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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. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. "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…

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  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. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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)

  16. 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).

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Dehydroepiandrosterone Derivatives as Potent Antiandrogens With Marginal Agonist Activity

    DTIC Science & Technology

    2011-07-01

    of the molecules, which was only marginally suppressed by the steroid derivatives. Figure 4 . The effects of DHEA derivatives on expression of...DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From - To) 4 . TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...physiological metabolite from dehydroepiandrosterone ( DHEA ) and a precursor of testosterone, has an intrinsic androgenic activity which was not

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. [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).

  12. 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

  13. 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).

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. [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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. [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.

  20. 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).

  1. 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.

  2. 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

  3. 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™.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. 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

  10. 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

  11. Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

    DTIC Science & Technology

    2015-05-01

    figure not shown). Figure 4. The effects of DHEA derivatives on the expression of PSA (A), AR ( B ), bFGF (C), VEGF (D), IL-6 (E), and MMP-9 ( F ...induced bladder carcinogenesis. Mol Carcinogen 52(2): 94-102, 2013. PMID: 22086872 10. Li Y, Zheng Y, Izumi K, Ishiguro H, Ye B , Li F , Miyamoto H...Ishiguro H, Ye B , Li F , Miyamoto H: Androgen activates β-catenin signaling in bladder cancer cells. Endocr-Relat Cancer 20(3): 293-304, 2013. 11. Izumi K

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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}.

  7. 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.

  8. 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.

  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. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  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. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

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

    PubMed

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

    2013-06-01

    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 occurring 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 (1)H and (13)C 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).

  12. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Mosquito larvicidal activity of active constituent derived from Chamaecyparis obtusa leaves against 3 mosquito species.

    PubMed

    Jang, Young-Su; Jeon, Ju-Hyun; Lee, Hoi-Seon

    2005-12-01

    Mosqutio larvicidal activity of Chamaecyparis obtusa leaf-derived materials against the 4th-stage larvae of Aedes aegypti (L.), Ochlerotatus togoi (Theobald), and Culex pipiens pallens (Coquillett) was examined in the laboratory. A crude methanol extract of C. obtusa leaves was found to be active (percent mortality rough) against the 3 species larvae; the hexane fraction of the methanol extract showed a strong larvicidal activity (100% mortality) at 100 ppm. The bioactive component in the C. obtusa leaf extract was characterized as beta-thujaplicin by spectroscopic analyses. The LC50 value of beta-thujaplicin was 2.91, 2.60, and 1.33 ppm against Ae. aegypti, Oc. togoi, and Cx. pipiens pallens larvae. This naturally occurring C. obtusa leaves-derived compound merits further study as a potential mosquito larval control agent or lead compound.

  2. [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.

  3. Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

    DTIC Science & Technology

    2012-07-01

    July 2011 - 30 June 2012 4 . TITLE AND SUBTITLE Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity 5a...Introduction…………………………………………………………….………..….. 1 Body………………………………………………………………………………….. 1 Key Research Accomplishments………………………………………….…….. 4 ...Reportable Outcomes……………………………………………………………… 4 Conclusion…………………………………………………………………………… 8 References……………………………………………………………………………. 9

  4. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  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. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.…

  7. 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

  8. 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

  9. 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.

  10. Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. 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.

  12. 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,...

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Antifungal, mosquito deterrent, and larvicidal activity of N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. Antimalarial Activity of Anthothecol Derived from Khaya anthotheca (Meliaceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. [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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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).

  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. 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

  19. Antiplatelet Activities of Newly Synthesized Derivatives of Piperlongumine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  20. Characterization of surface active materials derived from farm products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. 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.

  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 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

  4. 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

  5. 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.

  6. 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

  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. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  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. 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)

  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. 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

  19. 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.

  20. In vitro antioxidant activities of sulfated derivatives of polysaccharides extracted from Auricularia auricular.

    PubMed

    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.

  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. 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.

  3. 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

  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. Synthesis and antiproliferative activity of some ellipticine-like 11H-pyrido[a]carbazole derivatives.

    PubMed

    Ferlin, Maria Grazia; Gia, Ornella; Dalla Via, Lisa

    2011-10-04

    Some modified 11H-pyrido[a]carbazoles (11H-PyC) and their corresponding tetrahydro derivatives (11H-THPyC) were prepared. A common multistep pathway characterized by conventional reactions, including a Fischer-indole-type synthesis, yielded the tetracyclic compounds. To improve cytotoxicity, 11H-PyC and 11H-THPyC derivatives were endowed with a diethylaminoethyl side chain. The antiproliferative activity was assessed in three human tumor cell lines, and a number of derivatives showed a cytotoxic effect in agreement with their capacity to form a molecular intercalative complex with DNA and to interfere with the relaxation activity of DNA topoisomerase II. In contrast, three derivatives that exhibited significant antiproliferative efficacy, showed no inhibition of topoisomerase II, thus suggesting an unexpected and novel mode of action for these ellipticine-like compounds independent of topoisomerase II activity.

  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 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. [(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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  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. Activated carbons derived from oil palm empty-fruit bunches: application to environmental problems.

    PubMed

    Alam, Md Zahangir; Muyibi, Suleyman A; Mansor, Mariatul F; Wahid, Radziah

    2007-01-01

    Activated carbons derived from oil palm empty fruit bunches (EFB) were investigated to find the suitability of its application for removal of phenol in aqueous solution through adsorption process. Two types of activation namely; thermal activation at 300, 500 and 800 degrees C and physical activation at 150 degrees C (boiling treatment) were used for the production of the activated carbons. A control (untreated EFB) was used to compare the adsorption capacity of the activated carbons produced from these processes. The results indicated that the activated carbon derived at the temperature of 800 degrees C showed maximum absorption capacity in the aqueous solution of phenol. Batch adsorption studies showed an equilibrium time of 6 h for the activated carbon at 800 degrees C. It was observed that the adsorption capacity was higher at lower values of pH (2-3) and higher value of initial concentration of phenol (200-300 mg/L). The equilibrium data fitted better with the Freundlich adsorption isotherm compared to the Langmuir. Kinetic studies of phenol adsorption onto activated carbons were also studied to evaluate the adsorption rate. The estimated cost for production of activated carbon from EFB was shown in lower price (USD 0.50/kg of activated carbon) compared the activated carbon from other sources and processes.

  1. New amphiphilic neamine derivatives active against resistant Pseudomonas aeruginosa and their interactions with lipopolysaccharides.

    PubMed

    Sautrey, Guillaume; Zimmermann, Louis; Deleu, Magali; Delbar, Alicia; Souza Machado, Luiza; Jeannot, Katy; Van Bambeke, Françoise; Buyck, Julien M; Decout, Jean-Luc; Mingeot-Leclercq, Marie-Paule

    2014-08-01

    The development of novel antimicrobial agents is urgently required to curb the widespread emergence of multidrug-resistant bacteria like colistin-resistant Pseudomonas aeruginosa. We previously synthesized a series of amphiphilic neamine derivatives active against bacterial membranes, among which 3',6-di-O-[(2"-naphthyl)propyl]neamine (3',6-di2NP), 3',6-di-O-[(2"-naphthyl)butyl]neamine (3',6-di2NB), and 3',6-di-O-nonylneamine (3',6-diNn) showed high levels of activity and low levels of cytotoxicity (L. Zimmermann et al., J. Med. Chem. 56:7691-7705, 2013). We have now further characterized the activity of these derivatives against colistin-resistant P. aeruginosa and studied their mode of action; specifically, we characterized their ability to interact with lipopolysaccharide (LPS) and to alter the bacterial outer membrane (OM). The three amphiphilic neamine derivatives were active against clinical colistin-resistant strains (MICs, about 2 to 8 μg/ml), The most active one (3',6-diNn) was bactericidal at its MIC and inhibited biofilm formation at 2-fold its MIC. They cooperatively bound to LPSs, increasing the outer membrane permeability. Grafting long and linear alkyl chains (nonyl) optimized binding to LPS and outer membrane permeabilization. The effects of amphiphilic neamine derivatives on LPS micelles suggest changes in the cross-bridging of lipopolysaccharides and disordering in the hydrophobic core of the micelles. The molecular shape of the 3',6-dialkyl neamine derivatives induced by the nature of the grafted hydrophobic moieties (naphthylalkyl instead of alkyl) and the flexibility of the hydrophobic moiety are critical for their fluidifying effect and their ability to displace cations bridging LPS. Results from this work could be exploited for the development of new amphiphilic neamine derivatives active against colistin-resistant P. aeruginosa.

  2. Antioxydant activity of β-carboline derivatives in the LDL oxidation model.

    PubMed

    Hadjaz, Fariza; Besret, Soizic; Martin-Nizard, Françoise; Yous, Saïd; Dilly, Sébastien; Lebegue, Nicolas; Chavatte, Philippe; Duriez, Patrick; Berthelot, Pascal; Carato, Pascal

    2011-06-01

    A series of β-carboline compounds were synthesized, starting from compound GWC22, their antioxidant activity was determined by inhibition of lipid peroxidation. The oxidation of LDL was induced in the presence of CuSO4 or 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The protective actions of these compounds against the cytotoxicity were evaluated with lactate dehydrogenase (LDH) activity in bovine aortic endothelial cells (BAECs) and cellular vitality by measuring mitochondrial activity in the presence of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Most of compounds showed an higher antioxidant activity than GWC22 derivative (R=1.6 for 5 μM CuSO4). The best antioxidant activities are phenolic and benzyloxy derivatives with ratio R=1.9 to 2.8 for 1 μM CuSO4. These substances have protective actions and increase significantly the cell viability.

  3. Marine-derived Penicillium in Korea: diversity, enzyme activity, and antifungal properties.

    PubMed

    Park, Myung Soo; Fong, Jonathan J; Oh, Seung-Yoon; Kwon, Kae Kyoung; Sohn, Jae Hak; Lim, Young Woon

    2014-08-01

    The diversity of marine-derived Penicillium from Korea was investigated using morphological and multigene phylogenetic approaches, analyzing sequences of the internal transcribed spacer region, β-tubulin gene, and RNA polymerase subunit II gene. In addition, the biological activity of all isolated strains was evaluated. We tested for the extracellular enzyme activity of alginase, endoglucanase, and β-glucosidase, and antifungal activity against two plant pathogens (Colletotrichum acutatum and Fusarium oxysporum). A total of 184 strains of 36 Penicillium species were isolated, with 27 species being identified. The most common species were Penicillium polonicum (19.6 %), P. rubens (11.4 %), P. chrysogenum (11.4 %), and P. crustosum (10.9 %). The diversity of Penicillium strains isolated from soil (foreshore soil and sand) and marine macroorganisms was higher than the diversity of strains isolated from seawater. While many of the isolated strains showed alginase and β-glucosidase activity, no endoglucanase activity was found. More than half the strains (50.5 %) showed antifungal activity against at least one of the plant pathogens tested. Compared with other strains in this study, P. citrinum (strain SFC20140101-M662) showed high antifungal activity against both plant pathogens. The results reported here expand our knowledge of marine-derived Penicillium diversity. The relatively high proportion of strains that showed antifungal and enzyme activity demonstrates that marine-derived Penicillium have great potential to be used in the production of natural bioactive products for pharmaceutical and/or industrial use.

  4. 5-Nitro-2-furyl derivative actives against Trypanosoma cruzi: preliminary in vivo studies.

    PubMed

    Cabrera, Eliana; Murguiondo, Mariana González; Arias, Marelina González; Arredondo, Carolina; Pintos, Cristina; Aguirre, Gabriela; Fernández, Marcelo; Basmadjián, Yester; Rosa, Raquel; Pacheco, José Pedro; Raymondo, Stella; Di Maio, Rossanna; González, Mercedes; Cerecetto, Hugo

    2009-10-01

    Ten 5-nitro-2-furyl derivatives, with good to excellent in vitro anti-Trypanosoma cruzi activity, and nifurtimox were tested oral and intraperitoneally on healthy animals for its acute toxicity on murine models. According to animals' survival percentage, organ histological results, biochemical and haematological findings, three new derivatives, with toxicity like nifurtimox, were selected to test in vivo as antichagasic agents. Clearly, dependences between chemical structure and both acute toxicity and in vivo anti-T. cruzi activity were observed. 4-Hexyl-1-[3-(5-nitro-2-furyl)-2-propenylidene]semicarbazide displayed good profile as anti-T. cruzi agent and better acute toxicity profile than nifurtimox.

  5. ANTIPROLIFERATIVE ACTIVITY OF NOVEL ACETYLENIC DERIVATIVES OF BETULIN AGAINST G-361 HUMAN MELANOMA CELLS.

    PubMed

    Bębenek, Ewa; Chodurek, Ewa; Orchel, Arkadiusz; Dzierżewicz, Zofia; Boryczka, Stanisław

    2015-01-01

    Acetylenic derivatives of betulin were tested in vitro for their antiproliferative activity against G-361 human melanoma cells. Two types of betulin derivatives were studied: monoesters, obtained by modification of the hydroxyl group at C-28 position, and diesters modified at both C-28 and C-3 positions. To assess cell proliferation, a colorimetric sulforhodamine B based method was used. All the tested monoesters inhibited cellular growth and 28-O-propynoylbetulin showed the strongest cytotoxic effect. Esterification of the C-3 hydroxyl group of the molecule abolished its growth inhibitory activity.

  6. The chemistry and biological activity of heterocycle-fused quinolinone derivatives: A review.

    PubMed

    Shiro, Tomoya; Fukaya, Takayuki; Tobe, Masanori

    2015-06-05

    Among all heterocycles, the heterocycle-fused quinolinone scaffold is one of the privileged structures in drug discovery as heterocycle-fused quinolinone derivatives exhibit various biological activities allowing them to act as anti-inflammatory, anticancer, antidiabetic, and antipsychotic agents. This wide spectrum of biological activity has attracted a great deal of attention in the field of medicinal chemistry. In this review, we provide a comprehensive description of the biological and pharmacological properties of various heterocycle-fused quinolinone scaffolds and discuss the synthetic methods of some of their derivatives.

  7. Natural Product-Derived Small Molecule Activators of Hypoxia-Inducible Factor-1 (HIF-1)

    PubMed Central

    Nagle, Dale G.; Zhou, Yu-Dong

    2010-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a key mediator of oxygen homeostasis that was first identified as a transcription factor that is induced and activated by decreased oxygen tension. Upon activation, HIF-1 upregulates the transcription of genes that promote adaptation and survival under hypoxic conditions. HIF-1 is a heterodimer composed of an oxygen-regulated subunit known as HIF-1α and a constitutively expressed HIF-1β subunit. In general, the availability and activity of the HIF-1α subunit determines the activity of HIF-1. Subsequent studies have revealed that HIF-1 is also activated by environmental and physiological stimuli that range from iron chelators to hormones. Preclinical studies suggest that HIF-1 activation may be a valuable therapeutic approach to treat tissue ischemia and other ischemia/hypoxia-related disorders. The focus of this review is natural product-derived small molecule HIF-1 activators. Natural products, relatively low molecular weight organic compounds produced by plants, animals, and microbes, have been and continue to be a major source of new drugs and molecular probes. The majority of known natural product-derived HIF-1 activators were discovered through pharmacological evaluation of specifically selected individual compounds. The combination of natural products chemistry with appropriate high-throughput screening bioassays could provide an alternative approach to discover novel natural product-derived HIF-1 activators. Potent natural product-derived HIF-1 activators that exhibit a low level of toxicity and side effects hold promise as new treatment options for diseases such as myocardial and peripheral ischemia, and as chemopreventative agents that could be used to reduce the level of ischemia/reperfusion injury following heart attack and stroke. PMID:16842166

  8. Synthesis and antimicrobial activities of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives.

    PubMed

    Zhang, Qiu-Rong; Xue, Deng-Qi; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Ren, Jing-Li; Shan, Li-Hong; Liu, Hong-Min

    2014-02-15

    A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized in five steps from a common precursor, phthalic anhydride. Most of synthesized phthalazine derivatives showed inhibitory activity against Staphylococcus aureus. One of phthalazine derivatives 5l showed inhibitory activity against all tested bacterial and fungal strains.

  9. Wastewater treatment using low cost activated carbons derived from agricultural byproducts--a case study.

    PubMed

    Mohan, Dinesh; Singh, Kunwar P; Singh, Vinod K

    2008-04-15

    A variety of low cost activated carbons were developed from agricultural waste materials viz., coconut shell, coconut shell fibers and rice husk. The low cost activated carbons were fully characterized and utilized for the remediation of various pollutants viz., chemical oxygen demand (COD), heavy metals, anions, etc., from industrial wastewater. Sorption studies were carried out at different temperatures and particle sizes to study the effect of temperatures and surface areas. The removal of chloride and fluoride increased with rise in temperature while COD and metal ions removal decreased with increase in temperature, thereby, indicating the processes to be endothermic and exothermic, respectively. The kinetics of COD adsorption was also carried out at different temperatures to establish the sorption mechanism and to determine various kinetic parameters. The COD removal was 47-72% by coconut shell fiber carbon (ATFAC), 50-74% by coconut shell carbon (ATSAC) and 45-73% by rice husk carbon (ATRHC). Furthermore, COD removal kinetics by rice husk carbon, coconut shell carbon and coconut fiber carbon at different temperatures was approximately represented by a first order rate law. Results of this fundamental study demonstrate the effectiveness and feasibility of low cost activated carbons. The parameters obtained in this study can be fully utilized to establish fixed bed reactors on large scale to treat the contaminated water.

  10. Quantitative Structure-Cytotoxic Activity Relationship 1-(Benzoyloxy)urea and Its Derivative

    PubMed Central

    Hardjono, Suko; Siswodihardjo, Siswandono; Pramono, Purwanto; Darmanto, Win

    2016-01-01

    Drug development is originally carried out on a trial and error basis and it is cost-prohibitive. To minimize the trial and error risks, drug design is needed. One of the compound development processes to get a new drug is by designing a structure modification of the mother compound whose activities are recognized. A substitution of the mother compounds alters the physicochemical properties: lipophilic, electronic and steric properties. In Indonesia, one of medical treatments to cure cancer is through chemotherapy and hydroxyurea. Some derivatives, phenylthiourea, phenylurea, benzoylurea, thiourea and benzoylphenylurea, have been found to be anticancer drug candidates. To predict the activity of the drug compound before it is synthesized, the in-silico test is required. From the test, Rerank Score which is the energy of interaction between the receptor and the ligand molecule is then obtained. Hydroxyurea derivatives were synthesized by modifying Schotten-Baumann’s method by the addition of benzoyl group and its homologs resulted in the increase of lipophilic, electronic and steric properties, and cytotoxic activity. Synthesized compounds were 1-(benzoyloxy)urea and its derivatives. Structure characterization was obtained by the spectrum of UV, IR, H NMR, C NMR and Mass Spectrometer. Anticancer activity was carried out using MTT method on HeLa cells. The Quantitative Structure-Cytotoxic Activity Relationships of 1-(benzoyloxy)urea compound and its derivatives was calculated using SPSS. The chemical structure was described, namely: ClogP, π, σ, RS, CMR and Es; while, the cytotoxic activity was indicated by log (1 / IC50). The results show that the best equation of Quantitative Structure-Cytotoxic Activity Relationships (QSAR) of 1- (benzoyloxy)urea compound and its derivatives is Log 1/IC50 = - 0.205 (+ 0.068) σ – 0.051 (+ 0.022) Es – 1.911 (+ 0.020) PMID:27222144

  11. Factors influencing the antifolate activity of synthetic tea-derived catechins.

    PubMed

    Sáez-Ayala, Magalí; Fernández-Pérez, María Piedad; Chazarra, Soledad; Mchedlishvili, Nani; Tárraga-Tomás, Alberto; Rodríguez-López, José Neptuno

    2013-07-16

    Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

  12. Comparative effects of indole and aminoacetonitrile derivatives on dimethylnitrosamine-demethylase and aryl hydrocarbon hydroxylase activities.

    PubMed

    Arcos, J C; Myers, S C; Neuburger, B J; Argus, M F

    1980-04-01

    The effect of in vivo administration of indole and five 3-indolyl derivatives including L-tryptophan, as well as of aminoacetonitrile and 3 of its derivatives, were studied on the carcinogen-metabolizing hepatic mixed-function oxidases dimethylnitrosamine (DMN)-demethylase I and II and aryl hydrocarbon hydroxylase (AHH). Indole, 3-indolylmethanol, 3-indolyl-acetonitrile, 3-indolylacetone and L-tryptophan induce AHH activity from 3- to 6-fold of the control level, whereas beta-3-indolylethanol has no effect; the latter compound produces a 21% decrease of the endoplasmic reticulum content in the tissue. Only L-tryptophan induces DMN-demethylase I and only L-tryptophan and 3-indolylmethanol induce DMN-demethylase II, representing a doubling of enzyme activity in all 3 instances. Aminoacetonitrile is a potent repressor of DMN-demethylase I. Substitutions on the amino group bring about strong decrease or abolishment of mixed-function oxidase repressor activity; thus, iminodiacetonitrile has only about 1/5th the repressor activity of the parent compound, whereas nitrilotriacetonitrile and dimethylaminoacetonitrile appear to be inactive. Aminoacetonitrile and its derivatives studied have no effect on DMN-demethylase II and AHH activities. The mixed-function oxidase-modifying effects of the indole compounds and of aminoacetonitrile and its derivatives illustrate the potential complexity of effects of dietary constituents on the carcinogenic responses.

  13. Plant derived substances with anti-cancer activity: from folklore to practice

    PubMed Central

    Fridlender, Marcelo; Kapulnik, Yoram; Koltai, Hinanit

    2015-01-01

    Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70–95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early nineteenth century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next two decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin, and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity. PMID:26483815

  14. Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives

    PubMed Central

    Engwa, Godwill Azeh; Ayuk, Eugene Lekem; Igbojekwe, Benardeth Ujunwa; Unaegbu, Marcellus

    2016-01-01

    The global increase in oxidative stress related diseases such as cancer, cardiovascular, and inflammatory diseases caused by overwhelming level of free radicals in the body has encouraged the search for new antioxidant agents. Based on the ability of newly synthesized phenothiazine derivatives (6-chloro-11-azabenzo[a]phenothiazine-5-one and 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one) to oxidize H2O2, a known free radical to sulfoxide, this study assessed the in vitro and in vivo antioxidant activity. The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe3+ to Fe2+ and high ability to scavenge H2O2 free radical in vitro. These activities were comparable to ascorbic acid, a standard antioxidant. The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo. The malondialdehyde level in groups 1 and 2 animals was lower than that in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent suggesting the ability of the phenothiazine derivatives to prevent lipid membrane damage. AST and bilirubin levels were higher in group 2 animals which received 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one compared to group 3, the positive control. The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic. This activity may be due to the presence of electron donors such as sulfur as well as the richness of hydrogen in the additional benzene rings for substitution. Further study is needed to identify tolerable doses for possible therapeutic purposes. PMID:27127652

  15. Synthesis and cytotoxic activity of certain benzothiazole derivatives against human MCF-7 cancer cell line.

    PubMed

    Mohamed, Lamia W; Taher, Azza T; Rady, Ghada S; Ali, Mamdouh M; Mahmoud, Abeer E

    2016-10-04

    A new series of benzothiazole has been synthesized as cytotoxic agents. The new derivatives were tested for their cytotoxic activity toward the human breast cancer MCF-7 cell line against cisplatin as the reference drug. Many derivatives revealed good cytotoxic effect, whereas four of them, 4, 5c, 5d, and 6b, were more potent than cisplatin, with IC50 values being 8.64, 7.39, 7.56, and 5.15 μm compared to 13.33 μm of cisplatin. The four derivatives' cytotoxic activity was accompanied by regulating free radicals production, by increasing the activity of superoxide dismutase and depletion of intracellular reduced glutathione, catalase, and glutathione peroxidase activities, accordingly, the high production of hydrogen peroxide, nitric oxide, and other free radicals causing tumor cell death as monitored by reduction in the synthesis of protein and nucleic acids. Most of the tested compounds showed potent to moderate growth inhibitory activity; in particular, compound 6b exhibited the highest activity suggesting it is a lead compound in cytotoxic activity.

  16. Synthesis, antimicrobial evaluation, and structure-activity relationship of α-pinene derivatives.

    PubMed

    Dhar, Preeti; Chan, PuiYee; Cohen, Daniel T; Khawam, Fadi; Gibbons, Sarah; Snyder-Leiby, Teresa; Dickstein, Ellen; Rai, Prashant Kumar; Watal, Geeta

    2014-04-23

    Several (+)- and (-)-α-pinene derivatives were synthesized and evaluated for their antimicrobial activity toward Gram-positive bacteria Micrococcus luteus and Staphylococcus aureus, Gram-negative bacterium Escherichia coli, and the unicellular fungus Candida albicans using bioautographic assays. (+)-α-Pinene 1a showed modest activity against the test organisms, whereas (-)-α-pinene 1b showed no activity at the tested concentration. Of all the α-pinene derivatives evaluated, the β-lactam derivatives (10a and 10b) were the most antimicrobial. The increase in the antimicrobial activity of 10a compared to 1a ranged from nearly 3.5-fold (C. albicans) to 43-fold (S. aureus). The mean ± standard deviation for the zone of inhibition (mm) for 10a (C. albicans) was 31.9 ± 4.3 and that for S. aureus was 51.1 ± 2.9. Although (-)-α-pinene 1b was not active toward the test microorganisms, the corresponding β-lactam 10b, amino ester 13b, and amino alcohol 14b showed antimicrobial activity toward the test microorganisms. The increase in the antimicrobial activity of 10b compared to 1b ranged from 32-fold (S. aureus) to 73-fold (M. luteus). The mean ± standard deviation for the zone of inhibition (mm) for 10b (S. aureus) was 32.0 ± 0.60 and that for M. luteus was 73.2 ± 0.30.

  17. Cytotoxic Activity of Semi-Synthetic Derivatives of Elatol and Isoobtusol

    PubMed Central

    Lang, Karen L.; Silva, Izabella T.; Zimmermann, Lara A.; Lhullier, Cíntia; Mañalich Arana, Maria V.; Palermo, Jorge A.; Falkenberg, Miriam; Simões, Cláudia M. O.; Schenkel, Eloir P.; Durán, Fernando J.

    2012-01-01

    In the present study, the in vitro cytotoxic effects of six semi-synthetic derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical modifications were performed on the hydroxyl groups aiming to get derivatives of different polarity, namely the hemisuccinate, carbamate and sulfamate. The structural elucidation of the new derivatives was based on detailed NMR and MS spectroscopic analyses. The in vitro cytotoxicity of compounds 1 to 8 was evaluated against A459 and RD tumor cell lines with CC50 values ranging from 4.93 to 41.53 µM. These results suggest that the structural modifications performed on both compounds could be considered a good strategy to obtain more active derivatives. PMID:23170082

  18. Synthesis and antimicrobial activity of novel structural hybrids of benzofuroxan and benzothiazole derivatives.

    PubMed

    Chugunova, Elena; Boga, Carla; Sazykin, Ivan; Cino, Silvia; Micheletti, Gabriele; Mazzanti, Andrea; Sazykina, Marina; Burilov, Alexander; Khmelevtsova, Ludmila; Kostina, Natalia

    2015-03-26

    New compounds containing both benzofuroxan and benzothiazole scaffolds were synthesized through electrophile/nucleophile combination of nitrobenzofuroxan derivatives and 2-mercapto- or 2-aminobenzothiazole derivatives and their biological effect on the natural strain Vibrio genus and different bacterial lux-biosensors was studied. Among all the compounds synthesized, that obtained from 2-mercaptobenzothiazole and 7-chloro-4,6-dinitrobenzofuroxan was toxic for bacterial cells, and also able to activated the 1st type Quorum Sensing system. The reaction between 7-chloro-4,6-dinitrobenzofuroxan and 2-aminobenzothiazole derivatives gave two products, one bearing the benzofuroxan moiety linked to the exocyclic amino nitrogen, and the second derived from the attack of two molecules of electrophile to both the nitrogen atoms of the benzothiazole reagent. Their relative ratio is modifiable by tuning the reagents ratio and the reaction time.

  19. Activated carbons prepared from refuse derived fuel and their gold adsorption characteristics.

    PubMed

    Buah, William K; Williams, Paul T

    2010-02-01

    Activated carbons produced from refuse derived fuel (RDF), which had been prepared from municipal solid waste have been characterized and evaluated for their potential for gold adsorption from gold chloride solution. Pyrolysis of the RDF produced a char, which was then activated via steam gasification to produce activated carbons. Steam gasification of the char at 900 degrees C for 3 h yielded 73 wt% activated carbon. The derived activated carbon had a surface area of 500 m2 g(-1) and a total pore volume of 0.19 cm3 g(-1). The gold adsorption capacity of the activated carbon was 32.1 mg Au g(-1) of carbon when contacted with an acidified gold chloride solution. The gold adsorption capacity was comparable to that of a commercial activated carbon tested under the same conditions and was well in the range of values of activated carbons used in the gold industry. Demineralization of the RDF activated carbon in a 5 M HCl solution resulted in enhancement of its textural properties but a reduction in the gold adsorption rate, indicating that the metal content of the RDF activated carbon influenced its gold adsorption rate.

  20. Novel cycloalkylthiophene-imine derivatives bearing benzothiazole scaffold: synthesis, characterization and antiviral activity evaluation.

    PubMed

    Ke, Shaoyong; Wei, Yanhong; Yang, Ziwen; Wang, Kaimei; Liang, Ying; Shi, Liqiao

    2013-09-15

    A series of novel cycloalkylthiophene-imine derivatives containing benzothiazole unit were designed, synthesized and evaluated for their anti-viral activities. The bio-evaluation results indicated that some of the target compounds (such as 5g, 5i, 5u) exhibited good to moderate antiviral effect on CVB5, ADV7 and EV71 viruses, however, these compounds did not have inhibition activity against H1N1 virus. Especially, the compounds 4c and 4d also exhibited high antiviral activities, which provide a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration of active pharmacophores.

  1. Reduced Basal Transcriptional Activity of Central Nervous System-Derived HIV Type 1 Long Terminal Repeats

    PubMed Central

    Gray, Lachlan R.; Cowley, Daniel; Crespan, Emma; Welsh, Casey; Mackenzie, Charlene; Wesselingh, Steve L.; Gorry, Paul R.

    2013-01-01

    Abstract New evidence indicates that astrocytes of the central nervous system (CNS) are extensively infected with human immunodeficiency virus type 1 (HIV-1) in vivo. Although no new virus is produced, this nonproductive or restricted infection contributes to the pathogenesis of HIV-associated dementia (HAD) and compromises virus eradication strategies. The HIV-1 long terminal repeat (LTR) plays a critical role in regulating virus production from infected cells. Here, we determined whether LTRs derived from CNS and non-CNS compartments are genetically and functionally distinct and contribute to the restricted nature of astrocyte infection. CNS- and/or non-CNS-derived LTRs (n=82) were cloned from primary HIV-1 viruses isolated from autopsy tissues of seven patients who died with HAD. Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences. Functional analysis showed reduced basal transcriptional activity of CNS-derived LTRs in both astrocytes and T cells compared to that of non-CNS-derived LTRs. However, LTRs were heterogeneous in their responsiveness to activation by Tat. Therefore, using a relatively large, independent panel of primary HIV-1 LTRs derived from clinically well-characterized subjects, we show that LTRs segregate CNS- from non-CNS-derived tissues both genetically and functionally. The reduced basal transcriptional activity of LTRs derived from the CNS may contribute to the restricted HIV-1 infection of astrocytes and latent infection within the CNS. These findings have significance for understanding the molecular basis of HIV-1 persistence within cellular reservoirs of the CNS that need to be considered for strategies aimed at eradicating HIV-1. PMID:22924643

  2. Chemical composition and genotoxic activity of petroleum derivatives collected in two working environments

    SciTech Connect

    Pasquini, R.; Taningher, M.; Monarca, S.; Pala, M.; Angeli, G.

    1989-01-01

    Pitch and bitumen, two complex petroleum derivative mixtures, were studied for both their chemical composition and their mutagenic/DNA damaging activity. While bitumen revealed no genotoxic effect and low polycyclic aromatic hydrocarbons (PAHs) concentration, petroleum pitch showed a high concentration of mutagenic/carcinogenic PAHs, and also an elevated mutagenic activity when assayed by the Ames test, in the presence of postmitochondrial rat liver fractions. The in vitro mutagenic activity was detectable as frameshift mutation by assaying the pitch both as an in toto mixture and after HPLC fractionation, the most polar fractions being the most active. In contrast, both derivatives showed no in vivo DNA damage in rat liver, using the DNA alkaline elution technique and the fluorometric assay of DNA unwinding.

  3. Design and synthesis of chroman derivatives with dual anti-breast cancer and antiepileptic activities

    PubMed Central

    Rawat, Pinki; Verma, Saurabh Manaswita

    2016-01-01

    A series of chroman derivatives was designed, prepared, and examined for their anti-breast cancer and antiepileptic activities. All synthesized compounds yielded results that were in good agreement with spectral data. The bioassay showed that some of the resultant compounds exerted remarkable inhibitory effects on growth of human breast cancer cell line MCF-7. In particular, compound 6i (the concentration required for 50% inhibition of cell growth [GI50] =34.7 µM) exerted promising anticancer activity toward MCF-7 cell line. Additionally, compounds 6b, 6c, 6d, 6e, 6g, 6i, and 6l showed advanced antiepileptic activity than reference drugs. None of the compounds showed neurotoxicity, as determined by the rotarod test. The obtained results proved that these distinctive compounds could be relevant as models for future discovery and research, as well as for the production of more number of active derivatives. PMID:27621598

  4. Synthesis of indazole based diarylurea derivatives and their antiproliferative activity against tumor cell lines.

    PubMed

    Zhao, Cui-rong; Wang, Rui-qi; Li, Gang; Xue, Xiao-xia; Sun, Chang-jun; Qu, Xian-jun; Li, Wen-bao

    2013-04-01

    New series of indazole based diarylureas were synthesized and their anticancer activity against cancer cells H460, A549, OS-RC-2, HT-29, Lovo, HepG2, Bel-7402, SGC-7901 and MDA-MB-231 were examined. These derivatives of diarylureas, except azaindazole based diarylureas 5f, 5l and 5m, showed superior or similar activity against most of these selected cancer cell lines to the reference compound sorafenib. The effect of substituents on the indazole ring was also investigated. Derivatives with trifluoromenthy or halogen substituent on the indazole ring showed higher activity against the selected cancer cell lines than sorafenib. The acute toxicity assay showed that compounds 5a, 5b and 5i possessed lower toxicity than sorafenib. Compound 5i with 4-(trifluoromenthy)-1H-indazole and 4-(trifluoromenthy) benzene moieties exhibited the most potent anticancer activity.

  5. Antioxidant activity of galloyl quinic derivatives isolated from P. lentiscus leaves.

    PubMed

    Baratto, Maria Camilla; Tattini, Massimiliano; Galardi, Carlotta; Pinelli, Patrizia; Romani, Annalisa; Visioli, Francesco; Basosi, Riccardo; Pogni, Rebecca

    2003-04-01

    The antioxidant properties of galloyl quinic derivatives isolated from Pistacia lentiscus L. leaves have been investigated by means of Electron Paramagnetic Resonance spectroscopy (EPR) and UV-Vis spectrophotometry. Antioxidant properties have been also estimated using the biologically relevant LDL test. The scavenger activities of gallic acid, 5-O-galloyl, 3,5-O-digalloyl, 3,4,5-O-trigalloyl quinic acid derivatives, have been estimated against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide (O2) radical, and hydroxyl (OH) radical. On the whole, the scavenger activity raised as the number of galloyl groups on the quinic acid skeleton increased. The half-inhibition concentrations (IC50) of di- and tri-galloyl derivatives did not exceed 30 microM for all the tested free radicals. All the tested metabolites strongly reduced the oxidation of low-density lipoproteins (LDL), following a trend similar to that observed for the scavenger ability against OH radical.

  6. Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

    NASA Astrophysics Data System (ADS)

    Bębenek, Ewa; Chrobak, Elwira; Wietrzyk, Joanna; Kadela, Monika; Chrobak, Artur; Kusz, Joachim; Książek, Maria; Jastrzębska, Maria; Boryczka, Stanisław

    2016-02-01

    A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by 1H and 13C NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin 1. Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin 1 against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 μg/mL.

  7. A relativistic correlationless kinetic equation with radiation reaction fully incorporated

    NASA Astrophysics Data System (ADS)

    Lai, H. M.

    1984-06-01

    The Landau-Lifshitz expression for the Lorentz-Dirac equation is used to derive a relativistic correlationless kinetic equation for a system of electrons with radiation reaction fully incorporated. Various situations and possible applications are discussed.

  8. Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation.

    PubMed

    Ma, Chunhua; Cao, Jiangying; Liang, Xuewu; Huang, Yongxue; Wu, Ping; Li, Yingxia; Xu, Wenfang; Zhang, Yingjie

    2016-01-27

    Aminopeptidase N (APN/CD13) over-expressed on tumor cells and tumor microenvironment, plays critical roles in tumor invasion, metastasis and angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel leucine ureido derivatives as aminopeptidase N (APN/CD13) inhibitors. The results showed that compound 7a had the most potent inhibitory activity against APN with the IC50 value of 20 nM, which could be used for further anticancer agent research.

  9. Design, synthesis and aromatase inhibitory activities of novel indole-imidazole derivatives.

    PubMed

    Wang, Rui; Shi, Hong-Fan; Zhao, Jing-Feng; He, Yan-Ping; Zhang, Hong-Bin; Liu, Jian-Ping

    2013-03-15

    A series of novel indole-imidazole derivatives have been prepared and evaluated in vitro on the aromatase inhibitory activities. The results suggested that proton or a small electron-withdrawing group at para-position of the phenyl ring would enhance the inhibitory activities and any bulky group should be avoided in order to keep a relative small volume for this kind of molecules.

  10. Syntheses and Antibacterial Activity of N-Acylated Ciprofloxacin Derivatives Based on the Trimethyl Lock

    PubMed Central

    2015-01-01

    Several N-acyl ciprofloxacin quinone derivatives based on a trimethyl lock structure were synthesized, and their in vitro antibacterial activity against a panel of clinically relevant bacteria was evaluated. A few new analogues displayed enhanced activity against Gram-positive species compared to the parent drug. Additionally, studies of 8-Cip, which was the most potent compound tested, indicate that it may act through a dual-action mechanism. PMID:26101578

  11. Developmental delays and locomotor activity in the C57BL6/J mouse following neonatal exposure to the fully-brominated PBDE, decabromodiphenyl ether.

    PubMed

    Rice, Deborah C; Reeve, Elizabeth A; Herlihy, Aleece; Zoeller, R Thomas; Thompson, W Douglas; Markowski, Vincent P

    2007-01-01

    After several decades of commercial use, the flame retardant chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites have become pervasive environmental contaminants with a global distribution. PBDEs have entered the food chain and increasing levels can be detected in the human body. Decabrominated diphenyl ether (decaBDE) is currently the most widely used of the PBDEs in the United States. Despite its widespread use, little is known about the health effects of decaBDE. The current study examined the effects of neonatal exposure to decaBDE in the inbred C57BL6/J mouse. Neonatal male and female mice were exposed to a daily oral dose of 0, 6, or 20 mg/kg decaBDE from postnatal day 2 to 15. Three groups of endpoints were examined: the ontogeny of sensorimotor responses and serum thyroxine levels in immature animals, and locomotor activity in adult animals. In immature animals, 20 mg/kg/day produced developmental delays in the acquisition of the palpebral reflex. At this age, exposed males also showed a dose-related reduction of serum thyroxine levels. As adults, decaBDE exposure altered the normal sex- and age-specific characteristics of spontaneous locomotor activity. The most striking effect was an increase of activity during the first 1.5 h of the 2 h assessment in males exposed to 20 mg/kg/day decaBDE. These effects suggest that decaBDE is a developmental neurotoxicant that can produce long-term behavioral changes following a discrete period of neonatal exposure.

  12. 4-Methylcoumarin Derivatives Inhibit Human Neutrophil Oxidative Metabolism and Elastase Activity

    PubMed Central

    Fuzissaki, Carolina N.; Andrade, Micássio F.; Azzolini, Ana Elisa C.S.; Taleb-Contini, Silvia H.; Vermelho, Roberta B.; Lopes, João Luis C.; Lucisano-Valim, Yara Maria

    2013-01-01

    Abstract Increased neutrophil activation significantly contributes to the tissue damage in inflammatory illnesses; this phenomenon has motivated the search for new compounds to modulate their effector functions. Coumarins are natural products that are widely consumed in the human diet. We have evaluated the antioxidant and immunomodulator potential of five 4-methylcoumarin derivatives. We found that the 4-methylcoumarin derivatives inhibited the generation of reactive oxygen species by human neutrophils triggered by serum-opsonized zymosan or phorbol-12-myristate-13-acetate; this inhibition occurred in a concentration-dependent manner, as revealed by lucigenin- and luminol-enhanced chemiluminescence assays. Cytotoxicity did not mediate this inhibitory effect. The 7,8-dihydroxy-4-methylcoumarin suppressed the neutrophil oxidative metabolism more effectively than the 6,7- and 5,7-dihydroxy-4-methylcoumarins, but the 5,7- and 7,8-diacetoxy-4-methylcoumarins were less effective than their hydroxylated counterparts. An analysis of the biochemical pathways suggested that the 6,7- and 7,8-dihydroxy-4-methylcoumarins inhibit the protein kinase C-mediated signaling pathway, but 5,7-dihydroxy-4-methylcoumarin, as well as 5,7- and 7,8-diacetoxy-4-methylcoumarins do not significantly interfere in this pathway of the activation of the human neutrophil oxidative metabolism. The 4-methylcoumarin derivatives bearing the catechol group suppressed the elastase and myeloperoxidase activity and reduced the 1,1-diphenyl-2-picrylhydrazyl free radical the most strongly. Interestingly, the 5,7-dihydroxy-4-methylcoumarin scavenged hypochlorous acid more effectively than the o-dihydroxy-substituted 4-methylcoumarin derivatives, and the diacetoxylated 4-methylcoumarin derivatives scavenged hypochlorous acid as effectively as the 7,8-dihydroxy-4-methylcoumarin. The significant influence of small structural modifications in the inhibitory potential of 4-methylcoumarin derivatives on the

  13. Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inuloxins A-D (1-4) and a-costic acid (5), the phytotoxic compounds previously isolated from Inula viscosa, as well as synthetic derivatives of inuloxin A (compounds 6-10), inuloxin C (compound 11) and inuloxin D (compound 12) were tested in vitro for their activity against Leishmania donovani, the ...

  14. Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities

    PubMed Central

    2012-01-01

    Background Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants. Results A large series of tyrosyl esters (TyC2 to TyC18:1) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. Conclusion These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries. PMID:22264330

  15. Synthesis and biological activity of 5-(4-methoxyphenyl)-oxazole derivatives.

    PubMed

    Yamamuro, Daisuke; Uchida, Ryuji; Ohtawa, Masaki; Arima, Shiho; Futamura, Yushi; Katane, Masumi; Homma, Hiroshi; Nagamitsu, Tohru; Osada, Hiroyuki; Tomoda, Hiroshi

    2015-01-15

    5-(4'-Methoxyphenyl)-oxazole (MPO), originally reported as a synthetic compound, was isolated from fungal culture broth as an inhibitor of hatch and growth of Caenorhabditis elegans. Nineteen MPO derivatives were chemically synthesized, but showed no effect on C. elegans hatch and growth. These findings strongly suggested that the whole structure of MPO is essential for anti-C. elegans activity.

  16. Synthesis and larvicidal and adult topical activity of some hydrazide-hydrazone derivatives against Aedes aegypti

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of novel hydrazide-hydrazone derivatives were synthesized and evaluated for their larvicidal and adult topical activity against Aedes aegypti. The proposed structures of all the synthesized compounds were confirmed using elemental analysis, UV, IR, 1H-NMR, 13C-NMR and mass spectroscopy. Com...

  17. Synthesis, crystal structure and larvicidal activity of novel diamide derivatives against Culex pipiens

    PubMed Central

    2012-01-01

    Background Culex is an important mosquito as vectors for the transmission of serious diseases, such as filariasis, West Nile virus, dengue, yellow fever, chikungunya and other encephalitides. Nearly one billion people in the developing countries are at risk. In order to discover new bioactive molecules and pesticides acting on mosquito, we designed active amide structure and synthesized a series of novel diamide derivatives. Results A series of novel diamide derivatives were designed and synthesized. Their structures were characterized by 1 H NMR, FTIR and HRMS. The single crystal structure of compound 6n was determined to further elucidate the structure. Biological activities of these compounds were tested. Most of them exhibited higher mosquito larvicidal activity. Especially compound 6r displayed relatively good activity to reach 70% at 2 μg/mL. Conclusion A practical synthetic route to amide derivatives by the reaction of amide with another acid is presented. This study suggests that the diamide derivatives exhibited good effective against mosquito. PMID:22963735

  18. Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative

    SciTech Connect

    Fernandez, J.P.; Robbe, Y.; Chapat, J.P.; Chanal, J.L.; Genin, M.; Sentenac-Roumanou, H.; Fatome, M.

    1983-09-01

    Molecular biotransformation of 2-phenylthiazolidine (1) and its m-bromo derivative (2) in the mouse is followed by autoradiographic studies and assessed by analysis of urinary metabolites. Cysteamine (4) is one of the metabolites of compounds 1 and 2. Radioprotective activity and efficacy over a period of time of 1, 2, and 4 correlate closely with distribution and metabolism.

  19. Preparation, characterization, and antifungal activity of hymexazol-linked chitosan derivatives

    NASA Astrophysics Data System (ADS)

    Li, Yan; Qin, Yukun; Liu, Song; Li, Pengcheng; Xing, Rong'e.

    2016-09-01

    In this study, three hymexazol-linked chitosan derivatives (HML-CS) were synthesized and their structures confirmed by Fourier transform infrared and elemental analysis. Linkage ratios were measured by high performance liquid chromatography. The derivatives' antifungal activity against the plant pathogenic fungi Rhizoctonia solani CGMCC 3.28 and Gibberella zeae CGMCC 3.42 were investigated at concentrations of 100, 200, and 400 mg/L. These HML-CS derivatives exhibited stronger antifungal activity than CS alone. HML-CS-1 showed the best antifungal activity against G. zeae, whose antifungal index was 65.9% at 400 mg/L, and also showed the best antifungal activity against R. solani, whose antifungal index was 52.7% at 400 mg/L. This conjugation of CS and HML suggested the presence of synergistic effects between the moieties and indicated that these derivatives possessed great potential as novel fungicides and require further research for the development of applications in crop protection.

  20. Fully Employing Software Inspections Data

    NASA Technical Reports Server (NTRS)

    Shull, Forrest; Feldmann, Raimund L.; Seaman, Carolyn; Regardie, Myrna; Godfrey, Sally

    2009-01-01

    Software inspections provide a proven approach to quality assurance for software products of all kinds, including requirements, design, code, test plans, among others. Common to all inspections is the aim of finding and fixing defects as early as possible, and thereby providing cost savings by minimizing the amount of rework necessary later in the lifecycle. Measurement data, such as the number and type of found defects and the effort spent by the inspection team, provide not only direct feedback about the software product to the project team but are also valuable for process improvement activities. In this paper, we discuss NASA's use of software inspections and the rich set of data that has resulted. In particular, we present results from analysis of inspection data that illustrate the benefits of fully utilizing that data for process improvement at several levels. Examining such data across multiple inspections or projects allows team members to monitor and trigger cross project improvements. Such improvements may focus on the software development processes of the whole organization as well as improvements to the applied inspection process itself.

  1. Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.

    PubMed

    Costa, Eduarda C; Cassamale, Tatiana B; Carvalho, Diego B; Bosquiroli, Lauriane S S; Ojeda, Mariáh; Ximenes, Thalita V; Matos, Maria F C; Kadri, Mônica C T; Baroni, Adriano C M; Arruda, Carla C P

    2016-06-20

    Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

  2. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    A large number of 1,2,4-triazole-containing ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system stimulants, antianxiety, and antimicrobial agents. To overcome the rapid development of drug resistance, new agents should preferably have chemical characteristics that clearly differ from those of existing agents. Thus led to the design and synthesize the new antimicrobial agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and substituted benzoic acid and subsequently, treating with substituted benzaldehydes. Seventeen derivatives were synthesized and were biologically screened for antifungal and antibacterial activity. The newly synthesized derivatives of triazole showed antifungal activity against fungal species, Microsporum gypseum; and antibacterial activity against bacterial species, Staphylococcus aureus. It was observed that none of the compounds tested showed positive results for fungi Candida albicans fungi Aspergillus niger, nor against bacterial strain Escherichia coli. Strong antifungal effects were obtained for the synthesized compounds against M. gypseum and were superior or comparable to standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit strong antibacterial activity against S. aureus and were superior or comparable to standard drug streptomycin. It was found that among the triazole derivatives so synthesized, six of them, showed antifungal activity superior to ketoconazole while one of them, showed antibacterial activity superior to streptomycin. Thus, these can be the potential new molecule as an antimicrobial agent. PMID:26317080

  3. Relation between molecular electrostatic potential, several electronic properties and antibacterial activity of some synthetic furane derivatives

    NASA Astrophysics Data System (ADS)

    Monasterios, Melina; Avendaño, Milagros; Amaro, María Isabel; Infante, Wilson; Charris, Jaime

    2006-10-01

    The present work reports the preliminary evaluation of the antibacterial activity, molecular electrostatic potential (MEP) determination and relevant electronic properties for their behavior as one electron acceptor, of a serial of compounds, active and inactive analogues, derived form furan, that were previously synthesized within our investigation group, with the purpose of establishing the existence of a valid correlation between their antibacterial activity and those electrostatic and electronic properties. According to the balance between the positive and negative areas in combination with the size of the MEP's area it was determined that these derivatives exhibit activity against Gram-positive and Gram-negative bacteria or only against Gram-positive ones. We found no valid correlation between the single point energy, the energy associated to the lowest unoccupied molecular orbital (LUMO); LUMO's density, nucleophilic susceptibility, Log P and the dipole moment, with the experimental activity determined for them. This could be because this is an homologous serial where the properties derived from the electronic distribution just change between those molecules that have a nitro group (active) in contrast with those wherein this group is absent (inactive).

  4. Efficient heterologous expression and one-step purification of fully active c-terminal histidine-tagged uridine monophosphate kinase from Mycobacterium tuberculosis.

    PubMed

    Penpassakarn, Praweenuch; Chaiyen, Pimchai; Palittapongarnpim, Prasit

    2011-11-01

    Tuberculosis has long been recognized as one of the most significant public health problems. Finding novel antituberculous drugs is always a necessary approach for controlling the disease. Mycobacterium tuberculosis pyrH gene (Rv2883c) encodes for uridine monophosphate kinase (UMK), which is a key enzyme in the uridine nucleotide interconversion pathway. The enzyme is essential for M. tuberculosis to sustain growth and hence is a potential drug target. In this study, we have developed a rapid protocol for production and purification of M. tuberculosis UMK by cloning pyrH (Rv2883c) of M. tuberculosis H37Rv with the addition of 6-histidine residues to the C-terminus of the protein, and expressing in E. coli BL21-CodonPlus (DE3)-RIPL using an auto-induction medium. The enzyme was efficiently purified by a single-step TALON cobalt affinity chromatography with about 8 fold increase in specific activity, which was determined by a coupled assay with the pyruvate kinase and lactate dehydrogenase. The molecular mass of monomeric UMK was 28.2 kDa and that of the native enzyme was 217 kDa. The enzyme uses UMP as a substrate but not CMP and TMP and activity was enhanced by GTP. Measurements of enzyme kinetics revealed the kcat value of 7.6 +/- 0.4 U mg(-1) or 0.127 +/- 0.006 sec(-1).The protocol reported here can be used for expression of M. tuberculosis UMK in large quantity for formulating a high throughput target-based assay for screening anti-tuberculosis UMK compounds.

  5. High antitumor activity of pladienolide B and its derivative in gastric cancer.

    PubMed

    Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji

    2014-01-01

    The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.

  6. High antitumor activity of pladienolide B and its derivative in gastric cancer

    PubMed Central

    Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji

    2014-01-01

    The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6–4.0) and 1.2 ± 1.1 (range, 0.4–3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction. PMID:24635824

  7. Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity.

    PubMed

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

    2015-03-01

    There are several reports which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action of steroid derivatives at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, two dihydrotestosterone derivatives (compounds 5 and 10) were synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. In the first stage, 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 steroid derivatives. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the compound 5 was evaluated by measuring left ventricular pressure in absence or presence of following compounds; nifedipine, flutamide, indomethacin, prazosin, isoproterenol, propranolol and metoprolol. The results showed that the compound 5 significantly increased the perfusion pressure and coronary resistance in comparison with dihydrotestosterone, compound 10 and the control conditions. Other data indicate that 5 increase left ventricular pressure in a dose-dependent manner (0.001-100 nM); nevertheless, this phenomenon was significantly inhibited only by propranolol or metoprolol at a dose of 1 nM. These data suggest that positive inotropic activity induced by the compound 5 is through β1-adrenergic receptor however, this effect was independent of cAMP levels. 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.

  8. Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives.

    PubMed

    Song, Zi-Long; Wang, Mei-Juan; Li, Lanlan; Wu, Dan; Wang, Yu-Han; Yan, Li-Ting; Morris-Natschke, Susan L; Liu, Ying-Qian; Zhao, Yong-Long; Wang, Chih-Ya; Liu, Huanxiang; Goto, Masuo; Liu, Heng; Zhu, Gao-Xiang; Lee, Kuo-Hsiung

    2016-06-10

    In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure-activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π-π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.

  9. The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.

    PubMed

    Zhu, Wenjun; Frost, Emma E; Begum, Farhana; Vora, Parvez; Au, Kelvin; Gong, Yuewen; MacNeil, Brian; Pillai, Prakash; Namaka, Mike

    2012-08-01

    Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase. Recent studies alongside current treatment strategies, including glatiramer acetate, have revealed a potential role for brain-derived neurotrophic factor (BDNF) in MS. However, the exact role of BDNF is not fully understood. We used the experimental autoimmune encephalomyelitis (EAE) model of MS in adolescent female Lewis rats to identify the role of BDNF in disease progression. Dorsal root ganglia (DRG) and spinal cords were harvested for protein and gene expression analysis every 3 days post-disease induction (pdi) up to 15 days. We show significant increases in BDNF protein and gene expression in the DRG of EAE animals at 12 dpi, which correlates with peak neurological disability. BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi. However, there was no significant change in mRNA levels. We show evidence for the anterograde transport of BDNF protein from the DRG to the dorsal horn of the spinal cord via the dorsal roots. Increased levels of BDNF within the DRG and spinal cord in EAE may facilitate myelin repair and neuroprotection in the CNS. The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.

  10. Novel derivatives of monascus pigment having a high CETP inhibitory activity.

    PubMed

    Jang, Heeyoung; Choe, Deokyeong; Shin, Chul Soo

    2014-01-01

    The cholesteryl ester transfer protein (CETP), inhibition of which assists in maintaining a high level of high-density lipoprotein cholesterol in the blood, is a target for anti-atherosclerosis treatments. Orange monascus pigment was produced by a Monascus species in a 5 L jar fermenter and various derivative compounds were synthesised by incorporating 19 different L-amino acids into the orange pigment. Among them, the L-Thr and L-Tyr derivatives exhibited high inhibitory activities against the CETP reaction. The inhibitory activities of the L-Thr and L-Tyr derivatives increased in a dose-dependent manner, resulting in IC50 values of 1.0 and 2.3 μM, respectively. When CETP reactions in the presence of the derivatives were performed, the inhibition modes of the L-Thr and L-Tyr derivatives were non-competitive with inhibition constant (Ki) values of 2.7 and 4.3 μM, respectively.

  11. Anticancer Activity of Estradiol Derivatives: A Quantitative Structure--Activity Relationship Approach

    NASA Astrophysics Data System (ADS)

    Muranaka, Ken

    2001-10-01

    Commercial packages to implement modern QSAR (quantitative structure-activity relationship) techniques are highly priced; however, the essence of QSAR can be taught without them. Microsoft Excel was used to analyze published data on anticancer activities of estradiol analogs by a QSAR approach. The resulting QSAR equations highly correlate the structural features and physicochemical properties of the analogs with the observed biological activities by multiple linear regression.

  12. Antiarrhythmic activity of some xanthone derivatives with β1-adrenoceptor affinities in rats.

    PubMed

    Rapacz, Anna; Sapa, Jacek; Bednarski, Marek; Filipek, Barbara; Szkaradek, Natalia; Marona, Henryk

    2014-09-05

    A series of aminoalkanolic derivatives of xanthone with high affinity for β1-adrenoceptors was evaluated for antiarrhythmic activity in the model of ischemia-reperfusion in isolated hearts, as well as in barium chloride- and adrenaline-induced model of arrhythmia. In order to better understand biological activity of studied compounds, the influence on β2-adrenoceptors in guinea-pig trachea and vasorelaxant properties in rat aorta were evaluated. Furthermore, due to assessed antioxidant activity, some biochemical studies were also performed. All tested compounds showed prominent antiarrhythmic activity in the model of ventricular arrhythmias associated with coronary artery occlusion and reperfusion. In this experiment the most active was compound MH-97. Whereas, compound MH-82 was the most active in barium- and adrenaline-induced arrhythmia after i.v. or p.o. administration, respectively. These two compounds have higher affinity to β1-adrenoceptors than compound MH-87, thus it suggests that blocking properties of β1-adrenoceptors are involved in the observed antiarrhythmic effects. All studied compounds have revealed antagonistic potency for β2-adrenoceptors in tracheal smooth muscle, however weaker than that of propranolol. None of tested compounds demonstrated antioxidant effect. They also had weak calcium entry blocking activity. The results of this study suggest that new compounds with antiarrhythmic activity might be found in the group of xanthone derivatives.

  13. Fully Grouted Rock Bolts: An Analytical Investigation

    NASA Astrophysics Data System (ADS)

    He, L.; An, X. M.; Zhao, Z. Y.

    2015-05-01

    This paper analytically investigates the performance of fully grouted rock bolts in typical scenarios, including pullout test, suspending loosened block, and increasing joint aperture, respectively. The interface shear stress distribution follows the model proposed by Li and Stillborg (Int J Rock Mech Mining Sci 36:1013-1029, 1999), while the axial behavior of the bolt shank obeys the elasto-plastic (yielding-hardening) constitutive model of steel. Three different failure modes are taken into account: tensile failure of bolt shank, bolt shank being pulled out along the bolt/rock interface, and loss of face plate. The evolution of the interface shear stress and the axial tensile stress are examined for both long and short bolts under displacement and load boundary conditions. The derived charts are able to predict the load capacity of fully grouted bolts in pullout test, the minimum length requirement of the bolt to suspend a loosened block, and the maximum allowed opening displacement of a rock joint for a fully grouted bolt. In addition, different potential failure modes are specified. Full range load-displacement curves are produced and compared for various failure modes. The derived charts could be directly used in rock-bolting design.

  14. Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity

    PubMed Central

    2013-01-01

    Background Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option. Results A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 μg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops. Conclusions Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies. PMID:23409923

  15. Novel hydrazone derivatives containing pyridine amide moiety: Design, synthesis, and insecticidal activity.

    PubMed

    Yang, Zai-Bo; Hu, De-Yu; Zeng, Song; Song, Bao-An

    2016-02-15

    A series of novel hydrazone derivatives containing pyridine amide moiety were designed, synthesized, and evaluated for their insecticidal activity. Bioassays indicated that some of the target compounds exhibited good insecticidal activities against Nilaparvata lugens (N. lugens), Plutella xylostella (P. xylostella), Mythimna separata (M. separata), Helicoverpa armigera (H. armigera), Pyrausta nubilalis (P. nubilalis), and Culex pipiens pallens (C. pipiens pallens). In particular, compound 5j revealed excellent insecticidal activity against C. pipiens pallens, with the 50% lethal concentration (LC50) and the 95% lethal concentration (LC95) values of 2.44 and 5.76 mg/L, respectively, which were similar to those of chlorpyrifos (3.26 and 6.98 mg/L, respectively), tebufenozide (1.22 and 2.49 mg/L, respectively), and RH-5849 (2.61 and 6.37 mg/L, respectively). These results indicated that hydrazone derivatives containing pyridine amide moiety could be developed as novel and promising insecticides.

  16. New pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity.

    PubMed

    Carvalho, Rita C C; Martins, Wagner A; Silva, Tayara P; Kaiser, Carlos R; Bastos, Mônica M; Pinheiro, Luiz C S; Krettli, Antoniana U; Boechat, Núbia

    2016-04-15

    Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)n=2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n=4 and 7-chloroquinolinyl has displayed better activity (IC50=0.40 μM) than chloroquine. The primaquine derivative showed IC50=1.41 μM, being less toxic and more active than primaquine.

  17. Electrochemical synthesis of novel 1,3-indandione derivatives and evaluation of their antiplatelet aggregation activities.

    PubMed

    Amidi, Salimeh; Kobarfard, Farzad; Bayandori Moghaddam, Abdolmajid; Tabib, Kimia; Soleymani, Zohreh

    2013-01-01

    Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1,3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1,3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1,3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway.

  18. Electrochemical Synthesis of Novel 1,3-Indandione Derivatives and Evaluation of Their Antiplatelet Aggregation Activities

    PubMed Central

    Amidi, Salimeh; Kobarfard, Farzad; Bayandori Moghaddam, Abdolmajid; Tabib, Kimia; Soleymani, Zohreh

    2013-01-01

    Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1,3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1,3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1,3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway. PMID:24250677

  19. Synthesis, molecular docking and antiamnesic activity of selected 2- naphthyloxy derivatives.

    PubMed

    Piplani, Poonam; Singh, Paramveer; Sharma, Anuradha

    2013-05-01

    The present paper describes the design and synthesis of a series of some 2-naphthyloxy derivatives with their antiamnesic activity using mice as the animal model and piracetam as the reference drug. All the synthesized compounds were characterized by spectroscopic techniques and were screened for their efficacy as cognition enhancers by elevated plus maze test and acetylcholinestrase inhibitory assay. Molecular modeling and docking studies of the selected compounds into the crystal structure of acetylcholinestrase complexed with functional ligand succinylcholine using GRAMM software was performed in order to predict the affinity and orientation of the synthesized derivatives at the active site. The binding energy of ligands was calculated using ArgusLab software. The docking score and hydrogen bonds formed with surrounding amino acids show the good agreement with predicted binding affinities obtained by molecular docking studies, as verified by acetylcholinestrase activity.

  20. Synthesis and insect antifeedant activity of precocene derivatives with lactone moiety.

    PubMed

    Szczepanik, Maryla; Obara, Robert; Szumny, Antoni; Gabryś, Beata; Halarewicz-Pacan, Aleksandra; Nawrot, Jan; Wawrzeńczyk, Czesław

    2005-07-27

    Starting from precocenes I and II, four of their derivatives with a lactone moiety were obtained. The compounds have been assessed as antifeedants against several diverse insect species including the storage pests the confused flour beetle (Tribolium confusum Duv., larvae and adults), the granary weevil beetle (Sitophilus granarius L., adults), and the khapra beetle (Trogoderma granarium Ev., larvae) and against the herbivorous pest insects Colorado potato beetle (Leptinotarsa decemlineata Say, adults and larvae) and aphids (Myzus persicae Sulz.). Precocenes, especially precocene II, showed a very strong antifeedant effect against all storage pests and aphids. The introduction of a lactone moiety caused a decrease in antifeedant activity against these species. Both precocenes were moderately active against L. decemlineata adults. The best antifeedants to this species were precocene derivatives, especially iodolactones. The introduction of iodine into a molecule had a great effect on the antifeedant activity of those compounds.

  1. Quinic acid derivatives from Pimpinella brachycarpa exert anti-neuroinflammatory activity in lipopolysaccharide-induced microglia.

    PubMed

    Lee, Seung Young; Moon, Eunjung; Kim, Sun Yeou; Lee, Kang Ro

    2013-04-01

    Five new quinic acid derivatives (1-5), together with 10 known quinic acid derivatives (6-15), were isolated from the MeOH extract of Pimpinella brachycarpa (Umbelliferae). Their structures were established on the basis of spectroscopic analyses including extensive 2D NMR studies (COSY, HMQC and HMBC). Isolated compounds 1-15 were evaluated for their inhibitory activities on nitric oxide (NO) production in an activated murine microglial cell line. Compounds 2, 3, 8 and 11 significantly inhibited NO production without high cell toxicity in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cell line (IC50=4.66, 12.52, 9.04 and 12.11 μM, respectively).

  2. Antimicrobial Activity of Chitosan Derivatives Containing N-Quaternized Moieties in Its Backbone: A Review

    PubMed Central

    Martins, Alessandro F.; Facchi, Suelen P.; Follmann, Heveline D. M.; Pereira, Antonio G. B.; Rubira, Adley F.; Muniz, Edvani C.

    2014-01-01

    Chitosan, which is derived from a deacetylation reaction of chitin, has attractive antimicrobial activity. However, chitosan applications as a biocide are only effective in acidic medium due to its low solubility in neutral and basic conditions. Also, the positive charges carried by the protonated amine groups of chitosan (in acidic conditions) that are the driving force for its solubilization are also associated with its antimicrobial activity. Therefore, chemical modifications of chitosan are required to enhance its solubility and broaden the spectrum of its applications, including as biocide. Quaternization on the nitrogen atom of chitosan is the most used route to render water-soluble chitosan-derivatives, especially at physiological pH conditions. Recent reports in the literature demonstrate that such chitosan-derivatives present excellent antimicrobial activity due to permanent positive charge on nitrogen atoms side-bonded to the polymer backbone. This review presents some relevant work regarding the use of quaternized chitosan-derivatives obtained by different synthetic paths in applications as antimicrobial agents. PMID:25402643

  3. Inhibitory and Activating Effects of Some Flavonoid Derivatives on Human Pyruvate Kinase Isoenzyme M2.

    PubMed

    Adem, Sevki; Aslan, Abdulselam; Ahmed, Ishtiaq; Krohn, Karsten; Guler, Caglar; Comaklı, Veysel; Demirdag, Ramazan; Kuzu, Muslum

    2016-02-01

    Pyruvate kinase isoenzyme M2 (PKM2) is expressed excessively in many different cancer types and it plays an important role in the control of glucose metabolism. Thus, it is evaluated as an important target in the development of medication for cancer. The flavonoids comprise a large group of natural products with variable phenolic structures and occur mainly in plants. They are of great interest due to their biological properties. In this study, the effects of various flavonoid derivatives on the PKM2 enzyme activity were analyzed in vitro. The flavonoid derivatives 1 and 2 showed inhibition effect with IC50 values of <60 μM. IC50 values of compounds 3-8 were calculated as 134, 415, 145, 163, 295 μM, and 3.5 mM, respectively. The molecules 9-12 showed an activation effect with values of AC50 of less than 90 μM. The IC50 values of the derivatives 13-17 were calculated as 115, 150, 200, 221, and 275 μM, respectively. The results show that catechin derivatives can be probably used as lead compounds for the design of PKM2 enzyme activators and inhibitors.

  4. Immobilization of Zidovudine Derivatives on the SBA-15 Mesoporous Silica and Evaluation of Their Cytotoxic Activity.

    PubMed

    Lewandowski, Dawid; Lewandowska, Marta; Ruszkowski, Piotr; Pińska, Anita; Schroeder, Grzegorz

    2015-01-01

    Novel zidovudine derivatives, able to be covalently conjugated to silica surface, have been obtained and grafted to SBA-15 mesoporous silica. Cytotoxic activity of the hybrid organic-inorganic (zidovudine derivatives-silica) systems against HeLa and KB cell lines has been analyzed. Addition of folic acid had a positive influence on the cytotoxicity. Up to 69% of HeLa and 65% of KB tumor cells growth inhibition has been achieved at low silica concentration used (10 μg/mL).

  5. Identification and structure-activity relationship study of carvacrol derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors.

    PubMed

    Alokam, Reshma; Jeankumar, Variam Ullas; Sridevi, Jonnalagadda Padma; Matikonda, Siddharth Sai; Peddi, Santosh; Alvala, Mallika; Yogeeswari, Perumal; Sriram, Dharmarajan

    2014-08-01

    In the present study, we identified carvacrol, a major phenolic component of oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06 ± 0.4 µM. Virtual screening of the BITS-Pilani in-house database using the crystal structure of the MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified carvacrol as a potential lead. Further various carvacrol derivatives were evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and cytotoxicity as steps toward the derivation of structure-activity relationships (SAR) and lead optimization.

  6. Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators

    PubMed Central

    2013-01-01

    Adenosine 5′-monophosphate-activated protein kinase (AMPK) is emerging as a promising drug target for its regulatory function in both glucose and lipid metabolism. Compound PT1 (5) was originally identified from high throughput screening as a small molecule activator of AMPK through the antagonization of the autoinhibition in α subunits. In order to enhance its potency at AMPK and bioavailability, structure–activity relationship studies have been performed and resulted in a novel series of AMPK activators based on an alkene oxindole scaffold. Following their evaluation in pharmacological AMPK activation assays, lead compound 24 was identified to possess improved potency as well as favorable pharmacokinetic profile. In the diet-induced obesity (DIO) mouse model, compound 24 was found to improve glucose tolerance and alleviate insulin resistance. The in vitro and in vivo data for these alkene oxindoles warrant further studies for their potential therapeutic medications in metabolic associated diseases. PMID:24900695

  7. Synthesis and Biological Activity of 3-N-Substituted Estrogen Derivatives as Breast Cancer Agents

    PubMed Central

    Wan, Zhongliang; Musa, Musiliyu A; Joseph, Patrick; Cooperwood, John S.

    2013-01-01

    3-N-substituted-estrogen derivatives were synthesized and characterized. Their antiproliferative activities against human ER (+) MCF-7 (Breast), ER (−) MDA-MB-231 (breast) and Ishikawa (endometrial) cancer cell lines were determined after 72 hours drug exposure employing CellTiter-Glo assay at concentrations ranging from (0.01-100,000 nM). The antiproliferative activities of these compounds were compared to tamoxifen (TAM), 4-hydroxytamoxifen (4-OHT, active metabolite of tamoxifen) and raloxifene (RAL). In vitro results indicated that compound 5 (IC50 = 12μM) displayed comparable antiproliferative activity against MDA-MB 231 cell line; while compounds 6, 7 and 13 (IC50 = 12μM) displayed higher activity against MCF-7 and Ishikawa cell lines, in comparison to TAM activity (19-33μM). PMID:22876946

  8. Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives.

    PubMed

    Wang, Xuesong; Gao, Sumei; Yang, Jian; Gao, Yang; Wang, Ling; Tang, Xiaorong

    2016-01-01

    A series of heterocycle containing amide derivatives (1-28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim.

  9. Synthesis and antibacterial activities of some novel 17, 18-unsaturated carbonyl compounds derivated from josamycin.

    PubMed

    Zhao, Zhe-Hui; Jin, Long-Long; Xu, Yan-Peng; Liu, Chao; Wang, A-Peng; Lei, Ping-Sheng

    2017-04-01

    Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.

  10. The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: modifications at C12 and C7.

    PubMed

    Zhang, Wen-Ming; Yang, Teng; Pan, Xue-Ying; Liu, Xin-Lan; Lin, Hai-Xia; Gao, Zhao-Bing; Yang, Cai-Guang; Cui, Yong-Mei

    2017-02-15

    A series of 7-N-acylaminoethyl/propyloxime derivatives of dehydroabietic acid were synthesized and investigated for their antibacterial activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having trifluoromethyl phenyl/benzyl, halogen-substituted thiophenyl, benzothiophenyl or pyrrolyl moiety exhibited potent in vitro antibacterial activity. Among which, compounds 4m, 4x and 7j showed high antibacterial activity with minimum inhibitory concentration (MIC) values of 1.25-3.13 μg/mL against five multidrug-resistant S. aureus.

  11. Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators.

    PubMed

    Mao, Weiwei; Ning, Mengmeng; Liu, Zhiqing; Zhu, Qingzhang; Leng, Ying; Zhang, Ao

    2012-05-01

    A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.

  12. Structure-activity relationships of receptor binding of 1,4-dihydropyridine derivatives.

    PubMed

    Takahashi, Daiki; Oyunzul, Luvsandorj; Onoue, Satomi; Ito, Yoshihiko; Uchida, Shinya; Simsek, Rahime; Gunduz, Miyase Gozde; Safak, Chiat; Yamada, Shizuo

    2008-03-01

    The present study was undertaken to investigate binding activity of synthesized 1,4-dihydropyridine (1,4-DHP) derivatives (Compounds 1--124) to 1,4-DHP calcium channel antagonist receptors in rat brain. Sixteen 1,4-DHP derivatives inhibited specific (+)-[3H]PN 200-110 binding in rat brain in a concentration-dependent manner with IC50 value of 0.43 to 3.49 microM. Scatchard analysis revealed that compounds 54, 69, 85, like nifedipine, caused a significant increase in apparent dissociation constant (Kd) for (+)-[3H]PN 200-110, while compounds 68, 69 and 80 caused a significant decrease in maximal number of bindings sites (Bmax). These data suggest that compounds 68, 69 and 80 exert longer-acting antagonistic effects of 1,4-DHP receptors than compounds 54, 69 and 85. The structure-activity relationship study has revealed that 1) ester groups in 3- and 5-positions are the most effective, 2) the aryl group in the 4-position of 1,4-DHP ring is the basic requirement for optimal activity, 3) position and type of electron-withdrawing groups on phenyl group at position 4 would affect the receptor-binding activity. Furthermore, compound 58 exerted alpha1 receptor binding activity, being 1.6 times greater than 1,4-DHP receptors. Compounds 81, 84, 91, 94, 106, 108 and 109 showed significant binding of ATP-sensitive potassium (K ATP) channel, and the binding activities of compounds 81, 84, 108 and 109 were 1.6--3.8 times greater than the binding activity for 1,4-DHP receptors. Compounds 91 and 106 had similar binding activity for K ATP channel and 1,4-DHP receptors. In conclusion, the present study has shown that novel 1,4-DHP derivatives exert relatively high binding affinity to 1,4-DHP receptors and has revealed new aspect of structure-activity relationships of 1,4-DHP derivatives, especially hexahydroquinoline derivatives.

  13. Antileishmanial activity of semisynthetic lupane triterpenoids betulin and betulinic acid derivatives: synergistic effects with miltefosine.

    PubMed

    Sousa, Maria C; Varandas, Raquel; Santos, Rita C; Santos-Rosa, Manuel; Alves, Vera; Salvador, Jorge A R

    2014-01-01

    Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries, affecting more than 12 million people. The treatment consists in pentavalent antimony compounds, amphotericin B, pentamidine and miltefosine, among others. However, these current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, it is important to continue the search for new effective and less toxic treatments. The anti-Leishmania activity of sixteen semisynthetic lupane triterpenoids derivatives of betulin (BT01 to BT09) and betulinic acid (AB10 to AB16) were evaluated. Drug interactions between the active compounds and one current antileishmanial drug, miltefosine, were assessed using the fixed ratio isobologram method. In addition, effects on the cell cycle, apoptosis/necrosis events, morphology and DNA integrity were studied. The derivatives BT06 (3β-Hydroxy-(20R)-lupan-29-oxo-28-yl-1H-imidazole-1-carboxylate) and AB13 (28-(1H-imidazole-1-yl)-3,28-dioxo-lup-1,20(29)-dien-2-yl-1H-imidazole-1-carboxylate) were found to be the most active, with IC50 values of 50.8 µM and 25.8 µM, respectively. Interactions between these two compounds and miltefosine were classified as synergistic, with the most effective association being between AB13 and miltefosine, where decreases of IC50 values to 6 µM were observed, similar to the miltefosine activity alone. AB13 induced significant morphological changes, while both derivatives produced anti-proliferative activity through cell cycle arrest at the G0/G1 phase. Neither of these derivatives induced significant apoptosis/necrosis, as indicated by phosphatidylserine externalization and DNA fragmentation assays. In addition, neither of the derivatives induced death in macrophage cell lines. Thus, they do not present any potential risk of toxicity for the host cells. This study has identified the betulin derivative BT06 and the betulinic acid derivative AB13 as promising molecules

  14. Synthesis of optically active N-(2-pyridyloxiran-2-ylmethyl) benzenesulfonamide derivatives and their herbicidal activity.

    PubMed

    Hosokawa, A; Katsurada, M; Ikeda, O; Minami, N; Jikihara, T

    2001-07-01

    Novel herbicidally active sulfonamide compounds having a 2-arylsubstituted oxiranylmethyl structure are racemates due to a chiral carbon in the oxirane moiety. To clarify the stereochemical structure-activity relationship, we synthesized each enantiomer of 4-chloro-N-[2-(6-chloropyridin-2-yl)-2-oxiran-2-ylmethyl]-3,N-dimethylbenzenesulfonamide and N-[2-(6-chloropyridin-2-yl)-2-oxiran-2-ylmethyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-2-sulfonamide by chemical methods including Sharpless asymmetric chlorohydroxylation. The results of herbicidal tests indicated that the (S)-isomers were the active forms.

  15. Assessment of multifunctional activity of bioactive peptides derived from fermented milk by specific Lactobacillus plantarum strains.

    PubMed

    Aguilar-Toalá, J E; Santiago-López, L; Peres, C M; Peres, C; Garcia, H S; Vallejo-Cordoba, B; González-Córdova, A F; Hernández-Mendoza, A

    2017-01-01

    Milk-derived bioactive peptides with a single activity (e.g., antioxidant, immunomodulatory, or antimicrobial) have been previously well documented; however, few studies describe multifunctional bioactive peptides, which may be preferred over single-activity peptides, as they can simultaneously trigger, modulate, or inhibit multiple physiological pathways. Hence, the aim of this study was to assess the anti-inflammatory, antihemolytic, antioxidant, antimutagenic, and antimicrobial activities of crude extracts (CE) and peptide fractions (<3 and 3-10 kDa) obtained from fermented milks with specific Lactobacillus plantarum strains. Overall, CE showed higher activity than both peptide fractions (<3 and 3-10 kDa) in most of the activities assessed. Furthermore, activity of <3 kDa was generally higher, or at least equal, to the 3 to 10 kDa peptide fractions. In particular, L. plantarum 55 crude extract or their fractions showed the higher anti-inflammatory (723.68-1,759.43μg/mL of diclofenac sodium equivalents), antihemolytic (36.65-74.45% of inhibition), and antioxidant activity [282.8-362.3µmol of Trolox (Sigma-Aldrich, St. Louis, MO) equivalents]. These results provide valuable evidence of multifunctional role of peptides derived of fermented milk by the action of specific L. plantarum strains. Thus, they may be considered for the development of biotechnological products to be used to reduce the risk of disease or to enhance a certain physiological function.

  16. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    PubMed

    Bialek, Julia K; Dunay, Gábor A; Voges, Maike; Schäfer, Carola; Spohn, Michael; Stucka, Rolf; Hauber, Joachim; Lange, Ulrike C

    2016-01-01

    CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs), act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR), for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  17. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems

    PubMed Central

    Bialek, Julia K.; Dunay, Gábor A.; Voges, Maike; Schäfer, Carola; Spohn, Michael; Stucka, Rolf; Hauber, Joachim; Lange, Ulrike C.

    2016-01-01

    CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs), act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5’ long terminal repeat (LTR), for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination. PMID:27341108

  18. Synthesis and antifungal activity of 2H-1,4-benzoxazin-3(4H)-one derivatives.

    PubMed

    Śmist, Małgorzata; Kwiecień, Halina; Krawczyk, Maria

    2016-01-01

    A series of 2-alkyl-2H-1,4-benzoxazin-3(4H)-ones (4a-l) was easily synthesized by two-step process involving O-alkylation of 2-nitrophenols with methyl 2-bromoalkanoates and next "green" catalytic reductive cyclization of the obtained 2-nitro ester intermediates (3a-l). Further, 6,7-dibromo (5a-c) and N-acetyl (6) derivatives were prepared by bromination and acetylation of unsubstituted 2-alkyl-2H-1,4-benzoxazin-3(4H)-ones (4a-c). The novel compounds (3a-l, 4d-l, 5a-c and 6) were fully characterized by spectroscopic methods (MS, (1)H and (13)C NMR). 2-Alkyl-2H-1,4-benzoxazin-3(4H)-ones (4a-l, 5a-c and 6) were screened for antifungal activity. Preliminary assays were performed using two methods: in vitro against seven phytopathogenic fungi-Botrytis cinerea, Phythophtora cactorum, Rhizoctonia solani, Phoma betae, Fusarium culmorum, Fusarium oxysporum and Alternaria alternata-and in vivo against barley powdery mildew Blumeria graminis. The tested compounds displayed moderate to good antifungal activity at high concentration (200 mg L(-1)). The most potent compounds were 2-ethyl-2H-1,4-benzoxazin-3(4H)-one (4a), 2-ethyl-7-fluoro-2H-1,4-benzoxazin-3(4H)-one (4g) and 4-acetyl-2-ethyl-2H-1,4-benzoxazin-3(4H)-one (6), which completely inhibited the mycelial growth of seven agricultural fungi at the concentration of 200 mg L(-1) in the in vitro tests. Moreover, 2-ethyl-2H-1,4-benzoxazin-3(4H)-one (4a) and 4-acetyl-2-ethyl-2H-1,4-benzoxazin-3(4H)-one (6) were also screened for antifungal activity at concentrations of 100 mg L(-1) and 20 mg L(-1). In the concentration of 100 mg L(-1), the N-acetyl derivative (6) completely inhibited the growth of three strains of fungi (F. culmorum, P. cactorum and R. solani), while 2-ethyl-2H-1,4-benzoxazin-3(4H)-one (4a) completely inhibited only R. solani strain. At the concentration of 20 mg L(-1), compound 6 showed good activity only against P. cactorum strain (72%).

  19. Soluble Epoxide Hydrolase Inhibitory Activity of Selaginellin Derivatives from Selaginella tamariscina.

    PubMed

    Kim, Jang Hoon; Cho, Chong Woon; Tai, Bui Huu; Yang, Seo Young; Choi, Gug-Seoun; Kang, Jong Seong; Kim, Young Ho

    2015-12-02

    Selaginellin derivatives 1-3 isolated from Selaginella tamariscina were evaluated for their inhibition of soluble epoxide hydrolase (sEH) to demonstrate their potential for the treatment of cardiovascular disease. All selaginellin derivatives (1-3) inhibited sEH enzymatic activity and PHOME hydrolysis, in a dose-dependent manner, with IC50 values of 3.1 ± 0.1, 8.2 ± 2.2, and 4.2 ± 0.2 μM, respectively. We further determined that the derivatives function as non-competitive inhibitors. Moreover, the predicted that binding sites and interaction between 1-3 and sEH were solved by docking simulations. According to quantitative analysis, 1-3 were confirmed to have high content in the roots of S. tamariscina; among them, selaginellin 3 exhibited the highest content of 189.3 ± 0.0 μg/g.

  20. Monoterpene derivatives with anti-allergic activity from red peony root, the root of Paeonia lactiflora.

    PubMed

    Shi, Yan-Hong; Zhu, Shu; Ge, Yue-Wei; He, Yu-Min; Kazuma, Kohei; Wang, Zhengtao; Yoshimatsu, Kayo; Komatsu, Katsuko

    2016-01-01

    The methanolic extract and its subfractions from red peony root, the dried roots of Paeonia lactiflora Pallas showed potent antiallergic effects, as inhibition of immunoglobulin E (IgE)-mediated degranulation in rat basophil leukemia (RBL)-2H3 cells. Bioassay-guided fractionation led to the isolation of 16 monoterpene derivatives, including 3 new compounds, paeoniflorol (1), 4'-hydroxypaeoniflorigenone (2) and 4-epi-albiflorin (3), together with 13 known ones (4-16). The chemical structures of the new compounds were elucidated on the basis of spectroscopic and chemical evidences. Among the isolated monoterpene derivatives, nine compounds showed potent anti-allergic effects and compound 1 was the most effective. A primary structure-activity relationship of monoterpene derivatives was discussed.

  1. Potent and selective MAO-B inhibitory activity: amino- versus nitro-3-arylcoumarin derivatives.

    PubMed

    Matos, Maria João; Rodríguez-Enríquez, Fernanda; Vilar, Santiago; Santana, Lourdes; Uriarte, Eugenio; Hripcsak, George; Estrada, Martín; Rodríguez-Franco, María Isabel; Viña, Dolores

    2015-02-01

    In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B.

  2. Design, synthesis, antimicrobial activity and molecular modeling studies of novel benzofuroxan derivatives against Staphylococcus aureus.

    PubMed

    Jorge, Salomão Dória; Masunari, Andrea; Rangel-Yagui, Carlota Oliveira; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa

    2009-04-15

    Molecular modification is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N'-(benzofuroxan-5-yl)methylene]benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological profile. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 microg/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates.

  3. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

    PubMed

    Gaballah, Samir T; El-Nezhawy, Ahmed O H; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas

    2016-01-01

    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

  4. Synthesis of novel polybrominated benzimidazole derivatives-potential CK2 inhibitors with anticancer and proapoptotic activity.

    PubMed

    Łukowska-Chojnacka, Edyta; Wińska, Patrycja; Wielechowska, Monika; Poprzeczko, Martyna; Bretner, Maria

    2016-02-15

    The efficient method for the synthesis of novel cell permeable inhibitors of protein kinase CK2 with anticancer and proapoptotic activity has been developed. A series of polybrominated benzimiadazole derivatives substituted by various cyanoalkyl groups have been synthesized. Cyanoethyl derivatives were obtained by Michael type addition of 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole to acrylonitrile, whilst cyanomethyl, cyanopropyl and cyanobutyl analogs by N-alkylation of 4,5,6,7-tetrabromo-1H-benzimidazole and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole with appropriate cyanoalkyl halides. The inhibitory activity against protein kinase rhCK2α catalytic subunit and cytotoxicity against two human cancer cell lines: acute lymphocytic leukemia (CCRF-CEM) and breast (MCF-7) were evaluated for all newly synthesized compounds. Additionally, the proapoptotic activity toward leukemia cells and intracellular inhibition of CK2 for the most cytotoxic derivatives have been performed, demonstrating 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole as a new selective inhibitor of rhCK2 with twenty-fold better proapoptotic activity than parental compound (TBBi).

  5. Thermogenic activity of UCP1 in human white fat-derived beige adipocytes.

    PubMed

    Bartesaghi, Stefano; Hallen, Stefan; Huang, Li; Svensson, Per-Arne; Momo, Remi A; Wallin, Simonetta; Carlsson, Eva K; Forslöw, Anna; Seale, Patrick; Peng, Xiao-Rong

    2015-01-01

    Heat-producing beige/brite (brown-in-white) adipocytes in white adipose tissue have the potential to suppress metabolic disease in mice and hold great promise for the treatment of obesity and type 2 diabetes in humans. Here, we demonstrate that human adipose-derived stromal/progenitor cells (hASCs) from subcutaneous white adipose tissue can be efficiently converted into beige adipocytes. Upon pharmacological activation of peroxisome proliferator-activated receptor-γ, hASC-derived adipocytes activated beige fat-selective genes and a brown/beige fat-selective electron transport chain gene program. Importantly, hASC-derived beige fat cells displayed the bioenergetic characteristics of genuine brown fat cells, including a capacity for increased respiratory uncoupling in response to β-adrenergic agonists. Furthermore, knock-down experiments reveal that the thermogenic capacity of human beige fat cells was entirely dependent on the presence of Uncoupling protein 1. In summary, this study reveals that hASCs can be readily differentiated into beige adipocytes that, upon activation, undergo uncoupling protein 1-dependent thermogenesis.

  6. Comparative study on the antioxidant and anti-Toxoplasma activities of vanillin and its resorcinarene derivative.

    PubMed

    Oliveira, Claudio B S; Meurer, Ywlliane S R; Oliveira, Marianne G; Medeiros, Wendy M T Q; Silva, Francisco O N; Brito, Ana C F; Pontes, Daniel de L; Andrade-Neto, Valter F

    2014-05-07

    A resorcinarene derivative of vanillin, resvan, was synthesized and characterized by spectroscopic techniques. We measured the cytotoxicity (in vivo and in vitro), antioxidant and anti-Toxoplasma activities of vanillin and the resorcinarene compound. Here we show that vanillin has a dose-dependent behavior with IC50 of 645 µg/mL through an in vitro cytotoxicity assay. However, we could not observe any cytotoxic response at higher concentrations of resvan (IC50 > 2,000 µg/mL). The in vivo acute toxicity assays of vanillin and resvan exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg during the first 30 min, 24 h or 14 days after administration. The obtained derivative showed greater antioxidative activity (84.9%) when comparing to vanillin (19.4%) at 1,000 μg/mL. In addition, vanillin presents anti-Toxoplasma activity, while resvan does not show that feature. Our findings suggest that this particular derivative has an efficient antioxidant activity and a negligible cytotoxic effect, making it a potential target for further biological investigations.

  7. Mathematical models of antisickling activities of benzoic acid derivatives on red blood cells of sicklers.

    PubMed

    Fasanmade, A A; Olaniyi, A A; Ab-Yisak, W

    1994-12-01

    A classical drug design technique based on the quantitative structure--activity relationship is applied to a series of synthetic benzoic acid derivatives. Some of the active derivatives tested include; p-toluic acid, p-dimethyl-amino benzoic acid, p-fluorobenzoic acid, p-chlorobenzoic acid, m-chlorobenzoic acid, p-bromobenzoic acid, p-nitrobenzoic acid, and p-iodobenzoic acid. The Hansch lipophilicity, pi, and the Hammett electronic parameters; sigma, were found to predict activities of the agents on the reversal of sickle-shaped deoxygenated sickle red blood cell to normal morphology. A series of equations correlating the biological activities with the structure of the tested compounds were analysed using multiple regression techniques. The most applicable of the equations was found to be; Log BR = -A sigma + B pi--C pi 2 + K Interpretation of this equation in terms of the biological action of the drugs on red blood cells was attempted. In designing a potent antisickling agent, the benzoic acid should have strong electron donating group(s) attached to the benzene ring and should be made averagely lipophilic to satisfy the relationship derived in this study.

  8. Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives

    SciTech Connect

    Barros, Francisco W.A.; Bezerra, Daniel P.; Ferreira, Paulo M.P.; Cavalcanti, Bruno C.; Silva, Teresinha G.; Pitta, Marina G.R.; Lima, Maria do C.A. de; Galdino, Suely L.; Pitta, Ivan da R.; Costa-Lotufo, Letícia V.; Moraes, Manoel O.; Burbano, Rommel R.; Guecheva, Temenouga N.; Henriques, João A.P.; Pessoa, Cláudia

    2013-04-01

    Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione — AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione — AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl) -1,3-thiazolidine-2,4-dione — AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2, 4-dione — AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways. - Highlights: ► Thiazacridine derivatives induce mitochondrial-dependent apoptotic cell death. ► Thiazacridine derivatives inhibit DNA topoisomerase I action. ► Thiazacridine derivatives failed to cause genotoxicity on human lymphocytes.

  9. Activated carbon derived from waste coffee grounds for stable methane storage.

    PubMed

    Kemp, K Christian; Baek, Seung Bin; Lee, Wang-Geun; Meyyappan, M; Kim, Kwang S

    2015-09-25

    An activated carbon material derived from waste coffee grounds is shown to be an effective and stable medium for methane storage. The sample activated at 900 °C displays a surface area of 1040.3 m(2) g(-1) and a micropore volume of 0.574 cm(3) g(-1) and exhibits a stable CH4 adsorption capacity of ∼4.2 mmol g(-1) at 3.0 MPa and a temperature range of 298 ± 10 K. The same material exhibits an impressive hydrogen storage capacity of 1.75 wt% as well at 77 K and 100 kPa. Here, we also propose a mechanism for the formation of activated carbon from spent coffee grounds. At low temperatures, the material has two distinct types with low and high surface areas; however, activation at elevated temperatures drives off the low surface area carbon, leaving behind the porous high surface area activated carbon.

  10. Design, synthesis and antibacterial activity of isatin derivatives as FtsZ inhibitors

    NASA Astrophysics Data System (ADS)

    Lian, Zhi-Min; Sun, Juan; Zhu, Hai-Liang

    2016-08-01

    Seven isatin derivatives have been designed, and their chemical structures were characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. These compounds were evaluated for antimicrobial activities. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding models. All of the compounds exhibited better antibacterial activities. Interestingly, compound 5c and 5d exhibited better antibacterial activities with IC50 values of 0.03 and 0.05 μmol/mL against Staphylococcus aureus, respectively. Compound 5g displays antibacterial activity with IC50 values of 0.672 and 0.830 μmol/mL against Escherichia coli and Pseudomonas aeruginosa, respectively.

  11. Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin.

    PubMed

    Zhang, Zhi-Jun; Tian, Jing; Wang, Li-Ting; Wang, Mei-Juan; Nan, Xiang; Yang, Liu; Liu, Ying-Qian; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2014-01-01

    Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC₅₀: 1.41-1.76 μM) and 14e (IC₅₀: 1.72-2.01 μM) showed superior cytotoxic activity compared with etoposide (IC₅₀: 2.03 to >20 μM), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4'-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin's 4β position can significantly improve cytotoxic activity.

  12. In vivo and In vitro Anti-Inflammatory Activity of Indazole and Its Derivatives

    PubMed Central

    Muniappan, M.

    2016-01-01

    Introduction The inflammatory response is closely intertwined with the process of repair. However in some diseases the inflammatory response may be exaggerated and sustained without apparent benefit and even with severe adverse complications. For decades, we have been primarily relying upon Nonsteroidal (NSAID) and Steroidal Anti-Inflammatory agents for management of various inflammatory conditions. However, adverse effects of these drugs are severe which often leads to patient’s non-compliance with inadequate relief. Therefore, there has been a constant pursuit to develop newer anti - inflammatory treatment with fewer side effects. Aim The study was designed to investigate the possible anti- inflammatory activity of indazole, its derivatives and to further investigate the possible cellular mechanisms underlying the anti-inflammatory effect. Materials and Methods Carrageenan induced hind paw oedema in rats was employed to study the acute anti-inflammatory activity of indazole and its derivatives. Further, the role of cyclooxygenase – 2, pro-inflammatory cytokines like Tumour Necrosis Factor – α, Interleukin – 1β and free radical scavenging activity (LPO, DPPH and NO) in the action of indazole and its derivatives was investigated using in vitro assays. Results SPSS version 16.0 software was used for analyse the anti-inflamatory data. The IC50 values of indazole and its derivatives obtained in in vitro experiments were calculated by linear regression analysis. Indazole and its derivatives significantly, dose dependently and time dependently inhibited carrageenan induced hind paw oedema. In addition, the test compounds inhibited cyclooxygenase–2, pro-inflammatory cytokines and free radicals in a concentration dependent manner. Conclusion The results of the present study revealed the potential anti-inflammatory action of investigated indazoles. The inhibition of cyclooxygenase -2, cytokines and free radicals may contribute to the anti-inflammatory effect of

  13. Synthesis, characterization, and antifungal activity of novel inulin derivatives with chlorinated benzene.

    PubMed

    Guo, Zhanyong; Li, Qing; Wang, Gang; Dong, Fang; Zhou, Haoyuan; Zhang, Jing

    2014-01-01

    A group of novel inulin derivatives containing benzene or chlorinated benzene were synthesized by reaction of chloracetyl inulin (CAIL) with the Schiff bases of 4-amino-pyridine, including (2-pyridyl)acetyl inulin chloride (PAIL), 2-[4-(2-chlorobenzylideneamino)-pyridyl]acetyl inulin chloride (2CPAIL), 2-[4-(4-chlorobenzylideneamino)-pyridyl]acetyl inulin chloride (4CPAIL), and 2-[4-(2,4-dichlorobenzylideneamino)-pyridyl]acetyl inulin chloride (2,4DCPAIL). Their antifungal activity against three kinds of phytopathogens was estimated by hypha measurement in vitro. Of all the synthesized chitosan derivatives, 2,4DCPAIL inhibited the growth of the tested phytopathogens with inhibitory indices of 67%, 47%, and 43% against Colletotrichum lagenarium (Pass) Ell.et halst, Phomopsis asparagi (Sacc.) Bubak and Fusarium oxysporum (schl.) F.sp. niveum (F. oxysporum) respectively at 1.0 mg/mL. The results indicate that all the inulin derivatives have better antifungal activity than inulin, and the inhibitory index is affected by the chlorine atom grafted to the inulin derivatives.

  14. Structure-antitussive activity relationships of naltrindole derivatives. Identification of novel and potent antitussive agents.

    PubMed

    Sakami, Satoshi; Maeda, Masayuki; Kawai, Koji; Aoki, Takumi; Kawamura, Kuniaki; Fujii, Hideaki; Hasebe, Ko; Nakajima, Mayumi; Endo, Takashi; Ueno, Shinya; Ito, Tsuyoshi; Kamei, Junzo; Nagase, Hiroshi

    2008-08-14

    We have previously reported antitussive effects of naltrindole (NTI), a typical delta opioid receptor antagonist, in a rat model. The ED50 values of NTI by intraperitoneal and peroral injections were 104 microg/kg and 1840 microg/kg, respectively, comparable to those of codeine. Codeine, one of the most reliable centrally acting antitussive drugs, has micro agonist activity and thus the same side effects as morphine, e.g., constipation, dependency, and respiratory depression. Because NTI is a delta opioid antagonist, its derivatives have potential as highly potent antitussives, free from the mu opioid agonist side effects. We attempted to optimize the NTI derivatives to develop novel antitussive agents. On the basis of the studies of structure-antitussive activity relationships of alkyl substituted NTI derivatives, we designed NTI derivatives with extra ring fused structures. As a clinical candidate, we identified a highly potent new compound, (5R,9R,13S,14S)-17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5',6'-dihydro-3-methoxy-4'H-pyrrolo[3,2,1-ij]quinolino[2',1':6,7]morphinan-14-ol (5b) methanesulfonate (TRK-850) which was effective even by oral administration (ED50 6.40 microg/kg).

  15. Disubstituted thiourea derivatives and their activity on CNS: synthesis and biological evaluation.

    PubMed

    Stefanska, Joanna; Szulczyk, Daniel; Koziol, Anna E; Miroslaw, Barbara; Kedzierska, Ewa; Fidecka, Sylwia; Busonera, Bernardetta; Sanna, Giuseppina; Giliberti, Gabriele; La Colla, Paolo; Struga, Marta

    2012-09-01

    A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The (1)H NMR, (13)C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against gram-positive cocci, gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1-13) were examined for cytotoxicity, antitumor, and anti-HIV activity.

  16. New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum.

    PubMed

    Varela, Marina T; Lima, Marta L; Galuppo, Mariana K; Tempone, Andre G; de Oliveira, Alberto; Lago, João Henrique G; Fernandes, João Paulo S

    2017-03-29

    Alkylphenols isolated from Piper malacophyllum (Piperaceae), gibbilimbols A and B, showed interesting activity against the parasites Trypanosoma cruzi and Leishmania infantum. In continuation to our previous work, a new natural product from the essential oil of the leaves of P. malacophyllum was isolated, the 5-[(3E)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. The antiparasitic activity of the natural product was evaluated in vitro against these parasites, indicating potential against the promastigote/trypomastigote/amastigote forms (IC50 32-83 μM) of the parasites and low toxicity (CC50 >200 μM) to mammalian cells. The results obtained to the synthetic compounds indicated that the new derivatives maintained the promising antiparasitic activity, but the cytotoxicity was considerably lowered The amine derivative LINS03011 displayed the most potent IC50 values (13.3 and 16.7 μM) against amastigotes of T. cruzi and L. infantum, respectively, indicating comparable activity to the phenolic prototype LINS03003, with 3-fold decreased (CC50 73.5 μM) cytotoxicity, leading the selectivity index (SI) towards the parasites up to 24.5. In counterpart, LINS03011 has not shown membrane disruptor activity in Sytox Green model. In summary, this new set showed the hydroxyl is not essential for the antiparasitic activity, and its substitution could decrease the toxicity to mammalian cells. This article is protected by copyright. All rights reserved.

  17. Synthesis and Antimicrobial Activity of 9-O-Substituted Palmatine Derivatives

    PubMed Central

    Li, Z. C.; Kong, X. B.; Mai, W. P.; Sun, G. C.; Zhao, S. Z.

    2015-01-01

    A series of new palmatine derivatives with alkyl or alkyl with N-heterocyclic structures were designed and synthesized at C-9-O according to the principle of association. These compounds were characterised by 1H NMR, 13C NMR, ESI-MS and elemental analysis, and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. The results indicated that 9-O-substituted palmatine derivatives exhibit varying degrees of antimicrobial activity. Antibacterial activities of compounds (3a-f) against Gram +ve bacteria increased 2- to 64-fold than that of palmatine. The compounds (3a-f) possessed relatively weaker inhibitory effects against Gram −ve bacteria and fungi than that against Gram +ve bacteria. Antimicrobial activities of compounds (5a-e) are lower than that of compounds (3a-f). Compound 3d showed the highest antimicrobial activity of all the compounds. The LD50 values of compounds (3a-f) decreased as the alkyl side chain was elongated. Compound 3f showed least toxicity. PMID:26009653

  18. Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation

    PubMed Central

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Prencipe, Filippo; Lopez-Cara, Carlota; Rondanin, Riccardo; Simoni, Daniele; Hamel, Ernest; Grimaudo, Stefania; Pipitone, Rosaria Maria; Meli, Maria; Tolomeo, Manlio

    2015-01-01

    Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3′,4′,5′-trimethoxybenzoyl)-3-iodoacetamido-6-methoxybenzo[b]furan derivative 1 as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3′,4′,5′-trimethoxybenzoyl moiety at the 2-position of different benzoheterocycles such as benzo[b]furan, benzo[b]thiophene, indole and N-methylindole. Effects on biological activity of the iodoacetamido group and of different moieties (methyl and methoxy) at the C-3 to C-7 positions were examined. In the series of benzo[b]furan derivatives, moving the iodoacetylamino group from the C-4 to the C-5 or C-6 positions did not significantly affect antiproliferative activity. Compounds 4, 15, 20 and 23 blocked STAT5 signals and induced apoptosis of K562 BCR–ABL positive cells. For compound 23, the trimethoxybenzoyl moiety at the 2-position of the benzo[b]furan core was not essential for potent inhibition of STAT5 activation. PMID:26629859

  19. Phomentrioloxin, a fungal phytotoxin with potential herbicidal activity, and its derivatives: a structure-activity relationship study.

    PubMed

    Cimmino, Alessio; Andolfi, Anna; Zonno, Maria Chiara; Boari, Angela; Troise, Ciro; Motta, Andrea; Vurro, Maurizio; Ash, Gavin; Evidente, Antonio

    2013-10-09

    Phomentrioloxin is a phytotoxic geranylcyclohexenetriol produced in liquid culture by Phomopsis sp. (teleomorph: Diaporthe gulyae), a potential mycoherbicide proposed for the control of the annual weed Carthamus lanatus. In this study, seven derivatives obtained by chemical modifications of the toxin were assayed for phytotoxic, antimicrobial, and zootoxic activities, and the structure-activity relationships were examined. Each compound was tested on nonhost weedy and agrarian plants, fungi, Gram+ and Gram- bacteria, and on brine shrimp larvae. The results provide insights into an investigation of the structural requirements for activity. The hydroxy groups at C-2 and C-4 appeared to be important features for the phytotoxicity, as well as an unchanged cyclohexentriol ring. A role seemed also to be played by the unsaturations of the geranyl side chain. These findings could be useful for understanding the mechanisms of action of new natural products, for identifying the active sites, and possibly in devising new herbicides of natural origin.

  20. Enhanced adsorption of perfluorooctane sulfonate and perfluorooctanoate by bamboo-derived granular activated carbon.

    PubMed

    Deng, Shubo; Nie, Yao; Du, Ziwen; Huang, Qian; Meng, Pingping; Wang, Bin; Huang, Jun; Yu, Gang

    2015-01-23

    A bamboo-derived granular activated carbon with large pores was successfully prepared by KOH activation, and used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from aqueous solution. The granular activated carbon prepared at the KOH/C mass ratio of 4 and activation temperature of 900°C had fast and high adsorption for PFOS and PFOA. Their adsorption equilibrium was achieved within 24h, which was attributed to their fast diffusion in the micron-sized pores of activated carbon. This granular activated carbon exhibited the maximum adsorbed amount of 2.32mmol/g for PFOS and 1.15mmol/g for PFOA at pH 5.0, much higher than other granular and powdered activated carbons reported. The activated carbon prepared under the severe activation condition contained many enlarged pores, favorable for the adsorption of PFOS and PFOA. In addition, the spent activated carbon was hardly regenerated in NaOH/NaCl solution, while the regeneration efficiency was significantly enhanced in hot water and methanol/ethanol solution, indicating that hydrophobic interaction was mainly responsible for the adsorption. The regeneration percent was up to 98% using 50% ethanol solution at 45°C.

  1. Comparison of quantitative structure-activity relationship model performances on carboquinone derivatives.

    PubMed

    Bolboacă, Sorana-Daniela; Jäntschi, Lorentz

    2009-10-14

    Quantitative structure-activity relationship (qSAR) models are used to understand how the structure and activity of chemical compounds relate. In the present study, 37 carboquinone derivatives were evaluated and two different qSAR models were developed using members of the Molecular Descriptors Family (MDF) and the Molecular Descriptors Family on Vertices (MDFV). The usual parameters of regression models and the following estimators were defined and calculated in order to analyze the validity and to compare the models: Akaike's information criteria (three parameters), Schwarz (or Bayesian) information criterion, Amemiya prediction criterion, Hannan-Quinn criterion, Kubinyi function, Steiger's Z test, and Akaike's weights. The MDF and MDFV models proved to have the same estimation ability of the goodness-of-fit according to Steiger's Z test. The MDFV model proved to be the best model for the considered carboquinone derivatives according to the defined information and prediction criteria, Kubinyi function, and Akaike's weights.

  2. [Antibacterial Activity of Alkylated and Acylated Derivatives of Low-Molecular Weight Chitosan].

    PubMed

    Shagdarova, B Ts; Il'ina, A V; Varlamov, V P

    2016-01-01

    A number of alkylated (quaternized) and acylated derivatives of low-molecular weight chitosan were obtained. The structure and composition of the compounds were confirmed by the results of IR and PMR spectroscopy, as well as conductometric titration. The effect of the acyl substituent and the degree of substitution of N-(2-hydroxy-3-trimethylammonium) with the propyl fragment appended to amino groups of the C2 atom of polymer chains on antibacterial activity against typical representatives of gram-positive and gram-negative microorganisms (Staphylococcus epidermidis and Escherichia coli) was studied. The highest activity was in the case of N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride with the maximal substitution (98%). The minimal inhibitory concentration of the derivative was 0.48 µg/mL and 3.90 µg/mL for S. epidermis and E. coli, respectively.

  3. Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives

    PubMed Central

    Logashenko, Evgeniya B; Salomatina, Oksana V; Markov, A V; Korchagina, Dina V; Salakhutdinov, Nariman F; Tolstikov, Genrikh A; Vlassov, Valentin V; Zenkova, Marina A

    2011-01-01

    Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway. PMID:21328513

  4. Design, synthesis and cytotoxic activity of novel spin-labeled rotenone derivatives.

    PubMed

    Liu, Ying-Qian; Ohkoshi, Emika; Li, Lin-Hai; Yang, Liu; Lee, Kuo-Hsiung

    2012-01-15

    Three series of novel spin-labeled rotenone derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines, A-549, DU-145, KB and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tumor cell lines tested, with IC(50) values ranging from 0.075 to 0.738μg/mL. Remarkably, all of the compounds were more potent than paclitaxel against KBvin in vitro, and compounds 3a and 3d displayed the highest cytotoxicity against this cell line (IC(50) 0.075 and 0.092μg/mL, respectively). Based on the observed cytotoxicity, structure-activity relationships have been described.

  5. Uredinorubellins and caeruleoramularin, photodynamically active anthraquinone derivatives produced by two species of the genus ramularia.

    PubMed

    Miethbauer, Sebastian; Günther, Wolfgang; Schmidtke, Kai-Uwe; Heiser, Ingrid; Gräfe, Susanna; Gitter, Burkhard; Liebermann, Bernd

    2008-08-01

    Both the phytopathogenic fungus Ramularia collo-cygni and the hyperparasite R. uredinicola biosynthesize a number of red and yellow anthraquinone derivatives called rubellins. The new compounds uredinorubellins I and II, which were isolated from R. uredinicola, contribute to understanding the biosynthesis pathway that leads from simple anthraquinones to the rubellins. In addition, we isolated for the first time such simple compounds as chrysophanol and helminthsporin from both Ramularia species. A blue compound isolated from the mycelium of R. collo-cygni was revealed to be a unique 9,4-anthracenedione derivative. Structure elucidation by (1)H and (13)C NMR of the new but unstable compound caeruleoramularin was possible only by feeding the fungus different labeled (13)C acetates. The photodynamic activity of the uredinorubellins was comparable to rubellin D, whereas chrysophanol and caeruleoramularin did not display such activity.

  6. Phosphatidyl derivative of hydroxytyrosol. In vitro intestinal digestion, bioaccessibility, and its effect on antioxidant activity.

    PubMed

    Martin, Diana; Moran-Valero, Maria I; Casado, Víctor; Reglero, Guillermo; Torres, Carlos F

    2014-10-08

    Intestinal digestion of phosphatidyl derivatives of HT (PHT) and its bioaccessibility under in vitro conditions was performed. First, an in vitro intestinal digestion model for phospholipids was developed. The impact of digestion in the antioxidant ability of PHT was also assayed. PHT was progressively hydrolyzed to lyso-PHT. However, digestion was slower than the phospholipid control. Nevertheless, most hydrolysis products were found at the micellar phase fraction, meaning a high bioaccessibility. Either PHT or digested PHT showed lower antioxidant activity than HT. However, PHT improved its antioxidant ability after digestion, likely related to lyso-PHT. As a summary, the synthetic phosphatidyl derivative of HT as PHT is recognized by phospholipases during simulation of intestinal digestion, although less efficiently than analogous phospholipids. Nevertheless, taking into account the bioaccessibility and the antioxidant activity of digested PHT, the potential of carriers of HT under the form of phospholipids might be of interest.

  7. Fluorescein dye derivatives and their nanohybrids: Synthesis, characterization and antimicrobial activity.

    PubMed

    Negm, Nabel A; Abou Kana, Maram T H; Abd-Elaal, Ali A; Elwahy, Ahmed H M

    2016-09-01

    Fluorescein (resorcinolphthalein) is a synthetic organic photoactive dye compound soluble in water, alcohol and polar solvents. It is widely used as a fluorescent tracer in medicinal and biological applications and tumor infected tissues tracer. In this study, fluorescein (F) was condensed by five coupling agents namely: p,p-phenylene diamine, p-hydroxy aniline, o-hydroxy aniline, p-methoxy aniline and p-methyl aniline in a molar ratio of 2(F):1 (coupling agent). The chemical structures of the synthesized fluorescein derivatives were confirmed using: microelemental analysis, FTIR spectroscopy, 1H-NMR spectroscopy, and mass spectroscopy. The synthesized compounds were loaded on chemically prepared silver nanoparticles via reduction reaction of silver nitrate. The structures and properties of the formed fluorescein derivatives silver nanohybrids were determined using: UV/Vis spectroscopy, TEM images and dynamic light scattering (DLS). The synthesized compounds and their nanohybrids were evaluated for their antimicrobial activities against different bacterial strains and fungi. The results showed that the formed fluorescein derivatives silver nanohybrids are in moderate diameter range, and the loading of the synthesized compounds protect the silver nanoparticles against coagulation. The antimicrobial activity against the studied microorganisms was comparable to the standard used. Moreover, the antimicrobial activity was increased considerably in case of using fluorescein derivatives silver nanohybrids. The antimicrobial activities were correlated to the chemical structures of the compounds, diameter of the formed nanohybrids and to the nature of the tested bacterial strains. The mechanism of the antimicrobial action of the synthesized compounds and their nanohybrids was proposed.

  8. Activity Coefficient Derivatives of Ternary Systems Based on Scatchard's Neutral Electrolyte description

    SciTech Connect

    Miller, D G

    2007-05-16

    Activity coefficient derivatives with respect to molality are presented for the Scatchard Neutral Electrolyte description of a ternary common-ion electrolyte system. These quantities are needed for the calculation of 'diffusion Onsager coefficients' and in turn for tests of the Onsager Reciprocal Relations in diffusion. The usually-omitted b{sub 23} term is included. The direct SNE binary approximations and a further approximation are discussed. Binary evaluation strategies other than constant ionic strength are considered.

  9. D-ring modified novel isosteviol derivatives: design, synthesis and cytotoxic activity evaluation.

    PubMed

    Zhang, Tao; Lu, Li-Hui; Liu, Hao; Wang, Jun-Wei; Wang, Rui-Xue; Zhang, Yun-Xiao; Tao, Jing-Chao

    2012-09-15

    A series of polyhydric, amino alcohol and tricyclic derivatives were facilely synthesized by D-ring modification of isosteviol. These compounds were screened for their cytotoxic activities against four human tumor cell lines in vitro. Among them, the 15-α-aminomethyl-16-β-hydroxyl isosteviol 23 exhibits significant cytotoxicity superior to the positive control (cisplatin) against EC9706, PC-3 and HCT-116 cell lines.

  10. [Antiherpetic activity of netropsin derivatives as tested in experiments in laboratory animals].

    PubMed

    Andronova, V L; Grokhovskiĭ, S L; Deriabin, P G; Gurskiĭ, G V; Galegov, G A; L'vov, D K

    2012-01-01

    Two dimeric netropsin derivatives (Lys-bis-Nt 15Lys-bis-Nt) were comprehensively tested for antiviral and toxic activity in cell cultures and laboratory animals. The two compounds were found to provide effective and selective inhibition of reproduction of herpes simplex I both in cell culture Vero E6 and in brain of infected white mice, thereby increasing the survival rate and mean life expectation of treated animals as compared to control.

  11. Novel Plant-Derived Recombinant Human Interferons with Broad Spectrum Antiviral Activity

    DTIC Science & Technology

    2011-10-14

    proliferation rather than to a direct effect on the virus , Daudi inhibition assays were performed using an Epstein – Barr virus - transformed human B-cell...compared the antiviral activities of more than 1400 plant-derived, hybrid IFNs against three RNA viruses and one DNA virus from four different families...highly pathogenic viruses with varying sensitivities to type I IFN. In particular, the DNA virus , MPXV, was not expected to be as susceptible to the

  12. A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2 activity and upregulates DR5 in breast cancer cells.

    PubMed

    Chu, B; Liu, F; Li, L; Ding, C; Chen, K; Sun, Q; Shen, Z; Tan, Y; Tan, C; Jiang, Y

    2015-03-12

    Aberrant expression or function of epidermal growth factor receptor (EGFR) or the closely related human epidermal growth factor receptor 2 (HER2) can promote cell proliferation and survival, thereby contributing to tumorigenesis. Specific antibodies and low-molecular-weight tyrosine kinase inhibitors of both proteins are currently in clinical trials for cancer treatment. Benzimidazole derivatives possess diverse biological activities, including antitumor activity. However, the anticancer mechanism of 5a (a 2-aryl benzimidazole compound; 2-chloro-N-(2-p-tolyl-1H-benzo[d]imidazol-5-yl)acetamide, C(16)H(14)ClN(3)O, MW299), a novel 2-aryl benzimidazole derivative, toward breast cancer is largely unknown. Here, we demonstrate that 5a potently inhibited both EGFR and HER2 activity by reducing EGFR and HER2 tyrosine phosphorylation and preventing downstream activation of PI3K/Akt and MEK/Erk pathways in vitro and in vivo. We also show that 5a inhibited the phosphorylation of FOXO and promoted FOXO translocation from the cytoplasm into the nucleus, resulting in the G1-phase cell cycle arrest and apoptosis. Moreover, 5a potently induced apoptosis via the c-Jun N-terminal kinase (JNK)-mediated death receptor 5 upregulation in breast cancer cells. The antitumor activity of 5a was consistent with additional results demonstrating that 5a significantly reduced tumor volume in nude mice in vivo. Analysis of the primary breast cancer cell lines with HER2 overexpression further confirmed that 5a significantly inhibited Akt Ser473 and Bad Ser136 phosphorylation and reduced cyclin D3 expression. On the basis of our findings, further development of this 2-aryl benzimidazole derivative, a new class of multitarget anticancer agents, is warranted and represents a novel strategy for improving breast cancer treatment.

  13. Development of a Fully Automated, Web-Based, Tailored Intervention Promoting Regular Physical Activity Among Insufficiently Active Adults With Type 2 Diabetes: Integrating the I-Change Model, Self-Determination Theory, and Motivational Interviewing Components

    PubMed Central

    Moreau, Michel; Gagnon, Marie-Pierre

    2015-01-01

    Background Type 2 diabetes is a major challenge for Canadian public health authorities, and regular physical activity is a key factor in the management of this disease. Given that fewer than half of people with type 2 diabetes in Canada are sufficiently active to meet the recommendations, effective programs targeting the adoption of regular physical activity (PA) are in demand for this population. Many researchers argue that Web-based, tailored interventions targeting PA are a promising and effective avenue for sedentary populations like Canadians with type 2 diabetes, but few have described the detailed development of this kind of intervention. Objective This paper aims to describe the systematic development of the Web-based, tailored intervention, Diabète en Forme, promoting regular aerobic PA among adult Canadian francophones with type 2 diabetes. This paper can be used as a reference for health professionals interested in developing similar interventions. We also explored the integration of theoretical components derived from the I-Change Model, Self-Determination Theory, and Motivational Interviewing, which is a potential path for enhancing the effectiveness of tailored interventions on PA adoption and maintenance. Methods The intervention development was based on the program-planning model for tailored interventions of Kreuter et al. An additional step was added to the model to evaluate the intervention’s usability prior to the implementation phase. An 8-week intervention was developed. The key components of the intervention include a self-monitoring tool for PA behavior, a weekly action planning tool, and eight tailored motivational sessions based on attitude, self-efficacy, intention, type of motivation, PA behavior, and other constructs and techniques. Usability evaluation, a step added to the program-planning model, helped to make several improvements to the intervention prior to the implementation phase. Results The intervention development cost was

  14. Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of β-Dihydroagarofuran Derivatives.

    PubMed

    Zhao, Ximei; Xi, Xin; Hu, Zhan; Wu, Wenjun; Zhang, Jiwen

    2016-02-24

    The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 β-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT-135°, IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 μg/g, respectively, which were much lower than that of celangulin-V (327.6 μg/g). These results illustrated that β-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development.

  15. Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons

    PubMed Central

    Bradford, Aaron B; McNutt, Patrick M

    2015-01-01

    Functional synaptogenesis and network emergence are signature endpoints of neurogenesis. These behaviors provide higher-order confirmation that biochemical and cellular processes necessary for neurotransmitter release, post-synaptic detection and network propagation of neuronal activity have been properly expressed and coordinated among cells. The development of synaptic neurotransmission can therefore be considered a defining property of neurons. Although dissociated primary neuron cultures readily form functioning synapses and network behaviors in vitro, continuously cultured neurogenic cell lines have historically failed to meet these criteria. Therefore, in vitro-derived neuron models that develop synaptic transmission are critically needed for a wide array of studies, including molecular neuroscience, developmental neurogenesis, disease research and neurotoxicology. Over the last decade, neurons derived from various stem cell lines have shown varying ability to develop into functionally mature neurons. In this review, we will discuss the neurogenic potential of various stem cells populations, addressing strengths and weaknesses of each, with particular attention to the emergence of functional behaviors. We will propose methods to functionally characterize new stem cell-derived neuron (SCN) platforms to improve their reliability as physiological relevant models. Finally, we will review how synaptically active SCNs can be applied to accelerate research in a variety of areas. Ultimately, emphasizing the critical importance of synaptic activity and network responses as a marker of neuronal maturation is anticipated to result in in vitro findings that better translate to efficacious clinical treatments. PMID:26240679

  16. Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities.

    PubMed

    Zhou, Wu-Xi; Sun, Yuan-Yuan; Yuan, Wei-Hui; Zhao, Yu-Qing

    2017-03-18

    (20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH3-PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH3-PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH3-PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH3-PPD and its derivatives was tested and the results showed that the solubility of 25-OCH3-PPD sulfamic acid and diacid derivatives were better than that of 25-OCH3-PPD in water, which may provide valuable data for the research and development of new anti-tumor agents.

  17. Synthesis and characterization of 3-aminoquinoline derivatives and studies of photophysicochemical behaviour and antimicrobial activities

    NASA Astrophysics Data System (ADS)

    Zengin, Gulay; Nafea Al Kawaz, Ali Muayad; Zengin, Huseyin; Mert, Adem; Kucuk, Bedia

    2016-01-01

    A series of 3-aminoquinoline derivatives were synthesized, where their chemical structures were confirmed by various analytical techniques, such as, Elemental Analysis, Nuclear Magnetic Resonance Spectroscopy (1H and 13C NMR), Liquid Chromatography-Mass-Mass Spectroscopy (LC-MS-MS), Ultraviolet-Visible Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FTIR) and Photoluminescence (PL). The quinoline ring core, typical of aminoquinolines, and a naphthalene group was combined to devise (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives. These derivatives were designed and synthesized in light of the chemical and biological profiles of these important subunits. All the compounds were evaluated for their in vitro antibacterial and antifungal activities by the paper disc diffusion method with Gram-positive Bacillus subtilis, Bacillus megaterium and Staphylococcus aureus, Gram-negative Enterobacter aerogenes, Eschericha coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and yeasts Candida albicans, Saccharomyces cerevisiae and Yarrovia lipolytica. These compounds showed antimicrobial activities against Gram-positive and Gram-negative bacteria and several yeasts, and thus their activity was not restricted to any particular type of microorganism.

  18. Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM) Analyses.

    PubMed

    Mabkhot, Yahia Nasser; Alatibi, Fatima; El-Sayed, Nahed Nasser E; Al-Showiman, Salim; Kheder, Nabila Abdelshafy; Wadood, Abdul; Rauf, Abdur; Bawazeer, Saud; Hadda, Taibi Ben

    2016-02-17

    Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6-8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, ¹H-(13)C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn't guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

  19. Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

    PubMed Central

    Martinez, Zachary S.; Castro, Edison; Seong, Chang-Soo; Cerón, Maira R.

    2016-01-01

    Three compounds (1, 2, and 3) previously reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase were studied, but only fullerene derivatives 1 and 2 showed strong antiviral activity on the replication of HIV-1 in human CD4+ T cells. However, these compounds did not inhibit infection by single-round infection vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped viruses, indicating no effect on the early steps of the viral life cycle. In contrast, analysis of single-round infection VSV-G-pseudotyped HIV-1 produced in the presence of compound 1 or 2 showed a complete lack of infectivity in human CD4+ T cells, suggesting that the late stages of the HIV-1 life cycle were affected. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. However, Gag and Gag-Pol processing was affected, as evidenced by immunoblot analysis with an anti-p24 antibody and the measurement of virion-associated reverse transcriptase activity, ratifying the effect of the fullerene derivatives on virion maturation of the HIV-1 life cycle. Surprisingly, fullerenes 1 and 2 did not inhibit HIV-1 protease in an in vitro assay at the doses that potently blocked viral infectivity, suggesting a protease-independent mechanism of action. Highlighting the potential therapeutic relevance of fullerene derivatives, these compounds block infection by HIV-1 resistant to protease and maturation inhibitors. PMID:27431232

  20. Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.

    PubMed Central

    Dalloul, A H; Arock, M; Fourcade, C; Béranger, J Y; Jaffray, P; Debré, P; Mossalayi, M D

    1992-01-01

    Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production. Images PMID:1401061

  1. Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cells.

    PubMed

    Iwaszkiewicz-Grzes, Dorota; Cholewinski, Grzegorz; Kot-Wasik, Agata; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2017-03-01

    The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester 5a and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester 5b. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid 4b, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.

  2. Synthesis, Biological Activity, and Docking Study of Novel Isatin Coupled Thiazolidin-4-one Derivatives as Anticonvulsants.

    PubMed

    Nikalje, Anna P; Ansari, Altamash; Bari, Sanjay; Ugale, Vinod

    2015-06-01

    A series of 2-(substituted-phenyl)-3-(2-oxoindolin-3-ylidene)amino)-thiazolidin-4-one derivatives were designed and synthesized under microwave irradiation, using an eco-friendly, efficient, microwave-assisted synthetic protocol that involves cyclocondensation of 3-substituted benzylidine-hydrazono-indolin-2-one 3a-j with thioglycolic acid in dimethyl formamide (DMF) as solvent and anhydrous zinc chloride as a catalyst, keeping in view the structural requirement of the pharmacophore. The intermediate compounds 3a-j were obtained by condensation of the hydrazone of indoline-2,3-dione with aromatic aldehydes. The synthesized derivatives were evaluated for CNS depressant activity and anticonvulsant activity in mice using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) induced seizure tests. All the derivatives showed good CNS depressant activity and showed protection in the MES test, indicative of their ability to inhibit the seizure spread. A histopathological study was performed to evaluate liver toxicity caused by the synthesized compounds. The compounds were nontoxic. A computational study was performed, in which log P values were calculated experimentally. Virtual screening was performed by molecular docking of the designed compounds into the ATP binding sites of the NMDA and AMPA receptors, to predict if these compounds have analogous binding modes.

  3. [Synthesis of 1-furfuryl-indolin-2-one derivatives and preliminary evaluation of their antitumor activities].

    PubMed

    Dong, Xiao-Chun; Zhou, Fu-Sheng; Zheng, Jian-Bin; Wen, Ren

    2008-01-01

    In order to find new indolin-2-one derivatives as antitumor agents, a series of 3-pyrrole substituted 1-(5-formyl-2-furanylmethyl) indolin-2-one derivatives were designed and synthesized. 5-Formyl-2 ,4-dimethyl-lH-pyrrole-3-carboxylic acid ethyl ester was condensed with 5-substituted indolin-2-one 2a-2d to afford 3-[(pyrrol-2-yl) -methylidenyl] indolin-2-ones 3a-3d. Through N-alkylation, 1-(5-formyl-furfuryl) -indolin-2-one 4a-4d were prepared. Compounds 4a-4d were then condensed with indolin-2-one to afford bis-indolin-2-one derivatives 5a-5d. The structures of the synthesized compounds were determined by 1H NMR, MS and element analysis. Antitumor activities of all the synthesized compounds in vitro were tested. All the 12 synthesized compounds possess antitumor activities against SPC-A1 strain. Especially the compounds 5a-5d possess potent antitumor activities better than sunitinib. Their IC50 are all below 5 micromol x L(-1).

  4. Synthesis and anti-inflammatory activity of ent-kaurene derivatives.

    PubMed

    Hueso-Falcón, Idaira; Cuadrado, Irene; Cidre, Florencia; Amaro-Luis, Juan M; Ravelo, Angel G; Estevez-Braun, Ana; de Las Heras, Beatriz; Hortelano, Sonsoles

    2011-04-01

    A series of kaurene derivatives (1-63) were prepared and evaluated for anti-inflammatory activity. Thirteen of the tested compounds were able to inhibit NO production with an IC(50) between 2 and 10 μM. Compounds 11, 12, 14 and 23 showed low percentage of cell viability, whereas compounds 9, 10, 17, 28, 37, 48, 55, 61 and 62 were non-cytotoxic at the concentration up to 25 μM. Some structure-activity relationships were outlined. Compounds 28, 55 and 62, were selected as representative compounds and they potently inhibited the protein expression of NOS-2. We also determined that inhibition of NF-κB activation might be the mechanism involved in anti-inflammatory effects of these kaurene derivatives. As expected, cytokines IL-6, IL-1α, TNF-α and IFN-γ were downregulated in the presence of compound 28, 55 and 62 after stimulation with LPS. These results indicate that kaurene derivatives might be used for the design of new anti-inflammatory agents.

  5. Design, synthesis, and antiviral, fungicidal, and insecticidal activities of tetrahydro-β-carboline-3-carbohydrazide derivatives.

    PubMed

    Liu, Yongxian; Song, Hongjian; Huang, Yuanqiong; Li, Jiarui; Zhao, Sheng; Song, Yuchuan; Yang, Peiwen; Xiao, Zhixin; Liu, Yuxiu; Li, Yongqiang; Shang, Hui; Wang, Qingmin

    2014-10-15

    According to our previous research on the antiviral activity of β-carboline and tetrahydro-β-carboline derivatives, using (1S,3S)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carbohydrazide (1) as a lead compound, series of novel tetrahydro-β-carboline derivatives containing acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. Most of these compounds exhibited excellent antiviral activity both in vitro and in vivo. The in vivo inactivation, curative, and protection activities of compounds 8, 9, 12, 16, 28, 29, and 30 were much higher than that of ribavirin (37.6%, 39.4%, and 37.9% at 500 μg/mL) and the lead compound (40.0%, 42.3%, and 39.6% at 500 μg/mL). Especially, the in vitro and in vivo activities of compound 16 (36.9%, 33.6%, 30.2%, and 35.8%) at 100 μg/mL, which were very close to that of ribavirin (40.0% for in vitro activity) at 500 μg/mL. Compounds 9 and 29 were chosen for the field trials of antiviral efficacy against TMV (tobacco mosaic virus); the results exhibited that both compounds, especially compound 29, showed better activities than control plant virus inhibitors. At the same time, the fungicidal results showed that compounds 6, 9, and 11 exhibited good fungicidal activities against 14 kinds of phytopathogens. Additionally, compounds 3 and 23 exhibited moderate insecticidal activity against the four tested species of insects.

  6. Structure-activity relationship of (-) mammea A/BB derivatives against Leishmania amazonensis.

    PubMed

    Brenzan, Mislaine Adriana; Nakamura, Celso Vataru; Dias Filho, Benedito Prado; Ueda-Nakamura, Tânia; Young, Maria Claudia M; Côrrea, Arlene Gonçalves; Alvim, Joel; dos Santos, Adriana Oliveira; Cortez, Diógenes Aparício Garcia

    2008-11-01

    To study the structure-activity relationship of coumarin (-) mammea A/BB isolated from the CH(2)Cl(2) extract of Calophyllum brasiliense leaves, we evaluated the antileishmanial activity of natural, synthetic and derivatives of this coumarin, against promastigote and intracellular amastigote forms of Leishmania amazonensis, and their cytotoxicity to J774G8 murine macrophages. The derivatives were obtained by hydrogenation and methoxylation reactions. The compound structures were elucidated on the basis of spectroscopic data. The compounds 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), 7-hydroxy-5-methoxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-en-1-yl)-4-phenylcoumarin (4) and 5,7-dimethoxy-8-(1-methoxy-2-methylbutyl)-6-(3-methylbut-2-en-1-yl)-4 phenylcoumarin (6) were more biologically active than the compound (-) mammea A/BB (1) (7.4 microM), with IC(50) values from 0.9, 2.4 and 1.9 microM respectively; compound (3) displayed the highest activity. The compounds mammea B/BB (2), 5,7-dimethoxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-en-1-yl)-4-phenylcoumarin (5) and 5,7-dihydroxy-4-phenylcoumarin (7) were less active than (-) mammea A/BB (1), with IC(50) of 30.1, 15.1 and 60.2 microM respectively; compound (7) showed the lowest antileishmanial activity of all. Compounds (1), (3), (4) and (6) were active not only against promastigote forms of L. amazonensis, but also against intracellular amastigote forms with IC(50) of 14.3, 0.6, 34.0 and 22.2 microM, respectively. Interestingly, compound (3) showed the most antileishmanial activity of all. This study demonstrated that several aspects of the structure were important for antileishmanial activity.

  7. Additive effects on the improvement of insecticidal activity: Design, synthesis, and insecticidal activity of novel pymetrozine derivatives.

    PubMed

    Yang, Yan; Liu, Yuxiu; Song, Hongjian; Li, Yongqiang; Wang, Qingmin

    2016-02-01

    A series of new pymetrozine analogues containing both methyl on the imine carbon and phenoxy group at the pyridine ring were designed and synthesized. Their insecticidal activities against bean aphid (Aphis craccivora), mosquito larvae (Culex pipiens pallens), cotton bollworm (Helicoverpa armigera), corn borer (Ostrinia nubilalis) and oriental armyworm (Mythimna separata) were evaluated. The results of bioassays indicated that most of the target compounds showed good insecticidal activity against bean aphid; especially, IIIf (80%) and IIIl (80%) exhibited higher aphicidal activity than pymetrozine (30%) at 5mg/kg, and the two compounds still showed 20% and 30% mortality at 2.5mg/kg, respectively, whereas pymetrozine displayed no activity at the same concentration. These compounds exhibited a completely different structure-activity relationship to that of known pymetrozine derivatives, in which it is thought introducing alkyl group on the imine carbon could be detrimental to the activities. Our new result suggested that the methyl on the imine carbon and phenoxy group at the pyridine ring of phenoxy group may play additive effects on the improvement of aphicidal activity. Besides this, compound IIIs, containing an allyl at the para position of phenoxy group, exhibited excellent insecticidal activity against mosquito larvae, lepidoptera pests cotton bollworm, corn borer and oriental armyworm.

  8. "Click" reaction mediated synthesis of costunolide and dehydrocostuslactone derivatives and evaluation of their cytotoxic activity.

    PubMed

    Pavan Kumar, Ch; Devi, A; Ashok Yadav, P; Rao Vadaparthi, R; Shankaraiah, G; Sowjanya, P; Jain, Nishant; Suresh Babu, K

    2016-11-01

    As part of pharmacological-phytochemical integrated studies on medicinal plants from Indian flora, costunolide (1) and dehydrocostus lactone (2), were isolated as major phytochemicals from Saussurea lappa, a plant traditionally used in different Asian systems of medicine. A series of 1,4-disubstituted-1,2,3-triazoles conjugates were synthesized through diastereo selective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5j) & (7a-7j) were well characterized using modern spectroscopic techniques and evaluated for their anticancer activity against a panel of five human cancerous celllines. The results indicated that all the analogs displayed moderate cytotoxic activity.

  9. Synthesis and antituberculosis activity of novel unfolded and macrocyclic derivatives of ent-kaurane steviol.

    PubMed

    Khaybullin, Ravil N; Strobykina, Irina Yu; Dobrynin, Alexey B; Gubaydullin, Aidar T; Chestnova, Regina V; Babaev, Vasiliy M; Kataev, Vladimir E

    2012-11-15

    New derivatives of steviol 1, the aglycone of the glycosides of Stevia rebaudiana, including a novel class of semisynthetic diterpenoids, namely macrocyclic ent-kauranes were synthesized. These compounds possess antituberculosis activity inhibiting the in vitro growth of Mycobacterium Tuberculosis (H37R(V) strain) with MIC 5-20 μg/ml that is close to MIC 1 μg/ml demonstrated by antituberculosis drug isoniazid in control experiment. For the first time it was found that the change of ent-kaurane geometry (as in steviol 1) of tetracyclic diterpenoid skeleton to ent-beyerane one (as in isosteviol 2) influences on antituberculosis activity.

  10. Synthesis of Stilbene Derivatives: A Comparative Study of their Antioxidant Activities.

    PubMed

    Romero, Miguel A; González-Delgado, José A; Arteaga, Jesüs F

    2015-07-01

    A series of structurally simple compounds belonging to thestilbene family were synthesized by means of a Ti(III)-mediated methodology that allows access, in an efficient manner, to derivatives of dihydrostilbene, E-stilbene, and stilbene oxide, with high yields. The antioxidant activity of these compounds has been evaluated by means of two electrochemical assays, which provide complementary information, showing that the majority of these stilbene analogs exhibit significant antioxidant activity dependent on the electronic structure and functionalization of the molecule in each case.

  11. Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone

    PubMed Central

    2015-01-01

    Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells. PMID:24447064

  12. ESTABLISHING DERIVED TEXTUAL CONTROL IN ACTIVITY SCHEDULES WITH CHILDREN WITH AUTISM

    PubMed Central

    Miguel, Caio F; Yang, Heejean G; Finn, Heather E; Ahearn, William H

    2009-01-01

    Activity schedules are often used to facilitate task engagement and transition for children with autism. This study evaluated whether conditional discrimination training would serve to transfer the control from activity-schedule pictures to printed words (i.e., derived textual control). Two preschoolers with autism were taught to select pictures and printed words given their dictated names. Following training, participants could respond to printed words by completing the depicted task, match printed words to pictures, and read printed words without explicit training (i.e., emergent relations). PMID:20190932

  13. Semisynthesis and insecticidal activity of some fraxinellone derivatives modified in the B ring.

    PubMed

    Guo, Yong; Qu, Huan; Zhi, Xiaoyan; Yu, Xiang; Yang, Chun; Xu, Hui

    2013-12-11

    A series of novel fraxinellone derivatives modified at the C-1 or C-8 position in the B ring were prepared as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata Walker at 1 mg/mL. Five key steric configurations of compounds 2, 3, and 8f,g,j were further determined by single-crystal X-ray diffraction. It was found that the kinds and the amount of the reduction products of fraxinellone were related to the molar ratio between the reduction agent Red-Al and the substrate fraxinellone. Among all of the derivatives, compounds 2 and 8i,j,o displayed more promising insecticidal activity than their precursors fraxinellone and toosendanin. The preliminary structure-activity relationships revealed that the lactone (B-ring) of fraxinellone contributed to the observed insecticidal activity; the double bond at the C-2 position of fraxinellone was not necessary for the insecticidal activity; conversion of the oxygen atom of carbonyl group on the lactone of fraxinellone to a sulfur one does not improve the insecticidal activity; introduction of electron-withdrawing groups on the phenyl ring of 8f, to the benzoyloxy series, could result in more potent compounds.

  14. Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity.

    PubMed

    Mantu, Dorina; Antoci, Vasilichia; Moldoveanu, Costel; Zbancioc, Gheorghita; Mangalagiu, Ionel I

    2016-01-01

    The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

  15. Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives.

    PubMed

    Yang, Hui; Wang, Hao-Wen; Zhu, Teng-Wei; Yu, Le-Mao; Chen, Jian-Wen; Wang, Lu-Xia; Shi, Lei; Li, Ding; Gu, Lian-Quan; Huang, Zhi-Shu; An, Lin-Kun

    2017-02-15

    In our previous research, 9-bromo indolizinoquinoline-5,12-dione 1 has been found to be a good anti-MRSA agent. However, it had very low bioavailability in vivo possibly due to its low solubility in water. In order to obtain the derivatives with higher anti-MRSA activity and good water solubility, twenty eight bromo-substituted indolizinoquinoline-5,12-dione derivatives were synthesized in the present study. The antibacterial activity of the synthesized compounds was evaluated against one gram-negative and some gram-positive bacterial strains including 100 clinical MRSA strains. The UV assays were carried out to determine the solubility of six active compounds 16, 21, 23 and 27-29. The most potent compound 28 exhibited strong activity against clinical MRSA strains with both MIC50 and MIC90 values lower than 7.8 ng/mL. Compound 27 had good water solubility of 1.98 mg/mL and strong activity against clinical MRSA strains with MIC50 value of 63 ng/mL and MIC90 value of 125 ng/mL, 16-fold higher than that of Vancomycin.

  16. Enhanced water-solubility and antibacterial activity of novel chitosan derivatives modified with quaternary phosphonium salt.

    PubMed

    Zhu, Dan; Cheng, Honghao; Li, Jianna; Zhang, Wenwen; Shen, Yuanyuan; Chen, Shaojun; Ge, Zaochuan; Chen, Shiguo

    2016-04-01

    Chitosan (CS) has been widely recognized as an important biomaterial due to its good antimicrobial activity, biocompatibility and biodegradability. However, CS is insoluble in water in neutral and alkaline aqueous solution due to the linear aggregation of chain molecules and the formation of crystallinity. This is one of the key factors that limit its practical applications. Therefore, improving the solubility of CS in neutral and alkaline aqueous solution is a primary research direction for biomedical applications. In this paper, a reactive antibacterial compound (4-(2,5-Dioxo-pyrrolidin-1-yloxycarbonyl)-benzyl)-triphenyl-phosphonium bromide (NHS-QPS) was synthesized for chemical modification of CS, and a series of novel polymeric antimicrobial agents, N-quaternary phosphonium chitosan derivatives (N-QPCSxy, x=1-2,y=1-4) were obtained. The water solubilities and antibacterial activities of N-QPCSxy against Escherichia coli and Staphylococcus aureus were evaluated compare to CS. The water solubility of N-QPCSxy was all better than that of CS at neutral pH aqueous solution, particularly, N-QPCS14 can be soluble in water over the pH range of 3 to 12. The antibacterial activities of CS derivatives were improved by introducing quaternary phosphonium salt, and antibacterial activity of N-QPCSxy increases with degree of substitution. Overall, N-QPCS14 represents a novel antibacterial polymer material with good antibacterial activity, waters solubility and low cytotoxicity.

  17. Antiproliferative activity of essential oils derived from plants belonging to the Magnoliophyta division.

    PubMed

    Lampronti, Ilaria; Saab, Antoine M; Gambari, Roberto

    2006-10-01

    The essential oils obtained from different officinal plants of Lebanon, belonging to the Magnoliophyta division, have been tested for their antiproliferative activity on human erythroleukemic K562 cells. Satureja montana showed the most interesting biological activity in inhibiting the cell growth and inducing erythroid differentiation of K562 cells. The essential oil of Satureja montana was therefore analyzed using a GC/MS (gas chromatography/mass spectrometry) system in order to identify the major constituents and compare them with analysis performed on Satureja hortensis. We demonstrated that the essential oil composition varied with the species, the major constituent of Satureja hortensis being carvacrol (50.61%) and that of Satureja montana being alpha-terpineol (12.66%). In order to identify molecules possibly responsible for the biological activity, commercially available derivatives have been assayed on the K562 cell line. Satureja montana essential oil displayed different natural derivatives characterized by higher activity than those present in Satureja hortensis. The common active principles are alpha-pinene, gamma-terpinene, 4-terpineol, alpha-terpineol, tau-cadinene, tau-cadinol and caryophyllene. Both caryophyllene and alpha-terpineol showed important antiproliferative effects on K562 cells.

  18. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy.

    PubMed

    Shahzad, Khurrum; Bock, Fabian; Dong, Wei; Wang, Hongjie; Kopf, Stefan; Kohli, Shrey; Al-Dabet, Moh'd Mohanad; Ranjan, Satish; Wolter, Juliane; Wacker, Christian; Biemann, Ronald; Stoyanov, Stoyan; Reymann, Klaus; Söderkvist, Peter; Groß, Olaf; Schwenger, Vedat; Pahernik, Sascha; Nawroth, Peter P; Gröne, Herman-Josef; Madhusudhan, Thati; Isermann, Berend

    2015-01-01

    Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.

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

    PubMed

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

    2013-04-10

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

  20. Fully Integrating the Design Process

    SciTech Connect

    T.A. Bjornard; R.S. Bean

    2008-03-01

    The basic approach to designing nuclear facilities in the United States does not currently reflect the routine consideration of proliferation resistance and international safeguards. The fully integrated design process is an approach for bringing consideration of international safeguards and proliferation resistance, together with state safeguards and security, fully into the design process from the very beginning, while integrating them sensibly and synergistically with the other project functions. In view of the recently established GNEP principles agreed to by the United States and at least eighteen other countries, this paper explores such an integrated approach, and its potential to help fulfill the new internationally driven design requirements with improved efficiencies and reduced costs.

  1. Structure-Activity Relationships in the Cytoprotective Effect of Caffeic Acid Phenethyl Ester (CAPE) and Fluorinated Derivatives: Effects on Heme Oxygenase-1 Induction and Antioxidant Activities

    DTIC Science & Technology

    2010-03-09

    fluorinated derivatives: Effects on heme oxygenase-1 induction and antioxidant activities Xinyu Wang a,b, Salomon Stavchansky a, Sean M. Kerwin c, Phillip D...February 2010 Available online 9 March 2010 Keywords: Caffeic acid phenethyl ester Fluorinated derivative Cytoprotection Oxidative stress Human...acid phenethyl ester (CAPE) as a cytoprotective agent, six catechol ring fluorinated CAPE derivatives were evaluated for their cytoprotective

  2. Activation and measurement of NLRP3 inflammasome activity using IL-1β in human monocyte-derived dendritic cells.

    PubMed

    Fernandez, Melissa V; Miller, Elizabeth A; Bhardwaj, Nina

    2014-05-22

    Inflammatory processes resulting from the secretion of Interleukin (IL)-1 family cytokines by immune cells lead to local or systemic inflammation, tissue remodeling and repair, and virologic control(1) (,) (2) . Interleukin-1β is an essential element of the innate immune response and contributes to eliminate invading pathogens while preventing the establishment of persistent infection(1-5). Inflammasomes are the key signaling platform for the activation of interleukin 1 converting enzyme (ICE or Caspase-1). The NLRP3 inflammasome requires at least two signals in DCs to cause IL-1β secretion(6). Pro-IL-1β protein expression is limited in resting cells; therefore a priming signal is required for IL-1β transcription and protein expression. A second signal sensed by NLRP3 results in the formation of the multi-protein NLRP3 inflammasome. The ability of dendritic cells to respond to the signals required for IL-1β secretion can be tested using a synthetic purine, R848, which is sensed by TLR8 in human monocyte derived dendritic cells (moDCs) to prime cells, followed by activation of the NLRP3 inflammasome with the bacterial toxin and potassium ionophore, nigericin. Monocyte derived DCs are easily produced in culture and provide significantly more cells than purified human myeloid DCs. The method presented here differs from other inflammasome assays in that it uses in vitro human, instead of mouse derived, DCs thus allowing for the study of the inflammasome in human disease and infection.

  3. New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata.

    PubMed

    de Souza, Thiago Belarmino; Brito, Keila Mercês de Oliveira; Silva, Naiara Chaves; Rocha, Raissa Prado; de Sousa, Grasiely Faria; Duarte, Lucienir Pains; Coelho, Luiz Felipe Leomil; Dias, Amanda Latércia Tranches; Veloso, Marcia Paranho; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira

    2016-01-01

    A new series of glucosides modified in their saccharide units were synthesized, evaluated against Candida sp., and compared to prototype 1, an eugenol tetracetyl glucoside previously synthesized and shown to be active against Candida glabrata. Among the new glucosides, benzyl derivative 5 was the most promising, showing fungistatic activity at IC50 18.1 μm against Candida glabrata (threefold higher than fluconazole) and fungicidal activity with a low IC90 value of 36.2 μm. Moreover, the cytotoxic activity of compound 5 (CC50 : 580.9 μm), tested in peripheral blood mononuclear cells, suggests its potential as an agent to treat Candida glabrata infections, with a selectivity index of 32. The new eugenol glucoside 5 may be considered as a novel structural pattern in the development of new anti-Candida drugs.

  4. Analysis of the antimicrobial activities of a chemokine-derived peptide (CDAP-4) on Pseudomonas aeruginosa

    SciTech Connect

    Martinez-Becerra, Francisco; Dominguez-Ramirez, Lenin; Mendoza-Hernandez, Guillermo; Lopez-Vidal, Yolanda; Soldevila, Gloria . E-mail: garciaze@servidor.unam.mx

    2007-04-06

    Chemokines are key molecules involved in the control of leukocyte trafficking. Recently, a novel function as antimicrobial proteins has been described. CCL13 is the only member of the MCP chemokine subfamily displaying antimicrobial activity. To determine Key residues involved in its antimicrobial activity, CCL13 derived peptides were synthesized and tested against several bacterial strains, including Pseudomonas aeruginosa. One of these peptides, corresponding to the C-terminal region of CCL13 (CDAP-4) displayed good antimicrobial activity. Electron microscopy studies revealed remarkable morphological changes after CDAP-4 treatment. By computer modeling, CDAP-4 in {alpha} helical configuration generated a positive electrostatic potential that extended beyond the surface of the molecule. This feature is similar to other antimicrobial peptides. Altogether, these findings indicate that the antimicrobial activity was displayed by CCL13 resides to some extent at the C-terminal region. Furthermore, CDAP-4 could be considered a good antimicrobial candidate with a potential use against pathogens including P. aeruginosa.

  5. Carcinogenic Activity of Some Benz(a)Anthracene Derivatives in Newborn Mice

    PubMed Central

    Roe, F. J. C.; Dipple, A.; Mitchley, B. C. V.

    1972-01-01

    Equimolar doses of 7-methylbenz(a)anthracene and 3 of its derivatives were given to newborn male and female Swiss mice. All 4 substances tested increased the risk of tumour development compared with that seen in control mice given the vehicle, arachis oil, only. 7-Methylbenz(a)anthracene itself was the most actively tumorigenic of the compounds studied, giving rise to subcutaneous sarcomata at the site of injection, and multiple lung tumours and liver tumours. 7-Bromomethyl-12-methylbenz(a)-anthracene was similarly active in the lung and liver but evoked fewer subcutaneous sarcomata. 7-Bromomethylbenz(a)anthracene was seemingly slightly less active than either 7-methylbenz(a)anthracene or 7-bromomethyl-12-methylbenz(a)anthracene. 4-Chloro-7-bromomethylbenz(a)anthracene exhibited only marginal activity in that it slightly increased the risk of liver tumour development in male mice. PMID:4647396

  6. Deterrent activity of hops flavonoids and their derivatives against stored product pests.

    PubMed

    Jackowski, J; Popłoński, J; Twardowska, K; Magiera-Dulewicz, J; Hurej, M; Huszcza, E

    2017-02-16

    Five flavonoids from hops, two of their derivatives, along with naringenin used as a model compound, were tested for their antifeedant activity against three coleopteran stored product pests: Sitophilus granarius L., Tribolium confusum Duv. and Trogoderma granarium Everts. The introduction, into the tested flavonoid molecules, of additional structural fragments such as prenyl or dimethylpyran moiety, is proposed to significantly alter the deterrent activity of the compounds. The prenyl moiety in flavonoids increased the deterrent activity of these compounds in all three of the grain feeding species used in the tests. It is also concluded that the introduction of dimethylpyran moiety to the flavonoid structure increases its deterrent activity in S. granarius and T. confusum, but in one of the test insects, T. granarium, an increased feeding was observed in response to the introduction of dimethylpyran moiety to the flavonoid structure.

  7. The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives.

    PubMed

    Wang, Jing; Yang, Teng; Chen, Huang; Xu, Yun-Nan; Yu, Li-Fang; Liu, Ting; Tang, Jie; Yi, Zhengfang; Yang, Cai-Guang; Xue, Wei; Yang, Fan

    2017-02-15

    A series of novel 9, 13-disubstituted berberine derivatives have been synthesized and evaluated for the antibacterial activities against Staphylococcus aureus, including Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). Compound 20 shows the most potent activity against the growth of Newman strain, with a MIC value of 0.78 μg/mL, which is comparable with the positive control vancomycin. In addition, compound 20, 21, and 33 are highly antistaphylococcal active against five strains of multidrug-resistant S. aureus, with MIC values of 0.78-1.56 μg/mL. Of note, theses antibacterial active compounds have no obvious toxicity to the viability of human fibroblast (HAF) cells at the MIC concentration.

  8. Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus *

    PubMed Central

    Zhang, Hui; Zhang, Lu; Peng, Li-juan; Dong, Xiao-wu; Wu, Di; Wu, Vivian Chi-Hua; Feng, Feng-qin

    2012-01-01

    Fatty acids and derivatives (FADs) are resources for natural antimicrobials. In order to screen for additional potent antimicrobial agents, the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay. Monoglycerides of fatty acids were the most potent class of fatty acids, among which monotridecanoin possessed the most potent antimicrobial activity. The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR: R 2=0.942, Q 2 LOO=0.910; CoMFA: R 2=0.979, Q 2=0.588, respectively). Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structure-activity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents. PMID:22302421

  9. Structure-Activity Relations of Myxinidin, an Antibacterial Peptide Derived from the Epidermal Mucus of Hagfish

    PubMed Central

    Cantisani, Marco; Leone, Marilisa; Mignogna, Eleonora; Kampanaraki, Katerina; Falanga, Annarita; Morelli, Giancarlo

    2013-01-01

    The structure-activity relations of myxinidin, a peptide derived from epidermal mucus of hagfish, Myxine glutinosa L., were investigated. Analysis of key residues allowed us to design new peptides with increased efficiency. Antimicrobial activity of native and modified peptides demonstrated the key role of uncharged residues in the sequence; the loss of these residues reduces almost entirely myxinidin antimicrobial activity, while insertion of arginine at charged and uncharged position increases antimicrobial activity compared with that of native myxinidin. Particularly, we designed a peptide capable of achieving a high inhibitory effect on bacterial growth. Experiments were conducted using both Gram-negative and Gram-positive bacteria. Nuclear magnetic resonance (NMR) studies showed that myxinidin is able to form an amphipathic α-helical structure at the N terminus and a random coil region at the C terminus. PMID:24002100

  10. Synthesis, antimicrobial, antioxidant activities of novel 6-aryl-5-cyano thiouracil derivatives.

    PubMed

    Mohamed, M S; Youns, M M; Ahmed, N M

    2013-11-01

    A series of 6-aryl-5-cyano thiouracil derivatives (2a-c to 11a-c) was synthesized from 6-aryl-4-hydrazino-2-thioxo-1,2-dihydropyrimidine-5-carbonitriles (1a-c). The products were characterized by analytical and spectral data (IR, (1)H NMR, (13)C NMR and mass spectra). All compounds were screened for their in-vitro antibacterial and antifungal activities. Compounds 7a, 7g and 9a-c showed pronounced antimicrobial activity than standards. Some of the newly synthesized compounds were evaluated for antioxidant activity. Compounds 1c, 5c and 8c displayed promising free radical scavenging activity and found to be more potent than standard, ascorbic acid (vitamin C).

  11. Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity.

    PubMed

    Artyushin, Oleg I; Sharova, Elena V; Vinogradova, Natalya M; Genkina, Galina K; Moiseeva, Aleksandra A; Klemenkova, Zinaida S; Orshanskaya, Iana R; Shtro, Anna A; Kadyrova, Renata A; Zarubaev, Vladimir V; Yarovaya, Olga I; Salakhutdinov, Nariman F; Brel, Valery K

    2017-03-22

    A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.

  12. Characterization, refining and antioxidant activity of saccharides derived from hemicelluloses of wood and rice husks.

    PubMed

    Rivas, Sandra; Conde, Enma; Moure, Andrés; Domínguez, Herminia; Parajó, Juan Carlos

    2013-11-01

    Samples of rice husks, Eucalyptus globulus wood and Pinus pinaster wood (containing arabinoxylan, acetylated glucuronoxylan and acetylated glucomannan as major hemicellulose components, respectively) were subjected to autohydrolysis. The resulting liquid phases, containing mainly hemicellulose-derived saccharides, were refined by physicochemical methods to reduce their contents of monosaccharides and non-saccharide compounds. Raw autohydrolysis liquors and refined concentrates coming from aqueous treatments were assayed for antioxidant activity using the following assays: reducing power (FRAP), DPPH and ABTS radical scavenging activity and protection of β-carotene-linoleic emulsions from oxidation. The reducing power and radical scavenging capacity of the non refined fractions were comparable to the ones determined for the reference compound butylhydroxytoluene. Hemicellulose concentrated from the different feedstocks and refining protocols showed a dose dependent antioxidant activity in the range of concentrations evaluated. The in vitro antioxidant activity of concentrates correlated with their phenolic content.

  13. Discovery of 4-aminoquinazoline--urea derivatives as Aurora kinase inhibitors with antiproliferative activity.

    PubMed

    Cai, Jin; Li, Lili; Hong, Kwon Ho; Wu, Xiaoqing; Chen, Junqing; Wang, Peng; Cao, Meng; Zong, Xi; Ji, Min

    2014-11-01

    Two series of 20 novel 4-aminoquinazoline-urea derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activity against six human cancer cell lines (K562, U937, A549, NCI-H661, HT29 and LoVo) using the MTT-based assay. Most compounds showed significant antiproliferative activities against four solid tumor cell lines, but no or poor activities against two leukemia cell lines. Furthermore, the target compounds were screened for Aurora A/B kinases inhibitory activity. Among them, 7c, 7d, 8c, and 8d are more potent against Aurora A kinase than ZM447439. Docking study of compounds 7d and ZM447439 revealed that they bound strongly to the ATP-binding sites of Aurora A and B. Thus, they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting Aurora kinases.

  14. Microwave-assisted synthesis and antifungal activity of novel fused Osthole derivatives.

    PubMed

    Zhang, Ming-Zhi; Zhang, Rong-Rong; Wang, Jia-Qun; Yu, Xiang; Zhang, Ya-Ling; Wang, Qing-Qing; Zhang, Wei-Hua

    2016-11-29

    Based on the microwave-assisted synthetic protocol developed in our previous work, we have synthesized a series of novel furo[3,2-c]coumarins as fused Osthole derivatives, via the reaction of 4-hydroxycoumarins and β-ketoesters catalyzed by DMAP. All the target compounds were evaluated in vitro for their antifungal activity against six phytopathogenic fungi, some compounds exhibited potential activity in the primary assays. Especially compounds 6c, 7b, 8b and 8c (shown in Fig. 1) were the most active ones, EC50 values of these four compounds against Colletotrichum capsica, Botrytis cinerea and Rhizoctonia solani were further investigated. 6c was identified as the most promising candidate with the EC50 value at 0.110 μM against Botrytis cinerea and 0.040 μM against Colletotrichum capsica, respectively, representing better antifungal activity than that of the commonly used fungicide Azoxystrobin.

  15. Synthesis and structure-activity relationship of novel cinnamamide derivatives as antidepressant agents.

    PubMed

    Han, Min; Ma, Xiaohui; Jin, Yuanpeng; Zhou, Wangyi; Cao, Jing; Wang, Yahu; Zhou, Shuiping; Wang, Guocheng; Zhu, Yonghong

    2014-11-15

    Cinnamamide 3a, a leading compound with antidepressant-like activity, and its derivatives were synthesized and their antidepressant activity and structure-activity relationship were investigated. Most of the compounds with trifluoromethyl group in methylenedioxyphenyl moiety (3f, 4b-c and 6a-b) exhibited significant antidepressant activity, measured in terms of percentage decrease in immobility duration by tail suspension test. In addition, the dose-dependent antidepressant effect of the most potent compound 3f was subsequently confirmed in tail suspension test and forced swim test. The test results showed that 3f was equal to or more effective than the standard drug fluoxetine at a concentration of 10mg/kg. Furthermore, compound 3f did not show any central nervous system stimulant properties in the open-field test and the preliminary results were promising enough to warrant further detailed antidepressant research around this scaffold.

  16. Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity.

    PubMed

    Shi, Jing Bo; Tang, Wen Jian; Qi, Xing Bao; Li, Rong; Liu, Xin Hua

    2015-01-27

    A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 ± 0.08 μM. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity.

  17. Interhourly Variability Index of Geomagnetic Activity and Its Use in Deriving the Long-Term Variation of Solar Wind Speed

    DTIC Science & Technology

    2007-10-31

    CONTRACT NUMBER Interhourly variability index of geomagnetic activity and its use in deriving the long-term variation of solar wind speed 5b...detailed derivation of the interhourly variability (IHP) index of geomagnetic activity. The LHV index for a given geomagnetic element is mechanically... index is derived separately for stations in both hemispheres within six longitude sectors spanning the Earth using only local night hours. It is

  18. Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of β-Thujaplicin Derivatives.

    PubMed

    Fotopoulou, Theano; Ćirić, Ana; Kritsi, Eftichia; Calhelha, Ricardo C; Ferreira, Isabel C F R; Soković, Marina; Zoumpoulakis, Panagiotis; Koufaki, Maria

    2016-09-01

    Natural β-thujaplicin displays a remarkable array of biological activities for the prevention or treatment of various disorders while its tropolone scaffold inspired the synthesis of new analogs. The main goal of the current study was to evaluate the influence of 4-substituted piperazine moieties at position 7 of the β-thujaplicin scaffold, on the antimicrobial activity. In order to determine the biological activity of the β-thujaplicin derivatives, a microdilution method was used against a wide variety of bacteria and fungi. Pseudomonas aeruginosa PAO 1 was used for testing antiquorum and antibiofilm effects. Four human tumor cell lines (MCF-7, NCI-H460, HeLa, and HepG2) and a porcine liver derived cell line (PLP2) were used for testing antitumor and cytotoxic activity. The compounds present better antibacterial and antifungal activity in comparison with approved antimicrobials used as control agents. β-Thujaplicin showed strong antibacterial and antifungal activities against all tested species. Further studies of their antibacterial activity revealed that all compounds presented good antibiofilm and antiquorum effects. Fungi were more susceptible than bacteria to the tested compounds, with the exception of MK150, which possessed the best antibacterial effect. None of the tested compounds, at the GI50 values obtained for the tumor cell lines, have shown toxicity for non-tumor liver cells (PLP2). The prediction of physicochemical properties of the compounds was performed to further explain the structure-activity relationship. Finally, in order to explore a possible mechanism of action of the synthesized compounds, molecular docking studies were performed on CYP51 (14-a lanosterol demethylase), an important component of the fungal cell membrane.

  19. Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators.

    PubMed

    Bogerd, Hal P; Kornepati, Anand V R; Marshall, Joy B; Kennedy, Edward M; Cullen, Bryan R

    2015-12-29

    Whereas several mammalian proteins can restrict the replication of HIV-1 and other viruses, these are often not expressed in relevant target cells. A potential method to inhibit viral replication might therefore be to use synthetic transcription factors to induce restriction factor expression. In particular, mutants of the RNA-guided DNA binding protein Cas9 that have lost their DNA cleavage activity could be used to recruit transcription activation domains to specific promoters. However, initial experiments revealed only weak activation unless multiple promoter-specific single guide RNAs (sgRNAs) were used. Recently, the recruitment of multiple transcription activation domains by a single sgRNA, modified to contain MS2-derived stem loops that recruit fusion proteins consisting of the MS2 coat protein linked to transcription activation domains, was reported to induce otherwise silent cellular genes. Here, we demonstrate that such "synergistic activation mediators" can induce the expression of two restriction factors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally lack these proteins. We observed modest activation of endogenous A3G or A3B expression using single sgRNAs but high expression when two sgRNAs were used. Whereas the induced A3G and A3B proteins both blocked infection by an HIV-1 variant lacking a functional vif gene by inducing extensive dC-to-dU editing, only the induced A3B protein inhibited wild-type HIV-1. These data demonstrate that Cas9-derived transcriptional activators have the potential to be used for screens for endogenous genes that affect virus replication and raise the possibility that synthetic transcription factors might prove clinically useful if efficient delivery mechanisms could be developed.

  20. Synthesis of Resveratrol Derivatives and In Vitro Screening for Potential Cancer Chemopreventive Activities.

    PubMed

    Orsini, Fulvia; Verotta, Luisella; Klimo, Karin; Gerhäuser, Clarissa

    2016-06-01

    New resveratrol (trans-3,4',5-trihydroxystilbene) analogs were synthesized and screened for their in vitro cancer chemopreventive potential using various bioassays relevant for the prevention of carcinogenesis in humans: two assays to detect modulators of carcinogen metabolism (Cyp1A inhibition; determination of NAD(P)H/quinone reductase (QR) activity), three assays to identify radical scavenging and antioxidant properties (DPPH, ORAC, superoxide anion radicals in differentiated HL-60 cells), four assays to determine anti-inflammatory and anti-hormonal effects (iNOS, Cox-1 and aromatase inhibition, anti-estrogenic potential). 3,4',5-Tri-O-methyl resveratrol 1a was about sevenfold more active than resveratrol in inhibiting Cyp1A activity, it was a potent inducer of QR activity, and it showed pure anti-estrogenic activity (whereas resveratrol is a known mixed estrogen (ant)agonist with both estrogenic and anti-estrogenic properties). Dual estrogen ant-/agonist activity was restored in the mono-O-benzyl-substituted derivatives 4b (4'-O-benzyl resveratrol) and 5b (3-O-benzyl resveratrol). With respect to aromatase inhibition (Cyp19), which provided the highest number of actives, the benzyl-substituted series was more potent than the methyl-substituted derivatives of resveratrol, and 3-O-benzyl resveratrol 5b was about eightfold more active than resveratrol. Overall, 3,4',5-tri-O-pivaloyl resveratrol oxide 7c was identified as a potent inducer of phase 2 enzymes concomitant with inhibition of LPS-mediated iNOS induction.