. However, ML290 does not activate rodent RXFP1s and therefore cannot be tested in common preclinical animal models. Here we describe the production and analysis of a mouse transgenic model, a knock-out/knock-in of the human RXFP1 (hRXFP1) complementary DNA into the mouse Rxfp1 (mRxfp1) gene. Insertion of the vector into the mRxfp1 locus caused disruption of mRxfp1 and expression of hRXFP1. The transcriptional expression pattern of the hRXFP1 allele was similar to mRxfp1. Female mice homozygous for hRXFP1 showed relaxation of the pubic symphysis at parturition and normal development of mammary nipples and vaginal epithelium, indicating full complementation of mRxfp1 gene ablation. Intravenous injection of relaxin led to an increase in heart rate in humanized and wild-type females but not in Rxfp1-deficient mice, whereas ML290 increased heart rate in humanized but not wild-type animals, suggesting specific target engagement by ML290. Moreover, intraperitoneal injection of ML290 caused a decrease in blood osmolality. Taken together, our data show humanized RXFP1 mice can be used for testing relaxin receptor modulators in various preclinical studies. PMID:28825052

  7. Human Relaxin Receptor Is Fully Functional in Humanized Mice and Is Activated by Small Molecule Agonist ML290.

    PubMed

    Kaftanovskaya, Elena M; Soula, Mariluz; Myhr, Courtney; Ho, Brian A; Moore, Stefanie N; Yoo, Changwon; Cervantes, Briana; How, Javier; Marugan, Juan; Agoulnik, Irina U; Agoulnik, Alexander I

    2017-06-01

    Relaxin, a small peptide hormone of the insulin/relaxin family, demonstrated antifibrotic, organ protective, vasodilatory, and proangiogenic properties in clinical trials and several animal models of human diseases. Relaxin family peptide receptor 1 (RXFP1) is the relaxin cognate G protein-coupled receptor. We have identified a series of small molecule agonists of human RXFP1. The lead compound ML290 demonstrated preferred absorption, distribution, metabolism, and excretion profiles, is easy to synthesize, and has high stability in vivo. However, ML290 does not activate rodent RXFP1s and therefore cannot be tested in common preclinical animal models. Here we describe the production and analysis of a mouse transgenic model, a knock-out/knock-in of the human RXFP1 (hRXFP1) complementary DNA into the mouse Rxfp1 (mRxfp1) gene. Insertion of the vector into the mRxfp1 locus caused disruption of mRxfp1 and expression of hRXFP1. The transcriptional expression pattern of the hRXFP1 allele was similar to mRxfp1. Female mice homozygous for hRXFP1 showed relaxation of the pubic symphysis at parturition and normal development of mammary nipples and vaginal epithelium, indicating full complementation of mRxfp1 gene ablation. Intravenous injection of relaxin led to an increase in heart rate in humanized and wild-type females but not in Rxfp1-deficient mice, whereas ML290 increased heart rate in humanized but not wild-type animals, suggesting specific target engagement by ML290. Moreover, intraperitoneal injection of ML290 caused a decrease in blood osmolality. Taken together, our data show humanized RXFP1 mice can be used for testing relaxin receptor modulators in various preclinical studies.

  8. Synthesis and in vitro anticancer activities of some selenadiazole derivatives.

    PubMed

    Plano, Daniel; Moreno, Esther; Font, María; Encío, Ignacio; Palop, Juan Antonio; Sanmartín, Carmen

    2010-11-01

    A novel series of fourteen substituted selenadiazoles has been synthesized and the compounds tested for their in vitro antiproliferative and cytotoxic activities. The tests were carried out against leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54), and breast (MCF-7) cancer cells. In order to assess the selectivity of the compounds under investigation the assays were also carried out on two non-tumoral lines - one mammary (184B5) and one bronchial epithelium (BEAS-2B) cell line. Assay-based antiproliferative activity studies revealed that seven derivatives (2a, 2c, 2e, 2f, 2g, 3a, and 3b) exhibited good activity against MCF-7 cells: for instance, 2c and 2f inhibited cell growth with nanomolar GI₅₀ values. Compound 2f had a better antitumoral profile than vinorelbine and paclitaxel, two drugs that are used as first-line treatments in advanced, recurrent, and/or metastatic cancer. In the other cell lines the compounds showed moderate activity or were inactive - with the exception of 2a, which was also found to have antiproliferative activity. Modulation of the cell cycle and apoptotic effects of active compounds were further evaluated in MCF-7 cells. Of these, 6-bromo[1,2,5]selenadiazolo[3,4-b]pyridine (2a) was the most active, with an apoptogenic effect 3.9 times higher than that of camptothecin, which was used as a positive control. Compound 2a also provoked cell cycle arrest with a significant decrease in the G₀/G₁ phase cell population and an increase in S and G₂/M cells, thus suggesting mitotic arrest prior to metaphase.

  9. Urease inhibitory activities of β-boswellic acid derivatives

    PubMed Central

    2013-01-01

    Background and the purpose of the study Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. Methods 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme. Results It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM). Conclusion The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage. PMID:23351363

  10. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    PubMed

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.

    PubMed

    Vijayaraghavan, Shilpa; Mahajan, Supriya

    2017-04-15

    A series of 4-anilinoquinoline triazine derivatives were designed, synthesized and screened for in vivo antimalarial activity against a chloroquine-sensitive strain of Plasmodium berghei. The compounds were further subjected to in vitro antimalarial activity against chloroquine-resistant W2 strain of Plasmodium falciparum and β-haematin inhibition studies. All the compounds exhibited in vivo antimalarial activity better than that shown by the standard drug, chloroquine. Twelve out of fifteen compounds showed better inhibition than that of chloroquine against chloroquine-resistant W2 strain of Plasmodium falciparum. Ten compounds showed β-haematin inhibition, better than that of chloroquine, with IC50 values in the range of 18-25µM. One compound, 3k, was found to be better than artemisinin against W2 strain of Plasmodium falciparum and also displayed the best β-haematin inhibitory activity, thereby becoming eligible to be explored as a potential lead for antimalarial chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Synthesis, crystal structures, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives

    NASA Astrophysics Data System (ADS)

    Qi, De-Qiang; Yu, Chuan-Ming; You, Jin-Zong; Yang, Guang-Hui; Wang, Xue-Jie; Zhang, Yi-Ping

    2015-11-01

    A series of pyrazole-based 1,3,4-oxadiazole derivatives were rationally designed and synthesized in good yields by following a convenient route. All the newly synthesized molecules were fully characterized by IR, 1H NMR and elemental analysis. Eight compounds were structurally determined by single crystal X-ray diffraction analysis. The fluorescence properties of all the compounds were investigated in dimethyl sulfoxide media. In addition, these newly synthesized compounds were evaluated for in vitro inhibitory activity against commercial enzyme xanthine oxidase (XO) by measuring the formation of uric acid from xanthine. Among the compounds synthesized and tested, 3d and 3e were found to be moderate inhibitory activity against commercial XO with IC50 = 72.4 μM and 75.6 μM. The studies gave a new insight in further optimization of pyrazole-based 1,3,4-oxadiazole derivatives with excellent fluorescence properties and XO inhibitory activity.

  13. Antimalarial activity of 4-amidinoquinoline and 10-amidinobenzonaphthyridine derivatives.

    PubMed

    Korotchenko, Vasiliy; Sathunuru, Ramadas; Gerena, Lucia; Caridha, Diana; Li, Qigui; Kreishman-Deitrick, Mara; Smith, Philip L; Lin, Ai J

    2015-04-23

    Chloroquine (CQ) has been used as first line malaria therapeutic drug for decades. Emergence of CQ drug-resistant Plasmodium falciparum malaria throughout endemic areas of the world has limited its clinical value. Mefloquine (MQ) has been used as an effective malaria prophylactic drug due to its being long-acting and having a high potency against blood stage P. falciparum (Pf). However, serious CNS toxicity of MQ has compromised its clinical value as a prophylaxis drug. Therefore, new and inexpensive antimalarial drugs with no cross-resistance to CQ or CNS toxicity are urgently needed to combat this deadly human disease. In this study, a series of new 4-amidinoquinoline (4-AMQ) and 10-amidinobenzonaphthyridine (10-AMB) derivatives were designed, prepared, and assessed to search for new therapeutic agents to replace CQ and MQ. The new derivatives displayed high activity in vitro and in vivo, with no cross-resistance to CQ, and none were toxic in mice up to 160 mpk × 3. The best compound shows IC50 < 1 ng/mL against D6, W2 and C235 Pf clones, low inhibitory activity in hERG K(+) channel blockage testing, negativity in the Ames test, and 5/5 cure @ <15 mpk × 3 in mice infected with Plasmodium berghei. In addition to these desirable pharmacological profiles, compound 13b, one of the most active compounds, is metabolically stable in both human and mouse liver microsomal preparations and has a plasma t(1/2) of 50 h in mice, which made it a good MQ replacement candidate.

  14. Antifungal activity of topical microemulsion containing a thiophene derivative.

    PubMed

    Guimarães, Geovani Pereira; de Freitas Araújo Reis, Mysrayn Yargo; da Silva, Dayanne Tomaz Casimiro; Junior, Francisco Jaime Bezerra Mendonça; Converti, Attílio; Pessoa, Adalberto; de Lima Damasceno, Bolívar Ponciano Goulart; da Silva, José Alexsandro

    2014-01-01

    Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 μg . mL(-1)) and good activity against C. neoformans (MIC = 17 μg . mL(-1)). Candida species were susceptible to ME-5CN05 (70-140 μg . mL(-1)), but C. neoformans was much more, presenting a MIC value of 2.2 μg . mL(-1). The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.

  15. HMF and diastase activity in honeys: A fully validated approach and a chemometric analysis for identification of honey freshness and adulteration.

    PubMed

    Pasias, Ioannis N; Kiriakou, Ioannis K; Proestos, Charalampos

    2017-08-15

    A fully validated approach for the determination of diastase activity and hydroxymethylfurfural content in honeys were presented in accordance with the official methods. Methods were performed in real honey sample analysis and due to the vast number of collected data sets reliable conclusions about the correlation between the composition and the quality criteria were exported. The limits of detection and quantification were calculated. Accuracy, precision and uncertainty were estimated for the first time in the kinetic and spectrometric techniques using the certified reference material and the determined values were in good accordance with the certified values. PCA and cluster analysis were performed in order to examine the correlation among the artificial feeding of honeybees with carbohydrate supplements and the chemical composition and properties of the honey. Diastase activity, sucrose content and hydroxymethylfurfural content were easily differentiated and these parameters were used for indication of the adulteration of the honey. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.

    PubMed

    Roth, Howard S; Hergenrother, Paul J

    2016-01-01

    PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an indepth discussion of four derivatives on which extensive studies have been performed.

  17. Derivatives of Procaspase-Activating Compound 1 (PAC-1) and Anticancer Activities

    PubMed Central

    Roth, Howard S.; Hergenrother, Paul J.

    2016-01-01

    PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an in-depth discussion of four derivatives on which extensive studies have been performed. PMID:26630918

  18. Nanobionics of Pharmacologically Active Derivatives of Fullerene C60

    NASA Astrophysics Data System (ADS)

    Kotelnikova, R. A.; Bogdanov, G. N.; Frog, E. C.; Kotelnikov, A. I.; Shtolko, V. N.; Romanova, V. S.; Andreev, S. M.; Kushch, A. A.; Fedorova, N. E.; Medzhidova, A. A.; Miller, G. G.

    2003-12-01

    The physical-chemical mechanisms of pharmacologic functioning of amino acid derivatives of fullerene C60 (ADF) have been studied. ADF were shown to penetrate through the lipid bilayer of liposomes without destruction of membrane integrity. ADF are able to carry bivalent metal ions through phospholipid bilayer owing to the formation of complexes. It was shown that stereoisomers of ADF selectively penetrate into phospholipid membranes. In contrast to D-isomers, L-isomers penetrate through the phosphatidylcholine membrane into liposome interior. Stereo-specific effect of ADF enantiomers was also observed in reaction of peroxidation of lipids. Besides that, ADF bring about a substantial increase in the catalytic activity of monoaminoxidases A and B. The directed intraprotein electron transfer was studied by creating a donor-acceptor pair in a water solution in the presence of ADF. To realize the intraprotein electron transfer, the model system was produced on the base of apomyoglobin by incorporating ADF (electron acceptor) into the heme pocket of protein instead of removed heme. It was established that the fullerene C60 and its derivatives did not produce specific anti-C60 antibodies, both IgG and IgE classes, while ADF themselves are efficient adjuvants, i.e. they increased the antibody response to poor antigens. Some ADF were found to inhibit the human immunodeficiency virus and human cytomegalovirus infection.

  19. Salicin derivatives from Salix glandulosa and their biological activities.

    PubMed

    Kim, Chung Sub; Subedi, Lalita; Park, Kyoung Jin; Kim, Sun Yeou; Choi, Sang Un; Kim, Ki Hyun; Lee, Kang Ro

    2015-10-01

    Two new salicin derivatives, saliglandin (1) and 6'-O-(Z)-p-coumaroylsalicin (2), along with fourteen known analogues (3-16) were isolated from the twigs of Salix glandulosa Seemen. The structures of 1-16 were characterized by the use of NMR methods ((1)H and (13)C NMR, (1)H-(1)H COSY, HSQC and HMBC), chemical hydrolysis, and GC/MS. The full NMR data assignment of the known compounds 6, 13, and 14 are reported for the first time. Isolated compounds were evaluated for their nitric oxide (NO) inhibitory efficacy in lipopolysaccharide (LPS)-activated microglial cell (BV-2). Compounds 2, 5, 8-16 significantly inhibited NO production, compound 11 being the most efficacious (IC50 13.57 μM) respectively. Moreover, compound 16 dramatically increased the nerve growth factor (NGF) production (165.24 ± 11.1%) in C6 glioma cells. Taken together, these results revealed that salicin derivatives from Salix glandulosa might have potent effect as anti-neuroinflammatory agents.

  20. Bioelectrochemical activity of an electroactive macromolecular weight coenzyme derivative

    NASA Astrophysics Data System (ADS)

    Liu, Pu; Zheng, Haitao; Nie, Pingping; Wei, Yaotian; Feng, Zhenchao; Sun, Tao

    2009-07-01

    As coenzyme utilized by more than hundreds of dehydrogenases, the efficient immobilization and regeneration of nicotinamide adenine dinucleotide (NAD+) are of great importance and have practical applications in industrial, analytical and biomedical field. In this paper, an electroactive macromolecular weight coenzyme derivative (PEI-DHBNAD) was prepared by attaching both NAD+ and 3,4-dihydroxybenzaldehyde (3,4-DHB) to a water-soluble polyelectrolyte, poly(ethylenimine) (PEI). The functional polymer exhibited both electrochemical properties of catechol unites and coenzymatic activity of NAD moieties. The macromolecular NAD analogue showed a substantial degree of efficiency relative to free NAD+ with alcohol dehydrogenase (ADH) and glucose-6-phophate dehydrogenase (G6PDH), and a litter higher Michaelis-Menton constant (Km) was obtained for the coenzyme derivative than free NAD+. The bioelectrochemical properties of PEI-DHB-NAD were investigated by using G6PDH as the model enzyme, and both of them were retained on electrode surface by ultrafiltration membrane. The modified electrode showed typical response to substrate without the addition of free coenzyme, which indicated that PEI-DHB-NAD can carry out the electron transfer between electrode and NAD-dependent dehydrogenase. The utilization of polymer-based PEI-DHB-NAD is convenient for the immobilization of both electron mediator and coenzyme, and offers a practical approach for the construction of reagentless biosensors.

  1. Studies on the Synthesis of Derivatives of Marine-Derived Bostrycin and Their Structure-Activity Relationship against Tumor Cells

    PubMed Central

    Chen, Hong; Zhong, Lili; Long, Yuhua; Li, Jia; Wu, Jueheng; Liu, Lan; Chen, Shengping; Lin, Yongcheng; Li, Mengfeng; Zhu, Xun; She, Zhigang

    2012-01-01

    A series of new derivatives (5–29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR) of bostrycin derivatives was also discussed based on the obtained experimental data. PMID:22690152

  2. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  3. High selective antileishmanial activity of vanadium complex with stilbene derivative.

    PubMed

    Machado, Patrícia de Almeida; Mota, Vinícius Zamprogno; Cavalli, Ana Clara de Lima; de Carvalho, Gustavo Senra Gonçalves; Da Silva, Adilson David; Gameiro, Jacy; Cuin, Alexandre; Coimbra, Elaine Soares

    2015-08-01

    Leishmaniasis is a group of disease caused by different species of the parasite Leishmania affecting millions of people worldwide. Conventional therapy relies on multiple parenteral injections with pentavalent antimonials which exhibit high toxicity and various side effects have been reported. Hence, the research for an effective and low toxic effect drug is necessary. In the present work, the synthesis, spectroscopic and analytical characterizations of stilbene derivative (H2Salophen) and its vanadium complex (VOSalophen) are reported. Besides the chemical ancillary information, investigation of the leishmanicidal effects of these compounds were provided. The biological assays against promastigote and amastigote forms of L. amazonensis have been shown that VOSalophen exhibited a strong antiparasitic activity (IC50 of 6.65 and 3.51 μM, respectively). Furthermore, the leishmanicidal activity was concentration and time-dependent. Regarding toxicity and selectivity on mammalian cells, VOSalophen have not caused significant damage to human erythrocytes in all concentrations tested and VOSalophen was almost seven times more destructive for the intracellular parasite than for macrophages. Furthermore, the leishmanicidal activity of VOSalophen in promastigote forms of L. amazonensis could be associated to mitochondrial dysfunction and increase of the reactive oxygen species (ROS) production. In L. amazonensis-infected macrophages, VOSalophen induces ROS production and a microbicidal action NO-dependent. Our biological results indicate the effective and selective action of VOSalophen against L. amazonensis and the leishmanicidal effect can be associated to parasite disorders and immumodulatory effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Antiproliferative and antibacterial activity of some glutarimide derivatives.

    PubMed

    Popović-Djordjević, Jelena B; Klaus, Anita S; Žižak, Željko S; Matić, Ivana Z; Drakulić, Branko J

    2016-12-01

    Antiproliferative and antibacterial activities of nine glutarimide derivatives (1-9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9-27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6-8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10(-3 )mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

  5. Anti-cancer activity of carbamate derivatives of melampomagnolide B.

    PubMed

    Janganati, Venumadhav; Penthala, Narsimha Reddy; Madadi, Nikhil Reddy; Chen, Zheng; Crooks, Peter A

    2014-08-01

    Melampomagnolide B (MMB) is a natural sesquiterpene structurally related to parthenolide (PTL). We have shown that MMB exhibits anti-leukemic properties similar to PTL. Unlike PTL, the presence of a primary hydroxyl group in the MMB molecule allows the opportunity for examining the biological activity of a variety of conjugated analogs of MMB. We have now synthesized a series of carbamate analogs of MMB and evaluated these derivatives for anti-cancer activity against a panel of sixty human cancer cell lines. Analogs 6a and 6e exhibited promising anti-leukemic activity against human leukemia cell line CCRF-CEM with GI50 values of 680 and 620 nM, respectively. Analog 6a also showed GI50 values of 1.98 and 1.38 μM respectively, against RPMI-8226 and SR leukemia cell lines and GI50 values of 460 and 570 nM against MDA-MB-435 melanoma and MDA-MB-468 breast cancer cell lines, respectively. Analog 6e had GI50 values of 650 and 900 nM against HOP-92 non-small cell lung and RXF 393 renal cancer cell lines. Copyright © 2014. Published by Elsevier Ltd.

  6. Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis.

    PubMed

    Mata-Santos, T; Mata-Santos, H A; Carneiro, P F; De Moura, K C G; Fenalti, J M; Klafke, G B; Cruz, L A X; Martins, L H R; Pinto, N F; Pinto, M C F R; Berne, M E A; Da Silva, P E A; Scaini, C J

    2016-04-01

    Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.

  7. Synthesis and antileishmanial activity of novel buparvaquone oxime derivatives.

    PubMed

    Mäntylä, Antti; Rautio, Jarkko; Nevalainen, Tapio; Vepsälainen, Jouko; Juvonen, Risto; Kendrick, Howard; Garnier, Tracy; Croft, Simon L; Järvinen, Tomi

    2004-07-01

    Novel oxime derivatives (2, 3 and 5) of buparvaquone (1) and O-methyl-buparvaquone (4) were synthesized and their in vitro activities against Leishmania donovani, the causative agent of visceral leishmaniasis (VL), were determined. Buparvaquone-oxime (2) was also studied as a bioreversible prodrug structure of buparvaquone (1). Buparvaquone-oxime (2) released buparvaquone (1) in vitro when it was incubated with induced rat liver microsomes, which suggests that the oxime-structure is a useful prodrug template for developing novel prodrugs of buparvaquone and other hydroxynaphthoquinones. Moreover, the formation of NO(2)(-) , formed via oxidation of NO, was confirmed during the bioconversion. The release of NO from buparvaquone-oxime (2) may provide an additional therapeutic effect in the treatment of leishmaniasis. Buparvaquone-oxime (2) and buparvaquone-O-methyloxime (3) demonstrated moderate activity against amastigotes of the Leishmania species that causes VL. However, the studied oximes (2, 3) most probably did not release buparvaquone (1) and NO during the present in vitro experiment. Further in vivo studies are needed to verify the biological activity of buparvaquone-oximes in the treatment of leishmaniasis.

  8. Antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives.

    PubMed

    Zhang, Liang; Sathunuru, Ramadas; Caridha, Diana; Pybus, Brandon; O'Neil, Michael T; Kozar, Michael P; Lin, Ai J

    2011-10-13

    A series of new guanidylimidazole derivatives was prepared and evaluated in mice and Rhesus monkeys infected with malarial sporozoites. The majority of the new compounds showed poor metabolic stability and weak in vitro activities in three clones of Plasmodium falciparum. Compounds 8a, 8h, 9a, 16a, and 16e cured the mice infected with sporozoites of P. berghei at 160 and 320 mg/kg/day × 3 po. Compounds 8a showed better causal prophylactic activity than primaquine, tafenoquine, and Malarone in the Rhesus test. In the radical curative test, 8a cured one monkey and delayed relapse of another for 74 days at 30 mg/kg/day × 7 by im. By oral dosing, 8a delayed relapse 81 days for one and 32 days for other vs 11-12 days for control monkeys treated with 10 mg/kg of chloroquine by po alone. Compound 8h, which showed superior activity to 8a in mouse test, delayed the relapse of treated monkeys for 21-26 days at 30 mg/kg/day × 7 by oral.

  9. Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide.

    PubMed

    Iwai, Yuma; Takahashi, Hitoshi; Hatakeyama, Dai; Motoshima, Kazunori; Ishikawa, Minoru; Sugita, Kazuyuki; Hashimoto, Yuichi; Harada, Yuichi; Itamura, Shigeyuki; Odagiri, Takato; Tashiro, Masato; Sei, Yoshihisa; Yamaguchi, Kentaro; Kuzuhara, Takashi

    2010-07-15

    Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.

  10. Antibacterial Activity of Alanine-Derived Gemini Quaternary Ammonium Compounds.

    PubMed

    Piecuch, Agata; Obłąk, Ewa; Guz-Regner, Katarzyna

    The antibacterial activity of alanine-derived gemini quaternary ammonium salts (chlorides and bromides) with various spacer and alkyl chain lengths was investigated. The studied compounds exhibited a strong bactericidal effect, especially bromides with 10 and 12 carbon alkyl chains and 3 carbon spacer groups (TMPAL-10 Br and TMPAL-12 Br), with a short contact time. Both salts dislodged biofilms of Pseudomonas aeruginosa and Staphylococcus epidermidis, and were lethal to adherent cells of S. epidermidis. Bromide with 2 carbon spacer groups and 12 carbon alkyl chains (TMEAL-12 Br) effectively reduced microbial adhesion by coating polystyrene and silicone surfaces. The results obtained suggest that, after further studies, gemini QAS might be considered as antimicrobial agents in medicine or industry.

  11. Biological Activity of Coumarin Derivatives as Anti-Leishmanial Agents

    PubMed Central

    Mandlik, Vineetha; Patil, Sohan; Bopanna, Ramanamurthy; Basu, Sudipta; Singh, Shailza

    2016-01-01

    Cutaneous leishmaniasis affects nearly 0.7 to 1.3 million people annually. Treatment of this disease is difficult due to lack of appropriate medication and the growing problem of drug resistance. Natural compounds such as coumarins serve as complementary therapeutic agents in addition to the current treatment modalities. In this study, we have performed an in-silico screening of the coumarin derivatives and their anti-leishmanial properties has been explored both in-vitro and in-vivo. One of the compounds (compound 2) exhibited leishmanicidal activity and to further study its properties, nanoliposomal formulation of the compound was developed. Treatment of cutaneous lesions in BALB/c mice with compound 2 showed significantly reduced lesion size as compared to the untreated mice (p<0.05) suggesting that compound 2 may possess anti-leishmanial properties. PMID:27768694

  12. Antioxidant and Antiplatelet Activities in Extracts from Green and Fully Ripe Tomato Fruits (Solanum lycopersicum) and Pomace from Industrial Tomato Processing.

    PubMed

    Fuentes, Eduardo; Carle, Reinhold; Astudillo, Luis; Guzmán, Luis; Gutiérrez, Margarita; Carrasco, Gilda; Palomo, Iván

    2013-01-01

    The consumption of fruits and vegetables is accepted to be one of the strategies to reduce risk factors for these diseases. The aim of this study was to examine potential relationships between the antioxidant and the antiplatelet activities in green mature and fully ripe (red) tomatoes and of lycopene-rich byproducts of tomato paste processing such as pomace. The total phenol content of tomato components was the highest in peels, pulp, and in the mucilaginous myxotesta covering the tomato seeds with values 36.9 ± 0.8, 33.3 ± 00.5, and 17.6 ± 0.9 mg GAE/100 g, respectively (P < 0.05). Tomato peels had the highest antioxidant activity, both, as measured by the FRAP (46.9 ± 0.9  μ mol Fe(+2)/g, P < 0.05) and the DPPH assays (97.4 ± 0.2%, 1000  μ g/mL, P < 0.05). Pomace extracts showed the highest antiplatelet activity induced by ADP, collagen, TRAP-6, and arachidonic acid. While the maturation stage of the tomato fruit affected the antioxidant effect, antiplatelet activity was independent of fruit ripeness. Finally, based on the present results, tomato and its byproducts may be considered as a valuable source of antioxidant and antiplatelet activities.

  13. Antioxidant and Antiplatelet Activities in Extracts from Green and Fully Ripe Tomato Fruits (Solanum lycopersicum) and Pomace from Industrial Tomato Processing

    PubMed Central

    Fuentes, Eduardo; Carle, Reinhold; Astudillo, Luis; Guzmán, Luis; Gutiérrez, Margarita; Carrasco, Gilda; Palomo, Iván

    2013-01-01

    The consumption of fruits and vegetables is accepted to be one of the strategies to reduce risk factors for these diseases. The aim of this study was to examine potential relationships between the antioxidant and the antiplatelet activities in green mature and fully ripe (red) tomatoes and of lycopene-rich byproducts of tomato paste processing such as pomace. The total phenol content of tomato components was the highest in peels, pulp, and in the mucilaginous myxotesta covering the tomato seeds with values 36.9 ± 0.8, 33.3 ± 00.5, and 17.6 ± 0.9 mg GAE/100 g, respectively (P < 0.05). Tomato peels had the highest antioxidant activity, both, as measured by the FRAP (46.9 ± 0.9 μmol Fe+2/g, P < 0.05) and the DPPH assays (97.4 ± 0.2%, 1000 μg/mL, P < 0.05). Pomace extracts showed the highest antiplatelet activity induced by ADP, collagen, TRAP-6, and arachidonic acid. While the maturation stage of the tomato fruit affected the antioxidant effect, antiplatelet activity was independent of fruit ripeness. Finally, based on the present results, tomato and its byproducts may be considered as a valuable source of antioxidant and antiplatelet activities. PMID:23476707

  14. Mechanism of salt-induced activity enhancement of a marine-derived laccase, Lac15.

    PubMed

    Li, Jie; Xie, Yanan; Wang, Rui; Fang, Zemin; Fang, Wei; Zhang, Xuecheng; Xiao, Yazhong

    2017-09-05

    Laccase (benzenediol: oxygen oxidoreductases, EC1.10.3.2) is a multi-copper oxidase capable of oxidizing a variety of phenolic and other aromatic organic compounds. The catalytic power of laccase makes it an attractive candidate for potential applications in many areas of industry including biodegradation of organic pollutants and synthesis of novel drugs. Most laccases are vulnerable to high salt and have limited applications. However, some laccases are not only tolerant to but also activated by certain concentrations of salt and thus have great application potential. The mechanisms of salt-induced activity enhancement of laccases are unclear as yet. In this study, we used dynamic light scattering, size exclusion chromatography, analytical ultracentrifugation, intrinsic fluorescence emission, circular dichroism, ultraviolet-visible light absorption, and an enzymatic assay to investigate the potential correlation between the structure and activity of the marine-derived laccase, Lac15, whose activity is promoted by low concentrations of NaCl. The results showed that low concentrations of NaCl exert little influence on the protein structure, which was partially folded in the absence of the salt; moreover, the partially folded rather than the fully folded state seemed to be favorable for enzyme activity, and this partially folded state was distinctive from the so-called 'molten globule' occasionally observed in active enzymes. More data indicated that salt might promote laccase activity through mechanisms involving perturbation of specific local sites rather than a change in global structure. Potential binding sites for chloride ions and their roles in enzyme activity promotion are proposed.

  15. Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells

    PubMed Central

    Han, Xiao; Zha, Haoran; Yang, Fei; Guo, Bo; Zhu, Bo

    2017-01-01

    The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemical analysis and flow cytometry analysis of the tumor microenvironment, we demonstrated that TF-induced fibrin deposition, which is correlated with complement activation and myeloid-derived suppressor cell (MDSC) recruitment, is positively associated with tumor progression. C5aR antagonism blunted the effect of TF on tumor progression and decreased MDSC recruitment. In conclusion, our data suggested that in tumor microenvironment, TF-induced coagulation activated the complement system and subsequently recruited myeloid-derived suppressor cells to promote tumor growth, which brings new insights into the coagulation-induced complement activation within the tumor microenvironment during tumor progression. PMID:28106852

  16. Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells.

    PubMed

    Han, Xiao; Zha, Haoran; Yang, Fei; Guo, Bo; Zhu, Bo

    2017-01-19

    The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemical analysis and flow cytometry analysis of the tumor microenvironment, we demonstrated that TF-induced fibrin deposition, which is correlated with complement activation and myeloid-derived suppressor cell (MDSC) recruitment, is positively associated with tumor progression. C5aR antagonism blunted the effect of TF on tumor progression and decreased MDSC recruitment. In conclusion, our data suggested that in tumor microenvironment, TF-induced coagulation activated the complement system and subsequently recruited myeloid-derived suppressor cells to promote tumor growth, which brings new insights into the coagulation-induced complement activation within the tumor microenvironment during tumor progression.

  17. γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and the Na,K-ATPase activity effect.

    PubMed

    Alves, Silmara L G; Paixão, Natasha; Ferreira, Letícia G R; Santos, Felipe R S; Neves, Luiza D R; Oliveira, Gisele C; Cortes, Vanessa F; Salomé, Kahlil S; Barison, Andersson; Santos, Fabio V; Cenzi, Gisele; Varotti, Fernando P; Oliveira, Soraya M F; Taranto, Alex G; Comar, Moacyr; Silva, Luciana M; Noël, François; Quintas, Luis Eduardo M; Barbosa, Leandro A; Villar, José A F P

    2015-08-01

    Cardiotonic steroids (CS), natural compounds with traditional use in cardiology, have been recently suggested to exert potent anticancer effects. However, the repertoire of molecules with Na,K-ATPase activity and anticancer properties is limited. This paper describes the synthesis of 6 new digoxin derivatives substituted (on the C17-butenolide) with γ-benzylidene group and their cytotoxic effect on human fibroblast (WI-26 VA4) and cancer (HeLa and RKO) cell lines as well as their effect on Na,K-ATPase activity and expression. As digoxin, compound BD-4 was almost 100-fold more potent than the other derivatives for cytotoxicity with the three types of cells used and was also the only one able to fully inhibit the Na,K-ATPase of HeLa cells after 24h treatment. No change in the Na,K-ATPase α1 isoform protein expression was detected. On the other hand it was 30-40 fold less potent for direct Na,K-ATPase inhibition, when compared to the most potent derivatives, BD-1 and BD-3, and digoxin. The data presented here demonstrated that the anticancer effect of digoxin derivatives substituted with γ-benzylidene were not related with their inhibition of Na,K-ATPase activity or alteration of its expression, suggesting that this classical molecular mechanism of CS is not involved in the cytotoxic effect of our derivatives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Synthesis and antiproliferative activity of monocationic arylthiophene derivatives.

    PubMed

    Ismail, Mohamed A; Youssef, Magdy M; Arafa, Reem K; Al-Shihry, Shar S; El-Sayed, Wael M

    2017-01-27

    Eleven compounds of substituted 4-(5-arylthiophen-2-yl)benzamidines 4a-k were synthesized from their corresponding mononitriles via treatment with lithium trimethylsilylamide and subsequent de-protection with ethanol/hydrogen chloride. In vitro antiproliferative activities of the new monocationic arylthiophenes were evaluated against 60 human cell lines at NCI, USA. This class of compounds displayed promising submicromolar antiproliferative activities with the most potent compound being 4i (GI50 and TGI of 0.20 and 0.37 μM, respectively). On the other hand, most of the tested compounds exhibited LC50 at concentrations much higher than those they had GI50 at; ∼10× (for 4b) up to 228× (for 4e) which indicates lower lethality and efficient growth inhibition. Cancer cell lines, HCC-2998 colon, SNB-75 CNS, MDA-MB-435 melanoma, and MCF-7 breast cancer were the most responsive, with GI50s of 0.156, 0.165, 0.163, and 0.168 μM, respectively. The p-chlorophenyl derivatives 4e and 4i discerned themselves with GI50 values at 0.36 and 0.20 μM, respectively, and LC50 values at ∼83 and 36 μM, respectively, but safe to RBCs at 1000 μM. The cytotoxic activity data of these compounds in two normal cell lines; WI38 and WISH proved that they are very safe on normal cells. The plausible mechanism of action of the tested monocations was examined by evaluating their antioxidant power, nuclease-like DNA degradation aptitude and tyrosine kinase (TK) inhibition activities. The tested monocations showed potent activity in all assays. Compounds 4e and 4i caused 88 and 98%, respectively, inhibition in TK activity at 1 μM and the IC50 for 4i was 13 nM. The tested monocations have selective anticancer activity without insulting normal cells most probably due to inhibition of the key enzyme TK at nanomolar concentrations.

  19. Enhancement of Odor-Induced Activity in the Canine Brain by Zinc Nanoparticles: A Functional MRI Study in Fully Unrestrained Conscious Dogs.

    PubMed

    Jia, Hao; Pustovyy, Oleg M; Wang, Yun; Waggoner, Paul; Beyers, Ronald J; Schumacher, John; Wildey, Chester; Morrison, Edward; Salibi, Nouha; Denney, Thomas S; Vodyanoy, Vitaly J; Deshpande, Gopikrishna

    2016-01-01

    Using noninvasive in vivo functional magnetic resonance imaging (fMRI), we demonstrate that the enhancement of odorant response of olfactory receptor neurons by zinc nanoparticles leads to increase in activity in olfaction-related and higher order areas of the dog brain. To study conscious dogs, we employed behavioral training and optical motion tracking for reducing head motion artifacts. We obtained brain activation maps from dogs in both anesthetized state and fully conscious and unrestrained state. The enhancement effect of zinc nanoparticles was higher in conscious dogs with more activation in higher order areas as compared with anesthetized dogs. In conscious dogs, voxels in the olfactory bulb and hippocampus showed higher activity to odorants mixed with zinc nanoparticles as compared with pure odorants, odorants mixed with gold nanoparticles as well as zinc nanoparticles alone. These regions have been implicated in odor intensity processing in other species including humans. If the enhancement effect of zinc nanoparticles observed in vivo are confirmed by future behavioral studies, zinc nanoparticles may provide a way for enhancing the olfactory sensitivity of canines for detection of target substances such as explosives and contraband substances at very low concentrations, which would otherwise go undetected. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Simulation and optimization of ammonia removal at low temperature for a double channel oxidation ditch based on fully coupled activated sludge model (FCASM): a full-scale study.

    PubMed

    Yang, Min; Sun, Peide; Wang, Ruyi; Han, Jingyi; Wang, Jianqiao; Song, Yingqi; Cai, Jing; Tang, Xiudi

    2013-09-01

    An optimal operating condition for ammonia removal at low temperature, based on fully coupled activated sludge model (FCASM), was determined in a full-scale oxidation ditch process wastewater treatment plant (WWTP). The FCASM-based mechanisms model was calibrated and validated with the data measured on site. Several important kinetic parameters of the modified model were tested through respirometry experiment. Validated model was used to evaluate the relationship between ammonia removal and operating parameters, such as temperature (T), dissolved oxygen (DO), solid retention time (SRT) and hydraulic retention time of oxidation ditch (HRT). The simulated results showed that low temperature have a negative effect on the ammonia removal. Through orthogonal simulation tests of the last three factors and combination with the analysis of variance, the optimal operating mode acquired of DO, SRT, HRT for the WWTP at low temperature were 3.5 mg L(-1), 15 d and 14 h, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Anticholinesterase and antiacetylcholine activity of 1-phenylcyclohexylamine derivatives.

    PubMed

    Kloog, Y; Rehavi, M; Maayani, S; Sokolovsky, M

    1977-10-01

    The antiacetylcholine and anticholinesterase potencies of four 1-phenylcyclohexylamine derivatives were estimated by measuring their antagonism to the contractile response of smooth and striated muscles and their inhibition of cholinesterase activity. In addition, their affinities towards the central muscarinic receptor from mouse brain homogenate were determined by competition experiments in vitro. Relative to atropine, these drugs exerted mild antimuscarinic activity in both isolated smooth muscle and in the competition experiments. On the other hand, they were found to exert antinicotinic potencies equal to that of d-tubocurarine in the striated muscle. The concentration of (3H)-phencyclidine taken up by mouse brain in vivo could be correlated with its dissociation constants from the central muscarinic binding sites, as well as with the Ki values for acetylcholinesterase inhibition, both determined in vitro. Since these drugs have a similar rigid spatial molecular structure, it is proposed that the variations in the potency of their cholinergic interactions stemmed mainly from the structural changes in the region of the 'cationic head'.

  2. Synthesis of Thymoquinone derivatives and its activity analysis: In-silico approach

    NASA Astrophysics Data System (ADS)

    Ulfa, Siti Mariyah; Sholikhah, Shoimatus; Utomo, Edi Priyo

    2017-03-01

    Thymoquinone derivatives which synthesized in this research is bromoalkylquinones with alkyl chain consist of seven carbons (C7) and ten carbons (C10). The synthesis was carried out by oxidation of 2,3-dimethylhydroquinone followed by alkylation using reflux for 1.5 hours. The alkylation products were successfully characterized as 5-(7-bromoheptyl)-2,3-dimethyl-1,4-benzoquinone (C7) and 5-(10-bromodecyl)-2,3-dimethyl-1,4-benzoquinone (C10) in 31.93 and 16.89%, respectively. These compounds were fully characterized using FT-IR, 1H-NMR and 13C-NMR. Thus, the activity of C7 and C10 was analyzed by in silico approach with molecular docking using macromolecule model extracted from Protein Data Bank (PDB). Macromolecules used in this research is mitochondrial translocator protein (TSPO) as an antioxidant receptor, glycogen phosphorylase (GPA) as antidiabetic receptor and phosphatase tensin homolog (PTEN) as an anticancer agent. The result showed that C7 and C10 has a very good activity as antioxidant and antidiabetic agents with IC50 2.03 and 1.02 ppm (TSPO) and 16.98 and 14.88 ppm (GPA) compared with Thymoquinone. While the activity of C7 and C10 against PTEN gave the IC50 23.13 and 18.31 ppm showed a good candidate for an anticancer agent.

  3. New sorafenib derivatives: synthesis, antiproliferative activity against tumour cell lines and antimetabolic evaluation.

    PubMed

    Babić, Zeljka; Crkvenčić, Maja; Rajić, Zrinka; Mikecin, Ana-Matea; Kralj, Marijeta; Balzarini, Jan; Petrova, Mariya; Vanderleyden, Jos; Zorc, Branka

    2012-01-23

    Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a-e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a-e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a-e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a-e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a-e (IC(50) = 1-4.3 μmol·L-1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

  4. Characterization and cytotoxic activity of sulfated derivatives of polysaccharides from Agaricus brasiliensis

    PubMed Central

    Cardozo, F. T. G. S.; Camelini, C. M.; Cordeiro, M. N. S.; Mascarello, A.; Malagoli, B. G.; Larsen, I.; Rossi, M. J.; Nunes, R. J.; Braga, F. C.; Brandt, C.R.; Simões, C. M. O.

    2014-01-01

    Agaricus brasiliensis cell-wall polysaccharides isolated from fruiting body (FR) and mycelium (MI) and their respective sulfated derivatives (FR-S and MI-S) were chemically characterized using elemental analysis, TLC, FT-IR, NMR, HPLC, and thermal analysis. Cytotoxic activity was evaluated against A549 tumor cells by MTT and sulforhodamine assays. The average molecular weight (Mw) of FR and MI was estimated to be 609 and 310 kDa, respectively. FR-S (127 kDa) and MI-S (86 kDa) had lower Mw, probably due to hydrolysis occurred during the sulfation reaction. FR-S and MI-S presented ~14 % sulfur content in elemental analysis. Sulfation of samples was characterized by the appearance of two new absorption bands at 1253 and 810 cm−1 in the infrared spectra, related to S=O and C-S-O sulfate groups, respectively. Through 1H and 13C NMR analysis FR-S was characterized as a (1→6)-(1→3)-β-D-glucan fully sulfated at C-4 and C-6 terminal and partially sulfated at C-6 of (1→3)-β-D-glucan moiety. MI-S was shown to be a (1→3)-β-D-gluco-(1→2)-β-D-mannan, partially sulfated at C-2, C-3, C-4, and C-6, and fully sulfated at C-6 of the terminal residues. The combination of high degree of sulfation and low molecular weight was correlated with the increased cytotoxic activity (48 h of treatment) of both FR-S (EC50=605.6 μg/mL) and MI-S (EC50=342.1 μg/mL) compared to the non-sulfated polysaccharides FR and MI (EC50>1500 μg/mL). PMID:23511057

  5. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity.

    PubMed

    Cortes, Leonel A; Castro, Lorena; Pesce, Bárbara; Maya, Juan D; Ferreira, Jorge; Castro-Castillo, Vicente; Parra, Eduardo; Jara, José A; López-Muñoz, Rodrigo

    2015-01-01

    derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity.

  6. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity

    PubMed Central

    Cortes, Leonel A.; Castro, Lorena; Pesce, Bárbara; Maya, Juan D.; Ferreira, Jorge; Castro-Castillo, Vicente; Parra, Eduardo; Jara, José A.; López-Muñoz, Rodrigo

    2015-01-01

    Chagas disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP+) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP+-C8, TPP+-C10, TPP+-C11, and TPP+-C12, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP+-C10 and TPP+-C12 were the most potent in both models, with EC50 values (in isolated parasites) of 1.0 ± 0.6 and 1.0 ± 0.7 μM, respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 ± 0.6 μM). At 1 μM, TPP+-C10 and TPP+-C12 induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 μM, TPP+-C10 and TPP+-C12 significantly decreased the number of intracellular amastigotes (TPP+-C10: 24.3%, TPP+-C12: 19.0% of control measurements, as measured by DAPI staining) and the parasite’s DNA load (C10: 10%, C12: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP+-C10 and TPP+-C12 were the most potent compounds, significantly altering mitochondrial membrane potential at 1 μM (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 μM. Taken together, these results indicate that the TPP+-C10 and TPP+-C12 derivatives of gallic acid are

  7. Rotavirus activates dendritic cells derived from umbilical cord blood monocytes.

    PubMed

    Rosales-Martinez, D; Gutierrez-Xicotencatl, L; Badillo-Godinez, O; Lopez-Guerrero, D; Santana-Calderon, A; Cortez-Gomez, R; Ramirez-Pliego, O; Esquivel-Guadarrama, F

    2016-10-01

    Rotavirus is the most common cause of acute infectious diarrhea in human neonates and infants. However, the studies aimed at dissecting the anti-virus immune response have been mainly performed in adults. Dendritic cells (DCs) play a crucial role in innate and acquired immune responses. Therefore, it is very important to determine the response of neonatal and infant DCs to rotavirus and to compare it to the response of adult DCs. Thus, we determined the response of monocyte-derived DCs from umbilical cord blood (UCB) and adult peripheral blood (PB) to rotavirus in vitro. It was found that the rotavirus and its genome, composed of segmented doubled stranded RNA (dsRNA), induced the activation of neonatal DCs, as these cells up-regulated the levels of CD40, CD86, MHC II, TLR-3 and TLR-4, the production of cytokines IL-6, IL-12/23p40, IL-10, TGF-β (but not of IL-12p70), and the message for TNF-α and IFN-β. This activation enabled the neonatal DCs to induce a strong proliferation of allogeneic CD4(+) T cells and the production of IFN-γ. Moreover, neonatal DCs could be infected by rotavirus and sustain its replication. Neonatal DCs had a similar response as adult DCs towards rotavirus and its genome. However, adult DCs had a biased pro-inflammatory response compared to neonatal DCs, which showed a biased regulatory profile, as they produced higher levels of IL-10 and TGF-β, and were less efficient in inducing a Th1 type response. So it can be concluded that rotavirus and its genome can induce the activation of neonatal DCs in spite of their tolerogenic bias.

  8. Antimicrobial activity of nerolidol and its derivatives against airborne microbes and further biological activities.

    PubMed

    Krist, Sabine; Banovac, Daniel; Tabanca, Nurhayat; Wedge, David E; Gochev, Velizar K; Wanner, Jürgen; Schmidt, Erich; Jirovetz, Leopold

    2015-01-01

    Nerolidol and its derivatives, namely cis-nerolidol, O-methyl-nerolidol, O-ethyl-nerolidol, (-)-α-bisabolol, trans,trans-farnesol and its main natural source cabreuva essential oil, were tested for their antimicrobial activity against airborne microbes and antifungal properties against plant pathogens. Among the tested compounds, α-bisabolol was the most effective antimicrobial agent and trans,trans-farnesol showed the best antifungal activity.

  9. Antimicrobial activity of Nerolidol and its derivatives against airborne microbes and further biological activities

    USDA-ARS?s Scientific Manuscript database

    Nerolidol and its derivatives, namely cis-nerolidol, O-methyl-nerolidol, O-ethyl-nerolidol, (-)-alpha-bisabolol, trans,trans-farnesol and its main natural source Cabreuva essential oil, were tested for their antimicrobial activity against airborne microbes and antifungal properties against plant pat...

  10. Investigating magnetic activity in very stable stellar magnetic fields. Long-term photometric and spectroscopic study of the fully convective M4 dwarf V374 Pegasi

    NASA Astrophysics Data System (ADS)

    Vida, K.; Kriskovics, L.; Oláh, K.; Leitzinger, M.; Odert, P.; Kővári, Zs.; Korhonen, H.; Greimel, R.; Robb, R.; Csák, B.; Kovács, J.

    2016-05-01

    The ultrafast-rotating (Prot ≈ 0.44 d) fully convective single M4 dwarf V374 Peg is a well-known laboratory for studying intense stellar activity in a stable magnetic topology. As an observable proxy for the stellar magnetic field, we study the stability of the light curve, hence the spot configuration. We also measure the occurrence rate of flares and coronal mass ejections (CMEs). We have analysed spectroscopic observations, BV(RI)C photometry covering 5 yrs, and additional RC photometry that expands the temporal base over 16 yr. The light curve suggests an almost rigid-body rotation and a spot configuration that is stable over about 16 yrs, confirming the previous indications of a very stable magnetic field. We observed small changes on a nightly timescale and frequent flaring, including a possible sympathetic flare. The strongest flares seem to be more concentrated around the phase where the light curve indicates a smaller active region. Spectral data suggest a complex CME with falling-back and re-ejected material with a maximal projected velocity of ~675 km s-1. We observed a CME rate that is much lower than expected from extrapolations of the solar flare-CME relation to active stars. Tables of the photometry are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/590/A11

  11. Granular bamboo-derived activated carbon for high CO(2) adsorption: the dominant role of narrow micropores.

    PubMed

    Wei, Haoran; Deng, Shubo; Hu, Bingyin; Chen, Zhenhe; Wang, Bin; Huang, Jun; Yu, Gang

    2012-12-01

    Cost-effective biomass-derived activated carbons with a high CO(2) adsorption capacity are attractive for carbon capture. Bamboo was found to be a suitable precursor for activated carbon preparation through KOH activation. The bamboo size in the range of 10-200 mesh had little effect on CO(2) adsorption, whereas the KOH/C mass ratio and activation temperature had a significant impact on CO(2) adsorption. The bamboo-derived activated carbon had a high adsorption capacity and excellent selectivity for CO(2) , and also the adsorption process was highly reversible. The adsorbed amount of CO(2) on the granular activated carbon was up to 7.0 mmol g(-1) at 273 K and 1 bar, which was higher than almost all carbon materials. The pore characteristics of activated carbons responsible for high CO(2) adsorption were fully investigated. Based on the analysis of narrow micropore size distribution of several activated carbons prepared under different conditions, a more accurate micropore range contributing to CO(2) adsorption was proposed. The volume of micropores in the range of 0.33-0.82 nm had a good linear relationship with CO(2) adsorption at 273 K and 1 bar, and the narrow micropores of about 0.55 nm produced the major contribution, which could be used to evaluate CO(2) adsorption on activated carbons.

  12. In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates

    PubMed Central

    AbdelKhalek, Ahmed; Ashby, Charles R.; Patel, Bhargav A.; Talele, Tanaji T.; Seleem, Mohamed N.

    2016-01-01

    Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. However, their potential use as antibacterials has not been fully examined. In this study, we determined the spectrum of activity of seven rhodanine derivatives (compounds Rh 1–7) against clinical isolates of Gram-positive and Gram-negative bacterial strains and Candida albicans. We also synthesized and tested three additional compounds, ethyl ester and amide of rhodanine 2 (Rh 8 and Rh 10, respectively) and ethyl ester of rhodanine 3 (Rh 9) to determine the significance of the carboxyl group modification towards antibacterial activity and human serum albumin binding. A broth microdilution assay confirmed Rh 1–7 exhibit bactericidal activity against Gram-positive pathogens. Rh 2 had significant activity against various vancomycin-resistant (MIC90 = 4 μM) and methicillin-resistant (MIC90 = 4 μM) Staphylococcus aureus (VRSA and MRSA), Staphylococcus epidermidis (MIC = 4 μM) and vancomycin-resistant Enterococcus (VRE) strains (MIC90 = 8 μM). The rhodanine compounds exhibited potent activity against Bacillus spp., including Bacillus anthracis, with MIC range of 2–8 μM. In addition, they had potent activity against Clostridium difficile. The most potent compound, Rh 2, at 4 and 8 times its MIC, significantly decreased S. epidermidis biofilm mass by more than 35% and 45%, respectively. None of the rhodanine compounds showed antimicrobial activity (MIC > 128 μM) against various 1) Gram-negative pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella Typhimurium) or 2) strains of Candida albicans (MIC > 64 μM). The MTS assay confirmed that rhodanines were not toxic to

  13. A Retrospective Multicentre Cohort Review of Patient Characteristics and Surgical Aspects versus the Long-Term Outcomes for Recipients of a Fully Implantable Active Middle Ear Implant

    PubMed Central

    Lefebvre, Philippe P.; Gisbert, Javier; Cuda, Domenico; Tringali, Stéphane; Deveze, Arnaud

    2017-01-01

    Objective To summarise treatment outcomes compared to surgical and patient variables for a multicentre recipient cohort using a fully implantable active middle ear implant for hearing impairment. To describe the authors' preferred surgical technique to determine microphone placement. Study Design Multicentre retrospective, observational survey. Setting Five tertiary referral centres. Patients Carina recipients (66 ears, 62 subjects) using the current Cochlear® Carina® System or the legacy device, the Otologics® Fully Implantable Middle Ear, with a T2 transducer. Methods Patient file review and routine clinical review. Patient outcomes assessed were satisfaction, daily use and feedback reports at the first fitting and ≥12 months after implantation. Descriptive and statistical analysis of correlations of variables and their influence on outcomes was performed. Independently reported preferred methods for microphone placement are collectively summarised. Results The average implant experience was 3.5 years. Satisfaction increased significantly over time (p < 0.05). No correlation with covariates examined was observed. Feedback significantly decreased over time, showing a significant correlation with microphone location, primary motivation, gender, age at implantation, and contralateral hearing aid use (p < 0.05). Patient satisfaction was inversely correlated with reports of system feedback (p < 0.05). The implantable microphone was most commonly on the posterior inferior mastoid line, in 42/66 (65%) cases, correlating with less likelihood for feedback and consistent with author surgical preference. Conclusion Carina recipients in this study present as satisfied consistent daily users with very few reports of persistent feedback. As microphone location is an influencing factor, a careful surgical consideration of microphone placement is required. The authors prefer a posterior inferior mastoid line position whenever possible. PMID:28052264

  14. Subtle problems in activities of daily living after a transient ischemic attack or an apparently fully recovered non-disabling stroke.

    PubMed

    Verbraak, Marieke E; Hoeksma, Agnes F; Lindeboom, Robert; Kwa, Vincent I H

    2012-02-01

    Little is known about the effects on the performance of activities of daily living (ADL) and quality of life (QoL) of transient ischemic attack (TIA) or a nondisabling stroke (NDS) with a full recovery in 72 hours. The present study evaluated ADL performance and QoL, as well as symptoms of anxiety and depression, in patients at 1 and 6 months after a TIA or an NDS. Consecutive hospitalized TIA/NDS patients not requiring rehabilitation were assessed at 1 and 6 months after discharge from a hospital or emergency department. ADL performance was evaluated using the Assessment of Motor and Process Skills (AMPS), QoL was assessed with the Short Form 36 (SF-36), and depression and anxiety symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS). A total of 45 patients completed the follow-up. At 1 month after TIA/NDS, all patients were independent in ADL performance but had AMPS and SF-36 scores below the norm. In addition, 12 patients (27%) had anxiety symptoms, and 9 patients (20%) had symptoms of depression. Although initially considered fully recovered, 23 patients (51%) required rehabilitation after the first follow-up. After 6 months, their AMPS, SF-36, and HADS scores were lower than those of the patients who did not require rehabilitation after the first screening. Half of the patients with a TIA or an NDS who were initially considered fully recovered exhibited ADL limitations, decreased QoL, and symptoms of anxiety or depression after 6 months.

  15. [Griseochelin methyl ester, a new polyether derivative with antiviral activity].

    PubMed

    Tonew, E; Tonew, M; Graefe, U; Zöpel, P

    1988-10-01

    The methylester of griseochelin (1) is a new chemically-made antiviral derivate of the antibiotic griseochelin isolated from fermentations of Streptomyces griseus. It belongs to the polyether group and possesses antiviral activity against enveloped RNA and DNA viruses cultivated in chicken embryo cells (CEC), namely influenzavirus A/WSN, vesicularstomatitis virus (Indiana), vaccinia virus (Lister) and herpes simplex hominis virus type 1 (Kupka). The methylester of griseochelin failed to show virucidal effects on extracellular influenza vacciniavirus particles or to influence virus adsorption and penetration processes. The antibiotic in concentrations of 125-15 micrograms/ml inhibited the virus-induced cytopathic effect of the above mentioned viruses and caused over 90 per cent plaque reduction. Addition of 1 during a one-step growth cycle of influenzavirus A at 4 and 6 h p.i. resulted in complete suppression of virus multiplication at the control niveau of the virus yield accumulated to the same time point. A partial reversibility of the antiviral action against influenzavirus A could be achieved. Coxsackie A9 virus growth in human fibroblast cells was not affected by the inhibitor. Electron-optical observations showed a failure of the formation of the viral capside proteins of HSV type 1 at the second halftime of the replication cycle in CEC-infected and 1-treated cultures.

  16. Structure-activity relationships of bergenin derivatives effect on α-glucosidase inhibition.

    PubMed

    Kashima, Yusei; Yamaki, Hidehiko; Suzuki, Takuya; Miyazawa, Mitsuo

    2013-12-01

    The α-glucosidase inhibitory activities of bergenin derivatives were evaluated. Bergenin derivatives were synthesized from bergenin which is a characteristic compound of B. ligulata. A new bergenin derivative, 11-O-(3',4'-dimethoxybenzoyl)-bergenin showed the highest potent inhibitory activity among those of bergenin derivatives. The presence of substituents at 3',4'-position in bergenin derivatives altered the α-glucosidase inhibitory activity. 11-O-(3',4'-dimethoxybenzoyl)-bergenin was noncompetitive inhibitor for α-glucosidase. The present study reveals that bergenin derivatives could be classified as a new group of α-glucosidase inhibitors.

  17. Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

    DTIC Science & Technology

    2010-07-01

    or 9), although these compounds still showed anti-DHT effects (lanes 2 vs. 6, 8, or 10). Figure 4 . The effects of DHEA derivatives on PSA...2009 - 30 JUN 2010 4 . TITLE AND SUBTITLE Dehydroepiandrosterone Derivatives as Potent Antiandrogens 5a. CONTRACT NUMBER with Marginal Agonist...words) We hypothesized that dehydroepiandrosterone ( DHEA ) metabolites or their synthetic derivatives are able to bind to the androgen receptor with

  18. Molecular modeling, enzyme activity, anti-inflammatory and antiarthritic activities of newly synthesized quinazoline derivatives.

    PubMed

    Abuelizz, Hatem A; Hassane, Anouar El; Marzouk, Mohamed; Ezzeldin, Essam; Ali, Azza A; Al-Salahi, Rashad

    2017-08-09

    16 thioxoquinazolines were evaluated in vivo for anti-inflammatory activity using carrageenan-induced paw edema assay. In particular, out of the targets (1-16), compounds 4 and 6 displayed the highest anti-inflammatory activity (≥80%) and furtherly tested against complete Freund's adjuvant-induced arthritic rats. Significant reduction in the serum level of IL-1β, COX-2 and prostaglandin E2 in the complete Freund's adjuvant rats is demonstrated by compounds 4 and 6. Furthermore, compound 4 showed non-selective activity against COX-1 and COX 2, however, compound 6 was specific toward COX-2. Molecular docking study has demonstrated the possible binding modes of the active quinazolines 4 and 6 in the COX-2 active site. These targets could be used as templates for further development of new derivatives with potent anti-inflammatory activity.

  19. New active site oriented glyoxyl-agarose derivatives of Escherichia coli penicillin G acylase

    PubMed Central

    Cecchini, Davide A; Serra, Immacolata; Ubiali, Daniela; Terreni, Marco; Albertini, Alessandra M

    2007-01-01

    Background Immobilized Penicillin G Acylase (PGA) derivatives are biocatalysts that are industrially used for the hydrolysis of Penicillin G by fermentation and for the kinetically controlled synthesis of semi-synthetic β-lactam antibiotics. One of the most used supports for immobilization is glyoxyl-activated agarose, which binds the protein by reacting through its superficial Lys residues. Since in E. coli PGA Lys are also present near the active site, an immobilization that occurs through these residues may negatively affect the performance of the biocatalyst due to the difficult diffusion of the substrate into the active site. A preferential orientation of the enzyme with the active site far from the support surface would be desirable to avoid this problem. Results Here we report how it is possible to induce a preferential orientation of the protein during the binding process on aldehyde activated supports. A superficial region of PGA, which is located on the opposite side of the active site, is enriched in its Lys content. The binding of the enzyme onto the support is consequently forced through the Lys rich region, thus leaving the active site fully accessible to the substrate. Different mutants with an increasing number of Lys have been designed and, when active, immobilized onto glyoxyl agarose. The synthetic performances of these new catalysts were compared with those of the immobilized wild-type (wt) PGA. Our results show that, while the synthetic performance of the wt PGA sensitively decreases after immobilization, the Lys enriched mutants have similar performances to the free enzyme even after immobilization. We also report the observations made with other mutants which were unable to undergo a successful maturation process for the production of active enzymes or which resulted toxic for the host cell. Conclusion The desired orientation of immobilized PGA with the active site freely accessible can be obtained by increasing the density of Lys residues

  20. Activities and prevalence of proteobacteria members colonizing Echinacea purpurea fully account for in vitro macrophage activation exhibited by extracts of this botanical

    USDA-ARS?s Scientific Manuscript database

    Evidence supports the theory that the bacterial communities colonizing E. purpurea contribute to the innate immune enhancing activity of this botanical. Previously we reported that only about half of the variation in in vitro monocyte stimulating activity exhibited by E. purpurea extracts could be a...

  1. Activities and prevalence of proteobacteria members colonizing Echinacea purpurea fully account for in vitro macrophage activation exhibited by extracts of this botanical

    USDA-ARS?s Scientific Manuscript database

    Evidence supports the theory that bacterial communities colonizing Echinacea purpurea contribute to the innate immune enhancing activity of this botanical. Previously we reported that only about half of the variation in in vitro monocyte stimulating activity exhibited by E. purpurea extracts could ...

  2. A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo.

    PubMed

    Ebert, Tim; Smith, Sharon; Pancari, Greg; Clark, Desmond; Hampton, Richard; Secore, Susan; Towne, Victoria; Fan, Hongxia; Wang, Xin-Min; Wu, Xiaoqing; Ernst, Robin; Harvey, Barrett R; Finnefrock, Adam C; Wang, Fubao; Tan, Charles; Durr, Eberhard; Cope, Leslie; Anderson, Annaliesa; An, Zhiqiang; McNeely, Tessie

    2010-01-01

    A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated surface determinant B (IsdB) of Staphylococcus aureus was isolated from the Cambridge Antibody Technology (CAT) scFv antibody library. As compared to previously described IsdB specific murine monoclonals, CS-D7 has a unique, non-overlapping binding site on IsdB, and exhibits increased in vivo activity. The antibody recognizes a conformational epitope spanning amino acids 50 to 285 and has a binding affinity of 340 (± 75) pM for IsdB. CS-D7 bound to a wide variety of S. aureus strains, but not to an isdB deletion mutant. The antibody mediated opsonophagocytic (OP) killing in vitro and mediated significant protection in vivo. In a murine lethal sepsis model, the antibody conferred protection from death when dosed prior to challenge, but not when dosed after challenge. Importantly, in a central venous catheter (CVC) model in rats, the antibody reduced bacteremia and prevented colonization of indwelling catheters. Protection was observed when rats were dosed with CS-D7 prior to challenge as well as post challenge. IsdB is currently being investigated for clinical efficacy against S. aureus infection, and the activity of this human IsdB specific antibody supplements the growing body of evidence to support targeting this antigen for vaccine development.

  3. Platelet high-density lipoprotein activates transferrin-derived phagocytosis activators, MAPPs, following thrombin digestion.

    PubMed

    Sakamoto, Haruhiko; Wu, Bin; Nagai, Yumiko; Tanaka, Sumiko; Onodera, Masayuki; Ogawa, Takafumi; Ueno, Masaki

    2011-01-01

    Macromolecular activators of phagocytosis from platelets (MAPPs), transferrin-derived phagocytosis activators released from platelets, activate leukocytic phagocytosis via Fcγ receptors. It has been found that MAPPs can be prepared using stored platelets or their lysate. Using this artificial MAPP production system, it has been found that they can be produced from precursors (tetrameric and dimeric transferrins) following reaction with a low-molecular-weight (LMW) activator of MAPPs, which is liberated from a high-molecular-weight activator of MAPP (HMW activator) by reaction with thrombin. In this study, the HMW activator in platelet lysate was characterized by assaying phagocytosis of washed neutrophils. In an ultracentrifugation study of the platelet lysate, HMW activator activity was observed in the fraction corresponding to the density of high-density lipoprotein (HDL). The activity was observed in the apolipoproteins obtained from the HDL fraction. Among the apolipoproteins tested only apolipoprotein CIII showed the activity to produce MAPP in vitro. Affinity chromatography of the apolipoproteins from the HDL fraction of the platelet lysate using an anti-apolipoprotein CIII column revealed that the substance that binds with the antibody showed MAPP-forming activity. In a gel filtration study of thrombin-treated apolipoprotein CIII, a peak of LMW activator activity was observed for fractions with a molecular size smaller than that of apolipoprotein CIII. Finally, MAPP-forming activity of HDL obtained from the plasma was examined. MAPP was formed only when delipidized HDL was used. In conclusion, it is suggested that platelet HDL is the HMW activator and that this activation is achieved via apolipoprotein CIII after thrombin reaction in platelets.

  4. Antimicrobial activity of the synthesized non-allergenic urushiol derivatives.

    PubMed

    Cho, Jeong-Yong; Park, Keun Young; Kim, Seon-Jae; Oh, Sejong; Moon, Jae-Hak

    2015-01-01

    Synthesized urushiol derivatives possessing different carbon atomic length in the alkyl side chain inhibited the growth of food spoilage and pathogenic microorganisms. Particularly, non-allergenic 3-pentylcatechol showed a broad antimicrobial spectrum on an agar plate. Most food spoilage and pathogenic microorganisms were sensitive to urushiol derivatives in the liquid culture. The morphologies of the microorganisms were changed after treatment of 3-pentylcatechol.

  5. Synthesis and activity of a C-8 keto pleuromutilin derivative.

    PubMed

    Springer, Dane M; Sorenson, Margaret E; Huang, Stella; Connolly, Timothy P; Bronson, Joanne J; Matson, James A; Hanson, Ronald L; Brzozowski, David B; LaPorte, Thomas L; Patel, Ramesh N

    2003-05-19

    A C-8 keto pleuromutilin derivative has been synthesized from the biotransformation product 8-hydroxy mutilin. A key step in the process was the selective oxidation at C-8 of 8-hydroxy mutilin using tetrapropylammonium perruthenate. The presence of the C-8 keto group precipitated interesting intramolecular chemistry to afford a compound (10) with a novel pleuromutilin-derived ring system.

  6. Insect Cell-Derived Cofactors Become Fully Functional after Proteinase K and Heat Treatment for High-Fidelity Amplification of Glycosylphosphatidylinositol-Anchored Recombinant Scrapie and BSE Prion Proteins

    PubMed Central

    Imamura, Morikazu; Kato, Nobuko; Okada, Hiroyuki; Yoshioka, Miyako; Iwamaru, Yoshifumi; Shimizu, Yoshihisa; Mohri, Shirou; Yokoyama, Takashi; Murayama, Yuichi

    2013-01-01

    The central event in prion infection is the conformational conversion of host-encoded cellular prion protein (PrPC) into the pathogenic isoform (PrPSc). Diverse mammalian species possess the cofactors required for in vitro replication of PrPSc by protein-misfolding cyclic amplification (PMCA), but lower organisms, such as bacteria, yeasts, and insects, reportedly lack the essential cofactors. Various cellular components, such as RNA, lipids, and other identified cofactor molecules, are commonly distributed in both eukaryotes and prokaryotes, but the reasons for the absence of cofactor activity in lower organisms remain to be elucidated. Previously, we reported that brain-derived factors were necessary for the in vitro replication of glycosylphosphatidylinositol-anchored baculovirus-derived recombinant PrP (Bac-PrP). Here, we demonstrate that following protease digestion and heat treatment, insect cell lysates had the functional cofactor activity required for Bac-PrP replication by PMCA. Mammalian PrPSc seeds and Bac-PrPSc generated by PMCA using Bac-PrP and insect cell-derived cofactors showed similar pathogenicity and produced very similar lesions in the brains of inoculated mice. These results suggested that the essential cofactors required for the high-fidelity replication of mammalian PrPSc were present in the insect cells but that the cofactor activity was masked or inhibited in the native state. We suggest that not only RNA, but also DNA, are the key components of PMCA, although other cellular factors were necessary for the expression of the cofactor activity of nucleic acids. PMCA using only insect cell-derived substances (iPMCA) was highly useful for the ultrasensitive detection of PrPSc of some prion strains. PMID:24367521

  7. Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors.

    PubMed

    Murakami, Itsuo; Wakasa, Yukari; Yamashita, Shinji; Kurihara, Toshio; Zama, Kota; Kobayashi, Naoyuki; Mizutani, Yukiko; Mitsutake, Susumu; Shigyo, Tatsuro; Igarashi, Yasuyuki

    2011-08-24

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid

  8. Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors

    PubMed Central

    2011-01-01

    Background Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. Method Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. Results We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors

  9. Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals

    PubMed Central

    Kumamoto, Eiichi; Fujita, Tsugumi

    2016-01-01

    Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a pivotal role in regulating nociceptive transmission. The TRP channels are activated by various plant-derived chemicals. Although stereoisomers activate or modulate ion channels in a distinct manner, this phenomenon is not fully addressed for TRP channels. By applying the whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices, we found out that all of plant-derived chemicals, carvacrol, thymol, carvone and cineole, increase the frequency of spontaneous excitatory postsynaptic current, a measure of the spontaneous release of l-glutamate from nerve terminals, by activating TRP channels. The presynaptic activities were different between stereoisomers (carvacrol and thymol; (−)-carvone and (+)-carvone; 1,8-cineole and 1,4-cineole) in the extent or the types of TRP channels activated, indicating that TRP channels in the SG are activated by stereoisomers in a distinct manner. This result could serve to know the properties of the central terminal TRP channels that are targets of drugs for alleviating pain. PMID:27483289

  10. Synthesis, structural, theoretical studies and biological activities of 3-(arylamino)-2-phenyl-1H-inden-1-one derivative

    NASA Astrophysics Data System (ADS)

    El-Sheshtawy, Hamdy S.; Abou Baker, Ahmed M.

    2014-06-01

    Five derivatives of 2-phenyl-1H-indene-1-one have been prepared and fully characterized. Spectroscopic techniques such as FT-IR, 1H NMR, mass spectrometry, and elemental analysis were used to investigate the chemical structures and physical properties of the prepared compounds. The optimized structures and the distribution of the frontier molecular orbital were obtained using density functional theory (DFT) at B3LYP/6-311++G(d,p) level of theory. Additionally, the UV spectral properties of the indene compounds were corroborated by frontier orbital (HOMO and LUMO) calculations. Intramolecular charge transfer (ICT) peak has been observed in the UV spectra of the compounds and theoretically confirmed by the HOMO and LUMO analysis. The potential use of these compounds as antibacterial agents was investigated. The results show that indene-1-one derivatives have an antibacterial activity for both gram-negative (Pseudomonas aeruginosa) and gram-positive (Methicillin Resistant Staphylococcus aureus) bacteria.

  11. Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

    PubMed

    Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

    2003-01-01

    An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma-derived

  12. Antitumor activity of 3,4-ethylenedioxythiophene derivatives and quantitative structure-activity relationship analysis

    NASA Astrophysics Data System (ADS)

    Jukić, Marijana; Rastija, Vesna; Opačak-Bernardi, Teuta; Stolić, Ivana; Krstulović, Luka; Bajić, Miroslav; Glavaš-Obrovac, Ljubica

    2017-04-01

    The aim of this study was to evaluate nine newly synthesized amidine derivatives of 3,4- ethylenedioxythiophene (3,4-EDOT) for their cytotoxic activity against a panel of human cancer cell lines and to perform a quantitative structure-activity relationship (QSAR) analysis for the antitumor activity of a total of 27 3,4-ethylenedioxythiophene derivatives. Induction of apoptosis was investigated on the selected compounds, along with delivery options for the optimization of activity. The best obtained QSAR models include the following group of descriptors: BCUT, WHIM, 2D autocorrelations, 3D-MoRSE, GETAWAY descriptors, 2D frequency fingerprint and information indices. Obtained QSAR models should be relieved in elucidation of important physicochemical and structural requirements for this biological activity. Highly potent molecules have a symmetrical arrangement of substituents along the x axis, high frequency of distance between N and O atoms at topological distance 9, as well as between C and N atoms at topological distance 10, and more C atoms located at topological distances 6 and 3. Based on the conclusion given in the QSAR analysis, a new compound with possible great activity was proposed.

  13. Change in Conformation with Reduction of α-Helix Content Causes Loss of Neutrophil Binding Activity in Fully Cytotoxic Shiga Toxin 1*

    PubMed Central

    Brigotti, Maurizio; Carnicelli, Domenica; Arfilli, Valentina; Rocchi, Laura; Ricci, Francesca; Pagliaro, Pasqualepaolo; Tazzari, Pier Luigi; Vara, Antonio González; Amelia, Matteo; Manoli, Francesco; Monti, Sandra

    2011-01-01

    Shiga toxins (Stx) play an important role in the pathogenesis of hemolytic uremic syndrome, a life-threatening renal sequela of human intestinal infection caused by specific Escherichia coli strains. Stx target a restricted subset of human endothelial cells that possess the globotriaosylceramide receptor, like that in renal glomeruli. The toxins, composed of five B chains and a single enzymatic A chain, by removing adenines from ribosomes and DNA, trigger apoptosis and the production of pro-inflammatory cytokines in target cells. Because bacteria are confined to the gut, the toxins move to the kidney through the circulation. Polymorphonuclear leukocytes (PMN) have been indicated as the carriers that “piggyback” shuttle toxins to the kidney. However, there is no consensus on this topic, because not all laboratories have been able to reproduce the Stx/PMN interaction. Here, we demonstrate that conformational changes of Shiga toxin 1, with reduction of α-helix content and exposition to solvent of hydrophobic tryptophan residues, cause a loss of PMN binding activity. The partially unfolded toxin was found to express both enzymatic and globotriaosylceramide binding activities being fully active in intoxicating human endothelial cells; this suggests the presence of a distinct PMN-binding domain. By reviewing functional and structural data, we suggest that A chain moieties close to Trp-203 are recognized by PMN. Our findings could help explain the conflicting results regarding Stx/PMN interactions, especially as the groups reporting positive results obtained Stx by single-step affinity chromatography, which could have preserved the correct folding of Stx with respect to more complicated multi-step purification methods. PMID:21832076

  14. Anticancer activities of artemisinin and its bioactive derivatives.

    PubMed

    Firestone, Gary L; Sundar, Shyam N

    2009-10-30

    Artemisinin, a sesquiterpene lactone derived from the sweet wormwood plant Artemisia annua, and its bioactive derivatives exhibit potent anticancer effects in a variety of human cancer cell model systems. The pleiotropic response in cancer cells includes growth inhibition by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness. These effects of artemisinin and its derivatives result from perturbations of many cellular signalling pathways. This review provides a comprehensive discussion of these cellular responses, and considers the ramifications for the potential development of artemisinin-based compounds in anticancer therapeutic and preventative strategies.

  15. Synthesis and SAR studies of praziquantel derivatives with activity against Schistosoma japonicum.

    PubMed

    Wang, Wen-Long; Song, Li-Jun; Chen, Xia; Yin, Xu-Ren; Fan, Wen-Hua; Wang, Gu-Ping; Yu, Chuan-Xin; Feng, Bainian

    2013-07-31

    The synthesis and structure-activity relationship (SAR) studies of praziquantel derivatives with activity against adult Schistosoma japonicum are described. Several of them showed better worm killing activity than praziquantel and could serve as leads for further optimization.

  16. Synthesis, structure, theoretical calculations and biological activity of sulfonate active ester new derivatives

    NASA Astrophysics Data System (ADS)

    Ghazzali, Mohamed; Khattab, Sherine A. N.; Elnakady, Yasser A.; Al-Mekhlafi, Fahd A.; Al-Farhan, Khalid; El-Faham, Ayman

    2013-08-01

    A series of naphthyl and tolyl sulfonate ester were synthesized and characterized by H NMR. X-ray single crystal diffraction experiments established the molecular structure of three new sulfonate esters derivatives, and spectral data agree with these in solution. The observed hydrogen bonding is discussed on the basis of crystal structural analyses and DFT/MP2 geometry optimization quantum calculations. Antimicrobial activities were screened for selected compounds against three human cancer cell lines and Mosquito Culex pipiens larvae.

  17. A critical role of cardiac fibroblast-derived exosomes in activating renin angiotensin system in cardiomyocytes.

    PubMed

    Lyu, Linmao; Wang, Hui; Li, Bin; Qin, Qingyun; Qi, Lei; Nagarkatti, Mitzi; Nagarkatti, Prakash; Janicki, Joseph S; Wang, Xing Li; Cui, Taixing

    2015-12-01

    Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. However, the precise underlying mechanisms have not been fully delineated. Herein we report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy. In cultured CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT1R) and 2 (AT2R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFβ)1 or hydrogen peroxide did not. The CF-derived exosomes upregulated the expression of renin, angiotensinogen, AT1R, and AT2R, downregulated angiotensin-converting enzyme 2, and enhanced Ang II production in cultured cardiomyocytes. In addition, the CF exosome-induced cardiomyocyte hypertrophy was blocked by both AT1R and AT2R antagonists. Exosome inhibitors, GW4869 and dimethyl amiloride (DMA), inhibited CF-induced cardiomyocyte hypertrophy with little effect on Ang II-induced cardiomyocyte hypertrophy. Mechanistically, CF exosomes upregulated RAS in cardiomyocytes via the activation of mitogen-activated protein kinases (MAPKs) and Akt. Finally, Ang II-induced exosome release from cardiac fibroblasts and pathological cardiac hypertrophy were dramatically inhibited by GW4869 and DMA in mice. These findings demonstrate that Ang II stimulates CFs to release exosomes, which in turn increase Ang II production and its receptor expression in cardiomyocytes, thereby intensifying Ang II-induced pathological cardiac hypertrophy. Accordingly, specific targeting of Ang II-induced exosome release from CFs may serve as a novel therapeutic approach to treat cardiac pathological hypertrophy and heart failure.

  18. Accurate and Fully Automatic Hippocampus Segmentation Using Subject-Specific 3D Optimal Local Maps Into a Hybrid Active Contour Model

    PubMed Central

    Gkontra, Polyxeni; Daras, Petros; Maglaveras, Nicos

    2014-01-01

    Assessing the structural integrity of the hippocampus (HC) is an essential step toward prevention, diagnosis, and follow-up of various brain disorders due to the implication of the structural changes of the HC in those disorders. In this respect, the development of automatic segmentation methods that can accurately, reliably, and reproducibly segment the HC has attracted considerable attention over the past decades. This paper presents an innovative 3-D fully automatic method to be used on top of the multiatlas concept for the HC segmentation. The method is based on a subject-specific set of 3-D optimal local maps (OLMs) that locally control the influence of each energy term of a hybrid active contour model (ACM). The complete set of the OLMs for a set of training images is defined simultaneously via an optimization scheme. At the same time, the optimal ACM parameters are also calculated. Therefore, heuristic parameter fine-tuning is not required. Training OLMs are subsequently combined, by applying an extended multiatlas concept, to produce the OLMs that are anatomically more suitable to the test image. The proposed algorithm was tested on three different and publicly available data sets. Its accuracy was compared with that of state-of-the-art methods demonstrating the efficacy and robustness of the proposed method. PMID:27170866

  19. Two short sequences in OsNAR2.1 promoter are necessary for fully activating the nitrate induced gene expression in rice roots

    PubMed Central

    Liu, Xiaoqin; Feng, Huimin; Huang, Daimin; Song, Miaoquan; Fan, Xiaorong; Xu, Guohua

    2015-01-01

    Nitrate is an essential nitrogen source and serves as a signal to control growth and gene expression in plants. In rice, OsNAR2.1 is an essential partner of multiple OsNRT2 nitrate transporters for nitrate uptake over low and high concentration range. Previously, we have reported that −311 bp upstream fragment from the translational start site in the promoter of OsNAR2.1 gene is the nitrate responsive region. To identify the cis-acting DNA elements necessary for nitrate induced gene expression, we detected the expression of beta-glucuronidase (GUS) reporter in the transgenic rice driven by the OsNAR2.1 promoter with different lengths and site mutations of the 311 bp region. We found that −129 to −1 bp region is necessary for the nitrate-induced full activation of OsNAR2.1. Besides, the site mutations showed that the 20 bp fragment between −191 and −172 bp contains an enhancer binding site necessary to fully drive the OsNAR2.1 expression. Part of the 20 bp fragment is commonly presented in the sequences of different promoters of both the nitrate induced NAR2 genes and nitrite reductase NIR1 genes from various higher plants. These findings thus reveal the presence of conserved cis-acting element for mediating nitrate responses in plants. PMID:26150107

  20. Anticancer activity of TTAC-0001, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody, is associated with inhibition of tumor angiogenesis.

    PubMed

    Kim, Dong Geon; Jin, Younggeon; Jin, Juyoun; Yang, Heekyoung; Joo, Kyeung Min; Lee, Weon Sup; Shim, Sang Ryeol; Kim, Sung-Woo; Yoo, Jinsang; Lee, Sang Hoon; Yoo, Jin-San; Nam, Do-Hyun

    2015-01-01

    Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment.

  1. Synthesis, Acaricidal Activity, and Structure-Activity Relationships of Pyrazolyl Acrylonitrile Derivatives.

    PubMed

    Yu, Haibo; Cheng, Yan; Xu, Man; Song, Yuquan; Luo, Yanmei; Li, Bin

    2016-12-28

    A series of novel pyrazolyl acrylonitrile derivatives was designed, targeting Tetranychus cinnabarinus, and synthesized. Their structures were identified by combination of (1)H NMR, (13)C NMR, and MS spectra. The structures of compounds 18 and 19 were further confirmed by X-ray diffraction. Extensive greenhouse bioassays indicated that compound 19 exhibits excellent acaricidal activity against all developmental stages of T. cinnabarinus, which is better than the commercialized compounds cyenopyrafen and spirodiclofen. It was shown that the acute toxicity of compounds 19 to mammals is quite low. The structure-activity relationships are also discussed.

  2. Health promoting effects of brassica-derived phytochemicals: from chemopreventive and anti-inflammatory activities to epigenetic regulation.

    PubMed

    Wagner, Anika Eva; Terschluesen, Anna Maria; Rimbach, Gerald

    2013-01-01

    A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways.

  3. Design and comparative anticonvulsant activity assessment of CNS-active alkyl-carbamoyl imidazole derivatives.

    PubMed

    Mawasi, Hafiz; Bibi, David; Bialer, Meir

    2016-09-15

    A novel series of carbamoyl derivatives of alkylimidazole has been designed and their anticonvulsant activity was comparatively evaluated in the mice- and rats-maximal-electroshock (MES), subcutaneous-metrazol (scMet) seizure tests and the mice-6Hz psychomotor (6Hz) models. The ten new designed molecules contain in their chemical structure imidazole, alkyl side-chain and carbamate as three potential active moieties. In spite of the close structural features of the carbamoyl imidazole derivatives only compounds 7, 8, 13 and 16 were active at the MES test with ED50 values ranging from 12 to 20mg/kg coupled with high protective index (PI=TD50/ED50) values of 4.1-7.3 after ip administration to rats. A similar phenomenon was observed in mice where compounds 7, 8, 9, 12 had MES-ED50 values of 14-26mg/kg. Compounds 7 and 13 also demonstrated anticonvulsant activity in the 6Hz model with ED50 values of 32 and 44mg/kg, respectively. As the most active entities, compounds 7, 8 followed by 13 and 16, thus offer an optimal efficacy-safety profile and consequently, might be promising candidates for development as new antiepileptics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. New pleuromutilin derivatives with enhanced antimicrobial activity.II.Structure-activity correlations.

    PubMed

    Egger, H; Reinshagen, H

    1976-09-01

    Structural modification of the antibiotic pleuromutilin has afforded several derivatives with considerably enhanced activity against bacteria and mycoplasmas, and has permitted conclusions to be reached about structure-activity relationships. The carbonyl group in the five-membered ring and the hydroxyl group at C11 seem to be essential for activity. The vinyl group can be hydrogenated without loss of activity. Chemical modification at C14 offers the most possibilities for achieving the best activity and solubility properties. Mutilin, and other compounds with a free OH at C14, are inactive. It was shown that mutilin esters of substituted thioglycolic acids had distinctly superior MIC values, especially in combination with a tertiary amino group in the side chain, the latter group of derivatives having MIC values better than pleuromutilin by a factor of more than 10. Further variation within this group led to the development of 14-deoxy-14-[(2-diethylaminoethyl) thioacetoxy]-mutilin hydrogen fumarate (81.723 hfu, tiamulin) for extensive investigation of its chemotherapeutic potential.

  5. Biological activity, design, synthesis and structure activity relationship of some novel derivatives of curcumin containing sulfonamides.

    PubMed

    Lal, Jaggi; Gupta, Sushil K; Thavaselvam, D; Agarwal, Dau D

    2013-06-01

    Five series of curcumin derivatives with sulfonamides 3a-3e, 4a-4e, 5a-5e, 6a-6e and 7a-7e have been synthesized and evaluated for in vitro antibacterial activity against selected medically important gram-(+) and gram-(-) bacterial species viz. Staphylococcus aureus, Bacillus cereus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli, and antifungal activity against few pathogenic fungal species viz. Aspergillus niger, Aspergillus flavus, Trichoderma viride and Curvularia lunata. The cytotoxicity has been determined by measuring IC50 values against human cell lines HeLa, Hep G-2, QG-56 and HCT-116. Among the compounds screened, 3a-3e showed the most potent biological activity against tested bacteria and fungi. Compounds 3a-3e displayed higher cytotoxicity than curcumin. The curcumin derivatives were also evaluated for in vivo anti-inflammatory activity. In contrast, the compounds 6a-6e and 7a-7e showed dramatically decrease in biological activity. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. A pathogenic trace of Tannerella forsythia - shedding of soluble fully active tumor necrosis factor α from the macrophage surface by karilysin.

    PubMed

    Bryzek, D; Ksiazek, M; Bielecka, E; Karim, A Y; Potempa, B; Staniec, D; Koziel, J; Potempa, J

    2014-12-01

    Tannerella forsythia is implicated as a pathogen causing chronic and aggressive periodontitis. However, its virulence factors, including numerous putative proteases, are mostly uncharacterized. Karilysin is a newly described matrix metalloprotease-like enzyme of T. forsythia. Since pathogen-derived proteases may affect the host defense system via modulation of the cytokine network, the aim of this study was to determine the influence of karilysin on tumor necrosis factor-α (TNF-α). The results showed that karilysin cleaved the membrane form of TNF-α on the surface of macrophages, and that this led to an increased concentration of soluble TNF-α in the conditioned medium. Importantly, despite partial degradation of soluble TNF-α by karilysin, the released cytokine retained its biological activity, inducing apoptosis and stimulating autocrine pathway of pro-inflammatory gene expression. Notably, the observed effect required proteolytic activity by karilysin, since a catalytically inactive mutant of the enzyme did not affect TNF-α secretion. The shedding was independent of the activity of ADAM17, a major endogenous TNF-α converting enzyme. Karilysin-dependent TNF-α release from the cell surface is likely to occur in vivo because human plasma, the main constituent of gingival crevicular fluid, only slightly affected the sheddase activity of karilysin. Taken together, these results indicate that karilysin modulates the host immune response through regulation of TNF-α secretion, and should therefore be considered as a new virulence factor of T. forsythia.

  7. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives.

    PubMed

    Srivastava, Sanjay K; Jha, Amrita; Agarwal, Shiv K; Mukherjee, Rama; Burman, Anand C

    2007-11-01

    The disease of cancer has been ranked second after cardiovascular diseases and plant-derived molecules have played an important role for the treatment of cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Recently, epothilones are being emerging as future potential anti-tumor agents. However, targeted cancer therapy has now been rapidly expanding and small organic molecules are being exploited for this purpose. Amongst target specific small organic molecules, quinazoline was found as one of the most successful chemical class in cancer chemotherapy as three drugs namely Gefitinib, Erlotinib and Canertinib belong to this series. Now, quinazoline related chemical classes such as quinolines and naphthyridines are being exploited in cancer chemotherapy and a number of molecules such as compounds EKB-569 (52), HKI-272 (78) and SNS-595 (127a) are in different phases of clinical trials. This review presents the synthesis of quinolines and naphthyridines derivatives, screened for anticancer activity since year 2000. The synthesis of most potent derivatives in each prototype has been delineated. A brief structure activity relationship for each prototype has also been discussed. It has been observed that aniline group at C-4, aminoacrylamide substituents at C-6, cyano group at C-3 and alkoxy groups at C-7 in the quinoline ring play an important role for optimal activity. While aminopyrrolidine functionality at C-7, 2'-thiazolyl at N-1 and carboxy group at C-3 in 1,8-naphthyridine ring are essential for eliciting the cytotoxicity. This review would help the medicinal chemist to design and synthesize molecules for targeted cancer chemotherapy.

  8. Synthesis and Anti-Platelet Activity of Thiosulfonate Derivatives Containing a Quinone Moiety

    PubMed Central

    Bolibrukh, Khrystyna; Polovkovych, Svyatoslav; Khoumeri, Omar; Halenova, Tetyana; Nikolaeva, Irina; Savchuk, Olexiy; Terme, Thierry; Vanelle, Patrice; Lubenets, Vira; Novikov, Volodymyr

    2015-01-01

    Thiosulfonate derivatives based on quinones were synthesized for studying “structure-activity relationship” compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed. PMID:26839819

  9. WANTED: Fully Automated Indexing.

    ERIC Educational Resources Information Center

    Purcell, Royal

    1991-01-01

    Discussion of indexing focuses on the possibilities of fully automated indexing. Topics discussed include controlled indexing languages such as subject heading lists and thesauri, free indexing languages, natural indexing languages, computer-aided indexing, expert systems, and the need for greater creativity to further advance automated indexing.…

  10. Antioxidative and Anti-Inflammatory Activities of Galloyl Derivatives and Antidiabetic Activities of Acer ginnala

    PubMed Central

    Park, Kwan Hee; Yoon, Kyu Hyeong; Yin, Jun; Le, Thi Tam; Ahn, Hye Sin; Yoon, Seong Hye

    2017-01-01

    Chromatographic isolation of the 80% MeOH extract of Acer ginnala (AG) yielded seven galloyl derivatives: gallic acid (1), ginnalin B (2), acertannin (3), maplexin D (4), maplexin E (5), quercetin-3-O-(2′′-galloyl)-α-L-rhamnopyranoside (6), and kaempferol-3-O-(2′′-galloyl)-α-L-rhamnopyranoside (7). This is the first study to report the isolation of compounds 4 and 5 from AG. Galloyl derivatives 3–7 exhibited potent radical scavenging activities, with 5 and 7 showing particularly strong inhibitory activities against nitric oxide production in lipopolysaccharides- (LPS-) stimulated RAW264.7 cells. In addition, oral administration of AG extract (500 mg/kg b.w.) improved symptoms of hyperglycemia and blunted the increases in serum GOT/GPT levels in a rat model of streptozotocin-induced diabetes. These results suggest that galloyl derivatives (1–7) are antioxidant and anti-inflammatory agents and that AG extract has potential as a functional material or novel herbal medicine for treating diabetes mellitus. PMID:28348624

  11. Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

    PubMed Central

    de Araújo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendonça, Francisco J. B.; Barbosa-Filho, José M.

    2013-01-01

    The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

  12. Synthesis, structure-activity relationships and biological activity of new isatin derivatives as tyrosinase inhibitors.

    PubMed

    Gencer, Nahit; Sonmez, Fatih; Demir, Dudu; Arslan, Oktay; Kucukislamoglu, Mustafa

    2014-01-01

    A newly series of isatin derivatives (6a-t) containing alkyl/aryl urea groups were synthesized and their inhibitory effects on the diphenolase activity of banana tyrosinase were evaluated. Tyrosinase was purified from banana on an affinity gel comprised of Sepharose 4B-L-tyrosine-p-aminobenzoic acid. The results showed that all the synthesized compounds inhibited the tyrosinase enzyme activity. Among them, 1-(2,3-dioxoindolin-5-yl)-3-(4-nitrophenyl)urea (6l) was found to be most active compound (Ki = 24.96 µM). The inhibition kinetics was analysed by Lineweaver-Burk double reciprocal plots. It revealed that compound 6l was a competitive inhibitor. According to results of structure-activity relationship, generally, the compounds electron-donating group bonded to the phenyl ring have higher inhibitory activity against tyrosinase than halogen group bonded to the phenyl ring. The inhibitory activities of alkyl urea substituted compounds decreased with increasing carbon number of the alkyl groups at urea moiety. The halogen series at the para position of the phenyl ring showed a qualitative relationship for higher inhibitory activity with increasing size and polarizability. HOMOLUMO energy levels and dipole moments of some selected compounds (6a, 6d, 6h, 6l and 6o) were also calculated by Gaussian software.

  13. Derivatives of diphosphonic acids: synthesis and biological activity

    NASA Astrophysics Data System (ADS)

    Zolotukhina, M. M.; Krutikov, V. I.; Lavrent'ev, A. N.

    1993-07-01

    The scientific-technical and patent literature on the synthesis of derivatives of diphosphonic acids is surveyed. Various methods of synthesis of diphosphonate, phosphonylphosphinyl, and phosphonophosphate compounds are described. The principal aspects of the use of the above compounds in medicine, biochemistry, and agriculture are examined. The bibliography includes 174 references.

  14. New pleuromutilin derivatives with enhanced antimicrobial activity. I. Synthesis.

    PubMed

    Egger, H; Reinshagen, H

    1976-09-01

    A series of new derivatives of the antibiotic pleuromutilin, produced by some Basidiomycetes, was synthesized by chemical modification of natural pleuromutilin. Most of them contain basic functional groups in the side chain at C14 of the mutilin skeleton. The monotosylate of pleuromutilin was used as a versatile intermediate for displacement by N-, O- and S-nucleophiles.

  15. Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

    USDA-ARS?s Scientific Manuscript database

    Despite being an ancient disease, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. The emerging serious problem due to TB control and clinical management prompted us to synthesize novel series of heterocyclic substituted diphenyl ether derivatives and determ...

  16. Modeling thermal dynamics of active layer soils and near-surface permafrost using a fully coupled water and heat transport model

    USGS Publications Warehouse

    Jiang, Yueyang; Zhuang, Qianlai; O'Donnell, Jonathan A.

    2012-01-01

    Thawing and freezing processes are key components in permafrost dynamics, and these processes play an important role in regulating the hydrological and carbon cycles in the northern high latitudes. In the present study, we apply a well-developed soil thermal model that fully couples heat and water transport, to simulate the thawing and freezing processes at daily time steps across multiple sites that vary with vegetation cover, disturbance history, and climate. The model performance was evaluated by comparing modeled and measured soil temperatures at different depths. We use the model to explore the influence of climate, fire disturbance, and topography (north- and south-facing slopes) on soil thermal dynamics. Modeled soil temperatures agree well with measured values for both boreal forest and tundra ecosystems at the site level. Combustion of organic-soil horizons during wildfire alters the surface energy balance and increases the downward heat flux through the soil profile, resulting in the warming and thawing of near-surface permafrost. A projection of 21st century permafrost dynamics indicates that as the climate warms, active layer thickness will likely increase to more than 3 meters in the boreal forest site and deeper than one meter in the tundra site. Results from this coupled heat-water modeling approach represent faster thaw rates than previously simulated in other studies. We conclude that the discussed soil thermal model is able to well simulate the permafrost dynamics and could be used as a tool to analyze the influence of climate change and wildfire disturbance on permafrost thawing.

  17. Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

    PubMed

    Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

    2015-01-01

    The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

  18. [Fully implantable hearing systems].

    PubMed

    Maurer, J

    2009-03-01

    As yet comparatively little experience has been gained with fully implantable hearing systems, as the two systems available at present have only recently received CE permission for Europe and the FDA permissions are still pending in the USA. Additionally the technology is expensive and usually not covered by insurance companies. However, it could be shown that by careful patient selection and very careful surgical techniques, good results can be achieved with this highly sensitive technology, often with better patient satisfaction and hearing quality than with conventional hearing aids. To spread the technology further, the systems must also show reliable results on a broad application. Further surgery to change the batteries should not be necessary more frequently than with cardiac pacemakers. Not all technical problems are finally solved. However, it is to be foreseen that fully implantable hearing systems will be a good long-term alternative to conventional hearing aids for some patients.

  19. Antimalarial activity of anthothecol derived from Khaya anthotheca (Meliaceae).

    PubMed

    Lee, Sung-Eun; Kim, Mi-Ran; Kim, Jeong-Han; Takeoka, Gary R; Kim, Tae-Wan; Park, Byeoung-Soo

    2008-06-01

    Antimalarial activity of anthothecol, a limonoid of Khaya anthotheca (Meliaceae) against Plasmodium falciparum was tested using a [(3)H]-hypoxanthine and 48h culture assay in vitro. Anthotechol showed potent antimalarial activity against malaria parasites with IC(50) values of 1.4 and 0.17microM using two different assays. Also, gedunin had antimalarial activity with IC(50) values of 3.1 and 0.14microM. However, the citrus limonoids, limonin and obacunone did not show any antimalarial activity. The antimalarial activities were compared with the three currently used antimalarial medicines quinine, chloroquinine and artemisinin.

  20. A novel β-lactam derivative, albactam from the flowers of Albizia lebbeck with platelets anti-aggregatory activity in vitro.

    PubMed

    El-Gamal, Ali Ali; Abd-El-Halim, Mohamed Farag; Kalil, Ashraf Taha; Basudan, Omer Ahmed; Al-Rehaily, Adnan Jathlan; Ahmad, Mohamed Shamim; El-Tahir, Kamal Hussin; Al-Massarani, Shaza Mohamed; Abdel-Mageed, Wael Moustafa

    2015-03-01

    A novel β-lactam derivative, albactam, was isolated from the alcoholic extract of the flowers of Albizia lebbeck. It showed a significant anti-aggregatory activity against adenosine diphosphate and arachidonic acid induced guinea-pigs' platelets aggregation in vitro. Six more known compounds were also isolated and fully characterized by measuring 1D and 2D NMR, two of them are the triterpenes β-amyrin and 11α, 12α-oxidotaraxerol, two ceramide derivatives and two flavonoids, kampferol 3-O-rutinoside and rutin.

  1. Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation

    PubMed Central

    KAWASHIMA, NAGAKO; QU, HUANHUAN; LOBATON, MARLIN; ZHU, ZHENYUAN; SOLLOGOUB, MATTHIEU; CAVENEE, WEBSTER K.; HANDA, KAZUKO; HAKOMORI, SEN-ITIROH; ZHANG, YONGMIN

    2014-01-01

    Glycosphingolipids are components of essentially all mammalian cell membranes and are involved in a variety of significant cellular functions, including proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide (GM3) is known to inhibit the activation of epidermal growth factor receptor (EGFR). In the present study, an efficient method for the total chemical synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3 was developed. The structures of the synthesized compounds were fully characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In analyses of EGFR autophosphorylation and cell proliferation ([3H]-thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro-derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity. Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory effect on ΔEGFR, a splicing variant of EGFR that lacks exons 2–7 and is often found in human glioblastomas. The chemical synthesis of other GM3 derivatives using approaches similar to those described in the present study, has the potential to create more potent EGFR inhibitors to block cell growth or motility of a variety of types of cancer that express either wild-type EGFR or ΔEGFR. PMID:24944646

  2. Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation.

    PubMed

    Kawashima, Nagako; Qu, Huanhuan; Lobaton, Marlin; Zhu, Zhenyuan; Sollogoub, Matthieu; Cavenee, Webster K; Handa, Kazuko; Hakomori, Sen-Itiroh; Zhang, Yongmin

    2014-04-01

    Glycosphingolipids are components of essentially all mammalian cell membranes and are involved in a variety of significant cellular functions, including proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide (GM3) is known to inhibit the activation of epidermal growth factor receptor (EGFR). In the present study, an efficient method for the total chemical synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3 was developed. The structures of the synthesized compounds were fully characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In analyses of EGFR autophosphorylation and cell proliferation ([(3)H]-thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro-derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity. Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory effect on ΔEGFR, a splicing variant of EGFR that lacks exons 2-7 and is often found in human glioblastomas. The chemical synthesis of other GM3 derivatives using approaches similar to those described in the present study, has the potential to create more potent EGFR inhibitors to block cell growth or motility of a variety of types of cancer that express either wild-type EGFR or ΔEGFR.

  3. Antifungal, mosquito deterrent, and larvicidal activity of N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives

    USDA-ARS?s Scientific Manuscript database

    Hydrazone derivatives possess good antifungal and insecticidal activities and their structure are used in pesticide design. In the present study, ten hydrazone derivatives (2a-j) were evaluated for their antifungal activity against Colletotrichum, Botrytis, Fusarium and Phomopsis species and for the...

  4. Selective and reversible thiol-pegylation, an effective approach for purification and characterization of five fully active ficin (iso)forms from Ficus carica latex.

    PubMed

    Azarkan, Mohamed; Matagne, André; Wattiez, Ruddy; Bolle, Laetitia; Vandenameele, Julie; Baeyens-Volant, Danielle

    2011-10-01

    The latex of Ficus carica constitutes an important source of many proteolytic components known under the general term of ficin (EC 3.4.22.3) which belongs to the cysteine proteases of the papain family. So far, no data on the purification and characterization of individual forms of these proteases are available. An effective strategy was used to fractionate and purify to homogeneity five ficin forms, designated A, B, C, D1 and D2 according to their sequence of elution from a cation-exchange chromatographic support. Following rapid fractionation on a SP-Sepharose Fast Flow column, the different ficin forms were chemically modified by a specific and reversible monomethoxypolyethylene glycol (mPEG) reagent. In comparison with their un-derivatized counterparts, the mPEG-protein derivatives behaved differently on the ion-exchanger, allowing us for the first time to obtain five highly purified ficin molecular species titrating 1mol of thiol group per mole of enzyme. The purified ficins were characterized by de novo peptide sequencing and peptide mass fingerprinting analyzes, using mass spectrometry. Circular dichroism measurements indicated that all five ficins were highly structured, both in term of secondary and tertiary structure. Furthermore, analysis of far-UV CD spectra allowed calculation of their secondary structural content. Both these data and the molecular masses determined by MS reinforce the view that the enzymes belong to the family of papain-like proteases. The five ficin forms also displayed different specific amidase activities against small synthetic substrates like dl-BAPNA and Boc-Ala-Ala-Gly-pNA, suggesting some differences in their active site organization. Enzymatic activity of the five ficin forms was completely inhibited by specific cysteine and cysteine/serine proteases inhibitors but was unaffected by specific serine, aspartic and metallo proteases inhibitors.

  5. Antimalarial Activity of Anthothecol Derived from Khaya anthotheca (Meliaceae)

    USDA-ARS?s Scientific Manuscript database

    Antimalarial activity of anthothecol, a limonoid of Khaya anthotheca (Meliaceae) against Plasmodium falciparum was tested using a [3H]-hypoxanthine and 48 h culture assay in vitro. Anthothecol showed potent antimalarial activity against malarial parasites with IC50 values of 1.4 and 0.17 uM using t...

  6. Utilization of spent activated carbon to enhance the combustion efficiency of organic sludge derived fuel.

    PubMed

    Chen, Wei-Sheng; Lin, Chang-Wen; Chang, Fang-Chih; Lee, Wen-Jhy; Wu, Jhong-Lin

    2012-06-01

    This study examines the heating value and combustion efficiency of organic sludge derived fuel, spent activated carbon derived fuel, and derived fuel from a mixture of organic sludge and spent activated carbon. Spent activated carbon was sampled from an air pollution control device of an incinerator and characterized by XRD, XRF, TG/DTA, and SEM. The spent activated carbon was washed with deionized water and solvent (1N sulfuric acid) and then processed by the organic sludge derived fuel manufacturing process. After washing, the salt (chloride) and sulfide content could be reduced to 99% and 97%, respectively; in addition the carbon content and heating value were increased. Different ratios of spent activated carbon have been applied to the organic sludge derived fuel to reduce the NO(x) emission of the combustion.

  7. Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

    DTIC Science & Technology

    2013-07-01

    DATES COVERED 01 July 2012 – 30 June 2013 4 . TITLE AND SUBTITLE Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist...Page Introduction…………………………………………………………….………..….. 1 Body………………………………………………………………………………….. 1- 4 Key Research...In addition, we previously found that androstenediol (Adiol), a physiological metabolite from dehydroepiandrosterone ( DHEA ) and a precursor of

  8. Synthesis and Antibacterial Activity of Novel Pleuromutilin Derivatives.

    PubMed

    Liu, Huixian; Xiao, Sui; Zhang, Depeng; Mu, Shuhua; Zhang, Lifang; Wang, Xiaoyang; Xue, Feiqun

    2015-01-01

    In this study we describe the design, synthesis, and antibacterial activity of novel pleuromutilin analogs. A series of new compounds containing piperazine and alkylamino or arylamino groups was synthesized. The new compounds were characterized via (1)H-NMR, (13)C-NMR, Fourier transform (FT)-IR and MS, and were further evaluated for their in vitro activity against seven Gram-positive, and one Gram-negative, pathogens. Antibacterial data revealed that all compounds exhibited moderate to good antibacterial activities against sensitive Gram-positive pathogens. Specifically, 9d displayed the best activity: its activity to Staphylococcus aureus (ATCC25923) is 0.125 µg/mL, which is equal to the control compound tiamulin. The antibacterial activities of 9d to Streptococcus suis (minimum inhibitory concentration (MIC) of 2 µg/mL), Streptococcus agalactiae (MIC of 0.5 µg/mL), and Streptococcus dysgalactiae (MIC of 0.5 µg/mL) were also excellent compared with the control drug erythromycin (MIC of >128 µg/mL). The binding modes of these compounds with active sites were calculated using the programs of Molecular Operating Environment (MOE) and Pymol.

  9. Podophyllotoxin-derived insecticidal agents: part XIII--evaluation of insecticidal activity of podophyllotoxin derivatives against Brontispa longissima.

    PubMed

    Liu, Ying-Qian; Feng, Gang; Yang, Liu; Jing-Zhang; Li, Hong-Yu

    2011-09-01

    In an attempt to find the biorational insecticides for Brontispa longissima control, 12 podophyllotoxin (PPT) analogues were tested for their insecticidal activity against the fifth-instar larvae of B. longissima in vivo for the first time. Among all the tested compounds, especially compounds 6 and 8 showed more promising and pronounced insecticidal activity than toosendanin, a commercial insecticide derived from Melia azedarach. The different insecticidal activity range of compounds 1-12 indicated that the variation of chemical structures in the PPT skeleton markedly affected the activity profiles of this compound class, and some important structure-activity relationship information has been revealed. Together, these preliminary results may be useful in guiding further modification of PPTs in the development of potential new insecticides.

  10. Synthesis and Biological Activities of Oxadiazole Derivatives: A Review.

    PubMed

    Vaidya, Ankur; Jain, Shweta; Jain, Priyanka; Jain, Prachi; Tiwari, Nidhi; Jain, Roshni; Jain, Rashi; Jain, Abhishek K; Agrawal, Ram K

    2016-01-01

    Recently, there has been wide interest in compounds containing the oxadiazole scaffold because of their unique chemical structure and their broad spectrum of biological properties. This review provides readers with an overview of the main synthetic methodologies for oxadiazoles and of their broad spectrum of pharmacological activities such as, anti-microbial, anti-fungal activity, antiviral, anti-tubercular, anti-inflammatory, anti-convulsant, anti-angiogenic, anti-proliferative, analgesic, anti-oedema and in alzheimer activity, which were reported over the past years.

  11. Design, structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives/analogues.

    PubMed

    Sahu, Pramod K

    2016-10-04

    New fourteen 3,4-dihydropyrimidine derivatives/analogues of curcumin (2a-2n) were designed, synthesized and biologically evaluated for their cytotoxicity and antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines HeLa, HCT-116 and QG-56 by MTT assay method. From SAR study, it has been revealed that particularly, compound 2e and 2j (IC50 value 12.5 μM) have shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 3,4-dihydropyrimidines of curcumin, 2c, 2d, 2j and 2n exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally. Therefore, we conclude that physico-chemical analyses may prove structural features of curcumin analogues with their promising combined cytotoxicity/antioxidant activity and it is also concluded from virtual and practical screening that the compounds were varied to possess a broad range of lipophilic character, revealed by Log P values.

  12. Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity.

    PubMed

    Mohamad, Saharuddin Bin; Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Nakagawa, Yoshinori; Kawashima, Ken; Hori, Hitoshi

    2003-01-01

    Gc protein is the precursor for Gc protein-derived macrophage activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on its electrophoretic mobility. The difference in electrophoretic mobility is because of the difference in its posttranslational sugar moiety composition. We compared the difference between Gc protein and GcMAF electrophoretic mobility using the isoelectric focusing (IEF) method. The tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay and nitric oxide (NO) release. The difference in Gc protein and GcMAF electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated macrophage was detected, but no release of TNF and NO was detected. The difference of isoelectric focusing mobility in Gc protein and GcMAF would be useful to develop a GcMAF detection method. GcMAF increased macrophage tumoricidal activity but TNF and NO release were not involved in the mechanism.

  13. [Synthesis and antifatigue activities of new benzamide derivatives].

    PubMed

    Fan, Wu-Tu; Wu, Xiang-Long; Pan, Ya-Lei; Niu, Yin-Bo; Li, Chen-Rui; Mei, Qi-Bing

    2014-10-01

    To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.

  14. Pigment epithelium-derived factor protects cone photoreceptor-derived 661W cells from light damage through Akt activation.

    PubMed

    Rapp, Matthew; Woo, Grace; Al-Ubaidi, Muayyad R; Becerra, S Patricia; Subramanian, Preeti

    2014-01-01

    Pigment epithelium-derived factor (PEDF) can delay and prevent the death of photoreceptors in vivo. We investigated the survival activity of PEDF on cone photoreceptor-derived 661W cells in culture, the presence of PEDF receptor (PEDF-R) in these cells and the activation of prosurvival Akt. Cell death was induced by light exposure in the presence of 9-cis retinal. Cell viability assays showed that PEDF increased the number of 661W cells exposed to these conditions. Western blots showed that PEDF-treated 661W cells had a higher ratio of phosphorylated Akt to total Akt than untreated cells. The PEDF receptor PEDF-R was immunodetected in the plasma membrane fractions of 661W cells. The results demonstrated that PEDF can protect 661W cells against light-induced cell death and suggest that the binding of PEDF to cell surface PEDF-R triggers a prosurvival signaling pathway.

  15. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

    PubMed

    Stavrakov, Georgi; Valcheva, Violeta; Voynikov, Yulian; Philipova, Irena; Atanasova, Mariyana; Konstantinov, Spiro; Peikov, Plamen; Doytchinova, Irini

    2016-03-01

    The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non-toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. © 2015 John Wiley & Sons A/S.

  16. Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors. Pyrazole derivatives.

    PubMed

    Tanitame, Akihiko; Oyamada, Yoshihiro; Ofuji, Keiko; Fujimoto, Mika; Iwai, Noritaka; Hiyama, Yoichi; Suzuki, Kenji; Ito, Hideaki; Terauchi, Hideo; Kawasaki, Motoji; Nagai, Kazuo; Wachi, Masaaki; Yamagishi, Jun-ichi

    2004-07-01

    We have previously found that a pyrazole derivative 1 possesses antibacterial activity and inhibitory activity against DNA gyrase and topoisomerase IV. Here, we synthesized new pyrazole derivatives and found that 5-[(E)-2-(5-chloroindol-3-yl)vinyl]pyrazole 16 possesses potent antibacterial activity and selective inhibitory activity against bacterial topoisomerases. Many of the synthesized pyrazole derivatives were potent against clinically isolated quinolone- or coumarin-resistant Gram-positive strains and had minimal inhibitory concentration values against these strains equivalent to those against susceptible strains.

  17. Bimodal activated carbons derived from resorcinol-formaldehyde cryogels

    PubMed Central

    Szczurek, Andrzej; Amaral-Labat, Gisele; Fierro, Vanessa; Pizzi, Antonio; Celzard, Alain

    2011-01-01

    Resorcinol-formaldehyde cryogels prepared at different dilution ratios have been activated with phosphoric acid at 450 °C and compared with their carbonaceous counterparts obtained by pyrolysis at 900 °C. Whereas the latter were, as expected, highly mesoporous carbons, the former cryogels had very different pore textures. Highly diluted cryogels allowed preparation of microporous materials with high surface areas, but activation of initially dense cryogels led to almost non-porous carbons, with much lower surface areas than those obtained by pyrolysis. The optimal acid concentration for activation, corresponding to stoichiometry between molecules of acid and hydroxyl groups, was 2 M l−1, and the acid–cryogel contact time also had an optimal value. Such optimization allowed us to achieve surface areas and micropore volumes among the highest ever obtained by activation with H3PO4, close to 2200 m2 g−1 and 0.7 cm3 g−1, respectively. Activation of diluted cryogels with a lower acid concentration of 1.2 M l−1 led to authentic bimodal activated carbons, having a surface area as high as 1780 m2 g−1 and 0.6 cm3 g−1 of microporous volume easily accessible through a widely developed macroporosity. PMID:27877405

  18. Synthesis and antiproliferative activity of novel selenoester derivatives.

    PubMed

    Domínguez-Álvarez, Enrique; Plano, Daniel; Font, María; Calvo, Alfonso; Prior, Celia; Jacob, Claus; Palop, Juan Antonio; Sanmartín, Carmen

    2014-02-12

    A series of 31 new selenoesters were synthesized and their cytotoxic activity was evaluated against a prostate cancer cell line (PC-3). The most active compounds were also tested against three tumoural cell lines (MCF-7, A-549 and HT-29) and one non-tumour prostate cell line (RWPE-1). Thirteen compounds showed significant activity towards all tumour cells investigated, and some of them were even more potent than etoposide and cisplatin, which were used as reference drugs. Because of their pronounced potency and/or selectivity, four analogues (5, 21, 28 and 30), were selected in order to assess their redox properties related to a possible redox modulating activity. The glutathione peroxidase (GPx) assay showed slight activity for compound 30 and the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) assay showed a weak activity for compounds 5 and 28. The present results revealed that analogues 5, 21, 28 and 30 might serve as a useful starting point for the design of improved anti-tumour agents. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives.

    PubMed

    Abuelizz, Hatem A; Dib, Rabab El; Marzouk, Mohamed; Anouar, El-Hassane; A Maklad, Yousreya; N Attia, Hanan; Al-Salahi, Rashad

    2017-06-30

    A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1-24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204-0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

  20. Combined blockade of ADP receptors and PI3-kinase p110β fully prevents platelet and leukocyte activation during hypothermic extracorporeal circulation.

    PubMed

    Krajewski, Stefanie; Kurz, Julia; Geisler, Tobias; Peter, Karlheinz; Wendel, Hans Peter; Straub, Andreas

    2012-01-01

    Extracorporeal circulation (ECC) and hypothermia are used to maintain stable circulatory parameters and improve the ischemia tolerance of patients in cardiac surgery. However, ECC and hypothermia induce activation mechanisms in platelets and leukocytes, which are mediated by the platelet agonist ADP and the phosphoinositide-3-kinase (PI3K) p110β. Under clinical conditions these processes are associated with life-threatening complications including thromboembolism and inflammation. This study analyzes effects of ADP receptor P(2)Y(12) and P(2)Y(1) blockade and PI3K p110β inhibition on platelets and granulocytes during hypothermic ECC. Human blood was treated with the P(2)Y(12) antagonist 2-MeSAMP, the P(2)Y(1) antagonist MRS2179, the PI3K p110β inhibitor TGX-221, combinations thereof, or PBS and propylene glycol (controls). Under static in vitro conditions a concentration-dependent effect regarding the inhibition of ADP-induced platelet activation was found using 2-MeSAMP or TGX-221. Further inhibition of ADP-mediated effects was achieved with MRS2179. Next, blood was circulated in an ex vivo ECC model at 28°C for 30 minutes and various platelet and granulocyte markers were investigated using flow cytometry, ELISA and platelet count analysis. GPIIb/IIIa activation induced by hypothermic ECC was inhibited using TGX-221 alone or in combination with P(2)Y blockers (p<0.05), while no effect of hypothermic ECC or antiplatelet agents on GPIIb/IIIa and GPIbα expression and von Willebrand factor binding was observed. Sole P(2)Y and PI3K blockade or a combination thereof inhibited P-selectin expression on platelets and platelet-derived microparticles during hypothermic ECC (p<0.05). P(2)Y blockade alone or combined with TGX-221 prevented ECC-induced platelet-granulocyte aggregate formation (p<0.05). Platelet adhesion to the ECC surface, platelet loss and Mac-1 expression on granulocytes were inhibited by combined P(2)Y and PI3K blockade (p<0.05). Combined blockade of P

  1. Combined Blockade of ADP Receptors and PI3-Kinase p110β Fully Prevents Platelet and Leukocyte Activation during Hypothermic Extracorporeal Circulation

    PubMed Central

    Krajewski, Stefanie; Kurz, Julia; Geisler, Tobias; Peter, Karlheinz; Wendel, Hans Peter; Straub, Andreas

    2012-01-01

    Extracorporeal circulation (ECC) and hypothermia are used to maintain stable circulatory parameters and improve the ischemia tolerance of patients in cardiac surgery. However, ECC and hypothermia induce activation mechanisms in platelets and leukocytes, which are mediated by the platelet agonist ADP and the phosphoinositide-3-kinase (PI3K) p110β. Under clinical conditions these processes are associated with life-threatening complications including thromboembolism and inflammation. This study analyzes effects of ADP receptor P2Y12 and P2Y1 blockade and PI3K p110β inhibition on platelets and granulocytes during hypothermic ECC. Human blood was treated with the P2Y12 antagonist 2-MeSAMP, the P2Y1 antagonist MRS2179, the PI3K p110β inhibitor TGX-221, combinations thereof, or PBS and propylene glycol (controls). Under static in vitro conditions a concentration-dependent effect regarding the inhibition of ADP-induced platelet activation was found using 2-MeSAMP or TGX-221. Further inhibition of ADP-mediated effects was achieved with MRS2179. Next, blood was circulated in an ex vivo ECC model at 28°C for 30 minutes and various platelet and granulocyte markers were investigated using flow cytometry, ELISA and platelet count analysis. GPIIb/IIIa activation induced by hypothermic ECC was inhibited using TGX-221 alone or in combination with P2Y blockers (p<0.05), while no effect of hypothermic ECC or antiplatelet agents on GPIIb/IIIa and GPIbα expression and von Willebrand factor binding was observed. Sole P2Y and PI3K blockade or a combination thereof inhibited P-selectin expression on platelets and platelet-derived microparticles during hypothermic ECC (p<0.05). P2Y blockade alone or combined with TGX-221 prevented ECC-induced platelet-granulocyte aggregate formation (p<0.05). Platelet adhesion to the ECC surface, platelet loss and Mac-1 expression on granulocytes were inhibited by combined P2Y and PI3K blockade (p<0.05). Combined blockade of P2Y12, P2Y1 and PI3K p110

  2. Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives.

    PubMed

    Patel, Chandani; Bassin, Jatinder P; Scott, Mark; Flye, Jenna; Hunter, Ann P; Martin, Lee; Goyal, Madhu

    2016-06-30

    A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1-9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10-18. These were converted to the dibromo compounds 19-27 through reaction with bromine in glacial acetic acid. Compounds 19-27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28-72. Compounds 28-72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25-600 µg/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position.

  3. Antimalarial activity of thiosemicarbazones and purine derived nitriles

    PubMed Central

    Mallari, Jeremy P.; Guiguemde, Wendyam A.; Guy, R. Kiplin

    2009-01-01

    Malaria is a devastating illness caused by multiple species of the Plasmodium genus. The parasite’s food vacuole of falcipain proteases have been extensively studied as potential drug targets. Here we report the testing of two established cysteine protease inhibitor scaffolds against both chloroquine sensitive and chloroquine resistant parasites. A subset of purine derived nitriles killed the parasite with moderate potency, and these inhibitors do not seem to exert their antiproliferative effects as cysteine protease inhibitors. Compound potency was determined to be similar against both parasite strains, indicating a low probability of cross resistance with chloroquine. These compounds represent a novel antimalarial scaffold, and a potential starting point for the development new inhibitors. PMID:19447616

  4. Biological activity of A-289099: an orally active tubulin-binding indolyloxazoline derivative.

    PubMed

    Tahir, Stephen K; Nukkala, Michael A; Zielinski Mozny, Nicolette A; Credo, R Bruce; Warner, Robert B; Li, Qun; Woods, Keith W; Claiborne, Akiyo; Gwaltney, Stephen L; Frost, David J; Sham, Hing L; Rosenberg, Saul H; Ng, Shi-Chung

    2003-03-01

    In this report, we describe the antitumor activity of A-289099, an indolyloxazoline derivative with antimitotic activity. A-289099 decreased the proliferation of a variety of cells with EC(50) values ranging from 5.1 to 12.8 nM in a P-glycoprotein-independent manner. In cultured cells, microtubules depolymerized in a time- and dose-dependent manner when treated with A-289099. In competition-binding assays, A-298099 competed with [(3)H]colchicine for binding to tubulin (K(i) = 0.65 micro M); however, it did not compete with [(3)H]paclitaxel or [(3)H]vincristine. There was an accumulation of cells in G(2)-M after treatment with A-289099 for 8 h and a subsequent increase in a subdiploid population and an increase in caspase-3 activity, indicative of apoptosis after treatment for 24 and 48 h. The antitumor activities of A-289099 were evaluated using the syngeneic M5076 murine reticulum sarcoma flank tumor model. Animals size-matched for established tumors ( approximately 350 mm(3)) were dosed p.o. (50 mg/kg every day) for 11 days starting on day 10 postinoculation. Tumors from A-289099-treated animals regressed throughout the 11-day dosing period with a percentage of the average treated-tumor-volume divided by the average vehicle-control-tumor-volume (% T/C) value of 11% after treatment for 7 days. Examination of tumor sections revealed an increase in internucleosomal DNA fragmentation or cell death within the central core after drug-treatment. A decrease in the perfusion of tumors was observed after drug-treatment that was localized primarily to the central core and closely associated with the regions of cell death. In summary, our findings indicate A-289099 is a promising, orally active tubulin-binding compound with antitumor activity in vivo.

  5. Fully human antibodies from transgenic mouse and phage display platforms.

    PubMed

    Lonberg, Nils

    2008-08-01

    Over the past two decades, technologies have emerged for generating monoclonal antibodies (MAbs) derived from human immunoglobulin gene sequences. These fully human MAbs provide an alternative to re-engineered, or de-immunized, rodent MAbs as a source of low immunogenicity therapeutic antibodies. There are now two marketed fully human therapeutic MAbs, adalimumab and panitumumab, and several dozen more in various stages of human clinical testing. Most of the drugs, including adalimumab and panitumumab, were generated using either phage display or transgenic mouse platforms. The reported clinical experience with fully human MAbs demonstrates that these two platforms are, and should continue to be, a significant source of active and well tolerated experimental therapeutics. While this body of reported clinical data does not yet provide a clear distinction between the platforms, the available descriptions of the drug discovery processes used to identify the clinical candidates highlight one difference. It appears that lead optimization is more commonly applied to phage display derived leads than transgenic mouse derived leads.

  6. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  7. Preparation and antioxidant/pro-oxidant activities of 3-monosubstituted 5-hydroxyoxindole derivatives

    PubMed Central

    Yasuda, Daisuke; Takahashi, Kyoko; Ohe, Tomoyuki; Nakamura, Shigeo; Mashino, Tadahiko

    2016-01-01

    Antioxidant treatments have been expected to be a novel therapeutics for various oxidative stress-mediated disorders. Our previous study revealed that 5-hydroxyoxindole and its 3-phenacyl-3-hydroxy derivatives showed excellent antioxidant activities such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and lipid-peroxidation inhibitory activity. However, the DPPH radical scavenging activity of the 3,3-disubstituted derivatives was lower than that of the original 5-hydroxyoxindole. In the present study, we synthesized novel 3-monosubstituted 5-hydroxyoxindole derivatives that exhibited stronger DPPH radical scavenging activities and lipid peroxidation-inhibitory activities than the 3,3-disubstituted 5-hydroxyoxindoles. Moreover, the 3-monosubstituted 5-hydroxyoxindole derivatives showed neither an iron-mediated pro-oxidant effect nor a remarkable cytotoxicity against HL-60 cell lines except some of the highly lipophilic compounds. These results indicate that 3-monosubstituted 5-hydroxyoxindoles can be used as a promising antioxidant scaffold for drug discovery. PMID:27895383

  8. Design, synthesis and antiviral activity of 2-(3-amino-4-piperazinylphenyl)chromone derivatives.

    PubMed

    Kim, Mi Kyoung; Yoon, Hyunjun; Barnard, Dale Lynn; Chong, Youhoon

    2013-01-01

    Previously, we have confirmed that the antiviral activities of the chromone derivatives were controlled by the type as well as the position of the substituents attached to the chromone core structure. In the course of our ongoing efforts to optimize the antiviral activity of the chromone derivatives, we have been attempting to derivatize the chromone scaffold via introduction of various substituents. In this proof-of-concept study, we introduced a 3-amino-4-piperazinylphenyl functionality to the chromone scaffold and evaluated the antiviral activities of the resulting chromone derivatives. The synthesized 2-(3-amino-4-piperazinylphenyl)-chromones showed severe acute respiratory syndrome-corona virus (SARS-CoV)-specific antiviral activity. In particular, the 2-pyridinylpiperazinylphenyl substituents provided the resulting chromone derivatives with selective antiviral activity. Taken together, this result indicates the possible pharmacophoric role of the 2-pyridinylpiperazine functionality attached to the chromone scaffold, which warrants further in-depth structure-activity relationship study.

  9. Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

    PubMed

    Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

    2013-07-01

    A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Evaluation of activity inotropic of a new steroid derivative using an isolated rat heart model

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer; Landy, Campos-Ramos

    2014-01-01

    There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the estradiol derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine. The results showed that the OTBDS-estradiol-hexanoic acid derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that OTBDS-estradiol-hexanoic acid derivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); nevertheless, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These data suggest that positive inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative is via activation of L-type calcium channel. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs. PMID:24995077

  11. Evaluation of activity inotropic of a new steroid derivative using an isolated rat heart model.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer; Landy, Campos-Ramos

    2014-01-01

    There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the estradiol derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine. The results showed that the OTBDS-estradiol-hexanoic acid derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that OTBDS-estradiol-hexanoic acid derivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); nevertheless, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These data suggest that positive inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative is via activation of L-type calcium channel. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

  12. Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin.

    PubMed

    Hu, Guo-qiang; Hou, Li-li; Wang, Guo-qiang; Duan, Nan-nan; Wen, Xiao-yi; Cao, Tie-yao; Yin, Jun; Wang, Wei; Xie, Song-qiang; Huang, Wen-long

    2012-08-01

    To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).

  13. Synthesis and antibacterial activities of 1-alkyl-3-methacryloyl (acryloyl) of benzimidazolone (thione) derivatives.

    PubMed

    Wei, Shaopeng; Wu, Wenjun; Ji, Zhiqin

    2012-01-01

    A series of (28) 1-alkyl-3-methacryloyl (acryloyl)-benzimidazolone (thione) deriv-atives were synthesized. The structures of the new derivatives were confirmed by (1)H-NMR, (13)C-NMR and ESI-MS spectral analysis. The antibacterial activities of these compounds against several strains of bacteria, such as Bacillus cereus, Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated by methods of paper disc-diffusion and broth mciro-dilution. Methacryloyl derivatives displayed higher antibacterial activities against tested bacterial strains than those of acryloyl derivatives in in vitro tests. A structure-activity relationship (SAR) study revealed that the presences of the methacryloyl moieties is essential to the antibacterial activities of the compounds.

  14. Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity.

    PubMed

    Popadyuk, Irina I; Markov, Andrey V; Babich, Valeriya O; Salomatina, Oksana V; Logashenko, Evgeniya B; Zenkova, Marina A; Salakhutdinov, Nariman F

    2017-08-15

    A new library of deoxycholic acid derivatives bearing nitrogen-containing moieties at the C-3 position was synthesised from epoxy derivative 1 via an epoxide ring-opening reaction promoted by aliphatic or cyclic diamines and fully characterised by NMR and mass-spectroscopy. The synthesised compounds were screened for cytotoxicity against four human tumour cell lines. The results showed that some of the novel diamine-bearing derivatives displayed improved anti-proliferative activities over the parent compound DCA. Among them, a 1-methylpiperazine containing compound (6) showed promising activity and the highest selectivity against tumour cells of enterohepatic origin (HepG2: IC50=3.6µM, SI=9.0; HuTu-80: IC50=4.6µM, SI=6.9) and was identified as a lead molecule. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Unambiguous Synthesis and Prophylactic Antimalarial Activities of Imidazolidinedione Derivatives

    DTIC Science & Technology

    2005-05-04

    ever, the 8-aminoquinoline drugs caused serious lethal activity. hemolytic side effects in glucose-6- phosphate dehydro- Initially, the test material...isopropylguanidine (11) followed by acid hydrolysis of Oral efficacy is an essential consideration in search the t-Boc carbamate 2a, as shown in Scheme 2. These of...account for the species differences gum. The gummy HI salt was suspended in 200 mL of dry in oral activity observed. 17,18 The major hydrolysis CH2C12

  16. Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety.

    PubMed

    Shang, Ruofeng; Wang, Shengyu; Xu, Ximing; Yi, Yunpeng; Guo, Wenzhu; Yuliu; Liang, Jianping

    2013-01-01

    Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA.

  17. Synthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen and sulfur as heteroatoms.

    PubMed

    Dekić, Biljana R; Radulović, Niko S; Dekić, Vidoslav S; Vukićević, Rastko D; Palić, Radosav M

    2010-03-30

    Synthesis, spectral analysis and bioactivity of new coumarin derivatives are described in this paper. Eight new coumarin derivatives were synthesized in moderate to good yields by condensation of 4-chloro-3-nitrocoumarin and the corresponding heteroarylamine. The synthesized compounds were tested for their in vitro antimicrobial activity, in a standard disk diffusion assay, against thirteen strains of bacteria and three fungal strains. They have shown a wide range of activity - from one completely inactive compound to medium active ones.

  18. Brain-derived neurotrophic factor controls activity-dependent maturation of CA1 synapses by downregulating tonic activation of presynaptic kainate receptors.

    PubMed

    Sallert, Marko; Rantamäki, Tomi; Vesikansa, Aino; Anthoni, Heidi; Harju, Kirsi; Yli-Kauhaluoma, Jari; Taira, Tomi; Castren, Eero; Lauri, Sari E

    2009-09-09

    Immature hippocampal synapses express presynaptic kainate receptors (KARs), which tonically inhibit glutamate release. Presynaptic maturation involves activity-dependent downregulation of the tonic KAR activity and consequent increase in release probability; however, the molecular mechanisms underlying this developmental process are unknown. Here, we have investigated whether brain derived neurotrophic factor (BDNF), a secreted protein implicated in developmental plasticity in several areas of the brain, controls presynaptic maturation by regulating KARs. Application of BDNF in neonate hippocampal slices resulted in increase in synaptic transmission that fully occluded the immature-type KAR activity in area CA1. Conversely, genetic ablation of BDNF was associated with delayed synaptic maturation and persistent presynaptic KAR activity, suggesting a role for endogenous BDNF in the developmental regulation of KAR function. In addition, our data suggests a critical role for BDNF TrkB signaling in fast activity-dependent regulation of KARs. Selective acute inhibition of TrkB receptors using a chemical-genetic approach prevented rapid change in synapse dynamics and loss of tonic KAR activity that is typically seen in response to induction of LTP at immature synapses. Together, these data show that BDNF-TrkB-dependent maturation of glutamatergic synapses is tightly associated with a loss of endogenous KAR activity. The coordinated action of these two receptor mechanisms has immediate physiological relevance in controlling presynaptic efficacy and transmission dynamics at CA3-CA1 synapses at a stage of development when functional contact already exists but transmission is weak.

  19. Prenylated arylbenzofuran derivatives from Morus mesozygia with antioxidant activity.

    PubMed

    Kapche, Gilbert D W F; Fozing, Christian D; Donfack, Jean H; Fotso, Ghislain W; Amadou, Dawe; Tchana, Angèle N; Bezabih, Merhatibeb; Moundipa, Paul F; Ngadjui, Bonaventure T; Abegaz, Berhanu M

    2009-01-01

    Five prenylated arylbenzofurans, moracins Q-U, were isolated from Morus mesozygia (Moraceae). Their structures were elucidated on the basis of spectroscopic evidence. Along with these compounds, 3beta-acetoxyurs-12-en-11-one, marsformoxide, moracin C, moracin M, moracin K, artocarpesin, cycloartocarpesin, morachalcone A were also isolated. Four of the five compounds, (moracins R-U) displayed potent antioxidant activity.

  20. Characterization of surface active materials derived from farm products

    USDA-ARS?s Scientific Manuscript database

    Surface active materials obtained by chemical modification of plant protein isolates (lupin, barley, oat), corn starches (dextrin, normal, high amylose, and waxy) and soybean oil (soybean oil based polysoaps, SOPS) were investigated for their surface and interfacial properties using axisymmetric dro...

  1. Antiplatelet Activities of Newly Synthesized Derivatives of Piperlongumine

    USDA-ARS?s Scientific Manuscript database

    Piperlongumine, a pyridine alkaloid isolated from Piper longum L., exhibited a potential inhibitory effect on washed rabbit platelet aggregation induced by collagen, arachidonic acid (AA) and platelet activating factor (PAF), without affecting that induced by thrombin. Piperlongumine was used as a ...

  2. Synthesis and antitumor activity of some substituted indazole derivatives.

    PubMed

    Abbassi, Najat; Rakib, El Mostapha; Chicha, Hakima; Bouissane, Latifa; Hannioui, Abdellah; Aiello, Cinzia; Gangemi, Rosaria; Castagnola, Patrizio; Rosano, Camillo; Viale, Maurizio

    2014-06-01

    Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl]arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose-dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds.

  3. Fully Awake Breast Reduction.

    PubMed

    Filson, Simon A; Yarhi, Danielle; Ramon, Yitzhak

    2016-11-01

    The authors present 25 cases and an in-depth 4-minute video of fully awake aesthetic breast reduction, which was made possible by thoracic epidural anesthesia. There are obvious and important advantages to this technique. Not only does this allow for intraoperative patient cooperation (i.e., patient self-positioning and opinion for comparison of breasts), meaning a shorter and more efficient intraoperative time, there also is a reduction in postoperative pain, complications, recovery, and discharge times. The authors have also enjoyed great success and no complications with this technique in over 150 awake abdominoplasty/total body lift patients. The authors feel that the elimination of the need for general anesthesia by thoracic epidural sensorial-only anesthesia is a highly effective and efficient technique, with very few disadvantages/complications, providing advantages to both patients and surgeons. Therapeutic, IV.

  4. Fully automated protein purification

    PubMed Central

    Camper, DeMarco V.; Viola, Ronald E.

    2009-01-01

    Obtaining highly purified proteins is essential to begin investigating their functional and structural properties. The steps that are typically involved in purifying proteins can include an initial capture, intermediate purification, and a final polishing step. Completing these steps can take several days and require frequent attention to ensure success. Our goal was to design automated protocols that will allow the purification of proteins with minimal operator intervention. Separate methods have been produced and tested that automate the sample loading, column washing, sample elution and peak collection steps for ion-exchange, metal affinity, hydrophobic interaction and gel filtration chromatography. These individual methods are designed to be coupled and run sequentially in any order to achieve a flexible and fully automated protein purification protocol. PMID:19595984

  5. Thermodynamic Derivation of the Activation Energy for Ice Nucleation

    NASA Technical Reports Server (NTRS)

    Barahona, D.

    2015-01-01

    Cirrus clouds play a key role in the radiative and hydrological balance of the upper troposphere. Their correct representation in atmospheric models requires an understanding of the microscopic processes leading to ice nucleation. A key parameter in the theoretical description of ice nucleation is the activation energy, which controls the flux of water molecules from the bulk of the liquid to the solid during the early stages of ice formation. In most studies it is estimated by direct association with the bulk properties of water, typically viscosity and self-diffusivity. As the environment in the ice-liquid interface may differ from that of the bulk, this approach may introduce bias in calculated nucleation rates. In this work a theoretical model is proposed to describe the transfer of water molecules across the ice-liquid interface. Within this framework the activation energy naturally emerges from the combination of the energy required to break hydrogen bonds in the liquid, i.e., the bulk diffusion process, and the work dissipated from the molecular rearrangement of water molecules within the ice-liquid interface. The new expression is introduced into a generalized form of classical nucleation theory. Even though no nucleation rate measurements are used to fit any of the parameters of the theory the predicted nucleation rate is in good agreement with experimental results, even at temperature as low as 190 K, where it tends to be underestimated by most models. It is shown that the activation energy has a strong dependency on temperature and a weak dependency on water activity. Such dependencies are masked by thermodynamic effects at temperatures typical of homogeneous freezing of cloud droplets; however, they may affect the formation of ice in haze aerosol particles. The new model provides an independent estimation of the activation energy and the homogeneous ice nucleation rate, and it may help to improve the interpretation of experimental results and the

  6. Thermodynamic Derivation of the Activation Energy for Ice Nucleation

    NASA Technical Reports Server (NTRS)

    Barahona, D.

    2015-01-01

    Cirrus clouds play a key role in the radiative and hydrological balance of the upper troposphere. Their correct representation in atmospheric models requires an understanding of the microscopic processes leading to ice nucleation. A key parameter in the theoretical description of ice nucleation is the activation energy, which controls the flux of water molecules from the bulk of the liquid to the solid during the early stages of ice formation. In most studies it is estimated by direct association with the bulk properties of water, typically viscosity and self-diffusivity. As the environment in the ice-liquid interface may differ from that of the bulk, this approach may introduce bias in calculated nucleation rates. In this work a theoretical model is proposed to describe the transfer of water molecules across the ice-liquid interface. Within this framework the activation energy naturally emerges from the combination of the energy required to break hydrogen bonds in the liquid, i.e., the bulk diffusion process, and the work dissipated from the molecular rearrangement of water molecules within the ice-liquid interface. The new expression is introduced into a generalized form of classical nucleation theory. Even though no nucleation rate measurements are used to fit any of the parameters of the theory the predicted nucleation rate is in good agreement with experimental results, even at temperature as low as 190 K, where it tends to be underestimated by most models. It is shown that the activation energy has a strong dependency on temperature and a weak dependency on water activity. Such dependencies are masked by thermodynamic effects at temperatures typical of homogeneous freezing of cloud droplets; however, they may affect the formation of ice in haze aerosol particles. The new model provides an independent estimation of the activation energy and the homogeneous ice nucleation rate, and it may help to improve the interpretation of experimental results and the

  7. Anti-mycobacterial activity of thymine derivatives bearing boron clusters.

    PubMed

    Adamska, Anna; Rumijowska-Galewicz, Anna; Ruszczynska, Anna; Studzińska, Mirosława; Jabłońska, Agnieszka; Paradowska, Edyta; Bulska, Ewa; Munier-Lehmann, Hélene; Dziadek, Jarosław; Leśnikowski, Zbigniew J; Olejniczak, Agnieszka B

    2016-10-04

    A series of novel thymine derivatives bearing lipophilic, electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane or hydrophilic 7,8-dicarba-nido-undecaborate anions were synthesized. Synthesis was performed via copper(I)-catalysed Huisgen-Meldal-Sharpless 1,3-dipolar cycloaddition of N(1)-propargylthymine or N(1),N(3)-bispropargylthymine to 1-(3-azidopropyl)-1,2-dicarba-closo-dodecaborane. The obtained compounds were tested in vitro against Mycobacterium tuberculosis thymidylate kinase (TMPKmt) and as inhibitors of mycobacteria growth in culture using both saprophytic Mycobacterium smegmatis (M. smegmatis) and pathogenic Mycobacterium tuberculosis (M. tuberculosis) strains. The most potent TMPKmt inhibitor in the series contained two negatively charged 7,8-dicarba-nido-undecaborate modifications at positions 1 and 3 of thymine (9) and exhibited a Ki value of 1.5 μM. The most potent inhibitors of mycobacteria growth was compound 5 with one electron-neutral 1,2-dicarba-closo-dodecaborane modification at position 1 of thymine, and compound 8 with two modifications, at position 1 and 3. Both compounds completely inhibited M. smegmatis proliferation at a concentration of 100 μg/mL (0.25 mM and 0.15 mM, respectively).

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

    PubMed Central

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

    2016-01-01

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

  9. Hydrazide derivatives produce active oxygen species as hydrazine.

    PubMed

    Timperio, Anna Maria; Rinalducci, Sara; Zolla, Lello

    2005-12-01

    It is well documented that some hydrazines are quite sensitive to oxidation and may serve as the electron donor for the reduction of oxygen, whereas hydrazides are not believed to react directly with oxygen. Data presented in this paper show that both hydrazides and hydrazines share an N-N moiety, which is assumed to react with atmospheric oxygen and produce oxygen radicals, at various degrees of efficiency. Since spectrometric measurements of hydrazide just after solubilization showed that the molecular mass remains constant in the absence of oxygen, we can conclude that hydrazides do not react with the oxygen through a slow spontaneous hydrolytic release of hydrazine. However, hydrazine is more reactive than hydrazide, which requires hours rather than minutes to produce measurable quantities of radical species. Differences were also apparent for various substituted derivatives. The reaction was significantly enhanced by the presence of metal ions. Data reported here demonstrate that hydrazides cause irreversible damage to the prosthetic group of proteins as well as causing degradation of the polypeptide chain into small fragments.

  10. Antimutagenic activity of mitochondria-targeted plastoquinone derivative.

    PubMed

    Chistyakov, V A; Sazykina, M A; Alexandrova, A A; Belichenko, N I; Mashkina, E V; Gutnikova, L V; Zolotukhin, P V; Shkurat, T P

    2010-03-01

    The ability of cationic plastoquinone derivative 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to modify processes of spontaneous and induced mutagenesis was studied. It is shown that daily introduction of this compound into male Wistar rats in doses of 25 and 250 nmol/kg during two weeks decreases spontaneous level of chromosome aberrations in anaphase in the eye cornea from 0.39 +/- 0.09 to 0.13 +/- 0.08 and 0.14 +/- 0.05, respectively. The level of 8-hydroxy-2'-deoxyguanosine in blood serum of the investigated animals decreases from 32.12 +/- 1.55 to 25.90 +/- 2.26 and 25.76 +/- 1.50 ng/ml, respectively. These facts indicate that the decrease in spontaneous clastogenesis is caused by decreased level of DNA damage by endogenous reactive oxygen species. A higher dose of SkQ1 also decreases to control level chromosome aberrations caused by oxygen under pressure of 0.5 MPa for 60 min. It is also shown in experiments with bacterial biosensors that SkQ1 is able to efficiently protect cells against genotoxic effect of UV radiation at 300-400 nm.

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

    PubMed

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

    2016-02-18

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

  12. Anti-Inflammatory Activity of Tanzawaic Acid Derivatives from a Marine-Derived Fungus Penicillium steckii 108YD142

    PubMed Central

    Shin, Hee Jae; Pil, Gam Bang; Heo, Soo-Jin; Lee, Hyi-Seung; Lee, Jong Seok; Lee, Yeon-Ju; Lee, Jihoon; Won, Ho Shik

    2016-01-01

    Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4), and K (5). The structures of tanzawaic acid derivatives 1–5 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis. These compounds significantly inhibited nitric oxide (NO) production and the new tanzawaic acid Q (1) inhibited the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA expressions in RAW 264.7 macrophages. Additionally, compound 1 reduced the mRNA levels of inflammatory cytokines. Taken together, the results of this study demonstrated that the new tanzawaic acid derivative inhibits LPS-induced inflammation. This is the first report on the anti-inflammatory activity of tanzawaic acid Q (1). PMID:26761016

  13. Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model.

    PubMed

    Figueroa-Valverde, L; Díaz-Cedillo, F; García-Cervera, E; Pool Gómez, E; López-Ramos, M; Rosas-Nexticapa, M; Martinez-Camacho, R

    2013-10-01

    Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

  14. Novel macromolecules derived from coumarin: synthesis and antioxidant activity

    NASA Astrophysics Data System (ADS)

    Al-Amiery, Ahmed A.; Al-Majedy, Yasameen K.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2015-07-01

    The rational design of 4-hydroxycoumarins with tailor-made antioxidant activities is required nowadays due to the wide variety of pharmacologically significant, structurally interesting of coumarins and researcher orientation toward green chemistry and natural products. A simple and unique coumarins have been achieved by reaction of 4-hydroxycoumarin with aromatic aldehyde accompanied with the creation of a macromolecules have 2-aminothiazolidin-4-one. The molecular structures of the compounds were characterized by the Fourier transformation infrared and Nuclear magnetic resonance spectroscopies, in addition to CHN analysis. The scavenging abilities of new compounds against stable DPPH radical (DPPH•) and hydrogen peroxide were done and the results show that the compounds exhibited high antioxidant activates.

  15. Novel macromolecules derived from coumarin: synthesis and antioxidant activity

    PubMed Central

    Al-Amiery, Ahmed A.; Al-Majedy, Yasameen K.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2015-01-01

    The rational design of 4-hydroxycoumarins with tailor-made antioxidant activities is required nowadays due to the wide variety of pharmacologically significant, structurally interesting of coumarins and researcher orientation toward green chemistry and natural products. A simple and unique coumarins have been achieved by reaction of 4-hydroxycoumarin with aromatic aldehyde accompanied with the creation of a macromolecules have 2-aminothiazolidin-4-one. The molecular structures of the compounds were characterized by the Fourier transformation infrared and Nuclear magnetic resonance spectroscopies, in addition to CHN analysis. The scavenging abilities of new compounds against stable DPPH radical (DPPH•) and hydrogen peroxide were done and the results show that the compounds exhibited high antioxidant activates. PMID:26134661

  16. Novel macromolecules derived from coumarin: synthesis and antioxidant activity.

    PubMed

    Al-Amiery, Ahmed A; Al-Majedy, Yasameen K; Kadhum, Abdul Amir H; Mohamad, Abu Bakar

    2015-07-02

    The rational design of 4-hydroxycoumarins with tailor-made antioxidant activities is required nowadays due to the wide variety of pharmacologically significant, structurally interesting of coumarins and researcher orientation toward green chemistry and natural products. A simple and unique coumarins have been achieved by reaction of 4-hydroxycoumarin with aromatic aldehyde accompanied with the creation of a macromolecules have 2-aminothiazolidin-4-one. The molecular structures of the compounds were characterized by the Fourier transformation infrared and Nuclear magnetic resonance spectroscopies, in addition to CHN analysis. The scavenging abilities of new compounds against stable DPPH radical (DPPH•) and hydrogen peroxide were done and the results show that the compounds exhibited high antioxidant activates.

  17. Drug design based on pentaerythritol tetranitrate reductase: synthesis and antibacterial activity of Pogostone derivatives.

    PubMed

    Wang, Biao; Huang, Wei; Zhou, Jin; Tang, Xue; Chen, Yang; Peng, Cheng; Han, Bo

    2017-08-09

    Our previous work showed that Pogostone exerts antibacterial effects by targeting pentaerythritol tetranitrate reductase (PETNR). In order to develop derivatives of Pogostone with potent antibacterial activity, we performed molecular docking studies of Pogostone with PETNR and analyzed structure-activity relationships, which guided the structure design and the subsequent facile organocatalytic synthesis of Pogostone derivatives under mild reaction conditions. Several of the synthesized compounds showed antibacterial activity in vitro, including one compound (3h) that was highly effective against methicillin-resistant Staphylococcus aureus. These results suggest that Pogostone derivatives bearing functional groups on the side chain may be good leads for antibacterial drug development.

  18. Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases)

    PubMed Central

    Baqi, Younis; Weyler, Stefanie; Iqbal, Jamshed; Zimmermann, Herbert

    2008-01-01

    Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore and to analyze structure-activity relationships we synthesized a series of truncated derivatives and analogs of RB-2, including 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinones, 1-amino-2-methyl-4-arylaminoanthraquinones, 1-amino-4-bromoanthraquinone 2-sulfonic acid esters and sulfonamides, and bis-(1-amino-4-bromoanthraquinone) sulfonamides, and investigated them in preparations of rat NTPDase1, 2, and 3 using a capillary electrophoresis assay. Several 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinone derivatives inhibited E-NTPDases in a concentration-dependent manner. The 2-sulfonate group was found to be required for inhibitory activity, since 2-methyl-substituted derivatives were inactive. 1-Amino-2-sulfo-4-p-chloroanilinoanthraquinone (18) was identified as a nonselective competitive blocker of NTPDases1, 2, and 3 (Ki 16–18 μM), while 1-amino-2-sulfo-4-(2-naphthylamino)anthraquinone (21) was a potent inhibitor with preference for NTPDase1 (Ki 0.328 μM) and NTPDase3 (Ki 2.22 μM). Its isomer, 1-amino-2-sulfo-4-(1-naphthylamino)anthraquinone (20), was a potent and selective inhibitor of rat NTPDase3 (Ki 1.5 μM). PMID:18528783

  19. Phytotoxic activity of bibenzyl derivatives from the orchid Epidendrum rigidum.

    PubMed

    Hernández-Romero, Yanet; Acevedo, Laura; Sánchez, María de los Angeles; Shier, W Thomas; Abbas, Hamed K; Mata, Rachel

    2005-08-10

    A whole plant chloroform-methanol extract of the orchid Epidendrum rigidum inhibited radicle growth of Amaranthus hypochondriacus seedlings (IC50 = 300 microg/mL). Bioassay-guided fractionation furnished four phytotoxins, namely, gigantol (1), batatasin III (2), 2,3-dimethoxy-9,10-dihydrophenathrene-4,7-diol (9), and 3,4,9-trimethoxyphenanthrene-2,5-diol (11), along with the known flavonoids apigenin, vitexin, and isovetin and the triterterpenoids 24,24-dimethyl-9,19-cyclolanostane-25-en-3beta-ol (14) and 24-methyl-9,19-cyclolanostane-25-en-3beta-ol (15). Stilbenoids 1, 2, 9, and 11 inhibited radicle growth of A. hypochondriacus with IC50 values of 0.65, 0.1, 0.12, and 5.9 microM, respectively. Foliar application of gigantol (1) at 1 microM to 4 week old seedlings of A. hypochondriacus reduced shoot elongation by 69% and fresh weight accumulation by 54%. Bibenzyls 1 and 2, as well as synthetic analogues 4'-hydroxy-3,3',5-trimethoxybibenzyl (3), 3,3',4',5-tetramethoxybibenzyl (4), 3,4'-dihydroxy-5-methoxybibenzyl (5), 3'-O-methylbatatasin III (6), 3,3',5-trihydroxybibenzyl (7), and 3,4',5-trihydroxybibenzyl (8), were tested for phytotoxicity in axenic cultures of the small aquatic plant Lemna pausicostata. All bibenzyls derivatives except 7 and 8 inhibited growth and increased cellular leakage with IC50 values of 89.9-180 and 89.9-166 microM, respectively. The natural and synthetic bibenzyls showed marginal cytotoxicity on animal cells. The results suggest that orchid bibenzyls may be good lead compounds for the development of novel herbicidal agents.

  20. Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo

    PubMed Central

    Song, Jae-Hyoung; Kwon, Bo-Eun; Jang, Hongjun; Kang, Hyunju; Cho, Sungchan; Park, Kwisung; Ko, Hyun-Jeong; Kim, Hyoungsu

    2015-01-01

    Chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (EV71) by suppressing viral 3C protease (3Cpro) activity. In the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus B3 (CVB3), which belongs to the same genus (Enterovirus) as EV71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. We found that chrysin showed antiviral activity against CVB3 at 10 μM, but exhibited mild cellular cytotoxicity at 50 μM, prompting us to synthesize derivatives of chrysin to increase the antiviral activity and reduce its cytotoxicity. Among four 4-substituted benzyl derivatives derived from C(5) benzyl-protected derivatives 7, 9–11 had significant antiviral activity and showed the most potent activity against CVB3 with low cytotoxicity in Vero cells. Intraperitoneal injection of CVB3 in BALB/c mice with 1×106 TCID50 (50% tissue culture infective dose) of CVB3 induced acute pancreatitis with ablation of acinar cells and increased serum CXCL1 levels, whereas the daily administration of 9 for 5 days significantly alleviated the pancreatic inflammation and reduced the elevation in serum CXCL1 levels. Collectively, we assessed the anti-CVB3 activities of chrysin and its derivatives, and found that among 4-substituted benzyl derivatives, 9 exhibited the highest activity against CVB3 in vivo, and protected mice from CVB3-induced pancreatic damage, simultaneously lowering serum CXCL1 levels. PMID:26336587

  1. Synthesis and biological activity of glutamic acid derivatives.

    PubMed

    Receveur, J M; Guiramand, J; Récasens, M; Roumestant, M L; Viallefont, P; Martinez, J

    1998-01-20

    In order to develop new specific glutamate analogues at metabotropic glutamate receptors, Diels-Alder, 1-4 ionic and radical reactions were performed starting from (2S)-4-methyleneglutamic acid. Preliminary pharmacological evaluation by measuring IP accumulation using rat forebrain synaptoneurosomes has shown that (2S)-4-(2-phthalimidoethyl)glutamic acid (3a), (2S)-4-(4-phthalimidobutyl)glutamic acid (3b) and 1-[(S)-2-amino-2-carboxyethyl]-3,4-dimethylcyclohex-3-ene-1-carbox ylic acid (8) presented moderate antagonist activities.

  2. Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors.

    PubMed

    Thompson, Robert E; Liu, Xuyu; Ripoll-Rozada, Jorge; Alonso-García, Noelia; Parker, Benjamin L; Pereira, Pedro José Barbosa; Payne, Richard J

    2017-09-01

    Madanin-1 and chimadanin are two small cysteine-free thrombin inhibitors that facilitate blood feeding in the tick Haemaphysalis longicornis. Here, we report a post-translational modification-tyrosine sulfation-of these two proteins that is critical for potent anti-thrombotic and anticoagulant activity. Inhibitors produced in baculovirus-infected insect cells displayed heterogeneous sulfation of two tyrosine residues within each of the proteins. One-pot ligation-desulfurization chemistry enabled access to homogeneous samples of all possible sulfated variants of the proteins. Tyrosine sulfation of madanin-1 and chimadanin proved crucial for thrombin inhibitory activity, with the doubly sulfated variants three orders of magnitude more potent than the unmodified inhibitors. The three-dimensional structure of madanin-1 in complex with thrombin revealed a unique mode of inhibition, with the sulfated tyrosine residues binding to the basic exosite II of the protease. The importance of tyrosine sulfation within this family of thrombin inhibitors, together with their unique binding mode, paves the way for the development of anti-thrombotic drug leads based on these privileged scaffolds.

  3. Synthesis and Larvicidal Activity of Novel Thenoylhydrazide Derivatives.

    PubMed

    Song, Gao-Peng; Hu, De-Kun; Tian, Hao; Li, Ya-Sheng; Cao, Yun-Shen; Jin, Hong-Wei; Cui, Zi-Ning

    2016-03-10

    A pair of chemical isomeric structures of novel N-tert-butylphenyl thenoylhydrazide compounds I and II were designed and synthesized. Their structures were characterized by MS, IR, (1)H NMR, elemental analysis and X-ray single crystal diffraction. The regioselectivity of the Meerwein arylation reaction and the electrophilic substitution reaction of N-tert-butyl hydrazine were studied by density functional theory (DFT) quantum chemical method. The larvicidal tests revealed that some compounds I had excellent larvicidal activity against Culex pipiens pallens. As the candidates of insect growth regulators (IGRs), the larval growth inhibition and regulation against Culex pipiens pallens were examined for some compounds, especially I1 and I7. Compounds I1 and I7 were further indicated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). Finally, a molecular docking study of compound I7 was conducted, which was not only beneficial to understand the structure-activity relationship, but also useful for development of new IGRs for the control of mosquitos.

  4. Synthesis and Larvicidal Activity of Novel Thenoylhydrazide Derivatives

    PubMed Central

    Song, Gao-Peng; Hu, De-Kun; Tian, Hao; Li, Ya-Sheng; Cao, Yun-Shen; Jin, Hong-Wei; Cui, Zi-Ning

    2016-01-01

    A pair of chemical isomeric structures of novel N-tert-butylphenyl thenoylhydrazide compounds I and II were designed and synthesized. Their structures were characterized by MS, IR, 1H NMR, elemental analysis and X-ray single crystal diffraction. The regioselectivity of the Meerwein arylation reaction and the electrophilic substitution reaction of N-tert-butyl hydrazine were studied by density functional theory (DFT) quantum chemical method. The larvicidal tests revealed that some compounds I had excellent larvicidal activity against Culex pipiens pallens. As the candidates of insect growth regulators (IGRs), the larval growth inhibition and regulation against Culex pipiens pallens were examined for some compounds, especially I1 and I7. Compounds I1 and I7 were further indicated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). Finally, a molecular docking study of compound I7 was conducted, which was not only beneficial to understand the structure-activity relationship, but also useful for development of new IGRs for the control of mosquitos. PMID:26960713

  5. Fine-tuning of macrophage activation using synthetic rocaglate derivatives

    PubMed Central

    Bhattacharya, Bidisha; Chatterjee, Sujoy; Devine, William G.; Kobzik, Lester; Beeler, Aaron B.; Porco, John A.; Kramnik, Igor

    2016-01-01

    Drug-resistant bacteria represent a significant global threat. Given the dearth of new antibiotics, host-directed therapies (HDTs) are especially desirable. As IFN-gamma (IFNγ) plays a central role in host resistance to intracellular bacteria, including Mycobacterium tuberculosis, we searched for small molecules to augment the IFNγ response in macrophages. Using an interferon-inducible nuclear protein Ipr1 as a biomarker of macrophage activation, we performed a high-throughput screen and identified molecules that synergized with low concentration of IFNγ. Several active compounds belonged to the flavagline (rocaglate) family. In primary macrophages a subset of rocaglates 1) synergized with low concentrations of IFNγ in stimulating expression of a subset of IFN-inducible genes, including a key regulator of the IFNγ network, Irf1; 2) suppressed the expression of inducible nitric oxide synthase and type I IFN and 3) induced autophagy. These compounds may represent a basis for macrophage-directed therapies that fine-tune macrophage effector functions to combat intracellular pathogens and reduce inflammatory tissue damage. These therapies would be especially relevant to fighting drug-resistant pathogens, where improving host immunity may prove to be the ultimate resource. PMID:27086720

  6. Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors

    NASA Astrophysics Data System (ADS)

    Thompson, Robert E.; Liu, Xuyu; Ripoll-Rozada, Jorge; Alonso-García, Noelia; Parker, Benjamin L.; Pereira, Pedro José Barbosa; Payne, Richard J.

    2017-09-01

    Madanin-1 and chimadanin are two small cysteine-free thrombin inhibitors that facilitate blood feeding in the tick Haemaphysalis longicornis. Here, we report a post-translational modification—tyrosine sulfation—of these two proteins that is critical for potent anti-thrombotic and anticoagulant activity. Inhibitors produced in baculovirus-infected insect cells displayed heterogeneous sulfation of two tyrosine residues within each of the proteins. One-pot ligation-desulfurization chemistry enabled access to homogeneous samples of all possible sulfated variants of the proteins. Tyrosine sulfation of madanin-1 and chimadanin proved crucial for thrombin inhibitory activity, with the doubly sulfated variants three orders of magnitude more potent than the unmodified inhibitors. The three-dimensional structure of madanin-1 in complex with thrombin revealed a unique mode of inhibition, with the sulfated tyrosine residues binding to the basic exosite II of the protease. The importance of tyrosine sulfation within this family of thrombin inhibitors, together with their unique binding mode, paves the way for the development of anti-thrombotic drug leads based on these privileged scaffolds.

  7. Acylthiourea, acylurea, and acylguanidine derivatives with potent hedgehog inhibiting activity.

    PubMed

    Solinas, Antonio; Faure, Hélène; Roudaut, Hermine; Traiffort, Elisabeth; Schoenfelder, Angèle; Mann, André; Manetti, Fabrizio; Taddei, Maurizio; Ruat, Martial

    2012-02-23

    The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC(50) values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.

  8. Synthesis and Larvicidal Activity of Novel Thenoylhydrazide Derivatives

    NASA Astrophysics Data System (ADS)

    Song, Gao-Peng; Hu, De-Kun; Tian, Hao; Li, Ya-Sheng; Cao, Yun-Shen; Jin, Hong-Wei; Cui, Zi-Ning

    2016-03-01

    A pair of chemical isomeric structures of novel N-tert-butylphenyl thenoylhydrazide compounds I and II were designed and synthesized. Their structures were characterized by MS, IR, 1H NMR, elemental analysis and X-ray single crystal diffraction. The regioselectivity of the Meerwein arylation reaction and the electrophilic substitution reaction of N-tert-butyl hydrazine were studied by density functional theory (DFT) quantum chemical method. The larvicidal tests revealed that some compounds I had excellent larvicidal activity against Culex pipiens pallens. As the candidates of insect growth regulators (IGRs), the larval growth inhibition and regulation against Culex pipiens pallens were examined for some compounds, especially I1 and I7. Compounds I1 and I7 were further indicated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). Finally, a molecular docking study of compound I7 was conducted, which was not only beneficial to understand the structure-activity relationship, but also useful for development of new IGRs for the control of mosquitos.

  9. Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives.

    PubMed

    Zhang, Hengyuan; Zhu, Peiqing; Liu, Jie; Lin, Yan; Yao, Hequan; Jiang, Jieyun; Ye, Wencai; Wu, Xiaoming; Xu, Jinyi

    2015-02-01

    A collection of pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited significant antiproliferative activity. Especially compound 15e displayed the most potent activity with the IC50 values of 5.58 and 6.13μM against B16 and SF763 cancer cell lines, respectively. Furthermore, the significant in vivo antitumor activity of 15e was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

  10. 17 CFR 240.15a-1 - Securities activities of OTC derivatives dealers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... options, forwards, futures, swap agreements, or collars involving currencies, interest or other rates... activities of an OTC derivatives dealer. Such orders may: (1) Identify other permissible securities... through a registered broker or dealer (other than an OTC derivatives dealer) that, in the case of...

  11. Design, synthesis, and antibacterial activities of conformationally constrained kanamycin A derivatives.

    PubMed

    Zhang, Wenxuan; Chen, Ying; Liang, Qingzhao; Li, Hui; Jin, Hongwei; Zhang, Liangren; Meng, Xiangbao; Li, Zhongjun

    2013-01-18

    A series of conformationally constrained kanamycin A derivatives with a 2'-hydroxyl group in ring I and a 5-hydroxyl group in ring II tethered by carbon chains were designed and synthesized. Pivotal 5,2'-hydroxyl groups were exposed, and the kanamycin A intermediate was synthesized from 5, 2', 4″, 6″-di-O-benzylidene-protected tetraazidokanamycin A. Cyclic kanamycin A derivatives with intramolecular 8-, 9-, 10-, and 11-membered ethers were then prepared by cesium carbonate mediated Williamson ether synthesis or a ring-closing metathesis reaction. The kanamycin A derivatives were assayed against both susceptible and resistant bacterial strains. Although no derivative showed better antibacterial activities than kanamycin A, the antibacterial activities of these cyclic kanamycin A derivatives indeed varied with the length of the bridge. Moreover, different variations of activities were observed between the susceptible and resistant bacterial strains. More tightly constrained derivative 2 with a one-carbon bridge showed better activity than the others against susceptible strains, but it was much less effective for resistant bacterial strains than derivative 3 with a two-carbon bridge and derivative 6 with an unsaturated four-carbon bridge.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  13. Antistaphylococcal activity of bacteriophage derived chimeric protein P128.

    PubMed

    Vipra, Aradhana A; Desai, Srividya Narayanamurthy; Roy, Panchali; Patil, Raghu; Raj, Juliet Mohan; Narasimhaswamy, Nagalakshmi; Paul, Vivek Daniel; Chikkamadaiah, Ravisha; Sriram, Bharathi

    2012-03-22

    Bacterial drug resistance is one of the most significant challenges to human health today. In particular, effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) are urgently needed. A causal relationship between nasal commensal S. aureus and infection has been reported. Accordingly, elimination of nasal S. aureus reduces the risk of infection. Enzymes that degrade bacterial cell walls show promise as antibacterial agents. Bacteriophage-encoded bacterial cell wall-degrading enzymes exhibit intrinsic bactericidal activity. P128 is a chimeric protein that combines the lethal activity of the phage tail-associated muralytic enzyme of Phage K and the staphylococcal cell wall targeting-domain (SH3b) of lysostaphin.Here we report results of in vitro studies evaluating the susceptibility of staphylococcal strains to this novel protein. Using the broth microdilution method adapted for lysostaphin, we found that P128 is effective against S. aureus clinical strains including MRSA, methicillin-sensitive S. aureus (MSSA), and a mupirocin-resistant S. aureus. Minimum bactericidal concentrations and minimum inhibitory concentrations of P128 (1-64 μg/mL) were similar across the 32 S. aureus strains tested, demonstrating its bactericidal nature.In time-kill assays, P128 reduced colony-forming units by 99.99% within 1 h and inhibited growth up to 24 h.In an assay simulating topical application of P128 to skin or other biological surfaces, P128 hydrogel was efficacious when layered on cells seeded on solid media. P128 hydrogel was lethal to Staphylococci recovered from nares of healthy people and treated without any processing or culturing steps, indicating its in situ efficacy. This methodology used for in vitro assessment of P128 as an agent for eradicating nasal carriage is unique. The novel chimeric protein P128 is a staphylococcal cell wall-degrading enzyme under development for clearance of S. aureus nasal colonization and MRSA infection. The

  14. Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.

    PubMed

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2009-03-01

    Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5 microg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2 microg/ml) and trypanocidal (16.5 microg/ml) activities, respectively.

  15. Antimicrobial activity of antihypertensive food-derived peptides and selected alanine analogues.

    PubMed

    McClean, Stephen; Beggs, Louise B; Welch, Robert W

    2014-03-01

    This study evaluated four food-derived peptides with known antihypertensive activities for antimicrobial activity against pathogenic microorganisms, and assessed structure-function relationships using alanine analogues. The peptides (EVSLNSGYY, barley; PGTAVFK, soybean; TTMPLW, α-casein; VHLPP, α-zein) and the six alanine substitution peptides of PGTAVFK were synthesised, characterised and evaluated for antimicrobial activity using the bacteria, Escherichia coli, Staphylococcus aureus, and Micrococcus luteus and the yeast, Candida albicans. The peptides TTMPLW and PGTAVFK inhibited growth of all four microorganisms tested, with activities of a similar order of magnitude to ampicillin and ethanol controls. EVSLNSGYY inhibited the growth of the bacteria, but VHLPP showed no antimicrobial activity. The alanine analogue, PGAAVFK showed the highest overall antimicrobial activity and PGTAVFA showed no activity; overall, the activities of the analogues were consistent with their structures. Some peptides with antihypertensive activity also show antimicrobial activity, suggesting that food-derived peptides may exert beneficial effects via a number of mechanisms.

  16. Overexpression, purification, and pharmacological activity of a biosynthetically derived conopeptide

    SciTech Connect

    Kumar, Ganesan Senthil; Ramasamy, Palanisamy; Sikdar, Sujit K.; Sarma, Siddhartha P. . E-mail: sidd@mbu.iisc.ernet.in

    2005-09-30

    A high yielding fusion protein system based on the protein cytochrome b {sub 5} has been used for the production of novel 13-residue acyclic conopeptide. This peptide, Mo1659, can be liberated from the carrier protein using CNBr cleavage and subsequent purification using RP-HPLC methods. The yield of isotopically enriched peptides is high, ranging from 3 to 4 mg of purified peptide from a 500 ml culture, indicating that this system can be widely used for peptide production. Biosynthetic Mo1659 is active on non-inactivating K{sup +} channel much like the natural Mo1659, despite the absence of C-terminal amidation. Heteronuclear NMR studies show that the peptide exists in a conformational equilibrium involving proline-10. To our knowledge this is the first report of the production of an isotopically {sup 15}N/{sup 13}C-enriched conopeptide.

  17. Oxidative activation of benzidine and its derivatives by peroxidases.

    PubMed Central

    Josephy, P D

    1985-01-01

    Benzidine (4,4'-diaminobiphenyl) is a known human carcinogen; exposure to this substance resulted in an epidemic of bladder cancer among workers in the dye industry in Europe and North America. The chemical or enzymatic oxidation of benzidine proceeds via a racial cation detectable by electron spin resonance. Peroxidase-catalyzed oxidation of benzidine generates reactive electrophiles which readily form adducts with phenol and thiol compounds. The structures of these novel metabolites are described. Peroxidases, including prostaglandin synthase, catalyze benzidine binding to protein and nucleic acid; the nature of the resulting adducts is unknown. The relevance of these processes to benzidine carcinogenesis in vivo is the subject of research and debate. A central question remains: is benzidine activated in extra-hepatic target tissues such as bladder epithelium, or transported to these tissues following hepatic oxidative metabolism? PMID:3007087

  18. Poly(3-phenylthiophene) derivatives as active materials for electrochemical capacitors

    NASA Astrophysics Data System (ADS)

    Eissa, Mona M.

    Poly(3-(4-methylsulfonylphenyl)thiophenes) (PMSPT), (3-(4-cyanophenyl)-thiophene) (PCNPT), (3-(3,4-difluorophenyl)thiophene) (MPFPT), (3-(3,5difluorophenyl)thiophene) (MMFPT), and (3-(3-fluorophenyl)thiophene) (MFPT) polymers were prepared and electrochemically characterized in various organic electrolytes. The morphologies and electrochemical performance of the films were shown to depend on both the growth and cycling electrolytes. Constant current multicycle tests were performed on single cell devices using the type III capacitor configuration at high voltage (2.8-2.9 V) employing MPFPT, PCNPT, PMSPT and PFPT polymers. Energy and power densities of up to 50 Wh/kg and 5 kW/kg were achieved and excellent stabilities (up to 1200 n-doping/dedoping cycles) were demonstrated. Industrial practicum. The industrial practicum report on "Chemical Vapor Deposition of High Performance Polymeric Thin Films for Advanced Interconnect Applications" determined the copolymerization and characterization of four novel copolymers of Parylene-N by a CVD process at low temperature. These copolymers retain the advantages of the CVD process and also modify the properties of the Parylene homopolymer significantly such as lowering the dielectric constant from 2.65 to ˜2.0, increasing the thermal stability and enhancing the adhesion. Apprenticeship practicum. The study on "Synthesis, Characterization, and Catalytic Activity of The Zeolite Encapsulated Ruthenium hexadeca-fluorophthalocyanine Complexes" determined the catalytic activity of this fluorinated ruthenium phthalocyanine which was encapsulated in zeolite NaX during crystallization. Both the free complex RuFsb{16}Pc and the encapsulated (RuFsb{16}Pc-NaX) were found to be effective catalysts for the oxidation of cyclohexane with high efficiency and stability.

  19. Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid.

    PubMed

    Pertino, Mariano Walter; Vega, Celeste; Rolón, Miriam; Coronel, Cathia; Rojas de Arias, Antonieta; Schmeda-Hirschmann, Guillermo

    2017-02-28

    Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity.

  20. Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives.

    PubMed

    Guimarães, Keller G; de Freitas, Rossimiriam P; Ruiz, Ana L T G; Fiorito, Giovanna F; de Carvalho, João E; da Cunha, Elaine F F; Ramalho, Teodorico C; Alves, Rosemeire B

    2016-03-23

    A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL(-1)). This compound represents a promising matrix for developing new antiproliferative agents.

  1. New alkoxycarbonylalkyloxychalcones and their alpha, beta-dibromo derivatives of potential antimicrobial activity.

    PubMed

    Szajda, M; Kedzia, B

    1989-03-01

    New ortho, meta- and para-substituted alkoxycarbonylalkyloxychalcones and their alpha, beta-dibromo derivatives have been synthesized. It can be demonstrated that some of these compounds show antimicrobial activity.

  2. Androgenic-anabolic activities of some new synthesized steroidal pyrane, pyridine and thiopyrimidine derivatives.

    PubMed

    Abdalla, Mohamed M; Amr, Abd El-Galil E; Al-Omar, Mohamed A; Hussain, Azza A; Amer, Mohamed S

    2014-01-01

    In continuation of our previous work, fused steroidal derivatives with pyrane, pyridine, pyrimidine moieties were synthesized and evaluated as androgenic-anabolic agents. Some of the newly synthesized compounds are exhibited pronounced androgenic-anabolic activities.

  3. [Comparative anorexigenic activity and other pharmacological properties of quipazine and its N-acyl derivatives].

    PubMed

    Trubitsyna, T K; Asnina, V V; Mashkovskiĭ, M D

    1986-01-01

    In experiments on mice and rats quipazine exerts a moderate and short-term anorexigenic activity. N-acyl quipazine derivatives are markedly less toxic, do not exert anorexigenic action and influence weakly the serotoninergic and adrenergic systems.

  4. Equatorial wave activity derived from fluctuations in observed convection

    NASA Technical Reports Server (NTRS)

    Bergman, John W.; Salby, Murry L.

    1994-01-01

    The spectrum of equatorial wave activity propagating vertically into the stratosphere is calculated from high-resolution imagery of the global convective pattern. Synoptic Global Cloud Imagery (GCI), constructed from six satellites simultaneously observing the earth, is used to diabatically force the linearized primitive equations. Having resolution of 0.5 deg and 3 h, that imagery captures the dominant scales of organized convection, including several harmonics of the diurnal cycle. Its global coverage with high space-time resolution allows the GCI to represent heating variability and dynamical behavior excited by it over a wide range of scales. The dynamical response above the heating is evaluated globally in terms of a space-time spectrum of Hough modes, one which includes planetary-scale Kelvin waves, Rossby waves, and gravity waves down to the resolution of the GCI. The geopotential response, which is indicative of temperature fluctuations observed by satellite, is very red in frequency. Therefore, planetary-scale waves with periods longer than two days dominate the spectrum of geopotential, while high-frequency gravity waves make a comparatively small contribution. Some 80% of the geopotential variance is accounted for by the Kelvin and gravest-symmetric Rossby modes, while the Rossby-gravity mode is comparatively weak. In horizontal eddy motion, the excited wave spectrum is still dominated by planetary-scale components. However, meridional wind fluctuations associated with the Rossby-gravity mode have variance comparable to that of zonal wind fluctuations associated with the Kelvin mode, even though the Rossby-gravity mode is nearly invisible in the geopotential response. Estimates of tropospheric heating lead to amplitudes and propagation characteristics that are broadly consistent with satellite and radiosonde observations of wave activity in the lower stratosphere. The space-time spectrum of EP flux is significantly whiter than the response in either

  5. Antitumor activities of D-glucosamine and its derivatives*

    PubMed Central

    Zhang, Li; Liu, Wan-shun; Han, Bao-qin; Peng, Yan-fei; Wang, Dong-feng

    2006-01-01

    The growth inhibitory effects of D-glucosamine hydrochloride (GlcNH2·HCl), D-glucosamine (GlcNH2) and N-acetyl glucosamine (NAG) on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH2·HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH2·HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells. GlcNH2·HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125~500 mg/kg, dose of 250 mg/kg being the best. GlcNH2·HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH2·HCl is probably host-mediated and cytocidal. PMID:16845712

  6. Structure-activity relationships of phencyclidine derivatives in rat cerebellum.

    PubMed

    Pang, K; Johnson, S W; Maayani, S; Freedman, R

    1986-01-01

    The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.

  7. Synthesis and evaluation of 2,4-disubstituted quinazoline derivatives with potent anti-angiogenesis activities.

    PubMed

    Yu, Guangjin; Li, Zeng; Tang, Liang; Xiong, Qiru

    2014-06-26

    A series of 2,4-disubstituted quinazoline derivatives were designed and synthesized. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human umbilical vein endothelial cells (HUVECs). Among these compounds, 11d was the most potent agent, that also exhibited the highest anti-angiogenesis activities in the chick embryo chorioallantoic membrane (CAM) assay.

  8. Synthesis of novel quinoxalinone derivatives by conventional and microwave methods and assessing their biological activity.

    PubMed

    Nasir, Waqar; Munawar, Munawar Ali; Ahmed, Ejaz; Sharif, Ahsan; Ahmed, Saeed; Ayub, Amjad; Khan, Misbahul Ain; Nasim, Faizul Hassan

    2011-10-01

    In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis.

  9. Metal-Organic Frameworks derivatives for improving the catalytic activity of CO oxidation reaction.

    PubMed

    Ji, Wenlan; Xu, Zhiling; Liu, Pengfei; Zhang, Suoying; Zhou, Weiqiang; Li, Hongfeng; Zhang, Tao; Li, Linjie; Lu, Xiaohua; Wu, Jiansheng; Zhang, Weina; Huo, Fengwei

    2017-03-15

    Metal-Organic Frameworks (MOFs) based derivatives have attracted an increasing interest in various research fields. However, most of reported papers mainly focused on the pristine MOFs-based derivatives, and researches on the functional MOFs-based derivatives composites are rare. Here, a simple strategy was reported to design the functional MOFs based derivatives composites by the encapsulation of the metal nanoparticles (MNPs) in MOFs matrixes (MNPs@MOFs) and the high-temperature calcination of MNPs@MOFs composites. The as-prepared MNPs@metal oxide composites with the hierarchical pore structure exhibited excellent catalytic activity and high stability for CO oxidation reaction.

  10. A Community "Fully Alive."

    ERIC Educational Resources Information Center

    Ferre, Isolina

    1998-01-01

    Describes the efforts of the Missionary Servants of the Most Blessed Trinity's barrio residents to protect, represent, and help its troubled youth in Puerto Rico. Discusses various projects and activities created to involve youngsters in the community parish. (YKH)

  11. A Community "Fully Alive."

    ERIC Educational Resources Information Center

    Ferre, Isolina

    1998-01-01

    Describes the efforts of the Missionary Servants of the Most Blessed Trinity's barrio residents to protect, represent, and help its troubled youth in Puerto Rico. Discusses various projects and activities created to involve youngsters in the community parish. (YKH)

  12. Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma.

    PubMed

    Michaelsen, Friedrich-Wilhelm; Saeed, Mohamed E M; Schwarzkopf, Jörg; Efferth, Thomas

    2015-12-15

    Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet. Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145). A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells

  13. New enantiomeric fluorine-containing derivatives of sulforaphane: synthesis, absolute configurations and biological activity.

    PubMed

    Kiełbasiński, Piotr; Łuczak, Jerzy; Cierpiał, Tomasz; Błaszczyk, Jarosław; Sieroń, Lesław; Wiktorska, Katarzyna; Lubelska, Katarzyna; Milczarek, Małgorzata; Chilmończyk, Zdzisław

    2014-04-09

    Three pairs of enantiomers of the unknown sulforaphane analogs bearing organofluorine substituents bonded to the sulfinyl sulfur atom and having different number of methylene groups in the central carbon chain were synthesized and fully characterized, including determination of their absolute configurations. All the new compounds were tested in vitro for their cytotoxicity against melanoma cells to show increased activity in comparison with the natural sulforaphane. The influence of the particular structural changes in the molecule on the cytotoxicity is discussed.

  14. Ergosteroids V: preparation and biological activity of various D-ring derivatives in the 7-oxo-dehydroepiandrosterone series.

    PubMed

    Reich, Ieva L; Reich, Hans J; Kneer, Nancy; Lardy, Henry

    2002-03-01

    Our previous finding that D-ring seco derivatives of dehydroepiandrosterone retained biologic activity (Reich et al., Steroids 1998;63:542-53) motivated us to synthesize and test a number of steroids in which the D-ring is retained but altered in various ways. Several new steroids were synthesized and characterized by (1)H and (13)C NMR spectroscopy. The availability of a number of closely related compounds allowed detailed (13)C chemical shift correlations. Using the induction of two thermogenic enzymes in rats, liver mitochondrial glycerophosphate dehydrogenase (GPDH) and cytosolic malic enzyme, as criteria of biologic activity some 30 compounds were assayed. Hydroxylation of dehydroepiandrosterone (DHEA) at the 16 alpha position was previously shown to diminish activity (Lardy et al., Steroids 1998;63:158-65); the corresponding 7-oxo compound is fully active. Hydroxylation at the 15 beta position of DHEA, 7-oxo-DHEA, or 16 alpha-hydroxy-7-oxo-DHEA greatly diminished the induction of GPDH but induction of malic enzyme was retained. Most 5,15 diene steroids tested had 2 weak, or no, ability to enhance the formation of GPDH but did increase malic enzyme.

  15. Synthesis, antimalarial activity and molecular docking of hybrid 4-aminoquinoline-1,3,5-triazine derivatives.

    PubMed

    Bhat, Hans Raj; Singh, Udaya Pratap; Thakur, Anjali; Kumar Ghosh, Surajit; Gogoi, Kabita; Prakash, Anil; Singh, Ramendra K

    2015-10-01

    A series of novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized in a five-steps reaction and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Entire synthetic derivatives showed higher antimalarial activity on the sensitive strain while two compounds, viz., 9a and 9c displayed good activity against both the strains of P. falciparum. The observed activity was further substantiated by docking study on both wild and qradruple mutant type P. falciparum dihydrofolate reductase-thymidylate synthase (pf-DHFR-TS).

  16. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation. PMID:24839599

  17. Activity exerted by a testosterone derivative on myocardial injury using an ischemia/reperfusion model.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation.

  18. Molecular Design, Structural Analysis and Antifungal Activity of Derivatives of Peptide CGA-N46.

    PubMed

    Li, Rui-Fang; Lu, Zhi-Fang; Sun, Ya-Nan; Chen, Shi-Hua; Yi, Yan-Jie; Zhang, Hui-Ru; Yang, Shuo-Ye; Yu, Guang-Hai; Huang, Liang; Li, Chao-Nan

    2016-09-01

    Chromogranin A (CGA)-N46, a derived peptide of human chromogranin A, has antifungal activity. To further research the active domain of CGA-N46, a series of derivatives were designed by successively deleting amino acid from both terminus of CGA-N46, and the amino acid sequence of each derivative was analyzed by bioinformatic software. Based on the predicted physicochemical properties of the peptides, including half-life time in mammalian reticulocytes (in vitro), yeast (in vivo) and E. coli (in vivo), instability index, aliphatic index and grand average of hydropathicity (GRAVY), the secondary structure, net charge, the distribution of hydrophobic residues and hydrophilic residues, the final derivatives CGA-N15, CGA-N16, CGA-N12 and CGA-N8 were synthesized by solid-phase peptide synthesis. The results of bioinformatic analysis showed that CGA-N46 and its derivatives were α-helix, neutral or weak positive charge, hydrophilic, and CGA-N12 and CGA-N8 were more stable than the other derivatives. The results of circular dichroism confirmed that CGA-N46 and its derived peptides displayed α-helical structure in an aqueous solution and 30 mM sodium dodecylsulfate, but α-helical contents decreased in hydrophobic lipid vesicles. CGA-N15, CGA-N16, CGA-N12 and CGA-N8 had higher antifungal activities than their mother peptide CGA-N46. Among of the derived peptides, CGA-N12 showed the least hemolytic activity. In conclusion, we have successfully identified the active domain of CGA-N46 with strong antifungal activity and weak hemolytic activity, which provides the possibility to develop a new class of antibiotics.

  19. Testing fully depleted CCD

    NASA Astrophysics Data System (ADS)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  20. Endoglucanase activities and growth of marine-derived fungi isolated from the sponge Haliclona simulans.

    PubMed

    Baker, P W; Kennedy, J; Morrissey, J; O'Gara, F; Dobson, A D W; Marchesi, J R

    2010-05-01

    The conversion of cheap cellulosic biomass to more easily fermentable sugars requires the use of costly cellulases. We have isolated a series of marine sponge-derived fungi and screened these for cellulolytic activity to determine the potential of this unique environmental niche as a source of novel cellulase activities. Fungi were isolated from the marine sponge Haliclona simulans. Phylogenetic analysis of these and other fungi previously isolated from H. simulans showed fungi from three phyla with very few duplicate species. Cellulase activities were determined using plate-based assays using different media and sea water concentrations while extracellular cellulase activities were determined using 3,5-dinitrosalicylic acid (DNSA)-based assays. Total and specific cellulase activities were determined using a range of incubation temperatures and compared to those for the cellulase overproducing mutant Hypocrea jecorina QM9414. Several of the strains assayed produced total or relative endoglucanase activities that were higher than H. jecorina, particularly at lower reaction temperatures. Marine sponges harbour diverse fungal species and these fungi are a good source of endoglucanase activities. Analysis of the extracellular endoglucanase activities revealed that some of the marine-derived fungi produced high endoglucanase activities that were especially active at lower temperatures. Marine-derived fungi associated with coastal marine sponges are a novel source of highly active endoglucanases with significant activity at low temperatures and could be a source of novel cellulase activities.

  1. Synthesis and muscarinic activity of quinuclidinyl- and (1-azanorbornyl)pyrazine derivatives.

    PubMed

    Street, L J; Baker, R; Book, T; Reeve, A J; Saunders, J; Willson, T; Marwood, R S; Patel, S; Freedman, S B

    1992-01-24

    The synthesis and cortical muscarinic activity of a novel series of pyrazine-based agonists is described. Quinuclidine and azanorbornane derivatives were prepared either by reaction of lithiated pyrazines with azabicyclic ketones, followed by chlorination and reduction, or by reaction of the lithium enolate of the azabicyclic ester with 2-chloropyrazines followed by ester hydrolysis and decarboxylation. Substitution at all three positions of the heteroaromatic ring has been explored. Optimal muscarinic agonist activity was observed for unsubstituted pyrazines in the azanorbornane series. The exo-1-azanorbornane 18a is one of the most efficacious and potent centrally active muscarinic agonists known. Studies on the 3-substituted derivatives have provided evidence of the preferred conformation of these ligands for optimal muscarinic activity. Substitution at C6 gave ligands with increased affinity and reduced efficacy. Moving the position of the diazine ring nitrogens to give pyrimidine and pyridazine derivatives resulted in a significant loss of muscarinic activity.

  2. In Vitro Antioxidant Activities of Sulfated Derivatives of Polysaccharides Extracted from Auricularia auricular

    PubMed Central

    Zhang, Hua; Wang, Zhen-Yu; Yang, Lin; Yang, Xin; Wang, Xue; Zhang, Zhi

    2011-01-01

    In this research, two types of sulfated polysaccharide derivatives were successfully synthesized. Their antioxidant activities were investigated by employing various established in vitro systems. In addition, the degree of sulfation was evaluated using ion-chromatography and IR spectra. The results verify that, when employing scavenging superoxide radical tests, both the sulfation of acid Auricularia auricular polysaccharides (SAAAP) and the sulfation of neutral Auricularia auricular polysaccharides (SNAAP) derivatives possessed considerable antioxidant activity and had a more powerful antioxidant competence than that of the native non-sulfated polysaccharides (AAAP and NAAP). On the other hand, AAAP and NAAP exhibited stronger activity on scavenging both the hydroxyl radical and lipid peroxidation. Available data obtained with in vitro measurements indicates that the sulfated groups of AAAP and NAAP played an important role on antioxidant activity. In sum, the research demonstrates that the antioxidant activity of sulfated polysaccharide derivatives in vitro has a potential significance for seeking new natural antioxidant protective agents. PMID:21686185

  3. Design, synthesis, and insecticidal activity of some novel diacylhydrazine and acylhydrazone derivatives.

    PubMed

    Sun, Jialong; Zhou, Yuanming

    2015-03-30

    In this study a series of diacylhydrazine and acylhydrazone derivatives were designed and synthesized according to the method of active group combination and the principles of aromatic group bioisosterism. The structures of the novel derivatives were determined on the basis on 1H-NMR, IR and ESI-MS spectral data. All of the compounds were evaluated for their in vivo insecticidal activity against the third instar larvae of Spodoptera exigua Hiibner, Helicoverpa armigera Hubner, Plutella xyllostella Linnaeus and Pieris rapae Linne, respectively, at a concentration of 10 mg/L. The results showed that all of the derivatives displayed high insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, metaflumizone and tolfenpyrad, and approximately identical insecticidal activity against H. armigera, P. xyllostella and P. rapae as the references metaflumizone and tolfenpyrad.

  4. Synthesis of Novel Pyrimethanil Grafted Chitosan Derivatives with Enhanced Antifungal Activity

    PubMed Central

    Liu, Song; Xing, Ronge; Chen, Xiaolin

    2016-01-01

    In this study, three pyrimethanil grafted chitosan (PML-g-CS) derivatives were obtained. The structures of the conjugates were confirmed by FT-IR, 1H NMR, and EA. The grafting ratios were measured by HPLC. Antifungal properties of pyrimethanil grafted chitosan (PML-g-CS) derivatives against the plant pathogenic fungi Rhizoctonia solani and Gibberella zeae were investigated at concentrations of 100, 200, and 400 mg/L. The PML-g-CS derivatives showed enhanced antifungal activity in comparison with chitosan. The PML-g-CS-1 showed the best antifungal activity against R. solani, whose antifungal index was 58.32%. The PML-g-CS-2 showed the best antifungal activity against G. zeae, whose antifungal index was 53.48%. The conjugation of chitosan and pyrimethanil showed synergistic effect. The PML-g-CS derivatives we developed showed potential for further study and application in crop protection. PMID:27529072

  5. New acetylenic derivatives of betulin and betulone, synthesis and cytotoxic activity.

    PubMed

    Bębenek, Ewa; Kadela-Tomanek, Monika; Chrobak, Elwira; Wietrzyk, Joanna; Sadowska, Joanna; Boryczka, Stanisław

    2017-01-01

    Betulin 1 and its semisynthetic derivatives exhibit a cytotoxic activity toward various cancer cell lines. These compounds are a promising and potential anticancer candidates. A series of betulin derivatives was prepared and tested for the antiproliferative activity in vitro against T47D breast cancer, CCRF/CEM leukemia, HL-60 promyelocytic leukemia, SW707 colorectal, murine P388 leukemia, as well as BALB3T3 normal fibroblasts cell lines. Cisplatin and betulin 1 were used as a reference compounds. Some derivatives of betulin showed a higher cytotoxic activity than the parent compound 1. Two derivatives (5 and 17) were 24-fold potent than betulin 1 against the human promyelocytic leukemia cell line (HL-60), with an IC50 value of 0.3 µg/mL.

  6. Structure-activity relationships for the inhibition of DNA polymerase alpha by aphidicolin derivatives.

    PubMed Central

    Prasad, G; Edelson, R A; Gorycki, P D; Macdonald, T L

    1989-01-01

    Aphidicolin and 17 derivatives that have been structurally modified in the A- and D-rings were assessed for their ability to inhibit DNA polymerase alpha. No derivative surpassed the activity of aphidicolin; derivatives with structural alterations in the A-ring exhibited significantly greater loss of activity relative to derivatives with structural alterations in the D-ring. The conclusions of these studies indicate a critical role for the C-18 function in the interaction of aphidicolin with polymerase alpha. Molecular modelling studies could not identify structural features of the aphidicolin-dCTP "overlap" that is unique to dCTP, relative to the remaining dNTPs, and that is consistent with the extant structure-activity data. PMID:2505232

  7. [Hydrazine derivative modification of the activity of brain mitochondrial monoamine oxidases].

    PubMed

    Kalninia, I E; Baumanas, E A; Kaĭrane, Ch B; Gorkin, V Z

    1981-01-01

    Treatment of bovine brain stem mitochondria with hydrazine derivatives, which inhibited the monoamine oxidase activity (substrate: 5-hydroxytryptamine), was accompanied by appearance of the properties to deaminate histamine and cadaverine at a high rate. The same phenomenon was observed in vivo after treatment of mice with the hydrazine derivatives. The dramatic increase in histamine deaminating activity in brain was accompanied by a decrease in the tissue concentration of histamine. The hydrazine derivatives are considered as prooxidants stimulating via a free-radical mechanism lipid peroxidation in methyloleate solutions and in biomembranes (ref. 5) and causing qualitative alteration (transformation) in catalytic properties of monoamine oxidases of the tyre A, which acquire the histamine deaminating activity. A certain correlation was noted between the prooxidant effect of the hydrazine derivatives and the modification of catalytic properties of the membrane bound monoamine oxidases of brain mitochondria in vitro and in vivo.

  8. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives.

    PubMed

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a-b) as well as chalcone derivatives (3a-c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans.

  9. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

    PubMed Central

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b) as well as chalcone derivatives (3a–c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans. PMID:27877017

  10. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

    PubMed

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  11. Reduction of extracellular superoxide dismutase activity by decapeptide derived from FGF-receptor.

    PubMed

    Willems, J; Noppe, W; Slegers, H

    1995-11-01

    Several synthetic decapeptides containing an HAV tripeptide motif were tested for their ability to modulate the enzymatic activity of rat extracellular SOD, an enzyme which also contains an HAV motif. Out of nine decapeptides that were tested, only a FGF-receptor derived peptide was active as a negative modulator of enzyme activity. These results strengthen the thesis that HAV motifs are not only involved in homophilic interactions and suggest that soluble FGF-receptor molecules might moderate the activity of extracellular SOD.

  12. Haemolytic activity of formyl- and acetyl-derivatives of bile acids and their gramine salts.

    PubMed

    Kozanecka-Okupnik, Weronika; Jasiewicz, Beata; Pospieszny, Tomasz; Matuszak, Monika; Mrówczyńska, Lucyna

    2017-10-01

    Bile acids (lithocholic: LCA, deoxycholic: DCA and cholic: CA) and their formyl- and acetyl-derivatives can be used as starting material in chemical synthesis of compounds with different biological activity strongly depended on their chemical structures. Our previous studies showed that biological activity of bile acids salts with gramine toward human erythrocytes was significantly different from the activity of bile acids alone. Moreover, gramine effectively modified the membrane perturbing activity of other steroids. As a continuation of our work, the haemolytic activity of formyl- and acetyl-substituet bile acids as well as their gramine salts was studied in vitro. The structures of new compounds were confirmed by spectral (NMR, FT-IR) analysis, mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. The results shown that the haemolytic activity of formyl- and acetyl-LCA and DCA was significantly higher in comparison with their native forms at the whole concentration range. At high concentration, formyl derivative of CA was as effective as LCA and DCA derivatives whereas at lower concentration its haemolytic activity was at the level of original acid. The acetyl-CA was not active as membrane perturbing agents. Furthermore, gramine significantly decreased the membrane-perturbing activity of hydrophobic bile acids derivatives. The results obtained with the cellular system are in line with physicochemical calculation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Activation of Bone Marrow-Derived Microglia Promotes Photoreceptor Survival in Inherited Retinal Degeneration

    PubMed Central

    Sasahara, Manabu; Otani, Atsushi; Oishi, Akio; Kojima, Hiroshi; Yodoi, Yuko; Kameda, Takanori; Nakamura, Hajime; Yoshimura, Nagahisa

    2008-01-01

    The role of microglia in neurodegeneration is controversial, although microglial activation in the retina has been shown to provide an early response against infection, injury, ischemia, and degeneration. Here we show that endogenous bone marrow (BM)-derived microglia play a protective role in vascular and neural degeneration in the retinitis pigmentosa model of inherited retinal degeneration. BM-derived cells were recruited to the degenerating retina where they differentiated into microglia and subsequently localized to the degenerating vessels and neurons. Inhibition of stromal-derived factor-1 in the retina reduced the number of BM-derived microglia and accelerated the rate of neurovascular degeneration. Systemic depletion of myeloid progenitors also accelerated the degenerative process. Conversely, activation of BM-derived myeloid progenitors by systemic administration of both granulocyte colony-stimulating factor and erythropoietin resulted in the deceleration of retinal degeneration and the promotion of cone cell survival. These data indicate that BM-derived microglia may play a protective role in retinitis pigmentosa. Functional activation of BM-derived myeloid progenitors by cytokine therapy may provide a novel strategy for the treatment of inherited retinal degeneration and other neurodegenerative diseases, regardless of the underlying genetic defect. PMID:18483210

  14. Effects of chemically defined medium on early development of porcine embryos derived from parthenogenetic activation and cloning.

    PubMed

    Cao, Zubing; Sui, Liucai; Li, Yunsheng; Ji, Suofei; Zhang, Xiaorong; Zhang, Yunhai

    2012-08-01

    The present study was to investigate if a completely chemically defined medium (PZM-4) could support the early development of porcine embryos derived from parthenogenetic activation (PA) and cloning (somatic cell nuclear transfer, SCNT), and to lay the foundation for determining the physiological roles of certain supplements in this medium. Porcine embryos derived from PA and SCNT were cultured in media: PZM-3 (a chemically semi-defined medium), PZM-4 (a fully defined medium), and PZM-5 (an undefined medium). Early embryo development was observed. We found that the three medium groups (PZM-3, PZM-4 and PZM-5) exhibited no significant differences in cleavage rates of PA embryos (p > 0.05), while the blastocyst rate in PZM-3 was significantly higher than in PZM-4 and PZM-5 (78.9% vs. 36.0% and 52.3%) (p < 0.05). Moreover, total cell number per blastocyst in PZM-3 was clearly higher than in PZM-5 but similar to that in PZM-4. As for SCNT embryos, no significant differences were observed for the cleavage rates or the blastocyst rates among the three groups (p > 0.05). However, total cell number per blastocyst in PZM-3 was notably higher than in PZM-5, but was similar to that in PZM-4. In conclusion, our results suggested that the completely chemically defined medium PZM-4 can be used to efficiently support the early development of porcine PA and SCNT embryos.

  15. Synthesis and antiviral, insecticidal, and fungicidal activities of gossypol derivatives containing alkylimine, oxime or hydrazine moiety.

    PubMed

    Li, Ling; Li, Zheng; Wang, Kailiang; Liu, Yuxiu; Li, Yongqiang; Wang, Qingmin

    2016-02-01

    Gossypol is a part of the cotton plant's defense system against pathogens and herbivorous insects. To discover gossypol analogs with broad spectrum and high activity, a series of gossypol alkylamine Schiff base, oxime and hydrazone derivatives were synthesised and bioassayed. The biological results indicated that most of these derivatives exhibited higher anti-TMV activity than gossypol. Interestingly, the activities of compounds 10, 15, 18, 20, 23 and 26 were much higher than that of ribavirin. Furthermore, compound 26, which was low toxicity to rat, showed better activity than control plant virus inhibitors in the field. Additionally, allyl amine Schiff base (9) displayed remarkable insecticidal activities against Mythimna separata, Helicoverpa armigera and Ostrinia nubilalis, whereas (pyridin-3-yl)methanamine Schiff base (13) showed excellent activity against Culex pipiens pallens. The fungicidal results revealed that all of compounds exhibited good activity against Physalospora piricola.

  16. Synthesis, crystal structure, DFT analysis and fungicidal activity of a novel series O-substituted trifluoroatrolactamide derivatives

    NASA Astrophysics Data System (ADS)

    Yang, Hui-Hui; Cui, Can; Zhu, Cong; Li, Jian-Qiang; Wu, Rui; Tian, Lei; Zhao, Wei-Guang

    2017-01-01

    A series of O-substituted trifluoroatrolactamide derivatives has been synthesized and fully characterized by 1H NMR, 13C NMR, 19F NMR, HRMS and X-ray diffraction analyses. The fungicidal activity of these compounds was evaluated and the results showed that some of them exhibited potent in vitro fungicidal activity against Erysiphe graminis and Pyricularia oryzae. Their structure-property relationships were investigated using density functional theory calculations. The X-ray crystal structure of one of these compounds adopted a monoclinic space group with the following unit cell parameters: a = 24.285 (13) Å, b = 9.006 (5) Å, c = 9.794 (5) Å, β = 92.110 (9)º, V = 2140.6 (19) Å3 and Z = 4. A comparison of these experimental results with the theoretical values revealed that there was good agreement between the two sets of data. The subsequent biological evaluation of these compounds showed that some of them exhibited potent in vitro fungicidal activity against Erysiphe graminis and Pyricularia oryzae.

  17. The influence of thermal trauma on pro- and anticoagulant activity of erythrocyte-derived microvesicles.

    PubMed

    Levin, Grigory; Sukhareva, Ekaterina

    2016-11-01

    The goal of this research was to study the influence of erythrocyte-derived microvesicles on hemostasis parameters during burn. It was found that the number of microvesicles derived from washed erythrocytes of burn patients after 1 day of storage at 37°C was 4.2 times bigger than the number of microvesicles derived from erythrocytes of healthy donors. Hemocoagulation properties of erythrocyte-derived microvesicles of burn patients also change: according to the results of thromboelastography their procoagulant activity increases significantly, at the same time their antithrombin and fibrinilytic activity decrease. Thus, we can conclude that hepercoagulation during burn is to a certain extent caused by the disruption of the balance between procoagulant activity of erythrocyte-derived microvesicles and their antithrombin and fibrinolytic activity. Hypercoagulation effect of erythrocyte-derived microvesicles increases during burn not just because of their changed properties but also due to their increased number after thermal trauma. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  18. Novel Amino-Pyridine Functionalized Chitosan Quaternary Ammonium Derivatives: Design, Synthesis, and Antioxidant Activity.

    PubMed

    Li, Qing; Zhang, Caili; Tan, Wenqiang; Gu, Guodong; Guo, Zhanyong

    2017-01-18

    Chemical modification of chitosan is increasingly studied for its potential of providing new applications of chitosan. Here, a group of novel chitosan quaternary ammonium derivatives containing pyridine or amino-pyridine were designed and successfully synthesized through chemical modification of chitosan. Pyridine and amino-pyridine were used as functional groups to improve the antifungal activity of chitosan derivatives. The chitosan derivatives' antioxidant activity against hydroxyl-radical and 1,1-Diphenyl-2-picrylhydrazyl (DPPH)-radical was tested in vitro. The results showed that chitosan derivatives had better water solubility and stronger antioxidant activity compared with chitosan in all assays. Especially, compounds 3C and 3E (with 3-amino pyridine and 2,3-diamino pyridine as substitute respectively) exhibited stronger hydroxyl-radical and DPPH-radical scavenging ability than other synthesized compounds. These data demonstrated that the synergistic effect of the amino group and pyridine would improve the antioxidant activity of chitosan derivatives, and the position of the amino group on pyridine could influence the antioxidant property of chitosan derivatives.

  19. Chemical structures and biological activities of bis- and tetrakis-acridine derivatives: A review

    NASA Astrophysics Data System (ADS)

    Nowak, Katarzyna

    2017-10-01

    A review of the literature on the biological activity of bis-acridines (diacridines) and tetrakis-acridines (tetra-acridines) is presented. Chemical structures of the most active derivatives are provided. In particular, the last decade's literature on the subject is discussed.

  20. N-Arylpiperazine-1-carboxamide derivatives: a novel series of orally active nonsteroidal androgen receptor antagonists.

    PubMed

    Kinoyama, Isao; Taniguchi, Nobuaki; Kawaminami, Eiji; Nozawa, Eisuke; Koutoku, Hiroshi; Furutani, Takashi; Kudoh, Masafumi; Okada, Minoru

    2005-04-01

    A novel series of N-arylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Reporter assays indicated that trans-2,5-dimethylpiperazine derivatives are potent AR antagonists, and in this series trans-N-4-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,4-difluorophenyl)-2,5-dimethylpiperazine-1-carboxamide (18 g, YM-175735) exhibited the most potent antiandrogenic activity. Compared to bicalutamide, YM-175735 is an approximately 4-fold stronger AR antagonist and has slightly increased antiandrogenic activity, suggesting that YM-175735 may be useful in the treatment of prostate cancer.

  1. Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety

    PubMed Central

    Shang, Ruofeng; Wang, Shengyu; Xu, Ximing; Yi, Yunpeng; Guo, Wenzhu; YuLiu; Liang, Jianping

    2013-01-01

    Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA. PMID:24376551

  2. Aromatic glycosyl disulfide derivatives: evaluation of their inhibitory activities against Trypanosoma cruzi.

    PubMed

    Gutiérrez, Bessy; Muñoz, Christian; Osorio, Luis; Fehér, Krisztina; Illyés, Tünde-Zita; Papp, Zsuzsa; Kumar, Ambati Ashok; Kövér, Katalin E; Sagua, Hernán; Araya, Jorge E; Morales, Patricio; Szilágyi, László; González, Jorge

    2013-06-15

    Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(β-D-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values ranging from 4 to 11 μM at 37 °C. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 °C as well. Three further derivatives displayed similar activities against at least one of the three strains. Low cytotoxicities of the active compounds, tested on confluent HeLa, Vero and peritoneal macrophage cell cultures, resulted in significantly higher selectivity indices (SI) than that of the reference drug benznidazole. Remarkably, several molecules of the tested panel strongly inhibited the parasite release from T. cruzi infected HeLa cell cultures suggesting an effect against the intracellular development of T. cruzi amastigotes as well.

  3. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities.

    PubMed

    Yoon, Yeong Keng; Ali, Mohamed Ashraf; Wei, Ang Chee; Choon, Tan Soo; Osman, Hasnah; Parang, Keykavous; Shirazi, Amir Nasrolahi

    2014-01-15

    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.

  4. Synthesis and anticancer activity evaluation of some benzothiazole-piperazine derivatives.

    PubMed

    Gurdal, Enise Ece; Buclulgan, Ebru; Durmaz, Irem; Cetin-Atalay, Rengul; Yarim, Mine

    2015-01-01

    Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compounds cause apoptosis by cell cycle arrest at subG1 phase.

  5. Pomegranate-Derived Polyphenols Reduce Reactive Oxygen Species Production via SIRT3-Mediated SOD2 Activation

    PubMed Central

    Zhao, Chong; Sakaguchi, Takenori; Fujita, Kosuke; Ito, Hideyuki; Nishida, Norihisa; Nagatomo, Akifumi; Tanaka-Azuma, Yukimasa

    2016-01-01

    Pomegranate-derived polyphenols are expected to prevent life-style related diseases. In this study, we evaluated the ability of 8 pomegranate-derived polyphenols, along with other polyphenols, to augment SIRT3, a mammalian SIR2 homolog localized in mitochondria. We established a system for screening foods/food ingredients that augment the SIRT3 promoter in Caco-2 cells and identified 3 SIRT3-augmenting pomegranate-derived polyphenols (eucalbanin B, pomegraniin A, and eucarpanin T1). Among them, pomegraniin A activated superoxide dismutase 2 (SOD2) through SIRT3-mediated deacetylation, thereby reducing intracellular reactive oxygen species. The other SIRT3-augmenting polyphenols tested also activated SOD2, suggesting antioxidant activity. Our findings clarify the underlying mechanisms involved in the antioxidant activity of pomegraniin A. PMID:27840668

  6. Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic-salinomycin.

    PubMed

    Huczyński, Adam; Janczak, Jan; Stefańska, Joanna; Antoszczak, Michał; Brzezinski, Bogumil

    2012-07-15

    For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic-salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide derivatives have been screened for their in vitro antimicrobial activity against the typical gram-positive cocci, gram-negative rods and yeast-like organisms, as well as against a series of clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus. Amides of salinomycin have been found to show a wide range of activities, from inactive at 256 μg/mL to active with MIC of 2 μg/mL, comparable with salinomycin. As a result, phenyl amide (3b) was found to be the most active salinomycin derivative against gram-positive bacteria, MRSA and MSSA.

  7. Antitermite activities of coumarin derivatives and scopoletin from Protium javanicum Burm. f.

    PubMed

    Adfa, Morina; Yoshimura, Tsuyoshi; Komura, Kenichi; Koketsu, Mamoru

    2010-07-01

    The antitermite (termiticidal and antifeedant) activity of Protium javanicum Burm. f. extract was investigated. The ethyl acetate fraction was active. Scopoletin (1), quercetin, and stigmasterol were isolated by bioassay-guided fractionation. Scopoletin had the highest activity among the three compounds. In order to investigate the structure-activity relationship (SAR) of the methoxy and hydroxy groups at the C-6 and C-7 positions of the coumarin skeleton, we synthesized several coumarin derivatives whose chemical structures are similar to scopoletin. Scopoletin exhibited the strongest termiticidal activity among the 10 compounds tested, followed by 6-methoxycoumarin (3), 6-hydroxycoumarin (7), and umbelliferone (8). All compounds except coumarin (9) showed antifeedant activity.

  8. Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo.

    PubMed

    Song, Jae-Hyoung; Kwon, Bo-Eun; Jang, Hongjun; Kang, Hyunju; Cho, Sungchan; Park, Kwisung; Ko, Hyun-Jeong; Kim, Hyoungsu

    2015-09-01

    Chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (EV71) by suppressing viral 3C protease (3C(pro)) activity. In the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus B3 (CVB3), which belongs to the same genus (Enterovirus) as EV71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. We found that chrysin showed antiviral activity against CVB3 at 10 μM, but exhibited mild cellular cytotoxicity at 50 μM, prompting us to synthesize derivatives of chrysin to increase the antiviral activity and reduce its cytotoxicity. Among four 4-substituted benzyl derivatives derived from C(5) benzyl-protected derivatives 7, 9-11 had significant antiviral activity and showed the most potent activity against CVB3 with low cytotoxicity in Vero cells. Intraperitoneal injection of CVB3 in BALB/c mice with 1×10(6) TCID50 (50% tissue culture infective dose) of CVB3 induced acute pancreatitis with ablation of acinar cells and increased serum CXCL1 levels, whereas the daily administration of 9 for 5 days significantly alleviated the pancreatic inflammation and reduced the elevation in serum CXCL1 levels. Collectively, we assessed the anti-CVB3 activities of chrysin and its derivatives, and found that among 4-substituted benzyl derivatives, 9 exhibited the highest activity against CVB3 in vivo, and protected mice from CVB3-induced pancreatic damage, simultaneously lowering serum CXCL1 levels.

  9. Structures and antiviral activities of butyrolactone derivatives isolated from Aspergillus terreus MXH-23

    NASA Astrophysics Data System (ADS)

    Ma, Xinhua; Zhu, Tianjiao; Gu, Qianqun; Xi, Rui; Wang, Wei; Li, Dehai

    2014-12-01

    A new butyrolactone derivative, namely butyrolactone VIII ( 1), and six known butyrolactones ( 2-7) were separated from the ethyl acetate (EtOAc) extract of the fermentation broth of a fungus, Aspergillus terreus MXH-23. The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance (NMR) and mass spectrometry (MS). Known butyrolactone derivatives contain an α, β-unsaturated γ-lactone ring with α-hydroxyl and γ-benzyl, and butyrolactone VIII ( 1) was the first butyrolactones contains α-benzyl and γ-hydroxyl on α, β-unsaturated lactone ring. All of the butyrolactone derivatives were tested for their anti-influenza (H1N1) effects. Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified, derivative 1, did not.

  10. Synthesis and antioxidant and antitumor activity of novel pyridine, chromene, thiophene and thiazole derivatives.

    PubMed

    Fadda, Ahmed A; Berghot, Moged A; Amer, Fathy A; Badawy, Doria S; Bayoumy, Nesma M

    2012-05-01

    2-Tosylacetonitrile (1) when reacted with α,β-unsaturated nitriles 2a-c or a mixture of formaldehyde and 3-amino-2-substituted-pent-2-endinitriles 6a,b yielded pyridine derivatives 3a-c and 9a,b, respectively, while when subjected to react with salicylaldehyde yielded chromene derivatives 4 and 5, subsequently. The behavior of thiocarbamoyl derivative 10 derived from 1 towards some α-halogenated compounds have been investigated as well as its behavior towards elemental sulfur and phenyl isothiocyanate. Newly synthesized compounds were screened for their antioxidant activity, erythrocytes haemolysis and bleomycin-independent DNA damage. Some of the tested compounds exhibited promising activities. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Synthesis of Xylitan Derivatives and Preliminary Evaluation of in Vitro Trypanocidal Activity.

    PubMed

    Elias, Paula Regina; Coelho, Gleicekelly Silva; Xavier, Viviane Flores; Sales Junior, Policarpo Ademar; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; Carneiro, Claudia Martins; Camilo, Nilton Soares; Hilário, Flaviane Francisco; Taylor, Jason Guy

    2016-10-10

    A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration.

  12. Design, synthesis and biological activity of pyrazinamide derivatives for anti-Mycobacterium tuberculosis.

    PubMed

    Zhou, Shiyang; Yang, Shanbin; Huang, Gangliang

    2017-12-01

    A total of 11 pyrazinamide derivatives were designed and synthesised using pyrazinamide as the lead compound, which was optimised by structural modification with alkyl chains, six-membered rings, and bioisosterism, respectively. The target compounds were synthesised using pyrazinecarboxylic acid as the starting material by acylation, amidation, and alkylation, respectively. Their structures were confirmed by (1)H NMR, (13)C NMR, HRESIMS, and elemental analysis, respectively. The bioactivities of derivatives were assayed using bacteriostatic experiment and minimum inhibitory concentration experiment. It was showed that the derivatives had good inhibitory effect on Mycobacterium tuberculosis. The biological activity of derivative 1f was the best among all compounds, its antibacterial activity was 99.6%, and the minimum inhibitory concentration was 8.0 µg/mL.

  13. 1,8-Naphthyridine Derivatives: A Review of Multiple Biological Activities.

    PubMed

    Madaan, Alka; Verma, Ritu; Kumar, Vivek; Singh, Anu T; Jain, Swatantra K; Jaggi, Manu

    2015-12-01

    The 1,8-naphthyridine group of compounds have gained special attention of researchers on account of their demonstrating a variety of interesting biological activities. A wide range of biological properties establishes them as potent scaffolds in therapeutic and medicinal research. The broad spectrum of activities primarily includes antimicrobial, antiviral, anticancer, anti-inflammatory, and analgesic activities. 1,8-Naphthyridine derivatives have also exhibited potential applications in neurological disorders such as Alzheimer's disease, multiple sclerosis, and depression. In addition, these synthetic derivatives have been found to possess activities such as anti-osteoporotic (α(v)β(3) antagonists), anti-allergic, antimalarial, gastric antisecretory, bronchodilator, anticonvulsant, anti-hypertensive, platelet aggregation inhibition, anti-oxidant, EGFR inhibition, protein kinase inhibition, ionotropic agent, β-3 antagonist, MDR modulator, adenosine receptor agonist, adrenoceptor antagonist, and pesticide activities. In spite of the widespread application of the 1,8-naphythyridine scaffolds, only a limited number of review articles are available till date. In this review, we attempt to compile and discuss the key data available in the literature for the multiple biological activities of 1,8-naphthyridine derivatives, in a chronological manner. This review compilation (with 199 references) may be helpful in understanding the diverse biological properties of 1,8-naphthyridines and provide insights into their mechanism of action. This may direct future research in the synthesis of new derivatives and exploring this scaffold for other possible biological activities.

  14. Design, synthesis, cytotoxicities and DNA cleavage activities of dibenzoxepine and isoquinoline derivatives starting from dehydroabietylamine.

    PubMed

    Liu, Chao-Xiang; Lin, Zhong-Xiang; Zhou, Ai-Min

    2016-12-01

    A series of novel hexahydrodibenzoxepine and quinazoline derivatives were designed and synthesized starting from dehydroabietylamine. The cytotoxicities of the compounds against L02 and HepG2 cell lines were investigated. Meanwhile, the plasmid DNA (Escherichia coli) cleavage of several heterocyclic derivatives was studied. These compounds exhibit remarkable activities on plasmid DNA pBR322. Our study provides useful information for developing new and more potent antitumor agents.

  15. [(η(6)-Praziquantel)Cr(CO)3] derivatives with remarkable in vitro anti-schistosomal activity.

    PubMed

    Patra, Malay; Ingram, Katrin; Pierroz, Vanessa; Ferrari, Stefano; Spingler, Bernhard; Gasser, Robin B; Keiser, Jennifer; Gasser, Gilles

    2013-02-11

    The antischistosomal effect of two [(η(6)-praziquantel)Cr(CO)(3)] derivatives was investigated. The compounds (see figure: Cr purple, N blue, O red) were prepared in a one-step procedure from commercially available praziquantel. Both derivatives show a high in vitro activity against Schistosoma mansoni, a parasitic trematode, and only a minor cytotoxic effect on selected mammalian cell lines.

  16. Coronal temperatures of selected active cool stars as derived from low resolution Einstein observations

    NASA Technical Reports Server (NTRS)

    Vilhu, Osmi; Linsky, Jeffrey L.

    1990-01-01

    Mean coronal temperatures of some active G-K stars were derived from Rev1-processed Einstein-observatory's IPC-spectra. The combined X-ray and transition region emission line data are in rough agreement with static coronal loop models. Although the sample is too small to derive any statistically significant conclusions, it suggests that the mean coronal temperature depends linearly on the inverse Rossby-number, with saturation at short rotation periods.

  17. Synthesis and evaluation of antifungal activity of C21-steroidal derivatives.

    PubMed

    Huang, Lie-Jun; Wang, Bin; Zhang, Jian-Xin; Yuan, Chun-Mao; Gu, Wei; Mu, Shu-Zhen; Hao, Xiao-Jiang

    2016-04-15

    The antifungal activities of eleven C21-steroidal compounds isolated from Cynanchum wilfordii, together with thirty-six derivatives of caudatin and qingyangshengenin were evaluated on Sclerotinia sclerotiorum and other five fungal strains by the mycelium growth rate method. Four derivatives 1k, 1y, 10d, and 10j exhibited much stronger inhibitions on growth of S. sclerotiorum with IC50 values of 0.0084, 0.0049, 0.0053, and 0.0034 μM, respectively.

  18. Physiochemical, optical and biological activity of chitosan-chromone derivative for biomedical applications.

    PubMed

    Kumar, Santosh; Koh, Joonseok

    2012-01-01

    This paper describes the physiochemical, optical and biological activity of chitosan-chromone derivative. The chitosan-chromone derivative gels were prepared by reacting chitosan with chromone-3-carbaldehyde, followed by solvent exchange, filtration and drying by evaporation. The identity of Schiff base was confirmed by UV-Vis absorption spectroscopy and Fourier-transform infrared (FTIR) spectroscopy. The chitosan-chromone derivative was evaluated by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photoluminescence (PL) and circular dichroism (CD). The CD spectrum showed the chitosan-chromone derivative had a secondary helical structure. Microbiological screening results demonstrated the chitosan-chromone derivative had antimicrobial activity against Escherichia coli bacteria. The chitosan-chromone derivative did not have any adverse effect on the cellular proliferation of mouse embryonic fibroblasts (MEF) and did not lead to cellular toxicity in MEFs. These results suggest that the chitosan-chromone derivative gels may open a new perspective in biomedical applications.

  19. Physiochemical, Optical and Biological Activity of Chitosan-Chromone Derivative for Biomedical Applications

    PubMed Central

    Kumar, Santosh; Koh, Joonseok

    2012-01-01

    This paper describes the physiochemical, optical and biological activity of chitosan-chromone derivative. The chitosan-chromone derivative gels were prepared by reacting chitosan with chromone-3-carbaldehyde, followed by solvent exchange, filtration and drying by evaporation. The identity of Schiff base was confirmed by UV-Vis absorption spectroscopy and Fourier-transform infrared (FTIR) spectroscopy. The chitosan-chromone derivative was evaluated by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photoluminescence (PL) and circular dichroism (CD). The CD spectrum showed the chitosan-chromone derivative had a secondary helical structure. Microbiological screening results demonstrated the chitosan-chromone derivative had antimicrobial activity against Escherichia coli bacteria. The chitosan-chromone derivative did not have any adverse effect on the cellular proliferation of mouse embryonic fibroblasts (MEF) and did not lead to cellular toxicity in MEFs. These results suggest that the chitosan-chromone derivative gels may open a new perspective in biomedical applications. PMID:22754352

  20. Preparation and Physiological activities of sulphated derivative extracted from corn bran

    NASA Astrophysics Data System (ADS)

    Mo, Qing; Dai, Linghao; Ma, Jianjun; Zhao, Xiaojing; Zhu, Linghui

    2017-05-01

    In the present study, the sulphated derivative (S-CBP) with the degree of substitution (0.46) was successfully prepared from the polysaccharide extracted from corn bran. Compared with native polysaccharide, the structures of the sulphated derivative were confirmed by FT-IR and SEC-LLS and the molecular weight were changed by chemical modification. Sulfation enhanced the antioxidant activities in a dose-dependent way, which seemed to be dependent on the character of the substituted group. The results suggest that the sulphated derivative, extracted from corn bran, are potential natural antioxidant and blood fat reduce agent.

  1. Semisynthesis, Cytotoxic Activity, and Oral Availability of New Lipophilic 9-Substituted Camptothecin Derivatives

    PubMed Central

    2013-01-01

    Despite that 9-substituted camptothecins are promising candidates in cancer therapy, the limited accessibility to this position has reduced the studies of these derivatives to a few standard modifications. We report herein a novel semisynthetic route based on the Tscherniac–Einhorn reaction to synthesize new lipophilic camptothecin derivatives with amidomethyl and imidomethyl substitutions in position 9. Compounds were evaluated for their antiproliferative activity, topoisomerase I inhibition, and oral availability. Preliminary data demonstrated that bulky imidomethyl modification is an appropriate lipophilic substitution for an effective oral administration relative to topotecan. In addition, this general procedure paves the way for obtaining new camptothecin derivatives. PMID:24900725

  2. Synthesis, evaluation, and metabolism of novel [6]-shogaol derivatives as potent Nrf2 activators.

    PubMed

    Zhu, Yingdong; Wang, Pei; Zhao, Yantao; Yang, Chun; Clark, Anderson; Leung, TinChung; Chen, Xiaoxin; Sang, Shengmin

    2016-06-01

    Oxidative stress is a central component of many chronic diseases. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 p45-related factor 2 (Nrf2) system is a major regulatory pathway of cytoprotective genes against oxidative and electrophilic stress. Activation of the Nrf2 pathway plays crucial roles in the chemopreventive effects of various inducers. In this study, we developed a novel class of potent Nrf2 activators derived from ginger compound, [6]-shogaol (6S), using the Tg[glutathione S-transferase pi 1 (gstp1):green fluorescent protein (GFP)] transgenic zebrafish model. Investigation of structure-activity relationships of 6S derivatives indicates that the combination of an α,β-unsaturated carbonyl entity and a catechol moiety in one compound enhances the Tg(gstp1:GFP) fluorescence signal in zebrafish embryos. Chemical reaction and in vivo metabolism studies of the four most potent 6S derivatives showed that both α,β-unsaturated carbonyl entity and catechol moiety act as major active groups for conjugation with the sulfhydryl groups of the cysteine residues. In addition, we further demonstrated that 6S derivatives increased the expression of Nrf2 downstream target, heme oxygenase-1, in both a dose- and time-dependent manner. These results suggest that α,β-unsaturated carbonyl entity and catechol moiety of 6S derivatives may react with the cysteine residues of Keap1, disrupting the Keap1-Nrf2 complex, thereby liberating and activating Nrf2. Our findings of natural product-derived Nrf2 activators lead to design options of potent Nrf2 activators for further optimization.

  3. Synthesis, crystal structure, and insecticidal activity of novel N-alkyloxyoxalyl derivatives of 2-arylpyrrole.

    PubMed

    Zhao, Yu; Mao, Chunhui; Li, Yongqiang; Zhang, Pengxiang; Huang, Zhiqiang; Bi, Fuchun; Huang, Runqiu; Wang, Qingmin

    2008-08-27

    Two series of novel N-alkyloxyoxalyl derivatives of 2-arylpyrrole were synthesized, and their structures were characterized by (1)H NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities, and their insecticidal activities against oriental armyworm, mosquito, and spider mite are comparable to those of the commercialized Chlorfenapyr.

  4. Advances on Semisynthesis, Total Synthesis, and Structure-Activity Relationships of Honokiol and Magnolol Derivatives.

    PubMed

    Yang, Chun; Zhi, Xiaoyan; Xu, Hui

    2016-01-01

    Honokiol and magnolol (an isomer of honokiol) are small-molecule polyphenols isolated from the barks of Magnolia officinalis, which have been widely used in traditional Chinese and Japanese medicines. In the last decade, a variety of biological properties of honokiol and magnolol (e.g., anti-oxidativity, antitumor activity, anti-depressant activity, anti-inflammatory activity, neuroprotective activity, anti-diabetic activity, antiviral activity, and antimicrobial activity) have been reported. Meanwhile, certain mechanisms of action of some biological activities were also investigated. Moreover, many analogs of honokiol and magnolol were prepared by structural modification or total synthesis, and some exhibited very potent pharmacological activities with improved water solubility. Therefore, the present review will provide a systematic coverage on recent developments of honokiol and magnolol derivatives in regard to semisynthesis, total synthesis, and structure-activity relationships from 2000 up to now.

  5. 76 FR 35086 - Proposed Information Collection (Fully Developed Claim (Fully Developed Claims-Applications for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... Compensation, Pension, DIC, Death Pension, and/or Accrued Benefits)) Activity: Comment Request AGENCY: Veterans... Developed Claim (Fully Developed Claims--Applications for Compensation, Pension, DIC, Death Pension, and/or...

  6. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

    PubMed

    Koshiar, Ruzica Livaja; Somajo, Sofia; Norström, Eva; Dahlbäck, Björn

    2014-01-01

    Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte-derived microparticle

  7. Mast cells enhance T cell activation: Importance of mast cell-derived TNF

    NASA Astrophysics Data System (ADS)

    Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

    2005-05-01

    Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

  8. Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection

    PubMed Central

    Wisastra, Rosalina; Kok, Petra A.M; Eleftheriadis, Nikolaos; Baumgartner, Matthew P.; Camacho, Carlos J.; Haisma, Hidde J.; Dekker, Frank J.

    2013-01-01

    Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 μM, αKA of 0.38 μM and a β value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid, whereas the larger inhibitor 23d blocks the enzyme active site. PMID:24231650

  9. Origin of the inhibitory activity of 4-O-substituted sialic derivatives of human parainfluenza virus.

    PubMed

    Itoh, Yuji; Sando, Ayumi; Ikeda, Kiyoshi; Suzuki, Takashi; Tokiwa, Hiroaki

    2012-05-01

    Human parainfluenza virus (hPIV) is a serious human pathogen causing upper and lower respiratory tract disease, yet there are no effective vaccines or therapies to control parainfluenza virus infections. Recently, we found that 4-O-substituted sialic derivatives have potent inhibitory activity against hPIV-1, whereas the anti-influenza inhibitor Zanamivir was less inhibitory. To elucidate the origin of the high potency inhibitory activities of these 4-O-substituted derivatives, we performed correlated fragment molecular orbital (FMO)-interfragment interaction energy (IFIE) analysis for hemagglutinin-neuraminidase (HN) glycoprotein complexes of hPIV with the derivatives and compared them with those for Zanamivir. We found key interactions between the inhibitors and the hPIV HN glycoprotein and identified important factors for the inhibitory activity. These theoretical results will be useful for the development of novel anti-hPIV drugs.

  10. Ellagic acid derivatives from Syzygium cumini stem bark: investigation of their antiplasmodial activity.

    PubMed

    Simões-Pires, Claudia A; Vargas, Sandra; Marston, Andrew; Ioset, Jean-Robert; Paulo, Marçal Q; Matheeussen, An; Maes, Louis

    2009-10-01

    Bioguided fractionation of Syzygium cumini (Myrtaceae) bark decoction for antiplasmodial activity was performed, leading to the isolation of three known ellagic acid derivatives (ellagic acid, ellagic acid 4-O-alpha-L-2"-acetylrhamnopyranoside, 3-O-methylellagic acid 3'-O-alpha-L-rhamnopyranoside), as well as the new derivative 3-O-methylellagic acid 3'-O-beta-D-glucopyranoside. Activity investigation was based on the reduction of P. falciparum (PfK1) parasitaemia in vitro and the inhibition of beta-hematin formation, a known mechanism of action of some antimalarial drugs. Among the investigated ellagic acid derivatives, only ellagic acid was able to reduce P. falciparum parasitaemia in vitro and inhibit beta-hematin formation, suggesting that free hydroxyl groups are necessary for activity within this class of compounds.

  11. Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity.

    PubMed

    Tropak, Michael B; Zhang, Jianmin; Yonekawa, Sayuri; Rigat, Brigitte A; Aulakh, Virender S; Smith, Matthew R; Hwang, Hee-Jong; Ciufolini, Marco A; Mahuran, Don J

    2015-06-11

    In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward β-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 μM, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.

  12. Anticancer activity studies of cubebin isolated from Piper cubeba and its synthetic derivatives.

    PubMed

    Rajalekshmi, Dhanya S; Kabeer, Farha A; Madhusoodhanan, Arya R; Bahulayan, Arun K; Prathapan, Remani; Prakasan, Nisha; Varughese, Sunil; Nair, Mangalam S

    2016-04-01

    (-)-Cubebin, isolated from the seeds of Piper cubeba, and its five different types of derivatives (a total of 17), with varying functionalities, were tested for their in vitro anticancer activity against six human cancer cell lines (A549, K562, SiHa, KB, HCT116 and HT29) using MTT assay. Cubebin as well as its derivatives containing lactone and amide groups showed significant anticancer activity. In some of the tested cell lines, the amide derivatives showed higher activity. Morphological analysis indicated that these compounds act through apoptosis mediated pathway of cell death and we expect that these results will pave new paths in the development of novel anticancer agents by the derivatization of (-)-cubebin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Cytotoxic and proapototic activities of imidoselenocarbamate derivatives are dependent on the release of methylselenol.

    PubMed

    Zuazo, Alicia; Plano, Daniel; Ansó, Elena; Lizarraga, Elena; Font, María; Martínez Irujo, Juan J

    2012-11-19

    In the search for new molecules with potential antiangiogenic activity, we found that several imidoselenocarbamate derivatives effectively suppressed the expression of vascular endothelial growth factor (VEGF) induced by hypoxia in NCI-H157 tumor cells. Mechanistic studies indicated that these compounds inhibited STAT3 phosphorylation triggered by hypoxia, suggesting that inhibition of STAT3 function may play a role in VEGF inhibition. Moreover, these molecules showed interesting proapoptotic and antiproliferative effects. Both the presence of selenium, but not sulfur, and the nature of the radical substituents were important for activity. Interestingly, under hypoxic conditions, several methyl imidoselenocarbamate derivatives released methylselenol, a highly reactive and cytotoxic gas, which was responsible for their biological activities. The kinetics of the release of methylselenol by these molecules was highly dependent on the nature of the substituent radicals and correlated with their early proapoptotic activity. Our results support the notion that pharmacological activities reported for methyl imidoselenocarbamate derivatives are dependent on the release of methylselenol. Given the well-known antitumor activities of this compound, imidoselenocarbamate derivatives represent a promising approach to develop new drugs that release methylselenol in a controlled way.

  14. Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives.

    PubMed

    Song, Jae Min; Park, Ki Duk; Lee, Kwang Hee; Byun, Young Ho; Park, Ju Hee; Kim, Sung Han; Kim, Jae Hong; Seong, Baik Lin

    2007-11-01

    Catechin derivatives with different alkyl chain length and aromatic ring substitutions at the 3-hydroxyl group were synthesized from epigallocatechin (EGC) and (+)-catechin (C) and their anti-influenza viral activity were evaluated in vitro and in ovo. Pronounced antiviral activity was observed for derivatives carrying moderate chain length (7-9 carbons) as compared to those with aromatic rings, whereas the 5'-hydroxyl group of the trihydroxy benzyl moiety did not significantly contribute to antiviral activity. The derivatives exerted inhibitory effects for all six influenza subtypes tested including three major types of currently circulating human influenza viruses (A/H1N1, A/H3N2 and B type), H2N2 and H9N2 avian influenza virus. The compounds strongly inhibited adsorption of the viruses on red blood cell (RBC). They also restricted the growth of avian influenza virus in ovo with minimum inhibition concentration (MIC) of 5-10 microM far exceeding the neuraminidase (NA) inhibitor oseltamivir or M2 proton channel inhibitor amantadine. The antiviral activity appears to be mediated by interaction with hemagglutinin (HA)/viral membrane rendering HA less fusogenic at the initial stage of infection. The broad spectrum activity against various subtypes of influenza viruses may complement the limitations of current antivirals and contribute for managing potentially emerging influenza pandemic. The structure-activity data of catechin derivatives may usefully guideline future research endeavors for applying green tea catechins as alternative anti-viral agents.

  15. Antifungal Activities of Peptides Derived from Domain 5 of High-Molecular-Weight Kininogen

    PubMed Central

    Sonesson, Andreas; Nordahl, Emma Andersson; Malmsten, Martin; Schmidtchen, Artur

    2011-01-01

    In both immunocompromised and immunocompetent patients, Candida and Malassezia are causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind to Candida and other pathogens, leading to activation of the contact system. A cutaneous Candida infection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that antifungal peptide fragments are generated through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK, D5-derived peptides, as well as hydrophobically modified D5-derived peptides efficiently killed Candida and Malassezia. Furthermore, the antifungal activity of modified peptides was studied at physiological conditions. Binding of a D5-derived peptide, HKH20 (His479-His498), to the fungal cell membrane was visualized by fluorescence microscopy. Our data disclose a novel antifungal activity of D5-derived peptides and also show that proteolytic cleavage of HMWK results in fragments exerting antifungal activity. Of therapeutic interest is that structurally modified peptides show an enhanced antifungal activity. PMID:21941573

  16. Synthesis, Antiplatelet Activity and Cytotoxicity Assessment of Indole-Based Hydrazone Derivatives

    PubMed Central

    Haj Mohammad Ebrahim Tehrani, Kamaleddin; Esfahani Zadeh, Marjan; Mashayekhi, Vida; Hashemi, Maryam; Kobarfard, Farzad; Gharebaghi, Farhad; Mohebbi, Shohreh

    2015-01-01

    A series of indole-based aryl(aroyl)hydrazone analogs of antiplatelet indole-3-carboxaldehyde phenylhydrazone were synthesized by the Schiff base formation reaction and their antiplatelet activity was assessed using human platelet rich plasma. The platelet concentrate was obtained using a two-step centrifugation protocol and ADP, arachidonic acid and collagen were used as inducers of platelet aggregation. Based on the results, substituted phenylhydrazones showed promising activity. Among them, compound 1i was the most potent derivative with an IC50 comparable to that of indomethacin as a standard drug. The hydrazone derivatives were also tested for their cytotoxicity using on platelet concentrates and fibroblast L929 cells. The majority of the derivatives showed an acceptable selectivity towards antiplatelet aggregation activity. Based on the activity data, phenylhydrazone derivatives (1a-i) exhibited considerable antiplatelet activity and minimal toxic effect on platelet cells. The results of the present study could provide a better understanding of the structure activity relationship of antiplatelet indolehydrazones. PMID:26664374

  17. Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens.

    PubMed

    Scalon Cunha, Luis C; Andrade e Silva, Márcio L; Cardoso Furtado, Niege A J; Vinhólis, Adriana H C; Gomes Martins, Carlos H; da Silva Filho, Ademar A; Cunha, Wilson R

    2007-01-01

    Triterpene acids (ursolic, oleanoic, gypsogenic, and sumaresinolic acids) isolated from Miconia species, along with a mixture of ursolic and oleanolic acids and a mixture of maslinic and 2-a-hydroxyursolic acids, as well as ursolic acid derivatives were evaluated against the following microorganisms: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis, which are potentially responsible for the formation of dental caries in humans. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) during the evaluation of the antibacterial activity. All the isolated compounds, mixtures, and semi-synthetic derivatives displayed activity against all the tested bacteria, showing that they are promising antiplaque and anticaries agents. Ursolic and oleanolic acids displayed the most intense antibacterial effect, with MIC values ranging from 30 microg/mL to 80 microg/mL. The MIC values of ursolic acid derivatives, as well as those obtained for the mixture of ursolic and oleanolic acids showed that these compounds do not have higher antibacterial activity when compared with the activity observed with either ursolic acid or oleanolic acid alone. With regard to the structure-activity relationship of triterpene acids and derivatives, it is suggested that both hydroxy and carboxy groups present in the triterpenes are important for their antibacterial activity against oral pathogens.

  18. Highly-efficient fully resonant vertical couplers for InP active-passive monolithic integration using vertically phase matched waveguides.

    PubMed

    López, Oscar García; Lasaosa, Daniel; López-Amo, Manuel; Galarza, Marko

    2013-09-23

    A new active-passive monolithic integration approach for photonic components based on vertical evanescent coupling is presented. Two vertically stacked waveguides are used in order to provide full resonant power transfer between them and avoiding the need of tapered structures. Light confinement in each waveguide is achieved combining strong lateral asymmetric structures and bent waveguides, both defined during lithography. Low propagation losses for the active waveguide and coupling efficiencies to the passive section as high as 97% have been obtained.

  19. Silylation improves the photodynamic activity of tetraphenylporphyrin derivatives in vitro and in vivo.

    PubMed

    Horiuchi, Hiroaki; Hosaka, Masahiro; Mashio, Hiroyuki; Terata, Motoki; Ishida, Shintaro; Kyushin, Soichiro; Okutsu, Tetsuo; Takeuchi, Toshiyuki; Hiratsuka, Hiroshi

    2014-05-12

    The effects of silyl and hydrophilic groups on the photodynamic properties of tetraphenylporphyrin (TPP) derivatives have been studied in vitro and in vivo. Silylation led to an improvement in the quantum yield of singlet oxygen sensitization for both sulfo and carboxy derivatives, although the silylation did not affect other photophysical properties. Silylation also improved the cellular uptake efficiency for both sulfo and carboxy derivatives, enhancing the in vitro photodynamic activity of the photosensitizer in U251 human glioma cells. The carboxy derivative (SiTPPC4 ) was found to show higher cellular uptake efficiency and in vitro photodynamic activity than the corresponding sulfo derivative (SiTPPS4 ), which indicates that the carboxy group is a more promising hydrophilic group than the sulfo group in the silylated porphyrin. SiTPPC4 was found to show high selective accumulation efficiency in tumors, although almost no tumor selectivity was observed for the nonsilylated porphyrin. The concentration of SiTPPC4 in tumors was 13 times higher than that in muscle 12 h after drug administration. We also studied tumor response after treatment and found that silylation enhanced in vivo photodynamic activity significantly. SiTPPC4 shows higher photodynamic activity than NPe6 with white light irradiation.

  20. Anticancer activity of some polyamine derivatives on human prostate and breast cancer cell lines.

    PubMed

    Szumilak, Marta; Galdyszynska, Malgorzata; Dominska, Kamila; Stanczak, Andrzej; Piastowska-Ciesielska, Agnieszka

    2017-01-01

    The aim of this study was to expand our knowledge about anticancer activity of some polyamine derivatives with quinoline or chromane as terminal moieties. Tested compounds were evaluated in vitro towards metastatic human prostate adenocarcinoma (PC3), human carcinoma (DU145) and mammary gland adenocarcinoma (MCF7) cell lines. Cell viability was estimated on the basis of mitochondrial metabolic activity using water-soluble tetrazolium WST1 to establish effective concentrations of the tested compounds under experimental conditions. Cytotoxic potential of polyamine derivatives was determined by the measurement of lactate dehydrogenase activity released from damaged cells, changes in mitochondrial membrane potential, the cell cycle distribution analysis and apoptosis assay. It was revealed that the tested polyamine derivatives differed markedly in their antiproliferative activity. Bischromane derivative 5a exhibited a rather cytostatic than cytotoxic effect on the tested cells, whereas quinoline derivative 3a caused changes in cell membrane integrity, inhibited cell cycle progression, as well as induced apoptosis of prostate and breast cancer cells which suggest its potential application in cancer therapy.