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Sample records for design synthesis biological

  1. Molecular design, synthesis and evaluation of chemical biology tools

    NARCIS (Netherlands)

    Hoogenboom, Jorin

    2017-01-01

    Chapter 1 provides a perspective of synthetic organic chemistry as a discipline involved in the design, synthesis and evaluation of complex molecules. The reader is introduced with a brief history of synthetic organic chemistry, all the while dealing with different aspects of

  2. Design, Synthesis and Biological Evaluation of Quorum Sensing Modulators

    DEFF Research Database (Denmark)

    Hansen, Mette Reimert

    to intercept the communication system by synthetic non-native ligands and thereby lower the pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify new ligands with quorum sensing modulating activities, three types of AHL analogs were synthesized using different synthetic strategies....... Overall, 17 compounds were identified as quorum sensing activators with EC50 values in the low micromolar range. Two build/couple/pair strategies for the synthesis of structurally diverse small molecules are presented. In the first strategy, the Petasis 3-component reaction (Petasis 3-CR) of hydrazides...

  3. Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

    Czech Academy of Sciences Publication Activity Database

    Novotná, E.; Waisser, K.; Kuneš, J.; Palát, K.; Skálová, L.; Szotáková, B.; Buchta, V.; Stolaříková, J.; Ulmann, V.; Pávová, Marcela; Weber, Jan; Komrsková, J.; Hašková, P.; Vokřál, I.; Wsól, V.

    2017-01-01

    Roč. 350, č. 8 (2017), č. článku e1700020. ISSN 0365-6233 Institutional support: RVO:61388963 Keywords : biological activity * cytotoxicity * isocitrate lyase * isothiosemicarbazone * tuberculosis Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.994, year: 2016

  4. Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Konstantinos M. Kasiotis

    2017-09-01

    Full Text Available Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  5. Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Science.gov (United States)

    Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

    2017-09-01

    Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  6. Design synthesis and biological evaluation of 2-methylphenyl semicarbazone derivatives

    Directory of Open Access Journals (Sweden)

    Manmohan Singhal

    2011-03-01

    Full Text Available We have used pharmacophore hybridization technique of drug design and designed a pharmacophore model 2-methylphenylsemicarbazone which is having hydrogen acceptor site, hydrogen donor site, lipophilic site etc using ligandscout-2.02 software. A series of 2-methylphenyl-semicarbazone was synthesized and evaluated for their antipyretic activity using boiled cow milk induced pyrexia in rabbits. Compound 11 was the most active compound. The possible metabolites of some selected synthesized chalconesemicarbazones were predicted by computational method using Pallas version-3.1 ADME-Tox prediction software. The major pathway of metabolism was found to be p-hydroxylation and amide hydrolysis.

  7. Design, synthesis and biological evaluation of novel desmuramyldipeptide analogs.

    Science.gov (United States)

    Jakopin, Žiga; Corsini, Emanuela; Gobec, Martina; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

    2011-09-01

    A series of novel desmuramyldipeptides have been designed and synthesized as part of our search for therapeutically useful muramyldipeptide (MDP) analogs. Their immunomodulatory properties were initially assessed in vitro, evaluating their effect on lipopolysaccharide (LPS)-induced cytokine release in THP-1 cells. Following the initial screening, selected compounds were further investigated for immunomodulatory properties using LPS and phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells. The results confirmed the immunomodulatory properties of some of the synthesized desmuramyldipeptide analogs. Taken together, presented data confirmed the immunostimulatory effect of compound 44, MDP derivative incorporating a pyrido-fused [1,2]-benzisothiazole moiety, while for compounds 32 and 39, indole scaffold-based derivatives of MDP, an immunosuppressive effect was observed. Further studies will be necessary to address their potential therapeutic use as immunomodulatory drugs, both as immunostimulants or anti-inflammatory agents. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

    Science.gov (United States)

    Nicolaou, K C; Chen, Pengxi; Zhu, Shugao; Cai, Quan; Erande, Rohan D; Li, Ruofan; Sun, Hongbao; Pulukuri, Kiran Kumar; Rigol, Stephan; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

    2017-11-01

    A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.

  9. Design, synthesis, and biological evaluation of achiral analogs of duocarmycin SA.

    Science.gov (United States)

    Daniell, Kristen; Stewart, Michelle; Madsen, Erik; Le, Minh; Handl, Heather; Brooks, Natalie; Kiakos, Konstantinos; Hartley, John A; Lee, Moses

    2005-01-03

    The design, synthesis, as well as biochemical and biological evaluation of two novel achiral analogs of duocarmycin SA (DUMSA), 1 and 2, are described. Like CC-1065 and adozelesin, compounds 1 and 2 covalently reacted with adenine-N3 in AT-rich sequences and led to the formation of DNA strand breaks upon heating. The cytotoxicity of compounds 1 and 2 against human cancer cells (K562, LS174T) was determined using a MTT assay giving IC(50) values in the low nanomolar. Further cytotoxicity screening of compound 2 conducted by the NCI against a panel of 60 different human cancer cell lines indicated that it was particularly active against several solid tumor cells lines derived from the lung, colon, CNS, skin, and breast.

  10. Design, Synthesis and Biological Activity of Novel Reversible Peptidyl FVIIa Inhibitors Rh-Catalyzed Enantioselective Synthesis of Diaryl Amines

    DEFF Research Database (Denmark)

    Storgaard, Morten

    functional group tolerance. Unfortunately, these -aryl tetramic acids were too unreactive and ring opening toward the synthesis of the building block did not succeed. However, -aryl tetramic acids are still interesting compounds due to their potential biological activity. The building block 3.15 (P1......-catalyzed enantioselective synthesis of diaryl amines, which is an important class of compounds (Chapter 4). For example it is found in the third generation anti-histaminic agent levocetirizine. Development of efficient synthetic routes is therefore of considerably interest. The rhodium-catalyzed enantioselective synthesis...

  11. Design, synthesis, and biological testing of thiosalicylamides as a novel class of calcium channel blockers.

    Science.gov (United States)

    Mehanna, Ahmed S; Kim, Jin Yung

    2005-07-01

    The current research aimed to investigate the importance of the heterocyclic ring system in the structure of the cardiovascular drug diltiazem for its calcium channel blocking activity. The manuscript describes the design, synthesis, and biological testing of a total of 10 S-(p-methoxybenzyl), N-substituted thiosalicylamides as a series of non-cyclic compounds derived from diltiazem's structure. The new compounds maintained all diltiazem pharmacophores except the thiazepine ring system. In vitro evaluation of the new series for calcium channel blocking effects revealed moderate activities with IC50 values in the range of 4.8-56.0 microM. The data suggest that the ring system is not essential for activity; however, its absence leads to a considerable drop of activity relative to that of diltiazem (IC50=0.3 microM). Compounds of the current series showed optimum activity when the aliphatic alkyl chain on the salicylamide nitrogen is part of a piperidine or piperazine ring system substituted at the terminal nitrogen with a benzyl group.

  12. Design, Synthesis, and Biological Evaluation of Vanillin Hydroxamic Acid Derivatives as Novel Peptide Deformylase Inhibitors.

    Science.gov (United States)

    Gao, Jian; Qiu, Shengzhi; Liang, Li; Hao, Zhixiang; Zhou, Qianqian; Wang, Fanfan; Mou, Jie; Lin, Qisi

    2018-01-01

    Infectious disease is increasingly hampering human health, which challenge the discovery of new antibacterial target. Peptide deformylase (PDF), a metalloenzyme responsible for catalyzing the removal of the N-formyl group from nascent proteins, was considered as an important target in antibacterial drug discovery. Reported here are the design, synthesis and biological evaluation of vanillin hydroxamic acid derivatives. Analysis of the structure-activity relationships lead to the discovery of compound 8, which exhibits promising antibacterial activity against Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Aspergillus foetidus with the MIC value of 0.32 µg/ml, 0.32 µg/ml, 0.16 µg/ml and 0.16 µg/ml, respectively. Furthermore, molecular docking study was applied to elucidate binding interaction between compound 8 and PDF, which indicate that compound 8 not only shares the same binding pocket with actinonin, but also has a similar binding pattern. In silico pharmacokinetic and toxicity prediction studies also suggested that compound 8 has a relatively high drug score of 0.80, and has no risk of toxicity. Compound 8 might represent a promising scaffold for the further development of novel antibacterial drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Crestey, François; Jensen, Anders A.; Borch, Morten

    2013-01-01

    The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype...

  14. Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors

    DEFF Research Database (Denmark)

    Storgaard, Morten; Henriksen, Signe Teuber; Zaragoza, Florencio

    2011-01-01

    Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia...

  15. Synthetic Biology: Putting Synthesis into Biology

    Science.gov (United States)

    Liang, Jing; Luo, Yunzi; Zhao, Huimin

    2010-01-01

    The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

  16. PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics.

    Science.gov (United States)

    Marwaha, Alka; Goel, R K; Mahajan, Mohinder P

    2007-09-15

    Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compounds acting as cognition enhancers have been provided, which can be further exploited in search of such New Chemical Entities (NCEs).

  17. Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Marcin Szybinski

    2017-10-01

    Full Text Available Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR. Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol. The structures of the final products were confirmed by NMR, UV and mass spectroscopy. Their binding affinities for the full-length human VDR were determined and it was established that compound substituted at C-2 with exomethylene group showed significant binding to the receptor. This analog was also able to induce monocytic differentiation of HL-60 cells.

  18. Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors.

    Science.gov (United States)

    Reddy, Nimmanapalli P; Aparoy, Polamarasetty; Reddy, T Chandra Mohan; Achari, Chandrani; Sridhar, P Ramu; Reddanna, Pallu

    2010-08-15

    Ten novel mono- and di-O-prenylated chalcone derivatives were designed on the basis of a homology derived molecular model of 5-lipoxygenase (5-LOX). The compounds were docked into 5-LOX active site and the binding characteristics were quantified using LUDI. To verify our theoretical assumption, the molecules were synthesized and tested for their 5-LOX inhibitory activities. The synthesis was carried out by Claisen-Schmidt condensation reaction of mono- and di-O-prenylated acetophenones with appropriate aldehydes. 5-LOX in vitro inhibition assay showed higher potency of di-O-prenylated chalcones than their mono-O-prenylated chalcone analogs. Compound 5e exhibited good inhibition with an IC(50) at 4 microM. The overall trend for the binding energies calculated and LUDI score was in good qualitative agreement with the experimental data. Further, the compound 5e showed potent anti-proliferative effects (GI(50) at 9 microM) on breast cancer cell line, MCF-7. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

    Science.gov (United States)

    Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

    2018-05-15

    Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation.

    Science.gov (United States)

    Liu, Han-Bo; Gao, Wei-Wei; Tangadanchu, Vijai Kumar Reddy; Zhou, Cheng-He; Geng, Rong-Xia

    2018-01-01

    A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Noticeably, compound 7d could effectively inhibit the growth of A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 μg/mL, respectively. Further studies revealed that pyrimidine derivative 7d could exhibit bactericidal mode of action against both Gram positive (S. aureus and MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed low cell toxicity and did not obviously trigger the development of resistance in bacteria even after 16 passages. Furthermore, compound 7d was able to beneficially regulate reactive oxygen species (ROS) generation for an excellent safety profile. Molecular docking study revealed that compound 7d could bind with DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for antimicrobial mechanism disclosed that compound 7d could effectively intercalate into calf thymus DNA to form a steady supramolecular complex, which might further block DNA replication to exert the powerful bioactivities. The binding investigation of compound 7d with human serum albumins (HSA) revealed that this molecule could be effectively transported by HSA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Design, Synthesis, and Biological Activity of 1,2,3-Triazolobenzodiazepine BET Bromodomain Inhibitors.

    Science.gov (United States)

    Sharp, Phillip P; Garnier, Jean-Marc; Hatfaludi, Tamas; Xu, Zhen; Segal, David; Jarman, Kate E; Jousset, Hélène; Garnham, Alexandra; Feutrill, John T; Cuzzupe, Anthony; Hall, Peter; Taylor, Scott; Walkley, Carl R; Tyler, Dean; Dawson, Mark A; Czabotar, Peter; Wilks, Andrew F; Glaser, Stefan; Huang, David C S; Burns, Christopher J

    2017-12-14

    A number of diazepines are known to inhibit bromo- and extra-terminal domain (BET) proteins. Their BET inhibitory activity derives from the fusion of an acetyl-lysine mimetic heterocycle onto the diazepine framework. Herein we describe a straightforward, modular synthesis of novel 1,2,3-triazolobenzodiazepines and show that the 1,2,3-triazole acts as an effective acetyl-lysine mimetic heterocycle. Structure-based optimization of this series of compounds led to the development of potent BET bromodomain inhibitors with excellent activity against leukemic cells, concomitant with a reduction in c- MYC expression. These novel benzodiazepines therefore represent a promising class of therapeutic BET inhibitors.

  2. Brassinosteroids: synthesis and biological activities

    Czech Academy of Sciences Publication Activity Database

    Oklešťková, Jana; Rárová, Lucie; Kvasnica, Miroslav; Strnad, Miroslav

    2015-01-01

    Roč. 14, č. 6 (2015), s. 1053-1072 ISSN 1568-7767 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Brassinosteroids * Chemical synthesis * Plant biological activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.686, year: 2015

  3. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

  4. Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei.

    Science.gov (United States)

    Pham, ThanhTruc; Walden, Madeline; Butler, Christopher; Diaz-Gonzalez, Rosario; Pérez-Moreno, Guiomar; Ceballos-Pérez, Gloria; Gomez-Pérez, Veronica; García-Hernández, Raquel; Zecca, Henry; Krakoff, Emma; Kopec, Brian; Ichire, Ogar; Mackenzie, Caden; Pitot, Marika; Ruiz, Luis Miguel; Gamarro, Francisco; González-Pacanowska, Dolores; Navarro, Miguel; Dounay, Amy B

    2017-08-15

    In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Hai-Chao Wang

    2016-08-01

    Full Text Available A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against four cancer cell line variants (A549, MCF-7, HeLa, HepG2 with IC50 values of 0.46, 0.29, 0.15 and 0.21 μM respectively, which showed the most potent EGFR inhibition activities (IC50 = 0.08 μM for EGFR. Molecular modeling simulation studies were performed in order to predict the biological activity and activity relationship (SAR of these benzohydrazide derivatives. These results suggested that compound H20 may be a promising anticancer agent.

  6. Design Methodology - Design Synthesis

    DEFF Research Database (Denmark)

    Andreasen, Mogens Myrup

    2003-01-01

    Design Methodology is part of our practice and our knowledge about designing, and it has been strongly supported by the establishing and work of a design research community. The aim of this article is to broaden the reader¿s view of designing and Design Methodology. This is done by sketching...... the development of Design Methodology through time and sketching some important approaches and methods. The development is mainly forced by changing industrial condition, by the growth of IT support for designing, but also by the growth of insight into designing created by design researchers.......ABSTRACT Design Methodology shall be seen as our understanding of how to design; it is an early (emerging late 60ies) and original articulation of teachable and learnable methodics. The insight is based upon two sources: the nature of the designed artefacts and the nature of human designing. Today...

  7. Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors

    Directory of Open Access Journals (Sweden)

    Shuang Cao

    2016-07-01

    Full Text Available A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin. Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.

  8. Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

    Directory of Open Access Journals (Sweden)

    Ping Xu

    2013-05-01

    Full Text Available In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71 replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay.

  9. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Design, Synthesis and Biological Evaluation of C(6-Modified Celastrol Derivatives as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Kaiyong Tang

    2014-07-01

    Full Text Available New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468. The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84–0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

  11. Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents.

    Science.gov (United States)

    Labruère, Raphaël; Gautier, Benoît; Testud, Marlène; Seguin, Johanne; Lenoir, Christine; Desbène-Finck, Stéphanie; Helissey, Philippe; Garbay, Christiane; Chabot, Guy G; Vidal, Michel; Giorgi-Renault, Sylviane

    2010-12-03

    We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series.

  12. Extended N-Arylsulfonylindoles as 5-HT6 Receptor Antagonists: Design, Synthesis & Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Gonzalo Vera

    2016-08-01

    Full Text Available Based on a known pharmacophore model for 5-HT6 receptor antagonists, a series of novel extended derivatives of the N-arylsulfonyindole scaffold were designed and identified as a new class of 5-HT6 receptor modulators. Eight of the compounds exhibited moderate to high binding affinities and displayed antagonist profile in 5-HT6 receptor functional assays. Compounds 2-(4-(2-methoxyphenylpiperazin-1-yl-1-(1-tosyl-1H-indol-3-ylethanol (4b, 1-(1-(4-iodophenylsulfonyl-1H-indol-3-yl-2-(4-(2-methoxyphenylpiperazin-1-ylethanol (4g and 2-(4-(2-methoxyphenylpiperazin-1-yl-1-(1-(naphthalen-1-ylsulfonyl-1H-indol-3-ylethanol (4j showed the best binding affinity (4b pKi = 7.87; 4g pKi = 7.73; 4j pKi = 7.83. Additionally, compound 4j was identified as a highly potent antagonist (IC50 = 32 nM in calcium mobilisation functional assay.

  13. Design, synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol.

    Science.gov (United States)

    Du, Cheng; Dong, Ming-Hui; Ren, Yu-Jie; Jin, Lu; Xu, Cheng

    2017-09-01

    A new series of resveratrol heterocyclic analogs (4a-m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure-activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC 50  = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC 50  = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4'-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F 1 -ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.

  14. Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

    Science.gov (United States)

    Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

    2004-02-12

    A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

  15. Design, synthesis, and in vitro transfection biology of novel tocopherol based monocationic lipids: a structure-activity investigation.

    Science.gov (United States)

    Kedika, Bhavani; Patri, Srilakshmi V

    2011-01-27

    Herein, we report on the design, synthesis, and in vitro gene delivery efficacies of five novel tocopherol based cationic lipids (1-5) in transfecting CHO, B16F10, A-549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids (1-5) were evaluated by both β-galactosidase reporter gene expression and inverted fluorescent microscopic experiments. The results of the present structure-activity investigation convincingly demonstrate that the tocopherol based lipid with three hydroxyl groups in its headgroup region showed 4-fold better transfection efficiency than the commercial formulation. The results also demonstrate that these tocopherol based lipids may be targeted to liver. Transfection efficiency of all the relevant lipids was maintained even when the serum was present during the transfection conditions. The results indicated that the designed systems are quite capable of transferring the DNA into all four types of cells studied with low or no toxicity.

  16. Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

    Science.gov (United States)

    Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Buchman, Marek; Shah, Akshay A; Cen, Nicholas; McCurry, Megan D; Beabout, Kathryn; Shamoo, Yousif

    2017-11-08

    An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

  17. Opportunities for Merging Chemical and Biological Synthesis

    Science.gov (United States)

    Wallace, Stephen; Balskus, Emily P.

    2014-01-01

    Organic chemists and metabolic engineers use largely orthogonal technologies to access small molecules like pharmaceuticals and commodity chemicals. As the use of biological catalysts and engineered organisms for chemical production grows, it is becoming increasingly evident that future efforts for chemical manufacture will benefit from the integration and unified expansion of these two fields. This review will discuss approaches that combine chemical and biological synthesis for small molecule production. We highlight recent advances in combining enzymatic and non-enzymatic catalysis in vitro, discuss the application of design principles from organic chemistry for engineering non-biological reactivity into enzymes, and describe the development of biocompatible chemistry that can be interfaced with microbial metabolism. PMID:24747284

  18. Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents.

    Science.gov (United States)

    Jameel, Ehtesham; Meena, Poonam; Maqbool, Mudasir; Kumar, Jitendra; Ahmed, Waqar; Mumtazuddin, Syed; Tiwari, Manisha; Hoda, Nasimul; Jayaram, B

    2017-08-18

    In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC 50 values 0.065 and 0.092 μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ∼28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.

    Science.gov (United States)

    Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail

    2018-01-20

    Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC 50  stronger relaxant effects on the trachea than the reference compound cromakalim (EC 50  = 124 μM), in particular compounds B4, B7 and B16 (EC 50   57 μM for all, and EC 50  > 200 μM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC 50  = 30 μM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca 2+ channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 μM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Synthesis of nanoparticles and nanomaterials biological approaches

    CERN Document Server

    Abdullaeva, Zhypargul

    2017-01-01

    This book covers biological synthesis approaches for nanomaterials and nanoparticles, including introductory material on their structure, phase compositions and morphology, nanomaterials chemical, physical, and biological properties. The chapters of this book describe in sequence the synthesis of various nanoparticles by microorganisms, bacteria, yeast, algae, and actynomycetes; plant and plant extract-based synthesis; and green synthesis methods. Each chapter provides basic knowledge on the synthesis of nanomaterials, defines fundamental terms, and aims to build a solid foundation of knowledge, followed by explanations, examples, visual photographs, schemes, tables and illustrations. Each chapter also contains control questions, problem drills, as well as case studies that clarify theory and the explanations given in the text. This book is ideal for researchers and advanced graduate students in materials engineering, biotechnology, and nanotechnology fields. As a reference book this work is also appropriate ...

  1. Design, Synthesis and Biological Evaluation of Histone Deacetylase (HDAC) Inhibitors: Saha (Vorinostat) Analogs and Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity

    Science.gov (United States)

    Negmeldin, Ahmed Thabet

    HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools to help understand the HDAC-related cancer biology. Our strategy was based on synthesis and screening of several derivatives of the non-selective FDA approved drug SAHA substituted at different positions of the linker region. Several SAHA analogs modified at the C4 and C5 positions of the linker were synthesized. The new C4- and C5-modified SAHA libraries, along with the previously synthesized C2-modified SAHA analogs were screened in vitro and in cellulo for HDAC isoform selectivity. Interestingly, several analogs exhibited dual HDAC6/HDAC8 selectivity. Enantioselective syntheses of the pure enantiomers of some of the interesting analogs were performed and the enantiomers were screened in vitro. Among the most interesting analogs, ( R)-C4-benzyl SAHA displayed 520- to 1300-fold selectivity for HDAC6 and HDAC8 over HDAC1, 2, and 3, with IC50 values of 48 and 27 nM with HDAC6 and 8, respectively. Docking studies were performed to provide structural rationale for the observed selectivity of the new analogs. In addition, rational design, synthesis, and screening of several other biaryl indolyl benzamide HDAC inhibitors is discussed, and some showed modest HDAC1 selectivity. The new biaryl indolyl benzamides can be useful to further develop HDAC1 selective inhibitors. The dual HDAC6/8 selective

  2. Design, synthesis and biological activities of new brassinosteroid analogues with a phenyl group in the side chain

    Czech Academy of Sciences Publication Activity Database

    Kvasnica, Miroslav; Oklešťková, Jana; Bazgier, Václav; Rárová, L.; Kořínková, Petra; Mikulík, Jaromír; Buděšínský, Miloš; Béreš, T.; Berka, K.; Lu, Q.; Russinova, E.; Strnad, Miroslav

    2016-01-01

    Roč. 14, č. 37 (2016), s. 8691-8701 ISSN 1477-0520 R&D Projects: GA MŠk(CZ) LO1204; GA ČR GJ15-08202Y; GA MŠk(CZ) LM2015047 Institutional support: RVO:61389030 ; RVO:61388963 Keywords : ASYMMETRIC DIHYDROXYLATION * IMMUNOMODULATORY ACTIVITY * BRI1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.564, year: 2016

  3. Paradigms for biologically inspired design

    DEFF Research Database (Denmark)

    Lenau, T. A.; Metzea, A.-L.; Hesselberg, T.

    2018-01-01

    engineering, medical engineering, nanotechnology, photonics,environmental protection and agriculture. However, a major obstacle for the wider use of biologically inspired design isthe knowledge barrier that exist between the application engineers that have insight into how to design suitable productsand......Biologically inspired design is attracting increasing interest since it offers access to a huge biological repository of wellproven design principles that can be used for developing new and innovative products. Biological phenomena can inspireproduct innovation in as diverse areas as mechanical...... the biologists with detailed knowledge and experience in understanding how biological organisms function in theirenvironment. The biologically inspired design process can therefore be approached using different design paradigmsdepending on the dominant opportunities, challenges and knowledge characteristics...

  4. Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

    Science.gov (United States)

    Sabbah, Dima A; Hishmah, Bayan; Sweidan, Kamal; Bardaweel, Sanaa; AlDamen, Murad; Zhong, Haizhen A; Abu Khalaf, Reema; Hasan Ibrahim, Ameerah; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Mubarak, Mohammad S

    2018-01-01

    Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion.

    Science.gov (United States)

    Prescher, Horst; Frank, Martin; Gütgemann, Stephan; Kuhfeldt, Elena; Schweizer, Astrid; Nitschke, Lars; Watzl, Carsten; Brossmer, Reinhard

    2017-02-09

    Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion. The compounds are Sialic acid derivatives and bind with low micromolar K d values to Siglec-7. They display up to a 5000-fold enhanced affinity over the unmodified sialic acid scaffold αMe Neu5Ac, the smallest known natural Siglec-7 ligand. Our results provide a novel immuno-oncology strategy employing natural immunity in the fight against cancers, in particular blocking Siglec-7 with low molecular weight compounds.

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

    Science.gov (United States)

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

    2012-05-01

    A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have been designed synthesised and evaluated for their antimitotic activity. Compounds 4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 μM and 1.52 μM respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors

    DEFF Research Database (Denmark)

    Wu, Gaochan; Gao, Yun; Kang, Dongwei

    2018-01-01

    acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship...

  8. Towards Logical Designs In Biology

    Indian Academy of Sciences (India)

    Administrator

    thetic biology that envisions integrating designed circuits into living ... research student in the .... integrating an odd number of NOT gates in a circular fashion such that the .... end is rational design where the targeting of gene mutations to.

  9. Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

    Science.gov (United States)

    Kankanala, Jayakanth; Kirby, Karen A; Huber, Andrew D; Casey, Mary C; Wilson, Daniel J; Sarafianos, Stefan G; Wang, Zhengqiang

    2017-12-01

    Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have shown significant antiviral activities. We report herein the design, synthesis and biological evaluation of a novel N-hydroxy thienopyrimidine-2,3-dione chemotype (11) which potently and selectively inhibited RNase H with considerable potency against HIV-1 in cell culture. Current structure-activity-relationship (SAR) identified analogue 11d as a nanomolar inhibitor of RNase H (IC 50  = 0.04 μM) with decent antiviral potency (EC 50  = 7.4 μM) and no cytotoxicity (CC 50  > 100 μM). In extended biochemical assays compound 11d did not inhibit RT polymerase (pol) while inhibiting integrase strand transfer (INST) with 53 fold lower potency (IC 50  = 2.1 μM) than RNase H inhibition. Crystallographic and molecular modeling studies confirmed the RNase H active site binding mode. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Novel Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Takayama, Jun; Rao, Kalapala Venkateswar; Ratia, Kiira; Chaudhuri, Rima; Mulhearn, Debbie C.; Lee, Hyun; Nichols, Daniel B.; Baliji, Surendranath; Baker, Susan C.; Johnson, Michael E.; Mesecar, Andrew D. (Purdue); (UC); (UIC)

    2012-02-21

    The design, synthesis, X-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation SARS-CoV PLpro inhibitors are described. A new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. Subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent PLpro inhibition and antiviral activity against SARS-CoV infected Vero E6 cells. Interestingly, the (S)-Me inhibitor 15h (enzyme IC{sub 50} = 0.56 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) and the corresponding (R)-Me 15g (IC{sub 50} = 0.32 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) are the most potent compounds in this series, with nearly equivalent enzymatic inhibition and antiviral activity. A protein-ligand X-ray structure of 15g-bound SARS-CoV PLpro and a corresponding model of 15h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions.

  11. Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

    Science.gov (United States)

    Li, Minyong; Xia, Lin

    2007-11-01

    In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

  12. Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors

    Directory of Open Access Journals (Sweden)

    Ling Zhang

    2015-05-01

    Full Text Available A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking.

  13. Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2 inhibitors

    Directory of Open Access Journals (Sweden)

    Deema A. Al-Turki

    2017-01-01

    Full Text Available New series of 3,4-diaryl-2-thioxoimidazolidin-4-ones and 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles were designed, synthesized and evaluated for their activity as anti-inflammatory agents. Compounds 20, 21, 23 and 34 are highly selective inhibitors of COX-2 enzyme at a concentration of 100 mM relative to celecoxib, the standard reference. (±-3-(4-Phenoxy-phenyl-5-phenyl-2-thioxoimidazolidin-4-ones 23 exhibited the most active anti-inflammatory agent.

  14. Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists.

    Science.gov (United States)

    Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

    2012-07-15

    A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

    Science.gov (United States)

    Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

    2018-05-01

    Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

  16. New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: design, synthesis, crystal structures, and biological evaluation.

    Science.gov (United States)

    Zidar, Nace; Tomašić, Tihomir; Šink, Roman; Kovač, Andreja; Patin, Delphine; Blanot, Didier; Contreras-Martel, Carlos; Dessen, Andréa; Premru, Manica Müller; Zega, Anamarija; Gobec, Stanislav; Mašič, Lucija Peterlin; Kikelj, Danijel

    2011-11-01

    Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC(50) values up to 28 μM. Inhibitor 37, with an IC(50) of 34 μM, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 μg/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    International Nuclear Information System (INIS)

    Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M.; Mesecar, Andrew D.; Cushman, Mark

    2010-01-01

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC 50 0.59 μM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC 50 70 nM) and 84 (IC 50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC 50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC 50 1.7 μM and 0.27 μM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  18. Design, Synthesis and Biological Evaluation of Novel Bromophenol Derivatives Incorporating Indolin-2-One Moiety as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2015-02-01

    Full Text Available A series of bromophenol derivatives containing indolin-2-one moiety were designed and evaluated that for their anticancer activities against A549, Bel7402, HepG2, HeLa and HCT116 cancer cell lines using MTT assay in vitro. Among them, seven compounds (4g–4i, 5h, 6d, 7a, 7b showed potent activity against the tested five human cancer cell lines. Wound-healing assay demonstrated that compound 4g can be used as a potent compound for inactivating invasion and metastasis by inhibiting the migration of cancer cells. The structure–activity relationships (SARs of bromophenol derivatives had been discussed, which were useful for exploring and developing bromophenol derivatives as novel anticancer drugs.

  19. Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

    Science.gov (United States)

    Fang, Xue-Jie; Jeyakkumar, Ponmani; Avula, Srinivasa Rao; Zhou, Qian; Zhou, Cheng-He

    2016-06-01

    A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Biological synthesis of silver nanoparticles

    International Nuclear Information System (INIS)

    Maliszewska, I; Szewczyk, K; Waszak, K

    2009-01-01

    Fungus-mediated synthesis of silver nanoparticles is reported. The nanosilver was formed in contact with the cell-free filtrate of Penicillium strain studied. The nanoparticles were characterized by means of the UV-Vis spectroscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The synthesized nanosilver showed a absorbed maximum at 425 nm in the visible region. The SEM characterization of the fungus cells treated with silver nitrite indicated that the protein might be responsible for the reduction of silver ions. Transmission electron microscopy (TEM) micrograph showed formation of silver nanoparticles in the range of 10-100 nm.

  1. Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors.

    Science.gov (United States)

    Wu, Yuxiang; Pan, Miaobo; Dai, Yuxuan; Liu, Baomin; Cui, Jian; Shi, Wei; Qiu, Qianqian; Huang, Wenlong; Qian, Hai

    2016-05-15

    A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Novel Bifunctional Quinolonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, Biological Activities and Mechanism of Action

    Science.gov (United States)

    Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Artico, Marino; Lavecchia, Antonio; Marinelli, Luciana; Novellino, Ettore; Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria; Nencioni, Lucia; Palamara, Anna Teresa; Pommier, Yves; Marchand, Christophe

    2008-01-01

    The virally encoded integrase protein is an essential enzyme in the life cycle of the HIV-1 virus and represents an attractive and validated target in the development of therapeutics against HIV infection. Drugs that selectively inhibit this enzyme, when used in combination with inhibitors of reverse transcriptase and protease, are believed to be highly effective in suppressing the viral replication. Among the HIV-1 integrase inhibitors, the β-diketo acids (DKAs) represent a major lead for anti-HIV-1drug development. In this study, novel bifunctional quinolonyl diketo acid derivatives were designed, synthesized and tested for their inhibitory ability against HIV-1 integrase. The compounds are potent inhibitors of integrase activity. Particularly, derivative 8 is a potent IN inhibitor for both steps of the reaction (3′-processing and strand transfer) and exhibits both high antiviral activity against HIV-1 infected cells and low cytotoxicity. Molecular modeling studies provide a plausible mechanism of action, which is consistent with ligand SARs and enzyme photo-crosslinking experiments. PMID:16539381

  3. Design, synthesis, biological assessment and molecular docking studies of new 2-aminoimidazole-quinoxaline hybrids as potential anticancer agents

    Science.gov (United States)

    Ghanbarimasir, Zahra; Bekhradnia, Ahmadreza; Morteza-Semnani, Katayoun; Rafiei, Alireza; Razzaghi-Asl, Nima; Kardan, Mostafa

    2018-04-01

    In a search for novel antiproliferative agents, a series of quinoxaline derivatives containing 2-aminoimidazole (8a-8x) were designed and synthesized. The structures of synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, Mass Spectroscopy and analyzed using HSQC, COSY, ROESY, HMBC techniques. The anticancer activity of all derivatives were evaluated for colon cancer and breast cancer cell lines by the MTT assay and acridine orange/ethidium bromide double staining method. The anti-cancer effect in human colon cancer (HCT-116) and breast cancer (MCF-7) cell lines exhibited that compounds 8a, 8s, 8t, 8w, 8x appeared as potent antiproliferative agents and especially inhibited the human colon cancer cell proliferation with percentage of inhibition by over 50%. The most active compound was (E)-4-phenyl-1-((quinoxalin-2-ylmethylene)amino)-1H-imidazol-2-amine (8a) with the highest inhibition for MCF-7 (83.3%) and HCT-116 (70%) cell lines after 48 and 24 h, respectively. Molecular docking studies of these derivatives within c-kit active site as a validated target might be suggested them as appropriate candidates for further efforts toward more potent anticancer compounds.

  4. Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation.

    Science.gov (United States)

    Więckowska, Anna; Kołaczkowski, Marcin; Bucki, Adam; Godyń, Justyna; Marcinkowska, Monika; Więckowski, Krzysztof; Zaręba, Paula; Siwek, Agata; Kazek, Grzegorz; Głuch-Lutwin, Monika; Mierzejewski, Paweł; Bienkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Knez, Damijan; Wichur, Tomasz; Gobec, Stanislav; Malawska, Barbara

    2016-11-29

    As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT 6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT 6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT 6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT 6 receptor (K b  = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC 50 hAChE  = 12 nM, IC 50 hBuChE  = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Scior, Thomas; Guevara-García, José Antonio; Melendez, F J; Abdallah, Hassan H; Do, Quoc-Tuan; Bernard, Philippe

    2010-09-24

    Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B). The PTP1B acts as a negative regulator of insulin signaling by blocking the active site where phosphate hydrolysis of the insulin receptor takes place. TSAG001, [V(V)O(2)(OH)(picolinamide)], was characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy; IR: ν/cm(-1) 3,570 (NH), 1,627 (C=O, coordinated), 1,417 (C-N), 970/842 (O=V=O), 727 δ̣ (pyridine ring); (13)C NMR: 5 bands between 122 and 151 ppm and carbonyl C shifted to 180 ppm; and (1)H NMR: 4 broad bands from 7.6 to 8.2 ppm and NH(2) shifted to 8.8 ppm. In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during 24 hours. TSAG0101 shows blood glucose lowering effects in rats but it produced no alteration of basal- or glucose-induced insulin secretion on β cells during in vitro tests, all of which excludes a direct mechanism evidencing the extrapancreatic nature of its activity. The lethal dose (LD(50)) of TSAG0101 was determined in Wistar mice yielding a value of 412 mg/kg. This value is one of the highest among vanadium compounds and classifies it as a mild toxicity agent when compared with literature data. Due to its nonsubstituted, small-sized scaffold design, its remarkable complex stability, and low toxicity; TSAG0101 should be considered as an innovative insulin-mimetic principle with promising properties and, therefore, could become a new lead compound for potential nonpeptide PTP1B inhibitors in antidiabetic drug research. In view of the present work, the inhibitory concentration (IC(50)) and extended solution stability will be tested.

  6. Cephalostatin analogues--synthesis and biological activity.

    Science.gov (United States)

    Flessner, Timo; Jautelat, Rolf; Scholz, Ulrich; Winterfeldt, Ekkehard

    2004-01-01

    potency. However, one has to keep in mind, that even some of the symmetrical compounds (e.g. ritterazine K--96 nM in the NCI panel) still show strong cytostatic properties. Same trend was identified with simple analogues, e.g. compare 26 to 31. In addition to the basic requirement of overall substantial asymmetry for high activity there appears to be the necessity for a "polarity match" between both steroidal units (33)--as one has to be substantially more polar (high hydroxylation grade) than the other. (e.g. cephalostatin 1 (1): North 1--high hydroxylation grade--and South 1--low hydroxylation grade; or: ritterazine B (2): South 7--medium hydroxylation grade--and North G--very low hydroxylation grade). Not directly confirmed by Analogue Synthesis--some "polarity matched analogues" did not show appropriate activity, e.g. 198 and 197. 4 core moieties are privileged, meaning all highly active ritterazines/cephalostatins (see table 1) are constructed out of them. Namely these are North 1, South 1, South 7 and North G. Numerous analogues were prepared to probe questions regarding the mechanism of action of the cephalostatins, e.g. close cephalostatin analogues like 197 and 198 (70) with increased energy content in the spiroketal. However, so far the mechanism and mode of action of the cephalostatins remains unknown. In the absence of any structural information of the biological target(s), the understanding about the structural necessities for high cytostatic activity is still limited and thus the rational design of more simple, yet highly active analogues seems at the current stage elusive. Additionally, there are many open questions, e.g. how the "monomeric" OSW-1 (3) relates to the "dimeric" cephalostatins. It remains the hope that forthcoming studies will bring light into this so far nebulous area--enabling chemists in the long run to provide highly active analogues in substantial amounts for advanced pharmacological studies. In conclusion one can state that the first

  7. Biological synthesis of nanoparticles in biofilms.

    Science.gov (United States)

    Tanzil, Abid H; Sultana, Sujala T; Saunders, Steven R; Shi, Liang; Marsili, Enrico; Beyenal, Haluk

    2016-12-01

    The biological synthesis of nanoparticles (NPs) by bacteria and biofilms via extracellular redox reactions has received attention because of the minimization of harmful chemicals, low cost, and ease of culturing and downstream processing. Bioreduction mechanisms vary across bacteria and growth conditions, which leads to various sizes and shapes of biosynthesized NPs. NP synthesis in biofilms offers additional advantages, such as higher biomass concentrations and larger surface areas, which can lead to more efficient and scalable biosynthesis. Although biofilms have been used to produce NPs, the mechanistic details of NP formation are not well understood. In this review, we identify three critical areas of research and development needed to advance our understanding of NP production by biofilms: 1) synthesis, 2) mechanism and 3) stabilization. Advancement in these areas could result in the biosynthesis of NPs that are suitable for practical applications, especially in drug delivery and biocatalysis. Specifically, the current status of methods and mechanisms of nanoparticle synthesis and surface stabilization using planktonic bacteria and biofilms is discussed. We conclude that the use of biofilms to synthesize and stabilize NPs is underappreciated and could provide a new direction in biofilm-based NP production. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Total synthesis and biological investigation of (-)-promysalin.

    Science.gov (United States)

    Steele, Andrew D; Knouse, Kyle W; Keohane, Colleen E; Wuest, William M

    2015-06-17

    Compounds that specifically target pathogenic bacteria are greatly needed, and identifying the method by which they act would provide new avenues of treatment. Herein we report the concise, high-yielding total synthesis (eight steps, 35% yield) of promysalin, a natural product that displays antivirulence phenotypes against pathogenic bacteria. Guided by bioinformatics, four diastereomers were synthesized, and the relative and absolute stereochemistries were confirmed by spectral and biological analysis. Finally, we show for the first time that promysalin displays two antivirulence phenotypes: the dispersion of mature biofilms and the inhibition of pyoverdine production, hinting at a unique pathogenic-specific mechanism of action.

  9. Design Automation in Synthetic Biology.

    Science.gov (United States)

    Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

    2017-04-03

    Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  10. Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Sean Fyvie, W.; Brindisi, Margherita; Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

    2017-11-01

    Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

  11. Design, synthesis, and biological evaluation of enantiomeric beta-N-acetylhexosaminidase inhibitors LABNAc and DABNAc as potential agents against Tay-Sachs and Sandhoff disease.

    Science.gov (United States)

    Rountree, J S Shane; Butters, Terry D; Wormald, Mark R; Boomkamp, Stephanie D; Dwek, Raymond A; Asano, Naoki; Ikeda, Kyoko; Evinson, Emma L; Nash, Robert J; Fleet, George W J

    2009-03-01

    N-Acetylhexosaminidases are of considerable importance in mammals and are involved in various significant biological processes. In humans, deficiencies of these enzymes in the lysosome, resulting from inherited genetic defects, cause the glycolipid storage disorders Tay-Sachs and Sandhoff diseases. One promising therapy for these diseases involves the use of beta-N-acetylhexosaminidase inhibitors as chemical chaperones to enhance the enzyme activity above sub-critical levels. Herein we describe the synthesis and biological evaluation of a potent inhibitor, 2-acetamido-1,4-imino-1,2,4-trideoxy-L-arabinitol (LABNAc), in a high-yielding 11-step procedure from D-lyxonolactone. The N-benzyl and N-butyl analogues were also prepared and found to be potent inhibitors. The enantiomers DABNAc and NBn-DABNAc were synthesised from L-lyxonolactone, and were also evaluated. The L-iminosugar LABNAc and its derivatives were found to be potent noncompetitive inhibitors of some beta-N-acetylhexosaminidases, while the D-iminosugar DABNAc and its derivatives were found to be weaker competitive inhibitors. These results support previous work postulating that D-iminosugar mimics inhibit D-glycohydrolases competitively, and that their corresponding L-enantiomers show noncompetitive inhibition of these enzymes. Molecular modelling studies confirm that the spatial organisation in enantiomeric inhibitors leads to a different overlay with the monosaccharide substrate. Initial cell-based studies suggest that NBn-LABNAc can act as a chemical chaperone to enhance the deficient enzyme's activity to levels that may cause a positive pharmacological effect. LABNAc, NBn-LABNAc, and NBu-LABNAc are potent and selective inhibitors of beta-N-acetylhexosaminidase and may be useful as therapeutic agents for treating adult Tay-Sachs and Sandhoff diseases.

  12. Biological relevance and synthesis of C-substituted morpholine derivatives

    NARCIS (Netherlands)

    Wijtmans, R.; Vink, M.K.S.; Schoemaker, H.E.; Delft, F.L. van; Blaauw, R.H.; Rutjes, F.P.J.T.

    2004-01-01

    C-Functionalized morpholines are found in a variety of natural products and biologically active compounds, but have also for other reasons been applied in organic synthesis. This review deals with the biological relevance of C-substituted morpholines, their synthesis and important applications in

  13. Design, synthesis, and biological evaluation of 3-vinyl-quinoxalin-2(1H-one derivatives as novel antitumor inhibitors of FGFR1

    Directory of Open Access Journals (Sweden)

    Liu Z

    2016-05-01

    Full Text Available Zhiguo Liu,1,* Shufang Yu,1,* Di Chen,1 Guoliang Shen,1 Yu Wang,1 Leping Hou,2 Dan Lin,1 Jinsan Zhang,1 Faqing Ye1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 2Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: FGFR1 is well known as a molecular target in anticancer drug design. TKI258 plays an important role in RTK inhibitors. Utilizing TKI258 as a lead compound that contains a quinazolinone nucleus, we synthesized four series of 3-vinyl-quinoxalin-2(1H-one derivatives, a total of 27 compounds. We further evaluated these compounds for FGFR1 inhibition ability as well as cytotoxicity against four cancer cell lines (H460, B16-F10, Hela229, and Hct116 in vitro. Some compounds displayed good-to-excellent potency against the four tested cancer cell lines compared with TKI258. Structure–activity relationship analyses indicated that small substituents at the side chain of the 3-vinyl-quinoxalin-2(1H-one were more effective than large substituents. Lastly, we used molecular docking to obtain further insight into the interactions between the compounds and FGFR1. Keywords: FGFR1, synthesis, quinoxaline, antitumor activity, kinase inhibitor

  14. AIE Polymers: Synthesis, Properties, and Biological Applications.

    Science.gov (United States)

    Zhan, Ruoyu; Pan, Yutong; Manghnani, Purnima Naresh; Liu, Bin

    2017-05-01

    Aggregation-caused quenching (ACQ) is a general phenomenon that is faced by traditional fluorescent polymers. Aggregation-induced emission (AIE) is exactly opposite to ACQ. AIE molecules are almost nonemissive in their molecularly dissolved state, but they can be induced to show high fluorescence in the aggregated or solid state. Incorporation of AIE phenomenon into polymer design has yielded various polymers with AIE characteristics. In this review, the recent progress of AIE polymers for biological applications is summarized. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Design, Synthesis, and Applications of Carbon Nanohoops

    Science.gov (United States)

    2016-05-23

    rings via one electron reduction reactions was feasible. Therefore, the synthesis and spectroscopic investigations of these ring systems by reducing...Release; Distribution Unlimited UU UU UU UU 23-05-2016 15-Feb-2012 14-Feb-2016 Final Report: Design, Synthesis , and Applications of Carbon Nanohoops The...Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 Caron Nanohoops, paracyclophanes, carbon nanotubes, organic synthesis REPORT

  16. Biological design in science classrooms

    Science.gov (United States)

    Scott, Eugenie C.; Matzke, Nicholas J.

    2007-01-01

    Although evolutionary biology is replete with explanations for complex biological structures, scientists concerned about evolution education have been forced to confront “intelligent design” (ID), which rejects a natural origin for biological complexity. The content of ID is a subset of the claims made by the older “creation science” movement. Both creationist views contend that highly complex biological adaptations and even organisms categorically cannot result from natural causes but require a supernatural creative agent. Historically, ID arose from efforts to produce a form of creationism that would be less vulnerable to legal challenges and that would not overtly rely upon biblical literalism. Scientists do not use ID to explain nature, but because it has support from outside the scientific community, ID is nonetheless contributing substantially to a long-standing assault on the integrity of science education. PMID:17494747

  17. SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

    OpenAIRE

    El Mokhtar Essassi; R. Bouhfid; Y. Kandri Rodi; S. Ferfra; H. Benzeid; Y. Ramli

    2010-01-01

    Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

  18. Rational Design and Synthesis of Biologically Active Disubstituted 2(3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents.

    Science.gov (United States)

    Khokra, S L; Khan, S A; Choudhary, D; Hasan, S M; Ahmad, A; Husain, Asif

    2016-01-01

    Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery. A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies. The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug. Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

  19. Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

    OpenAIRE

    Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M

    2008-01-01

    Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward ...

  20. Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

    Science.gov (United States)

    Maheshwari, Neelesh; Karthikeyan, Chandrabose; Bhadada, Shraddha V; Sahi, Chandan; Verma, Amit K; Hari Narayana Moorthy, N S; Trivedi, Piyush

    2018-06-08

    Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC 50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6-nitro-1H-benzimidazol-1-yl-N-arylacetamides as Antiprotozoal Agents

    Directory of Open Access Journals (Sweden)

    Emanuel Hernández-Núñez

    2017-04-01

    Full Text Available Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6-nitro-1H-benzimidazol-1-yl-N-arylacetamides 1–8 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1–8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 1–8 were carried out through reaction of 5(6-nitro-1H-benzimidazol-2-amine (12 with 2-chlroactemides 10a–h, in the presence of K2CO3 and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites (Giardia intestinalis and Entamoeba histolytica and a urogenital tract parasite (Trichomonas vaginalis were tested. Compound 7 showed an IC50 of 3.95 μM and was 7 time more active against G. intestinalis than benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared with benznidazole.

  2. Biological synthesis and characterization of silver nanoparticles ...

    Indian Academy of Sciences (India)

    or less have engrossed great attention due to their unusual and captivating ... ical method of nanoparticles synthesis using microorgan- isms, enzyme and plant or plant .... mined using Student's t-test with two-way Anova was set at p ≤ 0.05. 3.

  3. Biological synthesis and characterization of intracellular gold ...

    Indian Academy of Sciences (India)

    In the present study, Aspergillus fumigatus was used for the intracellular synthesis of gold nanoparticles. Stable nanoparticles were produced when an aqueous solution of chloroauric acid (HAuCl4) was reduced by A. fumigatus biomass as the reducing agent. Production of nanoparticles was confirmed by the colour ...

  4. Design principles in biological networks

    Science.gov (United States)

    Goyal, Sidhartha

    Much of biology emerges from networks of interactions. Even in a single bacterium such as Escherichia coli, there are hundreds of coexisting gene and protein networks. Although biological networks are the outcome of evolution, various physical and biological constraints limit their functional capacity. The focus of this thesis is to understand how functional constraints such as optimal growth in mircoorganisms and information flow in signaling pathways shape the metabolic network of bacterium E. coli and the quorum sensing network of marine bacterium Vibrio harveyi, respectively. Metabolic networks convert basic elemental sources into complex building-blocks eventually leading to cell's growth. Therefore, typically, metabolic pathways are often coupled both by the use of a common substrate and by stoichiometric utilization of their products for cell growth. We showed that such a coupled network with product-feedback inhibition may exhibit limit-cycle oscillations which arise via a Hopf bifurcation. Furthermore, we analyzed several representative metabolic modules and find that, in all cases, simple product-feedback inhibition allows nearly optimal growth, in agreement with the predicted growth-rate by the flux-balance analysis (FBA). Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum sensing (QS) systems. The QS circuit of V. harveyi integrates and funnels different ecological information through a common phosphorelay cascade to a set of small regulatory RNAs (sRNAs) that enables collective behavior. We analyzed the signaling properties and information flow in the QS circuit, which provides a model for information flow in signaling networks more generally. A comparative study of post-transcriptional and conventional transcriptional regulation suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. Furthermore, we develop a new framework for analyzing signal

  5. Biosurfactants as green stabilizers for the biological synthesis of nanoparticles.

    Science.gov (United States)

    Kiran, G Seghal; Selvin, Joseph; Manilal, Aseer; Sujith, S

    2011-12-01

    Taking into consideration the needs of greener bioprocesses and novel enhancers for synthesis using microbial processes, biosurfactants, and/or biosurfactant producing microbes are emerging as an alternate source for the rapid synthesis of nanoparticles. A microemulsion technique using an oil-water-surfactant mixture was shown to be a promising approach for nanoparticle synthesis. Biosurfactants are natural surfactants derived from microbial origin composed mostly of sugar and fatty acid moieties, they have higher biodegradability, lower toxicity, and excellent biological activities. The biosurfactant mediated process and microbial synthesis of nanoparticles are now emerging as clean, nontoxic, and environmentally acceptable "green chemistry" procedures. The biosurfactant-mediated synthesis is superior to the methods of bacterial- or fungal-mediated nanoparticle synthesis, since biosurfactants reduce the formation of aggregates due to the electrostatic forces of attraction and facilitate a uniform morphology of the nanoparticles. In this review, we highlight the biosurfactant mediated synthesis of nanoparticles with relevant details including a greener bioprocess, sources of biosurfactants, and biological synthesized nanoparticles based on the available literature and laboratory findings.

  6. Applications of cell-free protein synthesis in synthetic biology: Interfacing bio-machinery with synthetic environments.

    Science.gov (United States)

    Lee, Kyung-Ho; Kim, Dong-Myung

    2013-11-01

    Synthetic biology is built on the synthesis, engineering, and assembly of biological parts. Proteins are the first components considered for the construction of systems with designed biological functions because proteins carry out most of the biological functions and chemical reactions inside cells. Protein synthesis is considered to comprise the most basic levels of the hierarchical structure of synthetic biology. Cell-free protein synthesis has emerged as a powerful technology that can potentially transform the concept of bioprocesses. With the ability to harness the synthetic power of biology without many of the constraints of cell-based systems, cell-free protein synthesis enables the rapid creation of protein molecules from diverse sources of genetic information. Cell-free protein synthesis is virtually free from the intrinsic constraints of cell-based methods and offers greater flexibility in system design and manipulability of biological synthetic machinery. Among its potential applications, cell-free protein synthesis can be combined with various man-made devices for rapid functional analysis of genomic sequences. This review covers recent efforts to integrate cell-free protein synthesis with various reaction devices and analytical platforms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Manchukonda

    Full Text Available Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol than the parent compound, noscapine (-5.505 kCal/mol and its existing derivatives (-5.563 to -6.412 kCal/mol. Free energy (ΔG bind calculations based on the linear interaction energy (LIE empirical equation utilizing Surface Generalized Born (SGB continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol. Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol. The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl noscapine (6f binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM, which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM. All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  8. Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes.

    Science.gov (United States)

    Philip, Jessica Elizabeth; Shahid, Muhammad; Prathapachandra Kurup, M R; Velayudhan, Mohanan Puzhavoorparambil

    2017-10-01

    Two chromone hydrazone ligands HL 1 and HL 2 were synthesized and characterized by elemental analyses, IR, 1 H NMR & 13 C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV-Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    El Mokhtar Essassi

    2010-04-01

    Full Text Available Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

  10. Computer-assisted spectral design and synthesis

    Science.gov (United States)

    Vadakkumpadan, Fijoy; Wang, Qiqi; Sun, Yinlong

    2005-01-01

    In this paper, we propose a computer-assisted approach for spectral design and synthesis. This approach starts with some initial spectrum, modifies it interactively, evaluates the change, and decides the optimal spectrum. Given a requested change as function of wavelength, we model the change function using a Gaussian function. When there is the metameric constraint, from the Gaussian function of request change, we propose a method to generate the change function such that the result spectrum has the same color as the initial spectrum. We have tested the proposed method with different initial spectra and change functions, and implemented an interactive graphics environment for spectral design and synthesis. The proposed approach and graphics implementation for spectral design and synthesis can be helpful for a number of applications such as lighting of building interiors, textile coloration, and pigment development of automobile paints, and spectral computer graphics.

  11. Bioinspiration: applying mechanical design to experimental biology.

    Science.gov (United States)

    Flammang, Brooke E; Porter, Marianne E

    2011-07-01

    The production of bioinspired and biomimetic constructs has fostered much collaboration between biologists and engineers, although the extent of biological accuracy employed in the designs produced has not always been a priority. Even the exact definitions of "bioinspired" and "biomimetic" differ among biologists, engineers, and industrial designers, leading to confusion regarding the level of integration and replication of biological principles and physiology. By any name, biologically-inspired mechanical constructs have become an increasingly important research tool in experimental biology, offering the opportunity to focus research by creating model organisms that can be easily manipulated to fill a desired parameter space of structural and functional repertoires. Innovative researchers with both biological and engineering backgrounds have found ways to use bioinspired models to explore the biomechanics of organisms from all kingdoms to answer a variety of different questions. Bringing together these biologists and engineers will hopefully result in an open discourse of techniques and fruitful collaborations for experimental and industrial endeavors.

  12. Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.

    Science.gov (United States)

    Zha, Xiaoming; Lamba, Doriano; Zhang, Lili; Lou, Yinghan; Xu, Changxu; Kang, Di; Chen, Li; Xu, Yungen; Zhang, Luyong; De Simone, Angela; Samez, Sarah; Pesaresi, Alessandro; Stojan, Jure; Lopez, Manuela G; Egea, Javier; Andrisano, Vincenza; Bartolini, Manuela

    2016-01-14

    Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both β-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 μM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.

  13. Pyrrolizidine alkaloids: occurrence, biology, and chemical synthesis.

    Science.gov (United States)

    Robertson, Jeremy; Stevens, Kiri

    2017-01-04

    Covering: 2013 up to the end of 2015This review covers the isolation and structure of new pyrrolizidines; pyrrolizidine biosynthesis; biological activity, including the occurrence of pyrrolizidines as toxic components or contaminants in foods and beverages; and formal and total syntheses of naturally-occurring pyrrolizidine alkaloids and closely related non-natural analogues.

  14. Synthesis, biological evaluation and molecular docking studies of ...

    African Journals Online (AJOL)

    Synthesis, biological evaluation and molecular docking studies of Mannich bases derived from 1, 3, 4-oxadiazole- 2-thiones as potential urease inhibitors. ... Mannich bases (5-17) were subjected to in silico screening as urease inhibitors, using crystal structure of urease (Protein Data Bank ID: 5FSE) as a model enzyme.

  15. Structure-based drug design, synthesis and biological assays of P. falciparum Atg3-Atg8 protein-protein interaction inhibitors

    Science.gov (United States)

    Villa, Stefania; Legnani, Laura; Colombo, Diego; Gelain, Arianna; Lammi, Carmen; Bongiorno, Daniele; Ilboudo, Denise P.; McGee, Kellen E.; Bosch, Jürgen; Grazioso, Giovanni

    2018-03-01

    The proteins involved in the autophagy (Atg) pathway have recently been considered promising targets for the development of new antimalarial drugs. In particular, inhibitors of the protein-protein interaction (PPI) between Atg3 and Atg8 of Plasmodium falciparum retarded the blood- and liver-stages of parasite growth. In this paper, we used computational techniques to design a new class of peptidomimetics mimicking the Atg3 interaction motif, which were then synthesized by click-chemistry. Surface plasmon resonance has been employed to measure the ability of these compounds to inhibit the Atg3-Atg8 reciprocal protein-protein interaction. Moreover, P. falciparum growth inhibition in red blood cell cultures was evaluated as well as the cyto-toxicity of the compounds.

  16. Design, synthesis, and biological activity of 5'-phenyl-1,2,5,6-tetrahydro-3,3'-bipyridine analogues as potential antagonists of nicotinic acetylcholine receptors.

    Science.gov (United States)

    Jin, Yafei; Huang, Xiaoqin; Papke, Roger L; Jutkiewicz, Emily M; Showalter, Hollis D; Zhan, Chang-Guo

    2017-09-15

    Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5'-phenyl-1,2,5,6-tetrahydro-3,3'-bipyridines (3a-3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then subsequent modifications were made on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist, which is highly selective for α3β4 nAChR (K i =123nM) over the α4β2 and α7 receptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Design, Synthesis, and Biological Evaluation of Peptidomimetic N-Substituted Cbz-4-Hyp-Hpa-Amides as Novel Inhibitors of Plasmodium falciparum.

    Science.gov (United States)

    Bacherikov, Valeriy A; Chittiboyina, Amar G; Avery, Mitchell A

    2017-08-01

    A new series of peptidomimetic N-substituted Cbz-4-Hyp-Hpa-amides were designed, synthesized, and evaluated for inhibition of the Plasmodium falciparum. Substituents on the N-atom of the amide group were selected alkyl-, allyl-, aryl-, 2-hydroxyethyl-, 2-cyanoethyl-, cyanomethyl-, 2-hydroxyethyl-, 2,2-diethoxyethyl-, or 2-ethoxy-2-oxoethylamino groups, and about of 40 new compounds were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial activity has been investigated as for the final peptide mimetics, and their immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4-hydroxyproline residue and 18 derivatives exhibited toxicity against P. falciparum. Of these agents, compound 23e was shown to have potent antimalarial activity with IC 50 528 ng/ml. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  18. Biological Systems Thinking for Control Engineering Design

    Directory of Open Access Journals (Sweden)

    D. J. Murray-Smith

    2004-01-01

    Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

  19. Natural product synthesis at the interface of chemistry and biology

    Science.gov (United States)

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  20. Design, synthesis, and biological evaluation of new 1,2,3-triazolo-2'-deoxy-2'-fluoro- 4'-azido nucleoside derivatives as potent anti-HBV agents.

    Science.gov (United States)

    Liu, Yuan; Peng, Youmei; Lu, Jingjing; Wang, Jingwen; Ma, Haoran; Song, Chuanjun; Liu, Bingjie; Qiao, Yan; Yu, Wenquan; Wu, Jie; Chang, Junbiao

    2018-01-01

    Novel drugs are urgently needed to combat hepatitis B virus (HBV) infection due to drug-resistant virus. In this paper, a series of novel 4-monosubstituted 2'-deoxy-2'-β-fluoro-4'-azido-β-d-arabinofuranosyl 1,2,3-triazole nucleoside analogues (1a-g) were designed, synthesized and screened for in vitro anti-HBV activity. At 5.0 μM in the cellular model, all the synthetic compounds display activities comparable to that of the positive control, lamivudine at 20 μM. Of the compounds tested, the amide-substituted analogue (1a) shows the most promising anti-HBV activity and low cytotoxicity in the cell model. In particular, it retains excellent activity against lamivudine-resistant HBV mutants. In duck HBV (DHBV)-infected duck models, both the serum and liver DHBV DNA levels (67.4% and 53.3%, respectively) were reduced markedly by the treatment with 1a. Analysis of the structure of HBV polymer/1a-triphosphate (1a-TP) complex shows that 1a-TP is stabilized by specific van der Waals interactions with the enzyme residues arising from 4-amino-1,2,3-triazole and the 4'-azido group. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability

    Directory of Open Access Journals (Sweden)

    Ahmed M. Gouda

    2016-02-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45–5.69 µM and 0.85–3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile.

  2. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

    Science.gov (United States)

    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  3. Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors.

    Science.gov (United States)

    Lan, Jin-Shuai; Zhang, Tong; Liu, Yun; Yang, Jing; Xie, Sai-Sai; Liu, Jing; Miao, Ze-Yang; Ding, Yue

    2017-06-16

    A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced β-amyloid (Aβ) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC 50 , 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Aβ aggregation (53.7% at 20 μM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Aβ (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-HydroxyalkylIsoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents

    Directory of Open Access Journals (Sweden)

    Dawid Panek

    2018-02-01

    Full Text Available The complex nature of Alzheimer’s disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hydroxyalkylisoindoline-1,3-diones was designed by modification of cholinesterase inhibitors toward β-secretase inhibition. All target compounds have been synthesized and tested against eel acetylcholinesterase (eeAChE, equine serum butyrylcholinesterase (eqBuChE, human β-secretase (hBACE-1, and β-amyloid (Aβ-aggregation. The most promising compound, 12 (2-(5-(benzylamino-4-hydroxypentylisoindoline-1,3-dione, displayed inhibitory potency against eeAChE (IC50 = 3.33 μM, hBACE-1 (43.7% at 50 μM, and Aβ-aggregation (24.9% at 10 μM. Molecular modeling studies have revealed possible interaction of compound 12 with the active sites of both enzymes—acetylcholinesterase and β-secretase. In conclusion: modifications of acetylcholinesterase inhibitors led to the discovery of a multipotent anti-Alzheimer’s agent, with moderate and balanced potency, capable of inhibiting acetylcholinesterase, a symptomatic target, and disease-modifying targets: β-secretase and Aβ-aggregation.

  5. Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property.

    Science.gov (United States)

    Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li

    2017-04-15

    Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K 3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H 2 O 2 /Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K 3-2 , can be considered as potential therapeutic agents for Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2017-11-01

    Full Text Available A series of bromophenol hybrids with N-containing heterocyclic moieties were designed, and their anticancer activities against a panel of five human cancer cell lines (A549, Bel7402, HepG2, HCT116 and Caco2 using MTT assay in vitro were explored. Among them, thirteen compounds (17a, 17b, 18a, 19a, 19b, 20a, 20b, 21a, 21b, 22a, 22b, 23a, and 23b exhibited significant inhibitory activity against the tested cancer cell lines. The structure-activity relationships (SARs of bromophenol derivatives were discussed. The promising candidate compound 17a could induce cell cycle arrest at G0/G1 phase and induce apoptosis in A549 cells, as well as caused DNA fragmentations, morphological changes and ROS generation by the mechanism studies. Furthermore, compound 17a suppression of Bcl-2 levels (decrease in the expression of the anti-apoptotic proteins Bcl-2 and down-regulation in the expression levels of Bcl-2 in A549 cells were observed, along with activation caspase-3 and PARP, which indicated that compound 17a induced A549 cells apoptosis in vitro through the ROS-mediated apoptotic pathway. These results might be useful for bromophenol derivatives to be explored and developed as novel anticancer drugs.

  7. Cancer stem cells CD133 inhibition and cytotoxicity of certain 3-phenylthiazolo[3,2-a]benzimidazoles: design, direct synthesis, crystal study and in vitro biological evaluation.

    Science.gov (United States)

    Al-Ansary, Ghada H; Eldehna, Wagdy M; Ghabbour, Hazem A; Al-Rashood, Sara T A; Al-Rashood, Khalid A; Eladwy, Radwa A; Al-Dhfyan, Abdullah; Kabil, Maha M; Abdel-Aziz, Hatem A

    2017-12-01

    Cancer stem cells (CSCs) have been objects of intensive study since their identification in 1994. Adopting a structural rigidification approach, a novel series of 3-phenylthiazolo[3,2-a]benzimidazoles 4a-d was designed and synthesised, in an attempt to develop potent anticancer agent that can target the bulk of tumour cells and CSCs. The anti-proliferative activity of the synthesised compounds was evaluated against two cell lines, namely; colon cancer HT-29 and triple negative breast cancer MDA-MB-468 cell lines. Also, their inhibitory activity against the cell surface expression of CD133 was examined. In particular, compound 4b emerged as a promising hit molecule as it manifested good antineoplastic potency against both tested cell lines (IC 50  = 9 and 12 μM, respectively), beside its ability to inhibit the cell surface expression of CD133 by 50% suggesting a promising potential of effectively controlling the tumour by eradicating the tumour bulk and inhibiting the proliferation of the CSCs. Moreover, compounds 4a and 4c showed moderate activity against HT-29 (IC 50  = 21 and 29 μM, respectively) and MDA-MB-468 (IC 50  = 23 and 24 μM, respectively) cell lines, while they inhibited the CD133 expression by 14% and 48%, respectively. Finally, a single crystal X-ray diffraction was recorded for compound 4d.

  8. Design synthesis and shape generation

    DEFF Research Database (Denmark)

    McKay, Alison; Chase, Scott Curland; Garner, Steven

    2009-01-01

    If we are to capitalise on the potential that a design approach might bring to innovation in business and society, we need to build a better understanding of the evolving skill-sets that designers will need and the contexts within which design might operate. This demands more discourse between...... of future design activity as part of Phase 2 of the UK's research council supported Designing for the 21st Century Research Initiative. Each of these contributions describes the origins of the project, the research team and their project aims, the research methods used and the new knowledge...... those involved in cutting edge practice, the researchers who help to uncover principles, codify knowledge and create theories and the educators who are nurturing future design talent. This book promotes such a discourse by reporting on the work of twenty research teams who explored different facets...

  9. Shape Synthesis in Mechanical Design

    OpenAIRE

    C. P. Teng; S. Bai; J. Angeles

    2007-01-01

    The shaping of structural elements in the area of mechanical design is a recurrent problem. The mechanical designer, as a rule, chooses what is believed to be the “simplest” shapes, such as the geometric primitives: lines, circles and, occasionally, conics. The use of higher-order curves is usually not even considered, not to speak of other curves than polynomials. However, the simplest geometric shapes are not necessarily the most suitable when the designed element must withstand loads that ...

  10. Design, Synthesis, and Biological Evaluation of 68Ga-DOTA-PA1 for Lung Cancer: A Novel PET Tracer for Multiple Somatostatin Receptor Imaging.

    Science.gov (United States)

    Liu, Fei; Liu, Teli; Xu, Xiaoxia; Guo, Xiaoyi; Li, Nan; Xiong, Chiyi; Li, Chun; Zhu, Hua; Yang, Zhi

    2018-02-05

    Most of the radiolabeled somatostatin analogues (SSAs) are specific for subtype somatostatin receptor 2 (SSTR 2 ). Lack of ligands targeting other subtypes of SSTRs, especially SSTR 1, SSTR 3 , and SSTR 5 , limited their applications in tumors of low SSTR 2 expression, including lung tumor. In this study, we aimed to design and synthesize a positron emission tomography (PET) radiotracer targeting multi-subtypes of SSTRs for PET imaging. PA1 peptide and its conjugate with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator or fluorescein isothiocyanate (FITC) at the N-terminal of the lysine position were synthesized. 68 Ga was chelated to DOTA-PA1 to obtain 68 Ga-DOTA-PA1 radiotracer. The stability, lipophilicity, binding affinity, and binding specificity of 68 Ga-DOTA-PA1 and FITC-PA1 were evaluated by various in vitro experiments. Micro-PET imaging of 68 Ga-DOTA-PA1 was performed in nude mice bearing A549 lung adenocarcinoma, as compared with 68 Ga-DOTA-(Tyr3)-octreotate ( 68 Ga-DOTA-TATE). Histological analysis of SSTR expression in A549 tumor tissues and human tumor tissues was conducted using immunofluorescence staining and immunohistochemical assay. 68 Ga-DOTA-PA1 had high radiochemical yield and radiochemical purity of over 95% and 99%, respectively. The radiotracer was stable in vitro in different buffers over a 2 h incubation period. Cell uptake of 68 Ga-DOTA-PA1 was 1.31-, 1.33-, and 1.90-fold that of 68 Ga-DOTA-TATE, which has high binding affinity only for SSTR 2 , after 2 h incubation in H520, PG, and A549 lung cancer cell lines, respectively. Micro-PET images of 68 Ga-DOTA-PA1 showed that the PET imaging signal correlated with the total expression of SSTRs, instead of SSTR 2 only, which was measured by Western blotting and immunofluorescence analysis in mice bearing A549 tumors. In summary, a novel PET radiotracer, 68 Ga-DOTA-PA1, targeting multi-subtypes of SSTRs, was successfully synthesized and was confirmed to be useful for PET

  11. Biological inspiration used for robots motion synthesis.

    Science.gov (United States)

    Zielińska, Teresa

    2009-01-01

    This work presents a biologically inspired method of gait generation. Bipedal gait pattern (for hip and knee joints) was taken into account giving the reference trajectories in a learning task. The four coupled oscillators were taught to generate the outputs similar to those in a human gait. After applying the correction functions the obtained generation method was validated using ZMP criterion. The formula suitable for real-time motion generation taking into account the positioning errors was also formulated. The small real robot prototype was tested to be able walk successfully following the elaborated motion pattern.

  12. Shape Synthesis in Mechanical Design

    Directory of Open Access Journals (Sweden)

    C. P. Teng

    2007-01-01

    Full Text Available The shaping of structural elements in the area of mechanical design is a recurrent problem. The mechanical designer, as a rule, chooses what is believed to be the “simplest” shapes, such as the geometric primitives: lines, circles and, occasionally, conics. The use of higher-order curves is usually not even considered, not to speak of other curves than polynomials. However, the simplest geometric shapes are not necessarily the most suitable when the designed element must withstand loads that can lead to failure-prone stress concentrations. Indeed, as mechanical designers have known for a while, stress concentrations occur, first and foremost, by virtue of either dramatic changes in curvature or extremely high values thereof. As an alternative, we propose here the use of smooth curves that can be simply generated using standard concepts such as non-parametric cubic splines. These curves can be readily used to produce either extruded surfaces or surfaces of revolution. 

  13. Synthesis and Design of Processing Networks

    DEFF Research Database (Denmark)

    Quaglia, Alberto; Sarup, Bent; Sin, Gürkan

    2012-01-01

    In this contribution, we propose an integrated business and engineering framework for synthesis and design of processing networks under uncertainty. In our framework, an adapted formulation of the transhipment problem is integrated with a superstructure, leading to a Stochastic Mixed Integer Non...... under market and technical uncertainty....

  14. Synthesis of potentially bioactive compounds and tools for biological studies

    International Nuclear Information System (INIS)

    Cappa, F.

    2014-01-01

    NMR spectroscopy is one of the most versatile tools for studying structural parameters of organic and bioorganic compounds. It became a highly suitable method to achieve spectra simplification of macromolecules in combination with isotope labeling techniques. This technique is used to study protein structures, folding properties and mechanisms of chemical and biochemical reactions. Proteins typically feature a high molecular mass showing a high number of spin systems, being responsible for increasingly difficult to interpret NMR spectra, which is why it is essential to introduce 13 C- and 15 N- isotopes to obtain reasonable signal intensities. The development of a new synthetic route towards 13 C-isotope labeled Phenylalanine or precursors thereof, starting from inexpensive and easily accessible labeled starting materials, is the main purpose of this work. Label sources such as [ 13 C]-acetic acid, [ 13 C]-formaldehyde, [ 13 C]-allyl alcohol and [ 13 C]-glycine will be used. The synthetic pathway will be carried out in a way where the position-selective incorporation of labeled isotopes can be performed. This important feature of the synthesis may open access towards newly designed NMR-experiments. Key steps for the tested route are ring closing metatheses as well as indium mediated reactions. The second part of this work focuses on the field of sugar chemistry, in particular on the family of deoxy sugars, components of many natural products, found in different plants, fungi and bacteria. Deoxy sugars also participate in a wide range of biological processes. Special focus is given to 3-deoxy sugars and the research of a versatile and flexible synthetic route for their preparation starting from the easily accessible D-glyceraldehyde. These sugars are found on Gram-negative bacteria where they are a key component of the lipopolysaccharides, or where they can take place in the biosynthesis of aromatic amino acids in bacteria and plants. Being able to perform this

  15. Cooperative catalysis designing efficient catalysts for synthesis

    CERN Document Server

    Peters, René

    2015-01-01

    Written by experts in the field, this is a much-needed overview of the rapidly emerging field of cooperative catalysis. The authors focus on the design and development of novel high-performance catalysts for applications in organic synthesis (particularly asymmetric synthesis), covering a broad range of topics, from the latest progress in Lewis acid / Br?nsted base catalysis to e.g. metal-assisted organocatalysis, cooperative metal/enzyme catalysis, and cooperative catalysis in polymerization reactions and on solid surfaces. The chapters are classified according to the type of cooperating acti

  16. Leveraging advances in biology to design biomaterials

    Science.gov (United States)

    Darnell, Max; Mooney, David J.

    2017-12-01

    Biomaterials have dramatically increased in functionality and complexity, allowing unprecedented control over the cells that interact with them. From these engineering advances arises the prospect of improved biomaterial-based therapies, yet practical constraints favour simplicity. Tools from the biology community are enabling high-resolution and high-throughput bioassays that, if incorporated into a biomaterial design framework, could help achieve unprecedented functionality while minimizing the complexity of designs by identifying the most important material parameters and biological outputs. However, to avoid data explosions and to effectively match the information content of an assay with the goal of the experiment, material screens and bioassays must be arranged in specific ways. By borrowing methods to design experiments and workflows from the bioprocess engineering community, we outline a framework for the incorporation of next-generation bioassays into biomaterials design to effectively optimize function while minimizing complexity. This framework can inspire biomaterials designs that maximize functionality and translatability.

  17. Synthesis and biological activity of radiolabeled phytosterols

    Energy Technology Data Exchange (ETDEWEB)

    De Palma, A.

    1984-01-01

    /sup 3/H and /sup 14/C-labeled phytosterols were synthesized for the purpose of elucidating insect sterol side-chain dealkylating mechanisms. Sitosterol, stigmasterol, and the 29-fluoro derivatives of these compounds, which are highly toxic, were labeled with /sup 3/H at C-29 in order to study the fate of the two-carbon dealkylation product in vivo and in vitro. The first rapid, reliable in vitro dealkylation bioassay was developed using doubly-labeled (29-/sup 3/H)-(24-/sup 14/C) fucosterol epoxides as the substrates, incubated with midgut preparations from Manduca sexta, the tobacco hornworm. Since C-28 and C-29 are lost in the dealkylation process, the extent of dealkylation is expressed as the change in the isotopic ratio when the system is partitioned between an organic solvent and water after incubation. As predicted, the /sup 3/H//sup 14/C ratio decreases in the organic layer as a function of time, due to loss of /sup 3/H into the aqueous phase as acetate or a biological equivalent. This ratio likewise increases in the aqueous phase for the same reason. The (29-/sup 3/H) phytosterols alone are reliable substrates for the first rapid in vivo bioassay of phytosterol dealkylation.

  18. Synthesis and biological activity of radiolabeled phytosterols

    International Nuclear Information System (INIS)

    De Palma, A.

    1984-01-01

    3 H and 14 C-labeled phytosterols were synthesized for the purpose of elucidating insect sterol side-chain dealkylating mechanisms. Sitosterol, stigmasterol, and the 29-fluoro derivatives of these compounds, which are highly toxic, were labeled with 3 H at C-29 in order to study the fate of the two-carbon dealkylation product in vivo and in vitro. The first rapid, reliable in vitro dealkylation bioassay was developed using doubly-labeled [29- 3 H]-[24- 14 C] fucosterol epoxides as the substrates, incubated with midgut preparations from Manduca sexta, the tobacco hornworm. Since C-28 and C-29 are lost in the dealkylation process, the extent of dealkylation is expressed as the change in the isotopic ratio when the system is partitioned between an organic solvent and water after incubation. As predicted, the 3 H/ 14 C ratio decreases in the organic layer as a function of time, due to loss of 3 H into the aqueous phase as acetate or a biological equivalent. This ratio likewise increases in the aqueous phase for the same reason. The [29- 3 H] phytosterols alone are reliable substrates for the first rapid in vivo bioassay of phytosterol dealkylation

  19. An engineering design approach to systems biology.

    Science.gov (United States)

    Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

    2017-07-17

    Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

  20. Biological conversion of coal synthesis gas to methane

    Energy Technology Data Exchange (ETDEWEB)

    Barik, S; Corder, R E; Clausen, E C; Gaddy, J L

    1987-09-01

    High temperatures and pressures are required, and therefore, high costs incurred during catalytic upgrading of coal synthesis gas to methane. Thus, the feasibility of biological reactions in converting synthesis gas to methane has been demonstrated in mixed and pure cultures. Complete conversion has been achieved in 2 hours with a mixed culture, and 45 minutes to 1.5 hours in pure cultures of P. productus and Methanothrix sp.. Typical sulfur levels involved during the process are found not to inhibit the bacteria and so sulfur does not have to be removed prior to biomethanation. Preliminary economic analyses indicate that coal gas may be biologically methanated for 50-60 cents/million Btu. Further studies with pure culture bacteria and increased pressure are expected to enhance biomethanation economics.

  1. Synthesis and Biological Evaluation of 7-Deoxy-Epothilone Analogues

    Directory of Open Access Journals (Sweden)

    Laura M. Woods

    2017-03-01

    Full Text Available The synthesis of two deoxygenated analogues of potent epothilones is reported in an effort to analyze the relative importance of molecular conformation and ligand–target interactions to biological activity. 7-deoxy-epothilone D and 7-deoxy-(S-14-methoxy-epothilone D were prepared through total synthesis and shown to maintain the conformational preferences of their biologically active parent congeners through computer modeling and nuclear magnetic resonance (NMR studies. The significant decrease in observed potency for each compound suggests that a hydrogen bond between the C7-hydroxyl group and the tubulin binding site plays a critical role in the energetics of binding in the epothilone class of polyketides.

  2. Synthesis and biological evaluation of febrifugine analogues.

    Science.gov (United States)

    Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

    2014-12-01

    A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

  3. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

  4. Design of Nanomaterial Synthesis by Aerosol Processes

    Science.gov (United States)

    Buesser, Beat; Pratsinis, Sotiris E.

    2013-01-01

    Aerosol synthesis of materials is a vibrant field of particle technology and chemical reaction engineering. Examples include the manufacture of carbon blacks, fumed SiO2, pigmentary TiO2, ZnO vulcanizing catalysts, filamentary Ni, and optical fibers, materials that impact transportation, construction, pharmaceuticals, energy, and communications. Parallel to this, development of novel, scalable aerosol processes has enabled synthesis of new functional nanomaterials (e.g., catalysts, biomaterials, electroceramics) and devices (e.g., gas sensors). This review provides an access point for engineers to the multiscale design of aerosol reactors for the synthesis of nanomaterials using continuum, mesoscale, molecular dynamics, and quantum mechanics models spanning 10 and 15 orders of magnitude in length and time, respectively. Key design features are the rapid chemistry; the high particle concentrations but low volume fractions; the attainment of a self-preserving particle size distribution by coagulation; the ratio of the characteristic times of coagulation and sintering, which controls the extent of particle aggregation; and the narrowing of the aggregate primary particle size distribution by sintering. PMID:22468598

  5. Synthesis and Biological Evaluation of Glycosidase Inhibitors: gem-Difluoromethylenated Nojirimycin Analogues

    DEFF Research Database (Denmark)

    Bols, Mikael; Wang, Ruo-Wen; Qiu, Xiao-Long

    2006-01-01

    In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem....... It is proposed that the unprotonated iminosugar is the species preferably bound by beta-glucosidase, due to the lower pK(a) value of iminosugar 6 than of 1 or 36, leaving iminosugars 1 and 36 mostly protonated at pH 5.0, while iminosugar 6 is not. Iminosugar 6 also displayed good and selective inhibition of beta...

  6. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

    Full Text Available Abstract Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This

  7. Informing biological design by integration of systems and synthetic biology.

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

    Science.gov (United States)

    Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

    2008-06-01

    Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

  9. Pareto Optimal Design for Synthetic Biology.

    Science.gov (United States)

    Patanè, Andrea; Santoro, Andrea; Costanza, Jole; Carapezza, Giovanni; Nicosia, Giuseppe

    2015-08-01

    Recent advances in synthetic biology call for robust, flexible and efficient in silico optimization methodologies. We present a Pareto design approach for the bi-level optimization problem associated to the overproduction of specific metabolites in Escherichia coli. Our method efficiently explores the high dimensional genetic manipulation space, finding a number of trade-offs between synthetic and biological objectives, hence furnishing a deeper biological insight to the addressed problem and important results for industrial purposes. We demonstrate the computational capabilities of our Pareto-oriented approach comparing it with state-of-the-art heuristics in the overproduction problems of i) 1,4-butanediol, ii) myristoyl-CoA, i ii) malonyl-CoA , iv) acetate and v) succinate. We show that our algorithms are able to gracefully adapt and scale to more complex models and more biologically-relevant simulations of the genetic manipulations allowed. The Results obtained for 1,4-butanediol overproduction significantly outperform results previously obtained, in terms of 1,4-butanediol to biomass formation ratio and knock-out costs. In particular overproduction percentage is of +662.7%, from 1.425 mmolh⁻¹gDW⁻¹ (wild type) to 10.869 mmolh⁻¹gDW⁻¹, with a knockout cost of 6. Whereas, Pareto-optimal designs we have found in fatty acid optimizations strictly dominate the ones obtained by the other methodologies, e.g., biomass and myristoyl-CoA exportation improvement of +21.43% (0.17 h⁻¹) and +5.19% (1.62 mmolh⁻¹gDW⁻¹), respectively. Furthermore CPU time required by our heuristic approach is more than halved. Finally we implement pathway oriented sensitivity analysis, epsilon-dominance analysis and robustness analysis to enhance our biological understanding of the problem and to improve the optimization algorithm capabilities.

  10. Green Synthesis of Metallic Nanoparticles via Biological Entities

    Directory of Open Access Journals (Sweden)

    Monaliben Shah

    2015-10-01

    Full Text Available Nanotechnology is the creation, manipulation and use of materials at the nanometre size scale (1 to 100 nm. At this size scale there are significant differences in many material properties that are normally not seen in the same materials at larger scales. Although nanoscale materials can be produced using a variety of traditional physical and chemical processes, it is now possible to biologically synthesize materials via environment-friendly green chemistry based techniques. In recent years, the convergence between nanotechnology and biology has created the new field of nanobiotechnology that incorporates the use of biological entities such as actinomycetes algae, bacteria, fungi, viruses, yeasts, and plants in a number of biochemical and biophysical processes. The biological synthesis via nanobiotechnology processes have a significant potential to boost nanoparticles production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. The aim of this review is to provide an overview of recent trends in synthesizing nanoparticles via biological entities and their potential applications.

  11. Green Synthesis of Metallic Nanoparticles via Biological Entities

    Science.gov (United States)

    Shah, Monaliben; Fawcett, Derek; Sharma, Shashi; Tripathy, Suraj Kumar; Poinern, Gérrard Eddy Jai

    2015-01-01

    Nanotechnology is the creation, manipulation and use of materials at the nanometre size scale (1 to 100 nm). At this size scale there are significant differences in many material properties that are normally not seen in the same materials at larger scales. Although nanoscale materials can be produced using a variety of traditional physical and chemical processes, it is now possible to biologically synthesize materials via environment-friendly green chemistry based techniques. In recent years, the convergence between nanotechnology and biology has created the new field of nanobiotechnology that incorporates the use of biological entities such as actinomycetes algae, bacteria, fungi, viruses, yeasts, and plants in a number of biochemical and biophysical processes. The biological synthesis via nanobiotechnology processes have a significant potential to boost nanoparticles production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. The aim of this review is to provide an overview of recent trends in synthesizing nanoparticles via biological entities and their potential applications. PMID:28793638

  12. Biologically inspired coupled antenna beampattern design

    Energy Technology Data Exchange (ETDEWEB)

    Akcakaya, Murat; Nehorai, Arye, E-mail: makcak2@ese.wustl.ed, E-mail: nehorai@ese.wustl.ed [Department of Electrical and Systems Engineering, Washington University in St Louis, St Louis, MO 63130 (United States)

    2010-12-15

    We propose to design a small-size transmission-coupled antenna array, and corresponding radiation pattern, having high performance inspired by the female Ormia ochracea's coupled ears. For reproduction purposes, the female Ormia is able to locate male crickets' call accurately despite the small distance between its ears compared with the incoming wavelength. This phenomenon has been explained by the mechanical coupling between the Ormia's ears, which has been modeled by a pair of differential equations. In this paper, we first solve these differential equations governing the Ormia ochracea's ear response, and convert the response to the pre-specified radio frequencies. We then apply the converted response of the biological coupling in the array factor of a uniform linear array composed of finite-length dipole antennas, and also include the undesired electromagnetic coupling due to the proximity of the elements. Moreover, we propose an algorithm to optimally choose the biologically inspired coupling for maximum array performance. In our numerical examples, we compute the radiation intensity of the designed system for binomial and uniform ordinary end-fire arrays, and demonstrate the improvement in the half-power beamwidth, sidelobe suppression and directivity of the radiation pattern due to the biologically inspired coupling.

  13. Computational Chemical Synthesis Analysis and Pathway Design

    Directory of Open Access Journals (Sweden)

    Fan Feng

    2018-06-01

    Full Text Available With the idea of retrosynthetic analysis, which was raised in the 1960s, chemical synthesis analysis and pathway design have been transformed from a complex problem to a regular process of structural simplification. This review aims to summarize the developments of computer-assisted synthetic analysis and design in recent years, and how machine-learning algorithms contributed to them. LHASA system started the pioneering work of designing semi-empirical reaction modes in computers, with its following rule-based and network-searching work not only expanding the databases, but also building new approaches to indicating reaction rules. Programs like ARChem Route Designer replaced hand-coded reaction modes with automatically-extracted rules, and programs like Chematica changed traditional designing into network searching. Afterward, with the help of machine learning, two-step models which combine reaction rules and statistical methods became the main stream. Recently, fully data-driven learning methods using deep neural networks which even do not require any prior knowledge, were applied into this field. Up to now, however, these methods still cannot replace experienced human organic chemists due to their relatively low accuracies. Future new algorithms with the aid of powerful computational hardware will make this topic promising and with good prospects.

  14. Biological upgrading of coal-derived synthesis gas: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Barik, S.; Johnson, E.R.; Ko, C.W.; Clausen, E.C.; Gaddy, J.L.

    1986-10-01

    The technical feasibility of the biological conversion of coal synthesis gas to methane has been demonstrated in the University of Arkansas laboratories. Cultures of microorganisms have been developed which achieve total conversion in the water gas shift and methanation reactions in either mixed or pure cultures. These cultures carry out these conversions at ordinary temperatures and pressures, without sulfur toxicity. Several microorganisms have been identified as having commercial potential for producing methane. These include a mixed culture of unidentified bacteria; P. productus which produces acetate, a methane precursor; and Methanothrix sp., which produces methane from acetate. These cultures have been used in mixed reactors and immobilized cell reactors to achieve total CO and H/sub 2/ conversion in a retention time of less than two hours, quite good for a biological reactor. Preliminary economic projections indicate that a biological methanation plant with a size of 5 x 10/sup 10/ Btu/day can be economically attractive. 42 refs., 26 figs., 86 tabs.

  15. Analog Electronic Filters Theory, Design and Synthesis

    CERN Document Server

    Dimopoulos, Hercules G

    2012-01-01

    Filters are essential subsystems in a huge variety of electronic systems. Filter applications are innumerable; they are used for noise reduction, demodulation, signal detection, multiplexing, sampling, sound and speech processing, transmission line equalization and image processing, to name just a few. In practice, no electronic system can exist without filters. They can be found in everything from power supplies to mobile phones and hard disk drives and from loudspeakers and MP3 players to home cinema systems and broadband Internet connections. This textbook introduces basic concepts and methods and the associated mathematical and computational tools employed in electronic filter theory, synthesis and design.  This book can be used as an integral part of undergraduate courses on analog electronic filters. Includes numerous, solved examples, applied examples and exercises for each chapter. Includes detailed coverage of active and passive filters in an independent but correlated manner. Emphasizes real filter...

  16. Design and synthesis of plasmonic magnetic nanoparticles

    International Nuclear Information System (INIS)

    Lim, Jit Kang; Tilton, Robert D.; Eggeman, Alexander; Majetich, Sara A.

    2007-01-01

    Core-shell nanoparticles containing both iron oxide and gold are proposed for bioseparation applications. The surface plasmon resonance of gold makes it possible to track the positions of individual particles, even when they are smaller than the optical diffraction limit. The synthesis of water-dispersible iron oxide-gold nanoparticles is described. Absorption spectra show the plasmon peaks for Au shells on silica particles, suggesting that thin shells may be sufficient to impart a strong surface plasmon resonance to iron oxide-gold nanoparticles. Dark field optical microscopy illustrates the feasibility of single-particle detection. Calculations of magnetophoretic and drag forces for particles of different sizes reveal design requirements for effective separation of these small particles

  17. Synthesis and design of optimal biorefinery

    DEFF Research Database (Denmark)

    Cheali, Peam

    analysed to enable risk-aware decision making. Theapplication of the developed analysis and decision support toolbox is highlightedthrough relevant biorefinery case studies: bioethanol, biogasoline or biodiesel production; algal biorefinery; and bioethanol-upgrading concepts are presented. This development...... environment. These challenges motivate thedevelopment of sustainable technologies for processing renewable feedstock for the production of fuels, chemicals and materials in what is commonly known as a biorefinery. The biorefinery concept is a term to describe one or more processes whichproduce various...... products from bio-based feedstock. Since there are several bio-basedfeedstock sources, this has motivated development of different conversion concepts producing various desired products. This results in a number of challenges for the synthesis and design of the optimal biorefinery concept at the early...

  18. Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

    Science.gov (United States)

    Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

    2007-01-01

    Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

  19. Biologically Active Macrocyclic Compounds – from Natural Products to Diversity‐Oriented Synthesis

    DEFF Research Database (Denmark)

    Madsen, Charlotte Marie; Clausen, Mads Hartvig

    2011-01-01

    Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent...... developments in the synthesis of macrocycles, with an emphasis on chemistry developed to generate libraries of putative biologically active compounds....

  20. synthesis and characterization of some poly functionalized heterocyclic derivatives of expected biological activity

    International Nuclear Information System (INIS)

    El-sayed, M.S.

    2001-01-01

    The present work was aimed and designed to fulfil The following objectives : 1- Continuation of the effort done by our research group in the field of chemistry of pyridinethione derivatives and their biological activities. 2- Synthesis of several new heterocyclic derivatives containing N and/or S using the laboratory available reagents. 3- Establishment of the structures of the newly synthesized heterocyclic compounds by the data of IR, 1 H-NMR, mass spectra in addition to the elemental analysis. 4- Synthesis of some of these heterocyclic derivatives via alternative routs and this used as a tool to confirm the structures of the newly synthesized heterocyclic derivatives. 5- study of the most probable mechanisms leading to the formation of the new heterocyclic derivatives. 6- The antimicrobial activity of some of the newly synthesized heterocyclic derivatives was tested against several types of organisms

  1. Creative design inspired by biological knowledge: Technologies and methods

    Science.gov (United States)

    Tan, Runhua; Liu, Wei; Cao, Guozhong; Shi, Yuan

    2018-05-01

    Biological knowledge is becoming an important source of inspiration for developing creative solutions to engineering design problems and even has a huge potential in formulating ideas that can help firms compete successfully in a dynamic market. To identify the technologies and methods that can facilitate the development of biologically inspired creative designs, this research briefly reviews the existing biological-knowledge-based theories and methods and examines the application of biological-knowledge-inspired designs in various fields. Afterward, this research thoroughly examines the four dimensions of key technologies that underlie the biologically inspired design (BID) process. This research then discusses the future development trends of the BID process before presenting the conclusions.

  2. Engineering Design of an Adaptive Leg Prosthesis Using Biological Principles

    DEFF Research Database (Denmark)

    Lenau, Torben Anker; Dentel, Andy; Invarsdottir, Thorunn

    2010-01-01

    The biomimetic design process is explored through a design case: An adaptive leg prosthesis. The aim is to investigate if the biomimetic design process can be carried out with a minimum of biological knowledge and without using advanced design methods. In the design case biomimetic design was suc...... was successfully carried out using library search resulting in 14 biological analogies for the design problem 'shape adaption'. It is proposed that search results are handled using special cards describing the biological phenomena and the functional principles....

  3. Design of Functional Polyesters for Electronic and Biological Applications

    OpenAIRE

    Nelson, Ashley Marie

    2015-01-01

    Melt polymerization and novel monomers enabled the synthesis of polyesters for electronic and biological applications. Inspiration from nature and a passion for environmental preservation instigated an emphasis on the incorporation of renewable resources into polymeric materials. Critical analysis of current research surrounding bisphenol-A replacements and ioncontaining segmented polyurethanes aided in identifying benchmark polymers, including limitations, challenges, and future needs. Struc...

  4. The synthesis method for design of electron flow sources

    Science.gov (United States)

    Alexahin, Yu I.; Molodozhenzev, A. Yu

    1997-01-01

    The synthesis method to design a relativistic magnetically - focused beam source is described in this paper. It allows to find a shape of electrodes necessary to produce laminar space charge flows. Electron guns with shielded cathodes designed with this method were analyzed using the EGUN code. The obtained results have shown the coincidence of the synthesis and analysis calculations [1]. This method of electron gun calculation may be applied for immersed electron flows - of interest for the EBIS electron gun design.

  5. Plant polyphenols: chemical properties, biological activities, and synthesis.

    Science.gov (United States)

    Quideau, Stéphane; Deffieux, Denis; Douat-Casassus, Céline; Pouységu, Laurent

    2011-01-17

    Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Designed synthesis of tunable amorphous carbon nanotubes (a ...

    Indian Academy of Sciences (India)

    Administrator

    Page 1. Electronic Supplementary Material. Graphical abstract. Designed synthesis of tunable amorphous carbon nanotubes (a-CNTs) by a novel route and their oxidation resistance properties by Longlong. Xu et al (pp 1397–1402).

  7. Synthesis, characterization and biological studies of copper oxide nanostructures

    Science.gov (United States)

    Jillani, Saquf; Jelani, Mohsan; Hassan, Najam Ul; Ahmad, Shahbaz; Hafeez, Muhammad

    2018-04-01

    The development of synthetic methods has been broadly accepted as an area of fundamental importance to the understanding and application of nanoscale materials. It allows the individual to modulate basic parameters such as morphology, particle size, size distributions, and composition. Several methods have been developed to synthesize CuO nanostructures with diverse morphologies, sizes, and dimensions using different chemical and physical based approaches. In this work, CuO nanostructures have been synthesized by aqueous precipitation method and simple chemical deposition method. The characterization of these products has been carried out by the x-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Fourier Transform Infrared (FTIR) and UV–vis spectroscopy. Biological activity such as antibacterial nature of synthesized CuO is also explored. XRD peaks analysis revealed the monoclinic crystalline phase of copper oxide nanostructures. While the rod-like and particle-like morphologies have been observed in SEM results. FTIR spectra have confirmed the formation of CuO nanoparticles by exhibiting its characteristic peaks corresponding to 494 cm‑1 and 604 cm‑1. The energy band gap of the as-prepared CuO nanostructures determined from UV–vis spectra is found to be 2.18 eV and 2.0 eV for precipitation and chemically deposited samples respectively. The antibacterial activity results described that the synthesized CuO nanoparticles showed better activity against Staphylococcus aureus. The investigated results suggested the synthesis of highly stable CuO nanoparticles with significant antibacterial activities.

  8. Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives.

    Science.gov (United States)

    Tian, Ye; Du, Deping; Rai, Diwakar; Wang, Liu; Liu, Huiqing; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

    2014-04-01

    In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC50 values from 5.98 to 0.07μM. Among the active compounds, 5a was found to be the most promising analogue with an EC50 of 0.07μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Finite element design for the HPHT synthesis of diamond

    Science.gov (United States)

    Li, Rui; Ding, Mingming; Shi, Tongfei

    2018-06-01

    The finite element method is used to simulate the steady-state temperature field in diamond synthesis cell. The 2D and 3D models of the China-type cubic press with large deformation of the synthesis cell was established successfully, which has been verified by situ measurements of synthesis cell. The assembly design, component design and process design for the HPHT synthesis of diamond based on the finite element simulation were presented one by one. The temperature field in a high-pressure synthetic cavity for diamond production is optimized by adjusting the cavity assembly. A series of analysis about the influence of the pressure media parameters on the temperature field are examined through adjusting the model parameters. Furthermore, the formation mechanism of wasteland was studied in detail. It indicates that the wasteland is inevitably exists in the synthesis sample, the distribution of growth region of the diamond with hex-octahedral is move to the center of the synthesis sample from near the heater as the power increasing, and the growth conditions of high quality diamond is locating at the center of the synthesis sample. These works can offer suggestion and advice to the development and optimization of a diamond production process.

  10. The biology of milk synthesis from a proteomics perspective

    NARCIS (Netherlands)

    Lu, J.

    2013-01-01

    Large variation in bovine milk composition of Dutch Holstein cows has been observed. The factors influencing the milk synthesis and secretion process in the mammary gland and the variations in this process lead to variation in milk composition. The understanding of milk synthesis was improved

  11. Method for innovative synthesis-design of chemical process flowsheets

    DEFF Research Database (Denmark)

    Kumar Tula, Anjan; Gani, Rafiqul

    Chemical process synthesis-design involve the identification of the processing route to reach a desired product from a specified set of raw materials, design of the operations involved in the processing route, the calculations of utility requirements, the calculations of waste and emission...... to the surrounding and many more. Different methods (knowledge-based [1], mathematical programming [2], hybrid, etc.) have been proposed and are also currently employed to solve these synthesis-design problems. D’ Anterroches [3] proposed a group contribution based approach to solve the synthesis-design problem...... of chemical processes, where, chemical process flowsheets could be synthesized in the same way as atoms or groups of atoms are synthesized to form molecules in computer aided molecular design (CAMD) techniques [4]. That, from a library of building blocks (functional process-groups) and a set of rules to join...

  12. Rendering Systems Visible for Design: Synthesis Maps as Constructivist Design Narratives

    Directory of Open Access Journals (Sweden)

    Peter Jones

    Full Text Available Synthesis maps integrate research evidence, system expertise, and design proposals into visual narratives. These narratives support communication and decision-making among stakeholders. Synthesis maps evolved from earlier visualization tools in systemics and design. They help stakeholders to understand design options for complex sociotechnical systems. Other visual approaches map complexity for effective collaboration across perspectives and knowledge domains. These help stakeholder groups to work in higher-order design contexts for sociotechnical or human-ecological systems. This article describes a constructivist pedagogy for collaborative learning in small teams of mixed-discipline designers. Synthesis mapping enables these teams to learn systems methods for design research in complex problem domains. Synthesis maps integrate knowledge from research cycles and iterative sensemaking to define a coherent design narrative. While synthesis maps may include formal system modeling techniques, they do not require them. Synthesis maps tangibly render research observations and design choices. As a hybrid system design method, synthesis maps are a contribution to the design genre of visual systems thinking.

  13. The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

    Science.gov (United States)

    Galdzicki, Michal; Clancy, Kevin P; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline Y; Rodriguez, Cesar A; Roehner, Nicholas; Wilson, Mandy L; Adam, Laura; Anderson, J Christopher; Bartley, Bryan A; Beal, Jacob; Chandran, Deepak; Chen, Joanna; Densmore, Douglas; Endy, Drew; Grünberg, Raik; Hallinan, Jennifer; Hillson, Nathan J; Johnson, Jeffrey D; Kuchinsky, Allan; Lux, Matthew; Misirli, Goksel; Peccoud, Jean; Plahar, Hector A; Sirin, Evren; Stan, Guy-Bart; Villalobos, Alan; Wipat, Anil; Gennari, John H; Myers, Chris J; Sauro, Herbert M

    2014-06-01

    The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

  14. Using Simple Manipulatives to Improve Student Comprehension of a Complex Biological Process: Protein Synthesis

    Science.gov (United States)

    Guzman, Karen; Bartlett, John

    2012-01-01

    Biological systems and living processes involve a complex interplay of biochemicals and macromolecular structures that can be challenging for undergraduate students to comprehend and, thus, misconceptions abound. Protein synthesis, or translation, is an example of a biological process for which students often hold many misconceptions. This article…

  15. Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

    Science.gov (United States)

    Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

    2017-01-02

    Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

  16. Toward scalable parts families for predictable design of biological circuits.

    Science.gov (United States)

    Lucks, Julius B; Qi, Lei; Whitaker, Weston R; Arkin, Adam P

    2008-12-01

    Our current ability to engineer biological circuits is hindered by design cycles that are costly in terms of time and money, with constructs failing to operate as desired, or evolving away from the desired function once deployed. Synthetic biologists seek to understand biological design principles and use them to create technologies that increase the efficiency of the genetic engineering design cycle. Central to the approach is the creation of biological parts--encapsulated functions that can be composited together to create new pathways with predictable behaviors. We define five desirable characteristics of biological parts--independence, reliability, tunability, orthogonality and composability, and review studies of small natural and synthetic biological circuits that provide insights into each of these characteristics. We propose that the creation of appropriate sets of families of parts with these properties is a prerequisite for efficient, predictable engineering of new function in cells and will enable a large increase in the sophistication of genetic engineering applications.

  17. Ethylene glycol monolayer protected nanoparticles: synthesis, characterization, and interactions with biological molecules.

    Science.gov (United States)

    Zheng, Ming; Li, Zhigang; Huang, Xueying

    2004-05-11

    The usefulness of the hybrid materials of nanoparticles and biological molecules on many occasions depends on how well one can achieve a rational design based on specific binding and programmable assembly. Nonspecific binding between nanoparticles and biomolecules is one of the major barriers for achieving their utilities in a biological system. In this paper, we demonstrate a new approach to eliminate nonspecific interactions between nanoparticles and biological molecules by shielding the nanoparticle with a monolayer of ethylene glycol. A direct synthesis of di-, tri-, and tetra(ethylene glycol)-protected gold nanoparticles (Au-S-EGn, n = 2, 3, and 4) was achieved under the condition that the water content was optimized in the range of 9-18% in the reaction mixture. With controlled ratio of [HAuCl4]/[EGn-SH] at 2, the synthesized particles have an average diameter of 3.5 nm and a surface plasma resonance band around 510 nm. Their surface structures were confirmed by 1H NMR spectra. These gold nanoparticles are bonded with a uniform monolayer with defined lengths of 0.8, 1.2, and 1.6 nm for Au-S-EG2, Au-S-EG3, and Au-S-EG4, respectively. They have great stabilities in aqueous solutions with a high concentration of electrolytes as well as in organic solvents. Thermogravimetric analysis revealed that the ethylene glycol monolayer coating is ca. 14% of the total nanoparticle weight. Biological binding tests by using ion-exchange chromatography and gel electrophoresis demonstrated that these Au-S-EGn (n = 2, 3, or 4) nanoparticles are free of any nonspecific bindings with various proteins, DNA, and RNA. These types of nanoparticles provide a fundamental starting material for designing hybrid materials composed of metallic nanoparticles and biomolecules.

  18. Synthesis-Based Software Architecture Design

    NARCIS (Netherlands)

    Tekinerdogan, B.; Aksit, Mehmet; Aksit, Mehmet

    2001-01-01

    During the last decade several architecture design approaches have been introduced. These approaches however have to cope with several obstacles and software architecture design remains a difficult problem. To cope with these obstacles this chapter introduces a novel architecture design approach.

  19. Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors

    Czech Academy of Sciences Publication Activity Database

    Lamie, P.F.; Philoppes, J.N.; Rárová, Lucie

    2018-01-01

    Roč. 351, 3-4 (2018), č. článku e1700311. ISSN 0365-6233 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : anti-inflammatory * cytotoxicity * diaryl imidazolone derivatives * molecular docking study Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemical research methods Impact factor: 1.994, year: 2016

  20. General aviation design synthesis utilizing interactive computer graphics

    Science.gov (United States)

    Galloway, T. L.; Smith, M. R.

    1976-01-01

    Interactive computer graphics is a fast growing area of computer application, due to such factors as substantial cost reductions in hardware, general availability of software, and expanded data communication networks. In addition to allowing faster and more meaningful input/output, computer graphics permits the use of data in graphic form to carry out parametric studies for configuration selection and for assessing the impact of advanced technologies on general aviation designs. The incorporation of interactive computer graphics into a NASA developed general aviation synthesis program is described, and the potential uses of the synthesis program in preliminary design are demonstrated.

  1. Design and Synthesis of Nonequilibrium Systems.

    Science.gov (United States)

    Cheng, Chuyang; McGonigal, Paul R; Stoddart, J Fraser; Astumian, R Dean

    2015-09-22

    The active transport of ions and molecules across cell membranes is essential to creating the concentration gradients that sustain life in all living organisms, be they bacteria, fungi, plants, animals or Homo sapiens. Nature uses active transport everywhere for everything. Molecular biologists have long been attracted to the study of active transport and continue to this day to investigate and elucidate the tertiary structures of the complex motor proteins that sustain it, while physicists, interested in nonequilibrium statistical mechanics, have developed theoretical models to describe the driven ratcheting motions that are crucial to its function. The increasingly detailed understanding that contemporary science has acquired relating to active transport, however, has yet to lead to the design and construction of artificial molecular motors capable of employing ratchet-driven motions that can also perform work against concentration gradients. Mechanically interlocked molecules (MIMs) in the form of pseudo- and semirotaxanes are showing some encouraging signs in meeting these goals. This review summarizes recent progress in making artificial molecular motors that can perform work by "pumping" tetracationic rings into high-energy states. The launching pad is a bistable [2]rotaxane whose dumbbell component contains two electron-donating recognition sites, one, a tetrathiafulvalene (TTF) unit, which interacts more strongly with the ring component, cyclobis(paraquat-p-phenylene) (CBPQT(4+)), containing two electron-accepting bipyridinium units, than does the other 1,5-dioxynaphthalene (DNP) unit. Switching can be induced electrochemically by oxidizing the TTF unit to a TTF(•+) radical cation, whereupon Coulombic repulsion takes care of moving the ring to the DNP unit. Reduction of the radical cation resets the switch. Molecular switches operate at, or close to, equilibrium. Any work done during one switching event is undone during the reset. Molecular motors, on the

  2. Biomolecular System Design: Architecture, Synthesis, and Simulation

    OpenAIRE

    Chiang , Katherine

    2015-01-01

    The advancements in systems and synthetic biology have been broadening the range of realizable systems with increasing complexity both in vitro and in vivo. Systems for digital logic operations, signal processing, analog computation, program flow control, as well as those composed of different functions – for example an on-site diagnostic system based on multiple biomarker measurements and signal processing – have been realized successfully. However, the efforts to date tend to tackle each de...

  3. Synthesis and biological evaluation of novel gramicidin s analogues

    NARCIS (Netherlands)

    Tuin, A.W.; Palachanis, D.K.; Buizert, A.; Grotenbreg, G.M.; Spalburg, E.; Neeling, A.J. de; Mars-Groenendijk, R.H.; Noort, D.; Marel, G.A. van der; Overkleeft, H.S.; Overhand, M.

    2009-01-01

    The synthesis of three new analogues of the cyclic cationic antimicrobial peptide Gramicidin S is described. These derivatives contain a modified turn region in which the DPhe-Pro motif has been replaced by a constrained furanoid sugar amino acid or a flexible linear aminoethoxy acetic acid moiety.

  4. The synthesis and biological activity of some bile acid derivatives

    International Nuclear Information System (INIS)

    Kadirov, A.Kh.; Khaydarov, K.Kh.; Giyosov, A.Sh.

    2000-01-01

    In this monograph authors present the modified technologic scheme of receiving of 3α, 7α, 12α-three hydro xi cholanic acid with using of available raw materials for the synthesis products and for receiving on its base drugs diluent cholesterol gallstones of gall-bladder and bile-ducts

  5. A preliminary synthesis of pollination biology in the Cape flora

    CSIR Research Space (South Africa)

    Rebelo, AG

    1987-01-01

    Full Text Available biology are covered. Chapters reviewing plant breeding systems, insect, bird, mammal and wind pollination, and gene flow are introduced by a perspective on the role of the fossil record in pollination biology. A speculative chapter on the constraints...

  6. Preliminary synthesis of pollination biology in the Cape flora

    CSIR Research Space (South Africa)

    Rebelo, AG

    1987-01-01

    Full Text Available biology are covered. Chapters reviewing plant breeding systems, insect, bird, mammal and wind pollination, and gene flow are introduced by a perspective on the role of the fossil record in pollination biology. A speculative chapter on the constraints...

  7. Teaching Process Design through Integrated Process Synthesis

    Science.gov (United States)

    Metzger, Matthew J.; Glasser, Benjamin J.; Patel, Bilal; Hildebrandt, Diane; Glasser, David

    2012-01-01

    The design course is an integral part of chemical engineering education. A novel approach to the design course was recently introduced at the University of the Witwatersrand, Johannesburg, South Africa. The course aimed to introduce students to systematic tools and techniques for setting and evaluating performance targets for processes, as well as…

  8. Solid-supported synthesis: From pharmacologically relevant heterocycles to biologically active surfaces

    DEFF Research Database (Denmark)

    Komnatnyy, Vitaly V.

    for solid-phase synthesis, methods for on - and off-bead screening of combinatorial libraries and their applic ation to various biological targets. The first part of the thesis is dedicated to the development of methodology for the synthesis of structurally diverse heterocyclic scaffolds via N...... methods for the controlled organo-functionalization of titanium, one of the most prominent materials in medicinal device industry, have been suggested . Initial acidic and oxidative treatment s of the metal surface genera te reactive hydroxyl moieties , which are subsequently modified with synthetically...... versatile amine -containing reagents. Subsequent applications in antimicrobial peptide synthesis, metal -catalysis, release from the surface, and polymer grafti ng, are also presented....

  9. Data Integration and Mining for Synthetic Biology Design.

    Science.gov (United States)

    Mısırlı, Göksel; Hallinan, Jennifer; Pocock, Matthew; Lord, Phillip; McLaughlin, James Alastair; Sauro, Herbert; Wipat, Anil

    2016-10-21

    One aim of synthetic biologists is to create novel and predictable biological systems from simpler modular parts. This approach is currently hampered by a lack of well-defined and characterized parts and devices. However, there is a wealth of existing biological information, which can be used to identify and characterize biological parts, and their design constraints in the literature and numerous biological databases. However, this information is spread among these databases in many different formats. New computational approaches are required to make this information available in an integrated format that is more amenable to data mining. A tried and tested approach to this problem is to map disparate data sources into a single data set, with common syntax and semantics, to produce a data warehouse or knowledge base. Ontologies have been used extensively in the life sciences, providing this common syntax and semantics as a model for a given biological domain, in a fashion that is amenable to computational analysis and reasoning. Here, we present an ontology for applications in synthetic biology design, SyBiOnt, which facilitates the modeling of information about biological parts and their relationships. SyBiOnt was used to create the SyBiOntKB knowledge base, incorporating and building upon existing life sciences ontologies and standards. The reasoning capabilities of ontologies were then applied to automate the mining of biological parts from this knowledge base. We propose that this approach will be useful to speed up synthetic biology design and ultimately help facilitate the automation of the biological engineering life cycle.

  10. Development of the Biological Experimental Design Concept Inventory (BEDCI)

    Science.gov (United States)

    Deane, Thomas; Nomme, Kathy; Jeffery, Erica; Pollock, Carol; Birol, Gulnur

    2014-01-01

    Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non-expert-like thinking in students and to evaluate the…

  11. Synthesis and biological evaluation of biaryl analogs of antitubulin compounds

    Energy Technology Data Exchange (ETDEWEB)

    Tozatti, Camila Santos Suniga; Khodyuk, Rejane Goncalves Diniz; Silva, Adriano Olimpio da; Santos, Edson dos Anjos dos; Amaral, Marcos Serrou do; Lima, Denis Pires de, E-mail: denis.lima@ufms.br [Centro de Ciencias Exatas e Tecnologia, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Hamel, Ernest [Screening Technologies Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, MD (United States)

    2012-07-01

    This paper reports the synthesis of methanones and esters bearing different substitution patterns as spacer groups between aromatic rings. This series of compounds can be considered phenstatin analogs. Two of the newly synthesized compounds, 5a and 5c, strongly inhibited tubulin polymerization and the binding of [{sup 3}H] colchicine to tubulin, suggesting that, akin to phenstatin and combretastatin A-4, they can bind to tubulin at the colchicine site. (author)

  12. Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors

    Directory of Open Access Journals (Sweden)

    Qing Liu

    2015-09-01

    Full Text Available Resveratrol (1, a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore, resveratrol derivatives were prepared to improve bioavailability and anti-melanogenesis activity. Nine resveratrol derivatives including five alkyl ether derivatives with C2H5, C4H9, C5H11, C6H13, and C8H17 (2a–2e and four ester derivatives with CH3, CH=C(CH32, CH(C2H5C4H9, C7H15 (3a–3d were newly synthesized and their effect on melanin synthesis were assessed. All the synthetic derivatives efficiently reduced the melanin content in α-MSH stimulated B16F10 melanoma cells. Further investigation showed that the inhibitory effect of 2a on melanin synthesis was achieved not by the inhibition of tyrosinase activity but by the inhibition of melanogenic enzyme expressions such as tyrosinase and tyrosinase-related protein (TRP-1. Our synthetic resveratrol derivatives have more lipophilic properties than resveratrol by the addition of alkyl or acyl chains to free hydroxyl moiety of resveratrol; thus, they are expected to show better bioavailability in skin application. Therefore, we suggest that our synthetic resveratrol derivatives might be promising candidates for better practical application to skin-whitening cosmetics.

  13. PLD based design with VHDL RTL design, synthesis and implementation

    CERN Document Server

    Taraate, Vaibbhav

    2017-01-01

    This book covers basic fundamentals of logic design and advanced RTL design concepts using VHDL. The book is organized to describe both simple and complex RTL design scenarios using VHDL. It gives practical information on the issues in ASIC prototyping using FPGAs, design challenges and how to overcome practical issues and concerns. It describes how to write an efficient RTL code using VHDL and how to improve the design performance. The design guidelines by using VHDL are also explained with the practical examples in this book. The book also covers the ALTERA and XILINX FPGA architecture and the design flow for the PLDs. The contents of this book will be useful to students, researchers, and professionals working in hardware design and optimization. The book can also be used as a text for graduate and professional development courses.

  14. Property Based Process and Product Synthesis and Design

    DEFF Research Database (Denmark)

    Eden, Mario Richard

    2003-01-01

    in terms of the constitutive (synthesis/design) variables instead of the process variables, thus providing the synthesis/design targets. The second reverse problem (reverse property prediction) solves the constitutive equations to identify unit operations, operating conditions and/or products by matching......This thesis describes the development of a general framework for solving process and product design problems. Targeting the desired performance of the system in a systematic manner relieves the iterative nature of conventional design techniques. Furthermore, conventional component based methods...... are not capable of handling problems, where the process or product objectives are driven by functionalities or properties rather than chemical constituency. The framework is meant to complement existing composition based methods by being able to handle property driven problems. By investigating the different...

  15. Robust synthetic biology design: stochastic game theory approach.

    Science.gov (United States)

    Chen, Bor-Sen; Chang, Chia-Hung; Lee, Hsiao-Ching

    2009-07-15

    Synthetic biology is to engineer artificial biological systems to investigate natural biological phenomena and for a variety of applications. However, the development of synthetic gene networks is still difficult and most newly created gene networks are non-functioning due to uncertain initial conditions and disturbances of extra-cellular environments on the host cell. At present, how to design a robust synthetic gene network to work properly under these uncertain factors is the most important topic of synthetic biology. A robust regulation design is proposed for a stochastic synthetic gene network to achieve the prescribed steady states under these uncertain factors from the minimax regulation perspective. This minimax regulation design problem can be transformed to an equivalent stochastic game problem. Since it is not easy to solve the robust regulation design problem of synthetic gene networks by non-linear stochastic game method directly, the Takagi-Sugeno (T-S) fuzzy model is proposed to approximate the non-linear synthetic gene network via the linear matrix inequality (LMI) technique through the Robust Control Toolbox in Matlab. Finally, an in silico example is given to illustrate the design procedure and to confirm the efficiency and efficacy of the proposed robust gene design method. http://www.ee.nthu.edu.tw/bschen/SyntheticBioDesign_supplement.pdf.

  16. Design and Synthesis of a Novel Class of Flavonoid Derivatives via Sequential Phosphorylation and its Application for Greener Nanoparticle Synthesis

    Science.gov (United States)

    Osonga, Francis Juma

    Flavonoids exhibit arrays of biological effects that are beneficial to humans, including anti-viral, anti-oxidative, anti-inflammatory and anti-carcinogenic effects. However, these applications have been hindered by their poor stability and solubility in common solvents. Consequently, there is significant interest in the modification of flavonoids to improve their solubility. This poor solubility is also believed to be responsible for its permeability and bioavailability. Hence the central goal of this work is to design synthetic strategies for the sequential protection of the -OH groups in order to produce phosphorylated quercetin and apigenin derivatives. This work is divided into two parts: the first part presents the design, synthesis, and characterization of novel flavonoid derivatives via global and sequential phosphorylation. The second part focuses on the application of the synthesized derivatives for greener nanoparticle synthesis. This work shows for the first time that sequential phosphorylation of Quercetin is feasible through the design of 4 new derivatives namely: 5,4'-O-Quercetin Diphosphate (QDPI), 4'-O-phosphate Quercetin (4'-QPI), 5,4'-Quercetin Diphosphate (5,4'-QDP) and monophosphate 4-QP. The synthesis of 4'-QP and 5, 4'-QDP was successful with 85% and 60.5% yields respectively. In addition, the progress towards the total synthesis of apigenin phosphate derivatives (7, 4'-ADP and 7-AP) is presented. The synthesized derivatives were characterized using 1H, 13C, and 31P NMR. The phosphorylated derivatives were subsequently explored as reducing agents for sustainable synthesis of gold, silver and copper nanoparticles. We have successfully demonstrated the photochemical synthesis of gold nanoplates of sizes ranging from 10 - 200 nm using water soluble QDP in the presence of sunlight. This work contributes immensely in promoting the ideals of green nanosynthesis by (i) eliminating the use of organic solvents in the nanosynthesis, (ii) exploiting the

  17. Predicting Translation Initiation Rates for Designing Synthetic Biology

    International Nuclear Information System (INIS)

    Reeve, Benjamin; Hargest, Thomas; Gilbert, Charlie; Ellis, Tom

    2014-01-01

    In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5′-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

  18. Design and synthesis of reactive separation systems

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, M.F.

    1992-01-01

    During the last decade there has been a rapid upturn in interest in reactive distillation. The chemical process industry recognizes the favorable economics of carrying out reaction simultaneously with distillation for certain classes of reacting systems, and many new processes have been built based on this technology. Interest is also increasing by academics and software vendors. Systematic design methods for reactive distillation systems have only recently begun to emerge. In this report we survey the available design techniques and point out the contributions made by our group at the University of Massachusetts.

  19. Design of the RFID for Storage of Biological Information

    OpenAIRE

    Sang-Hee Son; Seok-Man Kim; Yu-Lee Choi; Kyoung-Rok Cho

    2009-01-01

    Recent advances in RFID (radio frequency identification) technology promises to create a wireless circuitry capable of interfacing with biological systems for acquisition, identification and processing of biological data based on radio frequency interaction. Thus, the RFID tag can be attached not only to consumer products and form part of the supply chain, but also to animals, plants and in particular human body. This paper describes the strategy for the design of a novel RFID tag, which stor...

  20. Automated Design Framework for Synthetic Biology Exploiting Pareto Optimality.

    Science.gov (United States)

    Otero-Muras, Irene; Banga, Julio R

    2017-07-21

    In this work we consider Pareto optimality for automated design in synthetic biology. We present a generalized framework based on a mixed-integer dynamic optimization formulation that, given design specifications, allows the computation of Pareto optimal sets of designs, that is, the set of best trade-offs for the metrics of interest. We show how this framework can be used for (i) forward design, that is, finding the Pareto optimal set of synthetic designs for implementation, and (ii) reverse design, that is, analyzing and inferring motifs and/or design principles of gene regulatory networks from the Pareto set of optimal circuits. Finally, we illustrate the capabilities and performance of this framework considering four case studies. In the first problem we consider the forward design of an oscillator. In the remaining problems, we illustrate how to apply the reverse design approach to find motifs for stripe formation, rapid adaption, and fold-change detection, respectively.

  1. Computer-Aided Sustainable Process Synthesis-Design and Analysis

    DEFF Research Database (Denmark)

    Kumar Tula, Anjan

    -groups is that, the performance of the entire process can be evaluated from the contributions of the individual process-groups towards the selected flowsheet property (for example, energy consumed). The developed flowsheet property models include energy consumption, carbon footprint, product recovery, product......Process synthesis involves the investigation of chemical reactions needed to produce the desired product, selection of the separation techniques needed for downstream processing, as well as taking decisions on sequencing the involved separation operations. For an effective, efficient and flexible...... focuses on the development and application of a computer-aided framework for sustainable synthesis-design and analysis of process flowsheets by generating feasible alternatives covering the entire search space and includes analysis tools for sustainability, LCA and economics. The synthesis method is based...

  2. Design and Synthesis of Novel Antileishmanial Compounds

    Directory of Open Access Journals (Sweden)

    Melanie Loedige

    2015-01-01

    Full Text Available According to the WHO, infectious diseases, and in particular neglected tropical diseases in poor developing countries, still play a significant role in a vast number of deaths reported worldwide. Among them, leishmaniasis occurs as a complex and clinically diverse illness caused by protozoan Leishmania species which are transmitted through the bite of sandflies. They develop through a complex life cycle, from promastigotes in sandflies to amastigotes in humans. The severity of disease is determined by the type of infecting Leishmania species and also depends strongly on whether the parasite infection leads to a systemic involvement or not. Since the sensitivity towards diverse medicaments highly differs among the Leishmania species, it is advantageous to treat leishmaniasis with species-specific drugs. Towards this goal we report a synthetic methodology and characterization of novel small molecular agents active against both forms of L. major. This synthetic approach allows for rapid access to new active antileishmanial drug templates and their first derivatives in moderate to very good yields. Although the compounds reported here are bioactive, the detailed biological results are part of a more comprehensive study and will be reported separately by our collaborators.

  3. Synthesis and Biological Investigation of Antioxidant Pyrrolomorpholine Spiroketal Natural Products

    Science.gov (United States)

    Verano, Alyssa Leigh

    The pyrrolomorpholine spiroketal natural product family is comprised of epimeric furanose and pyranose isomers. These compounds were isolated from diverse plant species, all of which are used as traditional Chinese medicines for the treatment of a variety of diseases. Notably, the spiroketal natural products acortatarins A and B exhibit antioxidant activity in a diabetic renal cell model, significantly attenuating hyperglycemia-induced production of reactive oxygen species (ROS), a hallmark of diabetic nephropathy. The xylapyrrosides, additional members of the family, also inhibit t-butyl hydroperoxide-induced cytotoxicity in rat vascular smooth muscle cells. Accordingly, these natural products have therapeutic potential for the treatment of oxidative stress-related pathologies, and synthetic access would provide an exciting opportunity to investigate bioactivity and mechanism of action. Herein, we report the stereoselective synthesis of acortatarins A and B, furanose members of the pyrrolomorpholine spiroketal family. Our synthetic route was expanded to synthesize the pyranose congeners, thus completing entire D-enantiomeric family of natural products. Efficient access towards these scaffolds enabled systematic analogue synthesis, investigation of mechanism-of-action, and the discovery of novel antioxidants.

  4. [Update on the biology of heme synthesis in erythroid cells].

    Science.gov (United States)

    Fujiwara, Tohru; Harigae, Hideo

    2015-02-01

    Heme is a prosthetic group of hemoproteins playing important roles in oxygen transport, detoxification, circadian rhythm, microRNA processing, regulation of transcription, and translation. The majority of heme (-85%) is synthesized in red blood cells mainly for hemoglobin production, whereas hepatocytes account for most of the rest, functioning primarily in the synthesis of cytochrome P450 enzymes and mitochondrial respiratory enzymes. Thus, failure of heme biosynthesis causes severe inherited or acquired disorders in humans, including porphyria and sideroblastic anemia. The heme biosynthetic pathway is composed of eight enzymes that work in either mitochondria or the cytoplasm, which have been extensively researched and frequently reviewed. On the other hand, the mechanisms governing transport and intracellular trafficking of heme intermediates, as well as their potential links to human diseases, are poorly understood. Herein, we focus on recent understanding of the heme biosynthetic pathway and on human disorders due to defective heme synthesis in erythroid cells, such as X-linked sideroblastic anemia and erythropoietic protoporphyria.

  5. Synthesis and biological activity of new homolupanes and homolupane saponins

    Czech Academy of Sciences Publication Activity Database

    Sidoryk, K.; Korda, A.; Rárová, Lucie; Oklešťková, Jana; Strnad, Miroslav; Cmoch, P.; Pakulski, Z.; Gwardiak, K.; Karczewski, R.; Luboradzki, R.

    Roč. 71, č. 13 ( 2015 ), s. 2004-2012 ISSN 0040-4020 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Homobetulin * Homobetulinic acid * Glycosylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.645, year: 2015

  6. Synthesis, analysis and biological evaluation of new RGD mimetics

    Czech Academy of Sciences Publication Activity Database

    Balacheva, A. A.; Lambev, M. K.; Pashov, I.; Detcheva, R. L.; Sázelová, Petra; Momekov, G. Ts.; Kašička, Václav; Pajpanova, T. I.; Golovinsky, E. V.

    2017-01-01

    Roč. 49, SI E (2017), s. 7-10 ISSN 0324-1130. [Bulgarian Peptide Symposium /7./. Blagoevgrad, 10.06.2016-12.06.2016] Institutional support: RVO:61388963 Keywords : RGD * biological ly active peptides * cytotoxicity Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 0.238, year: 2016

  7. Occurrence, biological activity and synthesis of drimane sesquiterpenoids

    NARCIS (Netherlands)

    Jansen, B.J.M.; Groot, de Æ.

    2004-01-01

    In this review the names, structures and occurrence of all new drimanes and rearranged drimanes, which have been published between January 1990 and January 2003 have been collected. Subjects that have been treated are biosynthesis, analysis, biological activities, with special attention to cytotoxic

  8. Synthesis and biological evaluation of porphyrin-polyamine conjugates as potential agents in photodynamic therapy

    International Nuclear Information System (INIS)

    Lamarche, Francois

    2004-01-01

    The synthesis of photosensitizers that specifically recognize tumoral cells constitutes a challenging step in the field of photodynamic therapy. To this end, we designed a new class of porphyrins linked to natural polyamines (spermidine, spermine). As a first step, we synthesized para and ortho-carboxy-propyl-oxy-phenyl-tritolyl-porphyrins bearing spermidine or spermine. Then, we designed two precursors, N4-aminobutyl-spermidine-Boc2 and N4-aminobutyl-spermine-Boc3. These derivatives have been fixed on carboxy-porphyrins, protoporphyrin IX and chlorin e6. These new compounds have been characterized by MALDI spectrometry, UV-Visible and 1 H NMR spectroscopy. They have been found to produce singlet oxygen. Biological activity study of these photosensitizers has been realized on K562 cell line, irradiated with fluorescent bulbs. In vitro tests of these porphyrins have shown their photo-cytotoxic activity and protoporphyrins-polyamines have been able to trigger early apoptotic events. Finally, preliminary results obtained with chlorin e6-polyamines, irradiated with red light, seem to show that these structures are good candidates for an application in PDT. (author) [fr

  9. BASIC SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME PHOSPHORCONTATNING ORGANIC COMPOUNDS CONTAINING FRAGMENTS OF UREA AND TRYHLORETILAMID

    OpenAIRE

    Gushylyk B.

    2013-01-01

    Data about directions of synthesis and use of the phosphororganic compounds in technics, biology and medicine is presented in the paper. Antimicrobial activity of 51 phosphororganic salts and ilides containing urine and threechlor ethylenamide has been studied. Perspective of the development of effective antimicrobial substances has been determined

  10. BASIC SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME PHOSPHORCONTATNING ORGANIC COMPOUNDS CONTAINING FRAGMENTS OF UREA AND TRYHLORETILAMID

    Directory of Open Access Journals (Sweden)

    Gushylyk B.

    2013-10-01

    Full Text Available Data about directions of synthesis and use of the phosphororganic compounds in technics, biology and medicine is presented in the paper. Antimicrobial activity of 51 phosphororganic salts and ilides containing urine and threechlor ethylenamide has been studied. Perspective of the development of effective antimicrobial substances has been determined

  11. Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

    Directory of Open Access Journals (Sweden)

    Helena M. C. Ferraz

    2008-01-01

    Full Text Available The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

  12. Design, synthesis, and characterization of biomimetic oligomers

    DEFF Research Database (Denmark)

    Laursen, Jonas Striegler

    a helical arrangement found by DFT calculations. The designed oligomer indeed proved the existence of a ß-peptoid helical conformation by X-ray. Further studies of these compounds indicated a structured display in solution. These helices thus definitively show that the ß-peptoids should be considered......Peptides and proteins made from the 20 canonical amino acids are responsible for many processes necessary for organisms to function. Beside their composition, proteins obtain their activity and unique selectivity through an ability to display functionalities accurately in the three......, for their ability to mimic the structural elements seen in proteins. Two prominent peptidomimetics are ß-peptides and a-peptoids (N-alkylglycines), which have been shown to fold into helical and sheet-like arrangements. To expand the chemical space available for mimicking protein structure their features have been...

  13. Synthesis and biological evaluations of a series of thaxtomin analogues.

    Science.gov (United States)

    Zhang, Hongbo; Wang, Qingpeng; Ning, Xin; Hang, Hang; Ma, Jing; Yang, Xiande; Lu, Xiaolin; Zhang, Jiabao; Li, Yonghong; Niu, Congwei; Song, Haoran; Wang, Xin; Wang, Peng George

    2015-04-15

    Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive structure-activity relationship study screens four effective compounds, including thaxtomin A and thaxtomin C. It is indicated that 4-nitro indole fragment is essential for phytotoxicity, while benzyl and m-hydroxybenzyl substituents on the diketopiperazine ring are favorable for the efficacy. The N-methylations on indole and diketopiperazine show weak influence on the herbicidal activities. The four selected compounds show effective herbicidal activities against Brassica campestris, Amaranthus retroflexus, and Abutilon theophrasti, which are comparable or better than dichlobenil, even at a dosage of 187.5 g ha(-1). Moreover, these four compounds show good crop-selective properties to different crops and exhibit moderate protoporphyrinogen oxidase (PPO) enzyme inhibition. The antifungal results indicate that thaxtomin C displays inhibition to a wide range of fungi.

  14. Group Contribution Based Process Flowsheet Synthesis, Design and Modelling

    DEFF Research Database (Denmark)

    d'Anterroches, Loïc; Gani, Rafiqul

    2004-01-01

    This paper presents a process-group-contribution Method to model. simulate and synthesize a flowsheet. The process-group based representation of a flowsheet together with a process "property" model are presented. The process-group based synthesis method is developed on the basis of the computer...... aided molecular design methods and gives the ability to screen numerous process alternatives without the need to use the rigorous process simulation models. The process "property" model calculates the design targets for the generated flowsheet alternatives while a reverse modelling method (also...... developed) determines the design variables matching the target. A simple illustrative example highlighting the main features of the methodology is also presented....

  15. Plant oligoadenylates: enzymatic synthesis, isolation, and biological activities

    International Nuclear Information System (INIS)

    Devash, Y.; Reichman, M.; Sela, I.; Reichenbach, N.L.; Suhadolnik, R.J.

    1985-01-01

    An enzyme that converts [ 3 H, 32 P]ATP, with a 3 H: 32 P ratio of 1:1, to oligoadenylates with the same 3 H: 32 P ratio was increased in plants following treatment with human leukocyte interferon or plant antiviral factor or inoculation with tobacco mosaic virus. The enzyme was extracted from tobacco leaves, callus tissue cultures, or cell suspension cultures. The enzyme, a putative plant oligoadenylate synthetase, was immobilized on poly(rI) . poly(rC)-agarose columns and converted ATP into plant oligoadenylates. These oligoadenylates were displaced from DEAE-cellulose columns with 350 mM KCl buffer, dialyzed, and further purified by high-performance liquid chromatography (HPLC) and DEAE-cellulose gradient chromatography. In all steps of purification, the ratio of 3 H: 32 P in the oligoadenylates remained 1:1. The plant oligoadenylates isolated by displacement with 350 mM KCl had a molecular weight greater than 1000. The plant oligoadenylates had charges of 5- and 6-. HPLC resolved five peaks, three of which inhibited protein synthesis in reticulocyte and wheat germ systems. Partial structural elucidation of the plant oligoadenylates has been determined by enzymatic and chemical treatments. An adenylate with a 3',5'-phosphodiester and/or a pyrophosphoryl linkage with either 3'- or 5'-terminal phosphates is postulated on the basis of treatment of the oligoadenylates with T2 RNase, snake venom phosphodiesterase, and bacterial alkaline phosphatase and acid and alkaline hydrolyses. The plant oligoadenylates at 8 X 10(-7) M inhibit protein synthesis by 75% in lysates from rabbit reticulocytes and 45% in wheat germ cell-free systems

  16. Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Brindisi, Margherita; Nyalapatla, Prasanth R.; Takayama, Jun; Ella-Menye, Jean-Rene; Yashchuk, Sofiya; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

    2017-10-01

    Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 Å resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

  17. Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from Nephila clavata

    DEFF Research Database (Denmark)

    Barslund, Anne Fuglsang; Poulsen, Mette Homann; Bach, Tinna Brøbech

    2011-01-01

    Polyamine toxins from orb weaver spiders are attractive pharmacological tools particularly for studies of ionotropic glutamate (iGlu) receptors in the brain. These polyamine toxins are biosynthesized in a combinatorial manner, providing a plethora of related, but structurally complex toxins...... to be exploited in biological studies. Here, we have used solid-phase synthetic methodology for the efficient synthesis of Joro spider toxin-4 (JSTX-4) (1) from Nephila clavata, providing sufficient amounts of the toxin for biological evaluation at iGlu receptor subtypes using electrophysiology. Biological...

  18. Controlled polymer synthesis--from biomimicry towards synthetic biology.

    Science.gov (United States)

    Pasparakis, George; Krasnogor, Natalio; Cronin, Leroy; Davis, Benjamin G; Alexander, Cameron

    2010-01-01

    The controlled assembly of synthetic polymer structures is now possible with an unprecedented range of functional groups and molecular architectures. In this critical review we consider how the ability to create artificial materials over lengthscales ranging from a few nm to several microns is generating systems that not only begin to mimic those in nature but also may lead to exciting applications in synthetic biology (139 references).

  19. Allobetulin and Its Derivatives: Synthesis and Biological Activity

    Directory of Open Access Journals (Sweden)

    Talgat S. Seitembetov

    2011-03-01

    Full Text Available This review covers the chemistry of allobetulin analogs, including their formation by rearrangement from betulin derivatives, their further derivatisation, their fusion with heterocyclic rings, and any further rearrangements of allobetulin compounds including ring opening, ring contraction and ring expansion reactions. In the last part, the most important biological activities of allobetulin derivatives are listed. One hundred and fifteen references are cited and the relevant literature is covered, starting in 1922 up to the end of 2010.

  20. Design of synthetic biological logic circuits based on evolutionary algorithm.

    Science.gov (United States)

    Chuang, Chia-Hua; Lin, Chun-Liang; Chang, Yen-Chang; Jennawasin, Tanagorn; Chen, Po-Kuei

    2013-08-01

    The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.

  1. How Biology Teachers Can Respond to Intelligent Design

    Science.gov (United States)

    Mackenzie, Jim

    2010-01-01

    Teachers of biology and related subjects are increasingly meeting objections from students and their parents to the teaching of evolution and the exclusion of what is called the theory of Intelligent Design. This paper attempts to draw together arguments and evidence which may be used by such teachers. Four lessons are drawn from the 1982…

  2. Development of a new family of conformationally restricted peptides as potent nucleators of beta-turns. Design, synthesis, structure, and biological evaluation of a beta-lactam peptide analogue of melanostatin.

    Science.gov (United States)

    Palomo, Claudio; Aizpurua, Jesus M; Benito, Ana; Miranda, José Ignacio; Fratila, Raluca M; Matute, Carlos; Domercq, Maria; Gago, Federico; Martin-Santamaria, Sonsoles; Linden, Anthony

    2003-12-31

    Novel enantiopure (i)-(beta-lactam)-(Gly)-(i+3) peptide models, defined by the presence of a central alpha-alkyl-alpha-amino-beta-lactam ring placed as the (i+1) residue, have been synthesized in a totally stereocontrolled way by alpha-alkylation of suitable N-[bis(trimethylsilyl)methyl]-beta-lactams. The structural properties of these beta-lactam pseudopeptides have been studied by X-ray crystallography, Molecular Dynamics simulation, and NOESY-restrained NMR simulated annealing techniques, showing a strong tendency to form stable type II or type II' beta-turns either in the solid state or in highly coordinating DMSO solutions. Tetrapeptide models containing syn- or anti-alpha,beta-dialkyl-alpha-amino-beta-lactam rings have also been synthesized and their conformations analyzed, revealing that alpha-alkyl substitution is essential for beta-turn stabilization. A beta-lactam analogue of melanostatin (PLG amide) has also been prepared, characterized as a type-II beta-turn in DMSO-d6 solution, and tested by competitive binding assay as a dopaminergic D2 modulator in rat neuron cultured cells, displaying moderate agonist activity in the micromolar concentration range. On the basis of these results, a novel peptidomimetic design concept, based on the separation of constraint and recognition elements, is proposed.

  3. Re-evolution of the 2-phenylquinolines: ligand-based design, synthesis, and biological evaluation of a potent new class of Staphylococcus aureus NorA efflux pump inhibitors to combat antimicrobial resistance.

    Science.gov (United States)

    Sabatini, Stefano; Gosetto, Francesca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Sancineto, Luca; Manfroni, Giuseppe; Tabarrini, Oriana; Dimovska, Mirjana; Kaatz, Glenn W; Cecchetti, Violetta

    2013-06-27

    Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump.

  4. 2-Amido-3-(1H-Indol-3-yl-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies

    Directory of Open Access Journals (Sweden)

    Tong Chen

    2009-01-01

    Full Text Available The Plasmodium falciparum cysteine protease falcipain-2 (FP-2 is an important cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the search for potential malaria treatments. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on three regional optimizations of the lead (R-2-phenoxycarboxamido-3-(1H-indol-3-yl-N-benzylpropanamide(1, which was identified using structure-based virtual screening in conjunction with surface plasmon resonance (SPR-based binding assays. Four compounds – 1, 2b, 2k and 2l –showed moderate FP-2 inhibition activity, with IC50 values of 10.0-39.4 μM, and the inhibitory activityof compound 2k was ~3-fold better than that of the prototype compound 1 and may prove useful for the development of micromolar level FP-2 inhibitors. Preliminary SAR data was obtained, while molecular modeling revealed that introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in the C region would be likely to produce some additional H-bond interactions, which should consequently enhance molecular bioactivity.

  5. Design, synthesis, and biological activities of novel hexahydropyrazino[1,2-a]indole derivatives as potent inhibitors of apoptosis (IAP) proteins antagonists with improved membrane permeability across MDR1 expressing cells.

    Science.gov (United States)

    Shiokawa, Zenyu; Hashimoto, Kentaro; Saito, Bunnai; Oguro, Yuya; Sumi, Hiroyuki; Yabuki, Masato; Yoshimatsu, Mie; Kosugi, Yohei; Debori, Yasuyuki; Morishita, Nao; Dougan, Douglas R; Snell, Gyorgy P; Yoshida, Sei; Ishikawa, Tomoyasu

    2013-12-15

    We previously reported octahydropyrrolo[1,2-a]pyrazine derivative 2 (T-3256336) as a potent antagonist for inhibitors of apoptosis (IAP) proteins. Because compound 2 was susceptible to MDR1 mediated efflux, we developed another scaffold, hexahydropyrazino[1,2-a]indole, using structure-based drug design. The fused benzene ring of this scaffold was aimed at increasing the lipophilicity and decreasing the basicity of the scaffold to improve the membrane permeability across MDR1 expressing cells. We established a chiral pool synthetic route to yield the desired tricyclic chiral isomers. Chemical modification of the core scaffold led to a representative compound 50, which showed strong inhibition of IAP binding (X chromosome-linked IAP [XIAP]: IC50 23 nM and cellular IAP [cIAP]: IC50 1.1 nM) and cell growth inhibition (MDA-MB-231 cells: GI50 2.8 nM) with high permeability and low potential of MDR1 substrate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Discovery of novel, potent and low-toxicity angiotensin II receptor type 1 (AT1) blockers: Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazoles with a chiral center.

    Science.gov (United States)

    Han, Xiao-Feng; He, Xing; Wang, Miao; Xu, Di; Hao, Li-Ping; Liang, Ai-Hua; Zhang, Jun; Zhou, Zhi-Ming

    2015-10-20

    Novel angiotensin II receptor type 1 (AT1) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I] Sar(1) Ile(8)-Ang II, which was specifically bound to human AT1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC₅₀ = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC₅₀ = 7.3 nM), 14R (IC₅₀ = 6.3 nM), and 14S (IC₅₀ = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC₅₀ = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT1 receptor model in docking study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Synthesis, crystal structure and biological activity of novel diester cyclophanes

    International Nuclear Information System (INIS)

    Zhang, Pengfei; Yang, Bingqin; Fang, Xianwen; Cheng, Zhao; Yang, Meipan

    2012-01-01

    A series of novel diester cyclophanes was synthesized by esterification of 1,2-benzenedicarbonyl chloride with eight different diols under high dilution conditions. The structures of the compounds were verified by elemental analysis, 1 H nuclear magnetic resonance (NMR), IR spectroscopy and high resolution mass spectrometry (HRMS). The crystal structures of two compounds were characterized by single crystal X-ray diffractometry (XRD). All the new cyclophanes were evaluated for biological activities and the results showed that some of these compounds have low antibacterial or antifungal activities (author)

  8. Synthesis, crystal structure and biological activity of novel diester cyclophanes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengfei; Yang, Bingqin; Fang, Xianwen; Cheng, Zhao; Yang, Meipan, E-mail: yangbq@nwu.edu.cn [Department of Chemistry, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, Northwest University, Shaanxi (China)

    2012-10-15

    A series of novel diester cyclophanes was synthesized by esterification of 1,2-benzenedicarbonyl chloride with eight different diols under high dilution conditions. The structures of the compounds were verified by elemental analysis, {sup 1}H nuclear magnetic resonance (NMR), IR spectroscopy and high resolution mass spectrometry (HRMS). The crystal structures of two compounds were characterized by single crystal X-ray diffractometry (XRD). All the new cyclophanes were evaluated for biological activities and the results showed that some of these compounds have low antibacterial or antifungal activities (author)

  9. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

    Science.gov (United States)

    Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

    2016-01-01

    A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Larval biology of the crab Rhithropanopeus harrisii (Gould): a synthesis.

    Science.gov (United States)

    Forward, Richard B

    2009-06-01

    This synthesis reviews the physiological ecology and behavior of larvae of the benthic crab Rhithropanopeus harrisii, which occurs in low-salinity areas of estuaries. Larvae are released rhythmically around the time of high tide in tidal estuaries and in the 2-h interval after sunset in nontidal estuaries. As in most subtidal crustaceans, the timing of larval release is controlled by the developing embryos, which release peptide pheromones that stimulate larval release behavior by the female to synchronize the time of egg hatching. Larvae pass through four zoeal stages and a postlarval or megalopal stage that are planktonic before metamorphosis. They are retained near the adult population by means of an endogenous tidal rhythm in vertical migration. Larvae have several safeguards against predation: they undergo nocturnal diel vertical migration (DVM) and have a shadow response to avoid encountering predators, and they bear long spines as a deterrent. Photoresponses during DVM and the shadow response are enhanced by exposure to chemical cues from the mucus of predator fishes and ctenophores. The primary visual pigment has a spectral sensitivity maximum at about 500 nm, which is typical for zooplankton and matches the ambient spectrum at twilight. Larvae can detect vertical gradients in temperature, salinity, and hydrostatic pressure, which are used for depth regulation and avoidance of adverse environmental conditions. Characteristics that are related to the larval habitat and are common to other crab larval species are considered.

  11. Acetyl analogs of combretastatin A-4: synthesis and biological studies.

    Science.gov (United States)

    Babu, Balaji; Lee, Megan; Lee, Lauren; Strobel, Raymond; Brockway, Olivia; Nickols, Alexis; Sjoholm, Robert; Tzou, Samuel; Chavda, Sameer; Desta, Dereje; Fraley, Gregory; Siegfried, Adam; Pennington, William; Hartley, Rachel M; Westbrook, Cara; Mooberry, Susan L; Kiakos, Konstantinos; Hartley, John A; Lee, Moses

    2011-04-01

    The combretastatins have received significant attention because of their simple chemical structures, excellent antitumor efficacy and novel antivascular mechanisms of action. Herein, we report the synthesis of 20 novel acetyl analogs of CA-4 (1), synthesized from 3,4,5-trimethoxyphenylacetone that comprises the A ring of CA-4 with different aromatic aldehydes as the B ring. Molecular modeling studies indicate that these new compounds possess a 'twisted' conformation similar to CA-4. The new analogs effectively inhibit the growth of human and murine cancer cells. The most potent compounds 6k, 6s and 6t, have IC(50) values in the sub-μM range. Analog 6t has an IC(50) of 182 nM in MDA-MB-435 cells and has advantages over earlier analogs due to its enhanced water solubility (456 μM). This compound initiates microtubule depolymerization with an EC(50) value of 1.8 μM in A-10 cells. In a murine L1210 syngeneic tumor model 6t had antitumor activity and no apparent toxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Terminator Operon Reporter: combining a transcription termination switch with reporter technology for improved gene synthesis and synthetic biology applications.

    Science.gov (United States)

    Zampini, Massimiliano; Mur, Luis A J; Rees Stevens, Pauline; Pachebat, Justin A; Newbold, C James; Hayes, Finbarr; Kingston-Smith, Alison

    2016-05-25

    Synthetic biology is characterized by the development of novel and powerful DNA fabrication methods and by the application of engineering principles to biology. The current study describes Terminator Operon Reporter (TOR), a new gene assembly technology based on the conditional activation of a reporter gene in response to sequence errors occurring at the assembly stage of the synthetic element. These errors are monitored by a transcription terminator that is placed between the synthetic gene and reporter gene. Switching of this terminator between active and inactive states dictates the transcription status of the downstream reporter gene to provide a rapid and facile readout of the accuracy of synthetic assembly. Designed specifically and uniquely for the synthesis of protein coding genes in bacteria, TOR allows the rapid and cost-effective fabrication of synthetic constructs by employing oligonucleotides at the most basic purification level (desalted) and without the need for costly and time-consuming post-synthesis correction methods. Thus, TOR streamlines gene assembly approaches, which are central to the future development of synthetic biology.

  13. Solid-Phase Synthesis for the Construction of Biologically Interesting Molecules and the Total Synthesis of Trioxacarcin DC-45-A2

    DEFF Research Database (Denmark)

    Mikkelsen, Remi Jacob Thomsen

    . Furthermore a route to another key building block was developed featuring a Stille cross-coupling.Synthesis of Poly-fused Heterocycles. In the search for new biologically active compounds a methodology for the synthesis of polyfused heterocycles was investigated. This led to the development and optimization...

  14. Gold-Pluronic core-shell nanoparticles: synthesis, characterization and biological evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Timea; Boca, Sanda [Babes-Bolyai University, Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences and Faculty of Physics (Romania); Biro, Dominic [Sapientia University, Department of Mechanical Engineering, Faculty of Technical and Human Sciences (Romania); Baldeck, Patrice [Universite Joseph Fourier and CNRS, Laboratoire Interdisciplinaire de Physique, UMR 5588, CNRS (France); Astilean, Simion, E-mail: simion.astilean@phys.ubbcluj.ro [Babes-Bolyai University, Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences and Faculty of Physics (Romania)

    2013-04-15

    This study presents the synthesis of gold-Pluronic core-shell nanoparticles by a two-step method and investigates their biological impact on cancer cells, specifically nanoparticle internalization and cytotoxicity. Uniform, 9-10-nm-sized, hydrophobic gold nanoparticles were synthesized in organic phase by reducing gold salt with oleylamine, after which oleylamine-protected gold nanoparticles were phase-transferred into aqueous medium using Pluronic F127 block copolymer, resulting in gold-Pluronic core-shell nanoparticles with a mean hydrodynamic diameter of {approx}35 nm. The formation and phase-transfer of gold nanoparticles were analyzed by UV-Vis absorption spectroscopy, transmission electron microscopy, and dynamic light scattering. The obtained gold-Pluronic core-shell nanoparticles proved to be highly stable in salted solution. Cytotoxicity tests showed no modification of cellular viability in the presence of properly purified particles. Furthermore, dark-field cellular imaging demonstrated that gold-Pluronic nanoparticles were able to be efficiently uptaken by cells, being internalized through nonspecific endocytosis. The high stability, proven biocompatibility, and imaging properties of gold-Pluronic core-shell nanoparticles hold promise for relevant intracellular applications, with such a design providing the feasibility to combine all multiple functionalities in one nanoparticle for simultaneous detection and imaging.

  15. Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

    Directory of Open Access Journals (Sweden)

    Michalina Hebda

    2016-03-01

    Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

  16. Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies

    Directory of Open Access Journals (Sweden)

    André Luiz Lourenço

    2015-04-01

    Full Text Available The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations.

  17. Gold–Pluronic core–shell nanoparticles: synthesis, characterization and biological evaluation

    International Nuclear Information System (INIS)

    Simon, Timea; Boca, Sanda; Biro, Dominic; Baldeck, Patrice; Astilean, Simion

    2013-01-01

    This study presents the synthesis of gold–Pluronic core–shell nanoparticles by a two-step method and investigates their biological impact on cancer cells, specifically nanoparticle internalization and cytotoxicity. Uniform, 9–10-nm-sized, hydrophobic gold nanoparticles were synthesized in organic phase by reducing gold salt with oleylamine, after which oleylamine-protected gold nanoparticles were phase-transferred into aqueous medium using Pluronic F127 block copolymer, resulting in gold–Pluronic core–shell nanoparticles with a mean hydrodynamic diameter of ∼35 nm. The formation and phase-transfer of gold nanoparticles were analyzed by UV–Vis absorption spectroscopy, transmission electron microscopy, and dynamic light scattering. The obtained gold–Pluronic core–shell nanoparticles proved to be highly stable in salted solution. Cytotoxicity tests showed no modification of cellular viability in the presence of properly purified particles. Furthermore, dark-field cellular imaging demonstrated that gold–Pluronic nanoparticles were able to be efficiently uptaken by cells, being internalized through nonspecific endocytosis. The high stability, proven biocompatibility, and imaging properties of gold–Pluronic core–shell nanoparticles hold promise for relevant intracellular applications, with such a design providing the feasibility to combine all multiple functionalities in one nanoparticle for simultaneous detection and imaging.

  18. Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics.

    Science.gov (United States)

    Cheng, Kui; Zheng, Qing-Zhong; Hou, Jin; Zhou, Yang; Liu, Chang-Hong; Zhao, Jing; Zhu, Hai-Liang

    2010-04-01

    We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli beta-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13microg/mL and 0.39-3.13microg/mL against various bacteria. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Synthesis, characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Bhattacharya, Dipsikha; Sahu, Sumanta K.; Banerjee, Indranil; Das, Manasmita; Mishra, Debashish; Maiti, Tapas K.; Pramanik, Panchanan

    2011-01-01

    In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T 2 contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T 2 relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.

  20. Synthesis, radioiodination and biological evaluation of a novel phthalimide derivative

    International Nuclear Information System (INIS)

    Motaleb, M.A.; Abdel-Ghaney, I.Y.; Shamsel-Din, H.A.; Abdel-Bary, H.M.

    2016-01-01

    Biologically active novel phthalimide derivative, N-(5-(2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phthalimide (HPZPHT), was synthesized in excellent yield and characterized by IR, mass and 1 H NMR spectroscopy. It was radiolabeled with iodine-131 by direct electrophilic substitution reaction and radiochemical yield was determined by using different chromatographic techniques (HPLRC, paper chromatography and paper electrophoresis). 131 I-HPZPHT has high radiolabeling yield (98.00 ± 2.00 %), stability, solid tumor uptake and T/NT ratio (5.17 ± 0.03 at 30 min. post-injection) compared with many new tracers which have been developed in recent years. This study encourages the possible use of this tracer as a potential imaging and/or therapeutic agent for cancer. (author)

  1. Synthesis and Design of a Sustainable CO2 Utilization Network

    DEFF Research Database (Denmark)

    Frauzem, Rebecca; Gani, Rafiqul

    In response to increasing regulations and concern about the impact of greenhouse gases on the environment, carbon dioxide (CO2) emissions are targeted for reduction. One method is the conversion of CO2 to useful compounds via chemical reactions. However, conversion is still in its infancy...... and requires work for implementation at an industrial level. One aspect of this is the development of a methodology for the formulation and optimization of sustainable conversion processes. This methodology follows three stages for the process synthesis, design and more sustainable design. Using...

  2. The synthesis and biological evaluation of integrin receptor targeting molecules as potential radiopharmaceuticals

    Science.gov (United States)

    Pellegrini, Paul

    This thesis reports on the synthesis, characterisation and biological evaluation of a number of metal complexes designed to interact with the alphavbeta3 integrin receptor, an important biological target that is heavily involved in angiogenesis, and thus cancer related processes. Two approaches were used to synthesise the integrin-avid targets. The first was to attach a variety of bifunctional chelators (BFC's) for the incorporation of different metal centres to a known integrin antagonist, L-748,415, developed by Merck. The BFC's used were the hydrazinonicotinamide (HYNIC) and monoamine monoamide dithiol (MAMA) systems for coordination to Tc-99m and rhenium of which was used as a characterization surrogate for the unstable Tc core. The 1,4,7,10-tetraazacyclotridecanetetraacetic acid (TRITA) BFC was attached for the inclusion of copper and lutetium. This 'conjugate' approach was designed to yield information on how the BFC and the linker length would affect the affinity for the integrin receptor. The second approach was an 'integrated' method where the chelation moiety was integral to the biologically relevant part of the molecule, which in the case of the alphavbeta3 integrin receptor, is the arginine-glycine-aspartic acid (RGD) mimicking sequence. Two complexes were created with a modified MAMA derivative placed between a benzimidazole moiety (arginine mimick) and the aspartic acid mimicking terminal carboxylic acid to see how it would affect binding while keeping the molecular weight relatively low. The molecules were tested in vitro against purified human alphavbeta3 integrin receptor protein in a solid phase receptor binding assay to evaluate their inhibition constants against a molecule of known high affinity and selectivity in [I125]L-775,219, the I125 labelled alphavbeta3 integrin antagonist. The radiolabelled analogues were also tested in vivo against the A375 human melanoma cell line transplanted into balb/c nude mice as well as Fischer rats implanted

  3. Design control considerations for biologic-device combination products.

    Science.gov (United States)

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-03-01

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting

  4. Radiation Synthesis of Stimuli-Responsive Hydrogels for Biological Applications

    International Nuclear Information System (INIS)

    Eid, M.; Hegazy, S.A.

    2009-01-01

    Poly(acrylamide/maleic acid/gelatin) P(AAm/MA/G) hydrogel networks were synthesized by 60 Co gamma irradiation at different doses. The properties of the hydrogels such as gelation percent, porosity, and moisture retention were investigated. The swelling ratio (S), equilibrium water content (EWC) and diffusion characteristics, including equilibrium swelling ratio (ESR), diffusion constant (n) and diffusion coefficients (D) were investigated and a non-Fickian type of diffusion characteristics was found in all the swelling media for the diffusion of water into these hydrogels. Further, the swelling pattern of P(AAm/MA/G) hydrogels was studied in different physiological bio-fluids, ph and ionic/salt solutions and showed great responsiveness due to their ionic character. The penetration velocity (v) of these biological fluids into such hydrogels was also calculated and it was found to be the maximum in urea and the minimum in synthetic urine. The higher equilibrium water content of these hydrogels, promotes them to be used as biomedical/pharmaceutical technology. The caffeine release as a drug model has been studied at ph 1 and ph 7 to resemble the ph of the stomach and the intestine, respectively. The caffeine release was controlled by the hydrogel crosslinking density that caused in increase of the irradiation dose

  5. Hydroxyapatite synthesis on solid surfaces using a biological approach

    International Nuclear Information System (INIS)

    Wang, A; Mei, J; Tse, Y Y; Jones, I P; Sammons, R L

    2012-01-01

    Many naturally occurring mineralisation processes yield hydroxyapatite (HA) or related salts, but biological routes to calcification have not generally been exploited for production of hydroxyapatite for clinical and industrial applications. Serratia sp. NCIMB 40259 is a non-pathogenic Gram-negative bacterium which is capable of growing as a biofilm on many surfaces and can be used to form HA coatings on a variety of polymeric and metallic materials, including titanium. Here we review previous work and report the results of more recent studies on the influence of titanium compositional and surface properties on Serratia adherence and proliferation and biomineralisation on commercially pure titanium (cp Ti) discs and a Ti mesh. Bacterial adherence was equivalent on cpTi and Ti6Al4V, and biofilms formed on both rough and mirror-polished cpTi surfaces. Embedded alumina particles and alkali treatment did not noticeably alter the precipitation of Serratia HA, nor the structure of the coating in comparison with non-treated substrates. Coatings were retained after sintering at 800°C in argon, although the original curved plate-like crystals changed to nano-scale β-tricalcium phosphate particles. A phosphorous-rich diffusion zone formed at the coating-titanium interface. Bacterial mineralisation may have applications as a method for producing coatings on implants in non load-bearing sites, and non-clinical applications where a high surface area is the major concern.

  6. Hydroxyapatite synthesis on solid surfaces using a biological approach

    Science.gov (United States)

    Wang, A.; Mei, J.; Tse, Y. Y.; Jones, I. P.; Sammons, R. L.

    2012-12-01

    Many naturally occurring mineralisation processes yield hydroxyapatite (HA) or related salts, but biological routes to calcification have not generally been exploited for production of hydroxyapatite for clinical and industrial applications. Serratia sp. NCIMB 40259 is a non-pathogenic Gram-negative bacterium which is capable of growing as a biofilm on many surfaces and can be used to form HA coatings on a variety of polymeric and metallic materials, including titanium. Here we review previous work and report the results of more recent studies on the influence of titanium compositional and surface properties on Serratia adherence and proliferation and biomineralisation on commercially pure titanium (cp Ti) discs and a Ti mesh. Bacterial adherence was equivalent on cpTi and Ti6Al4V, and biofilms formed on both rough and mirror-polished cpTi surfaces. Embedded alumina particles and alkali treatment did not noticeably alter the precipitation of Serratia HA, nor the structure of the coating in comparison with non-treated substrates. Coatings were retained after sintering at 800°C in argon, although the original curved plate-like crystals changed to nano-scale β-tricalcium phosphate particles. A phosphorous-rich diffusion zone formed at the coating-titanium interface. Bacterial mineralisation may have applications as a method for producing coatings on implants in non load-bearing sites, and non-clinical applications where a high surface area is the major concern.

  7. Synthesis, physicochemical and biological properties of ethynyl piperidol derivatives

    International Nuclear Information System (INIS)

    Khalikov, D.Kh.

    2012-01-01

    The book presents the results of studies on the reactivity of some derivatives of ethynyl-piperidol in reactions of homo-and copolymerization, the numerical values of the constants of the initiation reaction, growth and chain termination, the parameters of molecular weight, molecular weight distribution and flexibility of polymer chins, triple-radical copolymerization results of ethynyl-piperidol derivatives with hydrophilic monomers and polyfunctional cross-linked polymers and high swelling hydrogels, as well as developed by the author the radiation-chemical grafting technique termed monomers on the surface of cellulose in a continuous manner. The experimental data on ethynyl-piperidol polymers involves with various low-, medium-and high substrates from model solutions and in biological fluids are given. On the example of three iodide ion sorption, bilirubin and serum albumin showed that for the thermodynamically favorable process make a significant contribution to the free energy terms due to the hypothetical ion exchange, the change in resonates concentration and cooperative interaction. The role of hydrophobic interaction in realization of this process is reviled. The data obtained were formulated and validated a number of scientific statements in the chemistry of biomedical polymers. The results of the practical implementation of a number of developments in medical practice are demonstrated. The hydrogel homo-and sorbent, dressings, which have shown high efficacy in the treatment of diseases complicated by endogenous and bacterial endotoxemia in acute radiation and combined radiation-thermal lesions, as well as kidney and live failure. (author)

  8. Synthesis, chemical and biological quality control of radioiodinated peptides

    International Nuclear Information System (INIS)

    Rafii, H.; Khalaj, A.; Beiki, D.; Motameidi, F.; Maloobi, M.; Karimian-dehghan, M.; Keshavarrzi, F.

    2002-01-01

    Iodinated compounds with I-131, 125 and 123 have been widely used for biochemical function studies. In conjunction with SPECT, [I-123] labelled proteins have various diagnostic and therapeutic applications in nuclear medicine. Preparation of some radioiodinated peptides with tyrosine and/or lysine groups on their main chain molecules can be carried out with both direct and indirect methods, but lack of these groups in molecule cause the molecule dose not lend itself for direct radioiodination. In this study, human IgG and Formyl-Methyl-Leucyl-Phenylalanine, FMLF, have been chosen as a model compounds for direct and indirect radioiodination respectively. Here, we will describe the labelling procedure of [I-125] IgG using chloramine-T as a suitable oxidant agent and [I-125 and I-131] FMLF by indirect method using ATE/SIB as a prosthetic group in multi-step reactions. The obtained results for chemical quality control of intermediate radioiodinated SIB by HPLC and two labelled IgG and FMLF will be also discussed. Biological results, biodistribution studies and SPECT scans on mice per-injected labelled FMLF show a low uptake of thyroid but a high at urine and bladder, perhaps because of low molecular weight of FMLF. In this case, it seems to be better to separate the reaction mixture of labelled FMLF by BPLC than Sephadex-G50 gel filtration. (Author)

  9. Pharmaceutical research at the AAEC Part I: Ligand synthesis and biological studies

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, J G [Australian Atomic Energy Commission Research Establishment, Lucas Heights

    1982-09-01

    Work on the synthesis of ligands capable of forming chelate complexes with technetium-99m as part of a search for tumour-localising radiopharmaceuticals is described. An account of the biological evaluation of a range of these compounds, in particular, benzimidazoles, sulphanilamides and acridines, and of the investigation of certain biochemical and biological properties affecting the clinical application of both ligands and radiopharmaceuticals is given. Interactions between therapeutic drugs and diagnostic radiopharmaceuticals are considered. The toxicological evaluation of a prospective hepatobiliary imaging agent, dimethyl-BIMIDA, is described.

  10. Design, synthesis and bioactivity evaluation of tribactam beta lactamase inhibitors.

    Science.gov (United States)

    Copar, Anton; Prevec, Tadeja; Anzic, Borut; Mesar, Tomaz; Selic, Lovro; Vilar, Mateja; Solmajer, Tom

    2002-03-25

    Known carbapenem compounds with inhibitory effect towards beta-lactamase enzymes are formed from bicyclical beta lactam structural scaffolds. On the basis of results from theoretical computational methods and molecular modelling we have designed and developed a synthetic route towards novel, biologically active tricyclic derivatives of carbapenems.

  11. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions.

    Science.gov (United States)

    Shaginian, Alex; Whitby, Landon R; Hong, Sukwon; Hwang, Inkyu; Farooqi, Bilal; Searcey, Mark; Chen, Jiandong; Vogt, Peter K; Boger, Dale L

    2009-04-22

    The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.

  12. Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

    International Nuclear Information System (INIS)

    Babkov, D A; Geisman, A N; Novikov, M S; Khandazhinskaya, A L

    2016-01-01

    The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references

  13. Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies

    Directory of Open Access Journals (Sweden)

    Bogumił Brycki

    2015-11-01

    Full Text Available The methods of synthesis as well as physical, spectroscopic (1H-NMR, 13C-NMR, and FT-IR, ESI-MS, and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods and potential pharmacological properties (PASS. Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.

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

    Directory of Open Access Journals (Sweden)

    Yunpeng Yi

    2017-06-01

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

  15. Synthesis and biological activity of pyridazine amides, hydrazones and hydrazides.

    Science.gov (United States)

    Buysse, Ann M; Yap, Maurice Ch; Hunter, Ricky; Babcock, Jonathan; Huang, Xinpei

    2017-04-01

    Optimization studies on compounds initially designed to be herbicides led to the discovery of a series of [6-(3-pyridyl)pyridazin-3-yl]amides exhibiting aphicidal properties. Systematic modifications of the amide moiety as well as the pyridine and pyridazine rings were carried out to determine if these changes could improve insecticidal potency. Structure-activity relationship (SAR) studies showed that changes to the pyridine and pyridazine rings generally resulted in a significant loss of insecticidal potency against green peach aphids [Myzus persicae (Sulzer)] and cotton aphids [(Aphis gossypii (Glover)]. However, replacement of the amide moiety with hydrazines, hydrazones, or hydrazides appeared to be tolerated, with small aliphatic substituents being especially potent. A series of aphicidal [6-(3-pyridyl)pyridazin-3-yl]amides were discovered as a result of random screening of compounds that were intially investigated as herbicides. Follow-up studies of the structure-activity relationship of these [6-(3-pyridyl)pyridazin-3-yl]amides showed that biosteric replacement of the amide moiety was widely tolerated suggesting that further opportunities for exploitation may exist for this new area of insecticidal chemistry. Insecticidal efficacy from the original hit, compound 1, to the efficacy of compound 14 produced greater than 10-fold potency improvement against Aphis gossypii and greater than 14-fold potency improvement against Myzus persicae. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  16. Design of the RFID for Storage of Biological Information

    Directory of Open Access Journals (Sweden)

    Sang-Hee Son

    2009-02-01

    Full Text Available Recent advances in RFID (radio frequency identification technology promises to create a wireless circuitry capable of interfacing with biological systems for acquisition, identification and processing of biological data based on radio frequency interaction. Thus, the RFID tag can be attached not only to consumer products and form part of the supply chain, but also to animals, plants and in particular human body. This paper describes the strategy for the design of a novel RFID tag, which stores vital biological information such as body temperature and blood pressure and heartbeat in accordance with the EPC global Class-1 standard. Biological data is obtained from a sensor technology that is based on resistance deviation-to-pulse width converter. The integrated chip consists of an analog front end, command interpreter, collision avoidance block, data storage, sensors, and interface circuitry. The system is capable of supporting heartbeats in the range of 40~200 beats per a minute and blood pressure 0~300mmHg. The proposed system employs collision free algorithm that supports access to single tag within a multiple tag environment. The approach facilitates intelligent management of patients in hospitals as part of an integrated healthcare management system.

  17. Design preferences and cognitive styles: experimentation by automated website synthesis.

    Science.gov (United States)

    Leung, Siu-Wai; Lee, John; Johnson, Chris; Robertson, David

    2012-06-29

    This article aims to demonstrate computational synthesis of Web-based experiments in undertaking experimentation on relationships among the participants' design preference, rationale, and cognitive test performance. The exemplified experiments were computationally synthesised, including the websites as materials, experiment protocols as methods, and cognitive tests as protocol modules. This work also exemplifies the use of a website synthesiser as an essential instrument enabling the participants to explore different possible designs, which were generated on the fly, before selection of preferred designs. The participants were given interactive tree and table generators so that they could explore some different ways of presenting causality information in tables and trees as the visualisation formats. The participants gave their preference ratings for the available designs, as well as their rationale (criteria) for their design decisions. The participants were also asked to take four cognitive tests, which focus on the aspects of visualisation and analogy-making. The relationships among preference ratings, rationale, and the results of cognitive tests were analysed by conservative non-parametric statistics including Wilcoxon test, Krustal-Wallis test, and Kendall correlation. In the test, 41 of the total 64 participants preferred graphical (tree-form) to tabular presentation. Despite the popular preference for graphical presentation, the given tabular presentation was generally rated to be easier than graphical presentation to interpret, especially by those who were scored lower in the visualization and analogy-making tests. This piece of evidence helps generate a hypothesis that design preferences are related to specific cognitive abilities. Without the use of computational synthesis, the experiment setup and scientific results would be impractical to obtain.

  18. Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Energy Technology Data Exchange (ETDEWEB)

    Silver, Pamela [Harvard Univ., Cambridge, MA (United States); SEED 2015 Conference Chair; Flach, Evan [American Institute of Chemical Engineers; SEED 2015 Conference Organizer

    2016-10-27

    Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international

  19. Constraining designs for synthesis and timing analysis a practical guide to synopsys design constraints (SDC)

    CERN Document Server

    Gangadharan, Sridhar

    2013-01-01

    This book serves as a hands-on guide to timing constraints in integrated circuit design.  Readers will learn to maximize performance of their IC designs, by specifying timing requirements correctly.  Coverage includes key aspects of the design flow impacted by timing constraints, including synthesis, static timing analysis and placement and routing.  Concepts needed for specifying timing requirements are explained in detail and then applied to specific stages in the design flow, all within the context of Synopsys Design Constraints (SDC), the industry-leading format for specifying constraints.  ·         Provides a hands-on guide to synthesis and timing analysis, using Synopsys Design Constraints (SDC), the industry-leading format for specifying constraints; ·         Includes key topics of interest to a synthesis, static timing analysis or  place and route engineer; ·         Explains which constraints command to use for ease of maintenance and reuse, given several options pos...

  20. Strategies for Assessment of the Biological Performance and Design of Hydroturbines

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, Thomas J.; Richmond, Marshall C.

    2011-05-05

    The biological response of fish to turbine passage has been of concern for several decades and emphasized recently by consideration of hydro as a 'green' power source. The current state-of-the-art of hydro-turbine biological performance assessment, while still inadequate, has advanced considerably the past 10 years. For example, the importance of assessment of exposure to pressure changes during turbine passage has been emphasized by findings of laboratory studies of rapid decompression. It is now very clear that hydroturbine biological assessment must consider the physiological state and behavior of fish at turbine entry and changes in physiological state that drive aspects of behavior during tailrace passage. Such considerations are in addition to concerns about exposure of fish to mechanical and pressure sources of injury during turbine passage. Experimental designs and assessment tools have evolved for acclimation of test fish, observation of test fish behavior at approach and upon exit from the turbine environment, and precise estimation of turbine passage mortality. Fish condition assessment continues to improve permitting better classification of observed injuries to injury mechanisms. Computational fluid dynamics (CFD) models and other computer models permit detailed investigation of the turbine passage environment and development of hypotheses that can be tested in field studies using live fish. Risk assessment techniques permit synthesis of laboratory and in-field study findings and estimation of population level effects over a wide range of turbine operation scenarios. Risk assessment is also evolving to provide input to turbine runner design. These developments, and others, have resulted in more productive biological performance assessment studies and will continue to evolve and improve the quantity and quality of information obtained from costly live fish hydroturbine passage studies. This paper reviews the history of hydro-turbine biological

  1. Artificial heartbeat: design and fabrication of a biologically inspired pump

    International Nuclear Information System (INIS)

    Walters, Peter; Stephenson, Robert; Lewis, Amy; Stinchcombe, Andrew; Ieropoulos, Ioannis

    2013-01-01

    We present a biologically inspired actuator exhibiting a novel pumping action. The design of the ‘artificial heartbeat’ actuator is inspired by physical principles derived from the structure and function of the human heart. The actuator employs NiTi artificial muscles and is powered by electrical energy generated by microbial fuel cells (MFCs). We describe the design and fabrication of the actuator and report the results of tests conducted to characterize its performance. This is the first artificial muscle-driven pump to be powered by MFCs fed on human urine. Results are presented in terms of the peak pumping pressure generated by the actuator, as well as for the volume of fluid transferred, when the actuator was powered by energy stored in a capacitor bank, which was charged by 24 MFCs fed on urine. The results demonstrate the potential for the artificial heartbeat actuator to be employed as a fluid circulation pump in future generations of MFC-powered robots (‘EcoBots’) that extract energy from organic waste. We also envisage that the actuator could in the future form part of a bio-robotic artwork or ‘bio-automaton’ that could help increase public awareness of research in robotics, bio-energy and biologically inspired design. (paper)

  2. Intelligent Agents for Design and Synthesis Environments: My Summary

    Science.gov (United States)

    Norvig, Peter

    1999-01-01

    This presentation gives a summary of intelligent agents for design synthesis environments. We'll start with the conclusions, and work backwards to justify them. First, an important assumption is that agents (whatever they are) are good for software engineering. This is especially true for software that operates in an uncertain, changing environment. The "real world" of physical artifacts is like that: uncertain in what we can measure, changing in that things are always breaking down, and we must interact with non-software entities. The second point is that software engineering techniques can contribute to good design. There may have been a time when we wanted to build simple artifacts containing little or no software. But modern aircraft and spacecraft are complex, and rely on a great deal of software. So better software engineering leads to better designed artifacts, especially when we are designing a series of related artifacts and can amortize the costs of software development. The third point is that agents are especially useful for design tasks, above and beyond their general usefulness for software engineering, and the usefulness of software engineering to design.

  3. Synthesis of hydroxyapatite with the use of calcium carbonate as of the biological precursor

    International Nuclear Information System (INIS)

    Aguilar, M.S.; Di Lello, B.C.; Queiroz, F.; Campos, N.C.; Campos, J.B.

    2014-01-01

    This work describes the synthesis of hydroxyapatite from calcium from biological materials such as shells carbonate. In the syntheses performed, the calcium carbonate of biological origin was used as the precursor and through a precipitation reaction with phosphoric acid, was converted into calcium hydroxide. Sequentially, the precipitate was aged, filtered, washed, dried and calcined, and then transformed into hydroxyapatite. The characterization of the powders was performed by X-DR (X-ray diffraction) and SEM (scanning electron microscopy). DR-X as determined hydroxyapatite calcium phosphate phase calcium. SEM revealed a morphology of finely divided particles. The method B.E.T. showed values of specific area and volume of micropores consistent with the literature. The results of the characterizations proved feasible to use for obtaining biological hydroxyapatite materials used in the reaction conditions.(author)

  4. Synthesis of biological active thiosemicarbazone and characterization of the interaction with human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wangshu; Shi, Lei; Hui, Guangquan [College of Chemistry and Environmental Science, Henan Normal University, Xinxiang 453007 (China); Cui, Fengling, E-mail: fenglingcui@hotmail.com [College of Chemistry and Environmental Science, Henan Normal University, Xinxiang 453007 (China)

    2013-02-15

    The synthesis of a new biological active reagent, 2-((1,4-dihydroxy)-9,10-anthraquinone) aldehyde thiosemicarbazone (DHAQTS), was designed. The interaction between DHAQTS and HSA was studied by fluorescence spectroscopy in combination with molecular modeling under simulation of physiological conditions. According to the results of fluorescence measurements, the quenching mechanism was suggested to be static. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. The number of binding sites (n) was calculated. Through the site marker competitive experiment, DHAQTS was confirmed to be located in site I of HSA. The binding distance r=2.83 nm between the donor HSA and acceptor DHAQTS was obtained according to Foerster's non-radiative energy transfer theory. The three-dimensional fluorescence spectral results showed the conformation and microenvironment of HSA changed in the presence of DHAQTS. The effects of common ions on the binding of DHAQTS to HSA were also evaluated. The experimental results were in agreement with the results obtained via a molecular docking study. - Highlights: Black-Right-Pointing-Pointer 2-((1,4-dihydroxy)-9,10-anthraquinone)aldehyde thiosemicarbazone (DHAQTS) was synthesized. Black-Right-Pointing-Pointer DHAQTS can quench the fluorescence of human serum albumin (HSA) by static quenching mechanism. Black-Right-Pointing-Pointer Hydrophobic interactions were the predominant intermolecular forces. Black-Right-Pointing-Pointer The competitive experiment was carried out to identify the DHAQTS binding site on HSA. Black-Right-Pointing-Pointer Three-dimensional spectra confirmed DHAQTS caused the conformational change of HSA.

  5. Synthesis of biological active thiosemicarbazone and characterization of the interaction with human serum albumin

    International Nuclear Information System (INIS)

    Yu, Wangshu; Shi, Lei; Hui, Guangquan; Cui, Fengling

    2013-01-01

    The synthesis of a new biological active reagent, 2-((1,4-dihydroxy)-9,10-anthraquinone) aldehyde thiosemicarbazone (DHAQTS), was designed. The interaction between DHAQTS and HSA was studied by fluorescence spectroscopy in combination with molecular modeling under simulation of physiological conditions. According to the results of fluorescence measurements, the quenching mechanism was suggested to be static. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. The number of binding sites (n) was calculated. Through the site marker competitive experiment, DHAQTS was confirmed to be located in site I of HSA. The binding distance r=2.83 nm between the donor HSA and acceptor DHAQTS was obtained according to Förster's non-radiative energy transfer theory. The three-dimensional fluorescence spectral results showed the conformation and microenvironment of HSA changed in the presence of DHAQTS. The effects of common ions on the binding of DHAQTS to HSA were also evaluated. The experimental results were in agreement with the results obtained via a molecular docking study. - Highlights: ► 2-((1,4-dihydroxy)-9,10-anthraquinone)aldehyde thiosemicarbazone (DHAQTS) was synthesized. ► DHAQTS can quench the fluorescence of human serum albumin (HSA) by static quenching mechanism. ► Hydrophobic interactions were the predominant intermolecular forces. ► The competitive experiment was carried out to identify the DHAQTS binding site on HSA. ► Three-dimensional spectra confirmed DHAQTS caused the conformational change of HSA.

  6. A systematic design method for robust synthetic biology to satisfy design specifications.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chih-Hung

    2009-06-30

    Synthetic biology is foreseen to have important applications in biotechnology and medicine, and is expected to contribute significantly to a better understanding of the functioning of complex biological systems. However, the development of synthetic gene networks is still difficult and most newly created gene networks are non-functioning due to intrinsic parameter uncertainties, external disturbances and functional variations of intra- and extra-cellular environments. The design method for a robust synthetic gene network that works properly in a host cell under these intrinsic parameter uncertainties and external disturbances is the most important topic in synthetic biology. In this study, we propose a stochastic model that includes parameter fluctuations and external disturbances to mimic the dynamic behaviors of a synthetic gene network in the host cell. Then, based on this stochastic model, four design specifications are introduced to guarantee that a synthetic gene network can achieve its desired steady state behavior in spite of parameter fluctuations, external disturbances and functional variations in the host cell. We propose a systematic method to select a set of appropriate design parameters for a synthetic gene network that will satisfy these design specifications so that the intrinsic parameter fluctuations can be tolerated, the external disturbances can be efficiently filtered, and most importantly, the desired steady states can be achieved. Thus the synthetic gene network can work properly in a host cell under intrinsic parameter uncertainties, external disturbances and functional variations. Finally, a design procedure for the robust synthetic gene network is developed and a design example is given in silico to confirm the performance of the proposed method. Based on four design specifications, a systematic design procedure is developed for designers to engineer a robust synthetic biology network that can achieve its desired steady state behavior

  7. Design and synthesis of DNA four-helix bundles

    Energy Technology Data Exchange (ETDEWEB)

    Rangnekar, Abhijit; Gothelf, Kurt V [Department of Chemistry, Centre for DNA Nanotechnology (CDNA) and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C (Denmark); LaBean, Thomas H, E-mail: kvg@chem.au.dk, E-mail: thl@cs.duke.edu [Department of Chemistry, Duke University, Durham, NC 27708 (United States)

    2011-06-10

    The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.

  8. Design and synthesis of DNA four-helix bundles

    International Nuclear Information System (INIS)

    Rangnekar, Abhijit; Gothelf, Kurt V; LaBean, Thomas H

    2011-01-01

    The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.

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

    Science.gov (United States)

    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 LD 50 values and the compounds were assumed non-carcinogenic when various animal models were studied computationally.

  10. Synthesis and Design of Integrated Process and Water Networks

    DEFF Research Database (Denmark)

    Handani, Zainatul B.; Quaglia, Alberto; Gani, Rafiqul

    2015-01-01

    This work presents the development of a systematic framework for a simultaneous synthesis and design of process and water networks using the superstructure-based optimization approach. In this framework, a new superstructure combining both networks is developed by attempting to consider all...... possible options with respect to the topology of the process and water networks, leading to Mixed Integer Non Linear Programming (MINLP) problem. A solution strategy to solve the multi-network problem accounts explicitly the interactions between the networks by selecting suitable technologies in order...... to transform raw materials into products and produce clean water to be reused in the process at the early stage of design. Since the connection between the process network and the wastewater treatment network is not a straight forward connection, a new converter interval is introduced in order to convert...

  11. Camels, Cormorants, and Kangaroo Rats: Integration and Synthesis in Organismal Biology After World War II.

    Science.gov (United States)

    Hagen, Joel B

    2015-01-01

    During the decades following World War II diverse groups of American biologists established a variety of distinctive approaches to organismal biology. Rhetorically, organismal biology could be used defensively to distinguish established research traditions from perceived threats from newly emerging fields such as molecular biology. But, organismal biologists were also interested in integrating biological disciplines and using a focus on organisms to synthesize levels of organization from molecules and cells to populations and communities. Part of this broad movement was the development of an area of research variously referred to as physiological ecology, environmental physiology, or ecophysiology. This area of research was distinctive in its self-conscious blend of field and laboratory practices and its explicit integration with other areas of biology such as ecology, animal behavior, and evolution in order to study adaptation. Comparing the intersecting careers of Knut Schmidt-Nielsen and George Bartholomew highlights two strikingly different approaches to physiological ecology. These alternative approaches to studying the interactions of organisms and environments also differed in important ways from the organismal biology championed by leading figures in the modern synthesis.

  12. Removal design report for the 108-F Biological Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Most of the 100-F facilities were deactivated with the reactor and have since been demolished. Of the dozen or so reactor-related structures, only the 105-F Reactor Building and the 108-F Biology Laboratory remain standing today. The 108-F Biology Laboratory was intended to be used as a facility for the mixing and addition of chemicals used in the treatment of the reactor cooling water. Shortly after F Reactor began operation, it was determined that the facility was not needed for this purpose. In 1949, the building was converted for use as a biological laboratory. In 1962, the lab was expanded by adding a three-story annex to the original four-story structure. The resulting lab had a floor area of approximately 2,883 m{sup 2} (main building and annex) that operated until 1973. The building contained 47 laboratories, a number of small offices, a conference room, administrative section, lunch and locker rooms, and a heavily shielded, high-energy exposure cell. The purpose of this removal design report is to establish the methods of decontamination and decommissioning and the supporting functions associated with facility removal and disposal.

  13. Removal design report for the 108-F Biological Laboratory

    International Nuclear Information System (INIS)

    1997-09-01

    Most of the 100-F facilities were deactivated with the reactor and have since been demolished. Of the dozen or so reactor-related structures, only the 105-F Reactor Building and the 108-F Biology Laboratory remain standing today. The 108-F Biology Laboratory was intended to be used as a facility for the mixing and addition of chemicals used in the treatment of the reactor cooling water. Shortly after F Reactor began operation, it was determined that the facility was not needed for this purpose. In 1949, the building was converted for use as a biological laboratory. In 1962, the lab was expanded by adding a three-story annex to the original four-story structure. The resulting lab had a floor area of approximately 2,883 m 2 (main building and annex) that operated until 1973. The building contained 47 laboratories, a number of small offices, a conference room, administrative section, lunch and locker rooms, and a heavily shielded, high-energy exposure cell. The purpose of this removal design report is to establish the methods of decontamination and decommissioning and the supporting functions associated with facility removal and disposal

  14. Biosimilars design and analysis of follow-on biologics

    CERN Document Server

    2013-01-01

    "This book extensively covers both statistical and regulatory considerations from design to analysis of biosimilarity. … it is well presented and comprehensively covers fundamental issues and some of the newly developed methods for biosimilarity studies. The book is very balanced between scientific aspects and regulatory requirements. In addition, the reference lists give readers helpful information. … a valuable resource for anyone interested and involved in biosimilarity studies."-Biometrics, September 2014"[Professor] Chow's book Biosimilars: Design and Analysis of Follow-On Biologics … is the first book ever written on this topic. I commend Professor Chow for his effort to introduce the topic … Overall, this is a worthwhile reference book for statisticians interested in understanding biosimilar product development and evaluation." -Yi Tsong, PhD, Center for Drug Evaluation and Research, US Food and Drug Administration, USA, in Journal of Biopharmaceutical Statistics>.

  15. Molecular Design of Bioinspired Nanostructures for Biomedical Applications: Synthesis, Self-Assembly and Functional Properties

    Science.gov (United States)

    Xu, Hesheng Victor; Zheng, Xin Ting; Mok, Beverly Yin Leng; Ibrahim, Salwa Ali; Yu, Yong; Tan, Yen Nee

    2016-08-01

    Biomolecules are the nanoscale building blocks of cells, which play multifaceted roles in the critical biological processes such as biomineralization in a living organism. In these processes, the biological molecules such as protein and nucleic acids use their exclusive biorecognition properties enabled from their unique chemical composition, shape and function to initiate a cascade of cellular events. The exceptional features of these biomolecules, coupled with the recent advancement in nanotechnology, have led to the emergence of a new research field that focuses on the molecular design of bioinspired nanostructures that inherit the extraordinary function of natural biomaterials. These “bioinspired” nanostructures could be formulated by biomimetic approaches through either self-assembling of biomolecules or acting as a biomolecular template/precursor to direct the synthesis of nanocomposite. In either situation, the resulting nanomaterials exhibit phenomenal biocompatibility, superb aqueous solubility and excellent colloidal stability, branding them exceptionally desirable for both in vitro and in vivo biomedical applications. In this review, we will present the recent developments in the preparation of “bioinspired” nanostructures through biomimetic self-assembly and biotemplating synthesis, as well as highlight their functional properties and potential applications in biomedical diagnostics and therapeutic delivery. Lastly, we will conclude this topic with some personal perspective on the challenges and future outlooks of the “bioinspired” nanostructures for nanomedicine.

  16. Design of fluidized-bed, biological denitrification systems

    International Nuclear Information System (INIS)

    Patton, B.D.; Hancher, C.W.; Pitt, W.W.; Walker, J.F.

    1982-01-01

    Many commercial processes yield nitrate-containing wastewaters that are being discharged to the environment because traditional recovery or disposal methods are economically unacceptable. The anticipated discharge limits (i.e., 10 to 20 g (NO 3 - )/m 3 ) being considered by many states will not allow continued release of these wastewaters. The new discharge standards can be met economically by use of the fluidizied-bed, biological denitrification process. Research and development studies were conducted with 0.05-, 0.10-, 0.20-, and 0.50-m-diam fluidized-bed bioreactor systems. Feed nitrate concentrations were in the 0 to 10,000 g (NO 3 - )/m 3 range. Using the data from these studies, rate expressions were developed for the destruction of nitrate as a function of nitrate concentration. Methods were also developed for sizing bioreactors and biomass control systems. The sizing methods for fluidized-bed denitrification systems are described, and support systems such as sampling and analysis, instrumentation and controls, utilities, and bacteria storage are discussed. Operation of the process is also briefly discussed to aid the designer. Using the methods presented in this report, fluidized-bed, biological denitrification systems can be designed to treat nitrate wastewater streams

  17. Evaluation of biological activities of nanocrystalline zirconia synthesis via combustion method

    International Nuclear Information System (INIS)

    Thakare, V.G.; Omanwar, S.K.; Bhatkar, V.B.; Wadegaokar, P.A.

    2016-01-01

    The objective of the following study was synthesis of nanocrystalline zirconia by modified solution combustion synthesis method and evaluation of its structural and biological properties. The sample was characterized by powder X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM) and evaluated for cytotoxicity study using 3T3 mouse fibroblast cells, the antibacterial property are investigated by spread plate method against E. coli bacterial pathogen and studied for degradation using phosphate buffered saline (PBS) solution. The XRD pattern shows that the monoclinic phase of nanocrystalline zirconia was obtained. The FESEM images showed that the prepared sample consists of particles in the range of 45 nm and homogenous particle size distribution. The sample of zirconia has excellent tissue biocompatibility and does not show any toxicity towards normal 3T3 mouse fibroblast cells. It also inhibited the bacterial growth. The sample shows stability at physiological condition and does not show degradation. (author)

  18. Organocatalytic Michael and Friedel–Crafts reactions in enantioselective synthesis of biologically active compounds

    International Nuclear Information System (INIS)

    Maltsev, O V; Beletskaya, Irina P; Zlotin, Sergei G

    2011-01-01

    Recent applications of organocatalytic Michael and Friedel–Crafts reactions in enantioselective synthesis of biologically active compounds: natural products, pharmaceutical agents and plant protection agents are reviewed. The key mechanisms of stereoinduction, types of organocatalysts and reagents used in these reactions are considered. The material is classified according to the type of newly formed bonds incorporating the asymmetric carbon atom, and the information for the most numerous C–C coupling reactions is systematized according to the natures of the electrophile and the nucleophile. The bibliography includes 433 references.

  19. Convergent synthesis of a deuterium-labeled serine dipeptide lipid for analysis of biological samples.

    Science.gov (United States)

    Dietz, Christopher; Clark, Robert B; Nichols, Frank C; Smith, Michael B

    2017-05-30

    Bacterial serine dipeptide lipids are known to promote inflammatory processes and are detected in human tissues associated with periodontal disease or atherosclerosis. Accurate quantification of bacterial serine lipid, specifically lipid 654 [((S)-15-methyl-3-((13-methyltetradecanoyl)oxy)hexadecanoyl)glycyl-l-serine, (3S)-l-serine] isolated from Porphyromonas gingivalis, in biological samples requires the preparation of a stable isotope internal standard for sample supplementation and subsequent mass spectrometric analysis. This report describes the convergent synthesis of a deuterium-substituted serine dipeptide lipid, which is an isotopically labeled homologue that represents a dominant form of serine dipeptide lipid recovered in bacteria. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Towards a framework for modular service design synthesis

    DEFF Research Database (Denmark)

    Løkkegaard, Martin; Mortensen, Niels Henrik; McAloone, Tim C.

    2016-01-01

    This paper seeks to improve the understanding of how service-based companies can benefit from developing and delivering service offerings from a standardised core of service modules, which are organised through a service architecture. Research within the field is relatively sparse, and there is s......This paper seeks to improve the understanding of how service-based companies can benefit from developing and delivering service offerings from a standardised core of service modules, which are organised through a service architecture. Research within the field is relatively sparse...... model for modular service design synthesis presented in this paper. The case study is based on internal documentation and a high level of interview data. Inductive research methods have been used for the analysis. The presented conceptual model defines three suggested dimensions (Market Segmentation...

  1. Optimization of MCM-48 synthesis using factorial design

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, A.R. do; Medeiros, R.L.B. de A.; Melo, M. A. de F.; Melo, D.M. de A. [Universitdade Federal do Rio Grande do Norte (UFRN), Natal (Brazil); Souza, M.J.B. de, E-mail: ale3ufs@yahoo.com.br [Universidade Federal de Sergipe (UFS), Sao Cristovao (Brazil)

    2016-10-15

    MCM-48 mesoporous materials were hydrothermally synthesized according to the 2{sup 2} factorial design by varying the crystallization time and temperature of the synthesis gel, and characterized by means of X-ray diffraction analysis and adsorption of N{sub 2} . In the crystallization temperature and time conditions used, specific areas between 924 to 1102 m{sup 2}.g{sup -1}, pore volumes between 0.015 to 0.087 cm{sup 3}.g{sup -1} and pore diameters between 3.2 to 4.0 nm were obtained. It was observed that for the syntheses performed at high temperature, the crystallization time should be reduced so that the material structure is formed. (author)

  2. Opuntia ficus indica peel derived pectin mediated hydroxyapatite nanoparticles: Synthesis, spectral characterization, biological and antimicrobial activities

    Science.gov (United States)

    Gopi, D.; Kanimozhi, K.; Kavitha, L.

    2015-04-01

    In the present study, we have adapted a facile and efficient green route for the synthesis of HAP nanoparticles using pectin as a template which was extracted from the peel of prickly pear (Opuntia ficus indica) fruits. The concentration of pectin plays a major role in the behavior of crystallinity, purity, morphology as well as biological property of the as-synthesized HAP nanoparticles. The extracted pectin and the as-synthesized nanoparticles were characterized by various analytical techniques. The in vitro apatite formation on the surface of the as-synthesized nanoparticles in simulated body fluid (SBF) for various days showed an enhanced bioactivity. Also, the antimicrobial activity was investigated using various microorganisms. All the results revealed the formation of pure, low crystalline and discrete granular like HAP nanoparticles of size around 25 nm with enhanced biological and antimicrobial activities. Hence the as-synthesized nanoparticles can act as a better bone regenerating material in the field of biomedicine.

  3. Book review: Biology and conservation of martens, sables, and fishers: A new synthesis

    Science.gov (United States)

    Jenkins, Kurt J.

    2013-01-01

    Mammals of the genus Martes, including martens, sables, and fishers, are mid-sized carnivores inhabiting many forested ecosystems throughout regions of North America, Europe, and Asia. This volume provides a comprehensive synthesis of the current state of knowledge pertaining to the biology and conservation of Martes species throughout the world. This volume will be an essential resource for mammalogists, resource managers, and applied ecologists involved in research or conservation of martens, sables, and fishers. For that matter, anyone seeking a full immersion in the modern world of Martes biology and conservation will not be disappointed. The volume has been carefully edited and reviewed, and the thoroughness with which the authors present and interpret recent advances in their specialty areas is really quite impressive.

  4. Synthesis, biological distribution and radiation dosimetry of Te-123m analogues of hexadecenoic acid

    International Nuclear Information System (INIS)

    Basmadjian, G.P.; Ice, R.D.; Mills, S.L.

    1982-01-01

    The synthesis and biological distribution of four Te-123m analogues of hexadecenoic acid in rats, rabbits and dogs were described for use as possible myocardial imaging agents. The heart-to-blood ratios ranged from 0.13 for 3-telluranonadecenoic acid in rats at 5 mins to 6.25 for 18-methyl-17-tellura-9-nonadecenoic acid in dogs at 24 hrs. The biological half-life of the Te-123m labelled fatty acids ranged from 26 to 583 hrs in the hearts of the test animals. These Te-123m fatty acids were retained in the heart longer than radioiodinated fatty acids and have acceptable absorbed doses to the various target organs. (U.K.)

  5. Surface capped fluorescent semiconductor nanoparticles: radiolytic synthesis and some of its biological applications

    International Nuclear Information System (INIS)

    Saha, A.

    2006-01-01

    Semiconductor nanocrystals or colloidal quantum dots (QD's) have generated great research interest because of their unusual properties arising out of quantum confinement effects. Many researchers in the field of nanotechnology focus on the 'high quality' semiconductor quantum dots. A good synthetic route should yield nanoparticles with narrow size distribution, good crystallinity, high photostability, desired surface properties and high photoluminescence quantum efficiency. In the domain of colloidal chemistry, reverse micellar synthesis, high temperature thermolysis using organometallic precursors and synthesis in aqueous media using polyphosphates or thiols as stabilizers are the most prominent ones. In contrast, γ-radiation assisted synthesis can offer a simplified approach to prepare size-controlled nanoparticles at room temperature. Syntheses of thiol-capped II-VI nanoparticles by radiolytic method, its characterization and some of its luminescence-based applications of biological relevance will be presented. The versatility of thiols (RSH) can be emphasized here as changing the R-group imparts different functionality to the particles and thus chemical behavior of the particles can be manipulated according to the application intended for. (authors)

  6. Synthesis of molecules of biological interest labelled with high specific activity tritium

    International Nuclear Information System (INIS)

    Petillot, Yves

    1975-01-01

    Labelled molecules are artificial organic compounds possessing one or several radioactive or steady isotopic atoms. Using tritium to label molecules presents several benefits: a raw material easy to obtain with a high purity and at reasonable cost; synthesised labelled molecules displaying high specific activities very interesting in molecular biology; high resolution of radiographies; relatively simple and quick introduction of tritium atoms in complex molecules. Thus, this report for graduation in organic chemistry addresses the synthesis and study of new labelled molecules which belong to families of organic compounds which have fundamental activities in biology: uridine 3 H-5,6 and thymidine 3 H-methyl which are nucleotides which intervene under the form of phosphates in the synthesis of nucleic acids, oestradiol 3 H-2,4,6,7 which is a powerful estrogenic hormone which naturally secreted by the ovary; and noradrenaline 3 H-1,1' and dopamine 3 H-1,2 which are usually secreted by adrenal medulla and have multiple actions on the nervous system

  7. Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

    Directory of Open Access Journals (Sweden)

    Louis P. Sandjo

    2015-09-01

    Full Text Available This review focuses on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone, dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues, which are synthesized for biological purposes are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity.

  8. Photoinduced catalytic synthesis of biologically important metabolites from formaldehyde and ammonia under plausible "prebiotic" conditions

    Science.gov (United States)

    Delidovich, I. V.; Taran, O. P.; Simonov, A. N.; Matvienko, L. G.; Parmon, V. N.

    2011-08-01

    The article analyzes new and previously reported data on several catalytic and photochemical processes yielding biologically important molecules. UV-irradiation of formaldehyde aqueous solution yields acetaldehyde, glyoxal, glycolaldehyde and glyceraldehyde, which can serve as precursors of more complex biochemically relevant compounds. Photolysis of aqueous solution of acetaldehyde and ammonium nitrate results in formation of alanine and pyruvic acid. Dehydration of glyceraldehyde catalyzed by zeolite HZSM-5-17 yields pyruvaldehyde. Monosaccharides are formed in the course of the phosphate-catalyzed aldol condensation reactions of glycolaldehyde, glyceraldehyde and formaldehyde. The possibility of the direct synthesis of tetroses, keto- and aldo-pentoses from pure formaldehyde due to the combination of the photochemical production of glycolahyde and phosphate-catalyzed carbohydrate chain growth is demonstrated. Erythrulose and 3-pentulose are the main products of such combined synthesis with selectivity up to 10%. Biologically relevant aldotetroses, aldo- and ketopentoses are more resistant to the photochemical destruction owing to the stabilization in hemiacetal cyclic forms. They are formed as products of isomerization of erythrulose and 3-pentulose. The conjugation of the concerned reactions results in a plausible route to the formation of sugars, amino and organic acids from formaldehyde and ammonia under presumed 'prebiotic' conditions.

  9. Design, Synthesis and Evaluation of Ribose-modified Anilinopyrimidine Derivatives as EGFR Tyrosine Kinase Inhibitors

    Science.gov (United States)

    Hu, Xiuqin; Wang, Disha; Tong, Yi; Tong, Linjiang; Wang, Xia; Zhu, Lili; Xie, Hua; Li, Shiliang; Yang, You; Xu, Yufang

    2017-11-01

    The synthesis of a series of ribose-modified anilinopyrimidine derivatives was efficiently achieved by utilizing DBU or tBuOLi-promoted coupling of ribosyl alcohols with 2,4,5-trichloropyrimidine as key step. Preliminary biological evaluation of this type of compounds as new EGFR tyrosine kinase inhibitors for combating EGFR L858R/T790M mutant associated with drug resistance in the treatment of non-small cell lung cancer revealed that 3-N-acryloyl-5-O-anilinopyrimidine ribose derivative 1a possessed potent and specific inhibitory activity against EGFR L858R/T790M over WT EGFR. Based upon molecular docking studies of the binding mode between compound 1a and EGFR, the distance between the Michael receptor and the pyrimidine scaffold is considered as an important factor for the inhibitory potency and future design of selective EGFR tyrosine kinase inhibitors against EGFR L858R/T790M mutants.

  10. Design and synthesis of diverse functional kinked nanowire structures for nanoelectronic bioprobes.

    Science.gov (United States)

    Xu, Lin; Jiang, Zhe; Qing, Quan; Mai, Liqiang; Zhang, Qingjie; Lieber, Charles M

    2013-02-13

    Functional kinked nanowires (KNWs) represent a new class of nanowire building blocks, in which functional devices, for example, nanoscale field-effect transistors (nanoFETs), are encoded in geometrically controlled nanowire superstructures during synthesis. The bottom-up control of both structure and function of KNWs enables construction of spatially isolated point-like nanoelectronic probes that are especially useful for monitoring biological systems where finely tuned feature size and structure are highly desired. Here we present three new types of functional KNWs including (1) the zero-degree KNW structures with two parallel heavily doped arms of U-shaped structures with a nanoFET at the tip of the "U", (2) series multiplexed functional KNW integrating multi-nanoFETs along the arm and at the tips of V-shaped structures, and (3) parallel multiplexed KNWs integrating nanoFETs at the two tips of W-shaped structures. First, U-shaped KNWs were synthesized with separations as small as 650 nm between the parallel arms and used to fabricate three-dimensional nanoFET probes at least 3 times smaller than previous V-shaped designs. In addition, multiple nanoFETs were encoded during synthesis in one of the arms/tip of V-shaped and distinct arms/tips of W-shaped KNWs. These new multiplexed KNW structures were structurally verified by optical and electron microscopy of dopant-selective etched samples and electrically characterized using scanning gate microscopy and transport measurements. The facile design and bottom-up synthesis of these diverse functional KNWs provides a growing toolbox of building blocks for fabricating highly compact and multiplexed three-dimensional nanoprobes for applications in life sciences, including intracellular and deep tissue/cell recordings.

  11. Synthesis of Biologically Active Natural Component 4-Hydroxyderricin Through Water-Accelerated [3,3]-Sigmatropic Rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sijun; Lee, Jaejun; Yoon, Hyunho; Jun, Jonggab [Hallym Univ., Chuncheon (Korea, Republic of)

    2013-09-15

    We report herein the practical and effective total synthesis of biologically active 4-hydroxyderricin, a poly-phenolic chalcone compound containing m-prenyl group at ring A. The key steps of the synthesis are Claisen-Schmidt condensation of the the two phenolic units 17 and 18 to chalcone 19 and the water-accelerated [3,3]-sigma-tropic rearrangement of 1,1-dimethyl-2-propenyl aryl ether 20 to introduce the m-prenyl unit in 4-hydroxyderricin. Two types of polyphenolic chalcones, 4-hydroxyderricin (1) and xanthoangelol (2), are especially rich in the plant, and the 4-hydroxyderricin exhibited the major responsibility for the various biological activities. Sugamoto reported the synthesis of 4-hydroxy-derricin via [1,3]-sigmatropic rearrangement of chalcone ether using montmorillonite K10 which showed relatively low rearrangement yield (Scheme 1), and this is the only reported total synthesis of 1 as far as we know.

  12. Science for Survival: The Modern Synthesis of Evolution and The Biological Sciences Curriculum Study

    Science.gov (United States)

    Green, Lisa Anne

    In this historical dissertation, I examined the process of curriculum development in the Biological Sciences Curriculum Study (BSCS) in the United States during the period 1959-1963. The presentation of evolution in the high school texts was based on a more robust form of Darwinian evolution which developed during the 1930s and 1940s called "the modern synthesis of evolution." Building primarily on the work of historians Vassiliki Smocovitis and John L. Rudolph, I used the archival papers and published writings of the four architects of the modern synthesis and the four most influential leaders of the BSCS in regards to evolution to investigate how the modern synthetic theory of evolution shaped the BSCS curriculum. The central question was "Why was evolution so important to the BSCS to make it the central theme of the texts?" Important answers to this question had already been offered in the historiography, but it was still not clear why every citizen in the world needed to understand evolution. I found that the emphasis on natural selection in the modern synthesis shifted the focus away from humans as passive participants to the recognition that humans are active agents in their own cultural and biological evolution. This required re-education of the world citizenry, which was accomplished in part by the BSCS textbooks. I also found that BSCS leaders Grobman, Glass, and Muller had serious concerns regarding the effects of nuclear radiation on the human gene pool, and were actively involved in informing th public. Lastly, I found that concerns of 1950s reform eugenicists were addressed in the BSCS textbooks, without mentioning eugenics by name. I suggest that the leaders of the BSCS, especially Bentley Glass and Hermann J. Muller, thought that students needed to understand genetics and evolution to be able to make some of the tough choices they might be called on to make as the dominant species on earth and the next reproductive generation in the nuclear age. This

  13. Designing and Implementing a New Advanced Level Biology Course

    Science.gov (United States)

    Hall, Angela; Reiss, Michael J.; Rowell, Cathy; Scott, Anne

    2003-01-01

    Salters-Nuffield Advanced Biology is a new advanced level biology course, piloted from September 2002 in England with around 1200 students. This paper discusses the reasons for developing a new advanced biology course at this time, the philosophy of the project and how the materials are being written and the specification devised. The aim of the…

  14. Synthesis, reactions and biological activity of some new bis-heterocyclic ring compounds containing sulphur atom

    Science.gov (United States)

    2013-01-01

    Background The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application. Results A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3–9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and β-glucuronidase and α-glucosidase inhibitory activities. Compound 3 (IC50 = 56.26 ± 3.18 μM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50 = 105.9 ± 1.1 μM). Compounds 8a (IC50 = 13.2 ± 0.34 μM) and 8b (IC50 = 14.1 ± 0.28 μM) found as potent inhibitor of α-glucusidase several fold more active than the standard acarbose (IC50 = 841 ± 1.73 μM). Most promising results were obtained in β-glucuronidase enzyme inhibition assay. Compounds 5 (IC50 = 0.13 ± 0.019 μM), 6 (IC50 = 19.9 ± 0.285 μM), 8a (IC50 = 1.2 ± 0.0785 μM) and 9 (IC50 = 0.003 ± 0.09 μM) showed a potent inhibition of β-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM). Conclusions Synthesis, characterization, and in vitro biological activity of a series of

  15. Evolutionary systems biology: historical and philosophical perspectives on an emerging synthesis.

    Science.gov (United States)

    O'Malley, Maureen A

    2012-01-01

    Systems biology (SB) is at least a decade old now and maturing rapidly. A more recent field, evolutionary systems biology (ESB), is in the process of further developing system-level approaches through the expansion of their explanatory and potentially predictive scope. This chapter will outline the varieties of ESB existing today by tracing the diverse roots and fusions that make up this integrative project. My approach is philosophical and historical. As well as examining the recent origins of ESB, I will reflect on its central features and the different clusters of research it comprises. In its broadest interpretation, ESB consists of five overlapping approaches: comparative and correlational ESB; network architecture ESB; network property ESB; population genetics ESB; and finally, standard evolutionary questions answered with SB methods. After outlining each approach with examples, I will examine some strong general claims about ESB, particularly that it can be viewed as the next step toward a fuller modern synthesis of evolutionary biology (EB), and that it is also the way forward for evolutionary and systems medicine. I will conclude with a discussion of whether the emerging field of ESB has the capacity to combine an even broader scope of research aims and efforts than it presently does.

  16. Synthesis, structural studies and biological properties of new TBA analogues containing an acyclic nucleotide.

    Science.gov (United States)

    Coppola, Teresa; Varra, Michela; Oliviero, Giorgia; Galeone, Aldo; D'Isa, Giuliana; Mayol, Luciano; Morelli, Elena; Bucci, Maria-Rosaria; Vellecco, Valentina; Cirino, Giuseppe; Borbone, Nicola

    2008-09-01

    A new modified acyclic nucleoside, namely N(1)-(3-hydroxy-2-hydroxymethyl-2-methylpropyl)-thymidine, was synthesized and transformed into a building block useful for oligonucleotide (ON) automated synthesis. A series of modified thrombin binding aptamers (TBAs) in which the new acyclic nucleoside replaces, one at the time, the thymidine residues were then synthesized and characterized by UV, CD, MS, and (1)H NMR. The biological activity of the resulting TBAs was tested by Prothrombin Time assay (PT assay) and by purified fibrinogen clotting assay. From a structural point of view, nearly all the new TBA analogues show a similar behavior as the unmodified counterpart, being able to fold into a bimolecular or monomolecular quadruplex structure depending on the nature of monovalent cations (sodium or potassium) coordinated in the quadruplex core. From the comparison of structural and biological data, some important structure-activity relationships emerged, particularly when the modification involved the TT loops. In agreement with previous studies we found that the folding ability of TBA analogues is more affected by modifications involving positions 4 and 13, rather than positions 3 and 12. On the other hand, the highest anti-thrombin activities were detected for aptamers containing the modification at T13 or T12 positions, thus indicating that the effects produced by the introduction of the acyclic nucleoside on the biological activity are not tightly connected with structure stabilities. It is noteworthy that the modification at T7 produces an ON being more stable and active than the natural TBA.

  17. Synthesis method for using in the design of an electron gun for gyrotion

    International Nuclear Information System (INIS)

    Silva, C.A.B.

    1987-09-01

    In this work a synthesis method is applied to the design of an electron gun for a 94GHz gyrotron. Using the synthesis method, it is found the shape of the electrodes compatible with the laminar flow which minimizes the action of space change on the electron velocity dispersion. A sistematic procedure is presented to fuid the parameters of the synthesis method which, in turn, are closely related to the characteristics of the aptoclechonic system. (author) [pt

  18. Computer design synthesis of a below knee-Syme prosthesis

    Science.gov (United States)

    Elangovan, P. T.; Ghista, D. N.; Alwar, R. S.

    1979-01-01

    A detailed design synthesis analysis of the BK Syme prosthesis is provided, to determine the socket's cutout orientation size and shape, cutout fillet shape, socket wall thickness distribution and the reinforced fiber distribution in the socket wall, for a minimally stressed structurally safe lightweight prosthesis. For analysis purposes, the most adverse socket loading is obtained at the push-off stage of gait; this loading is idealized as an axial in-plane loading on the bottom edge of the circular cylindrical socket shell whose top edge is considered fixed. Finite element stress analysis of the socket shell (with uniform and graded wall thickness) are performed for various orientations of the cutout and for various types of corner fillets. A lateral cutout with a streamline fillet is recommended. The wall material (i.e., thickness) distribution is determined so as to minimize the stresses, while ensuring that the wall material's stress limits are not exceeded. For such a maximally stressed lightweight socket shell, the panels in the neighborhood of the cutout are checked to ensure that they do not buckle under their acquired stresses. A fiber-reinforced laminated composite socket shell is also analyzed in order to recommend optimum variables in orientations and densities of reinforcing fibers.

  19. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    Science.gov (United States)

    Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

    2015-04-01

    Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Design, Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives

    Directory of Open Access Journals (Sweden)

    Anwei Ding

    2013-08-01

    Full Text Available A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole. Compounds M28, M33, and M35 showed higher inhibitory activity against influenza virus H3N2 with their TC50 values being 96.4, 71.0 and 75.4 μM, respectively. Preliminary biological activity evaluation indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through the introduction of halogen into the structure of schizonepetin.

  1. Designing and implementing a new advanced level biology course.

    OpenAIRE

    Hall, Angela; Reiss, Michael; Rowell, Cathy; Scott, C.; Scott, Anne

    2003-01-01

    Salters-Nuffield Advanced Biology is a new advanced level biology course currently being piloted from September 2002 in England with around 1200 students. This paper discusses the reasons for developing a new advanced biology course at this time, the philosophy of the project and how the materials are being written and the specification devised. The aim of the project is to provide an up-to-date course that interests students, is considered appropriate by teachers and other professionals in b...

  2. SYNTHESIS AND BIOLOGIC PROPERTIES OF SOME 1-(ALCHYLPHENYL-3-(4-(3-(PYRIDIN-2-ILACRYLOYLPHENYLTHIOUREA

    Directory of Open Access Journals (Sweden)

    A. Popusoi

    2013-06-01

    Full Text Available This paper describe the synthesis of some 1-(alchylaril-3-(4-(3-pyridin-2-il acryloylphenylthiourea obtained by condensation of 2-pyridincarboxaldehide with some derivatives of 4-acetylphenilthioureas in basic medium or by addition of aliphatic and aromatic amines to the correspondingisothiocyanatopropenones. 12 new compounds were obtained and their biological properties were analysed. The substituted thioureas by pyridine radicals, morpholine and phenol show a maximum bacteriostatic activity for Gram positive microorganisms like: Staphylococcus Aureus and Enterococcus Faecalis at the minimum inhibitory concentration 9.37-37.5 μM. Antifungal activity for Candida Albicans, Aspergillus Niger, AspergillusFumigatus, Penicillium is weak, in minimum inhibitory concentration 600->600 μM. The leukemia activity like inhibitor (HL-60, is 84-96.9% at the concentration 10-5mol/l and 15- 20% and at the concentrations 10-6, 10-7mol/l.

  3. In vitro synthesis of biologically active transcripts of tomato black ring virus satellite RNA.

    Science.gov (United States)

    Greif, C; Hemmer, O; Demangeat, G; Fritsch, C

    1990-04-01

    Synthetic transcripts of tomato black ring virus satellite RNA (TBRV satRNA), isolate L, were prepared from cDNA cloned in the Bluescribe transcription vector. Transcripts with 49 (T49L) or two (T2GL) extra nucleotides at their 5' ends and 42 extra nucleotides at their 3' ends were able to induce, but to different extents, the synthesis in vitro of the satRNA-encoded 48K protein. However, when inoculated into Chenopodium quinoa together with TBRV L genomic RNAs, only T2GL was biologically active, in the presence or absence of a 5' cap analogue in the transcription reactions. Analysis of the 5' and 3' termini of the satRNA isolated from plants showed that nonviral extensions were not maintained in the transcript progeny.

  4. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Alessandra Mirtes Marques Neves Gonçalves

    2014-07-01

    Full Text Available Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.

  5. Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects

    Directory of Open Access Journals (Sweden)

    Angel Catalá

    2013-01-01

    Full Text Available I have been involved in research on polyunsaturated fatty acids since 1964 and this review is intended to cover some of the most important aspects of this work. Polyunsaturated fatty acids have followed me during my whole scientific career and I have published a number of studies concerned with different aspects of them such as chemical synthesis, enzymatic formation, metabolism, transport, physical, chemical, and catalytic properties of a reconstructed desaturase system in liposomes, lipid peroxidation, and their effects. The first project I became involved in was the organic synthesis of [1-14C] eicosa-11,14-dienoic acid, with the aim of demonstrating the participation of that compound as a possible intermediary in the biosynthesis of arachidonic acid “in vivo.” From 1966 to 1982, I was involved in several projects that study the metabolism of polyunsaturated fatty acids. In the eighties, we studied fatty acid binding protein. From 1990 up to now, our laboratory has been interested in the lipid peroxidation of biological membranes from various tissues and different species as well as liposomes prepared with phospholipids rich in PUFAs. We tested the effect of many antioxidants such as alpha tocopherol, vitamin A, melatonin and its structural analogues, and conjugated linoleic acid, among others.

  6. Modular Synthesis of Biologically Active Phosphatidic Acid Probes Using Click Chemistry

    Science.gov (United States)

    Smith, Matthew D.; Sudhahar, Christopher G.; Gong, Denghuang; Stahelin, Robert V.

    2018-01-01

    Phosphatidic acid (PA) is an important signaling lipid that plays roles in a range of biological processes including both physiological and pathophysiological events. PA is one of a number of signaling lipids that can act as site-specific ligands for protein receptors in binding events that enforce membrane-association and generally regulate both receptor function and subcellular localization. However, elucidation of the full scope of PA activities has proven problematic, primarily due to the lack of a consensus sequence among PA-binding receptors. Thus, experimental approaches, such as those employing lipid probes, are necessary for characterizing interactions at the molecular level. Herein, we describe an efficient modular approach to the synthesis of a range of PA probes that employs a late stage introduction of reporter groups. This strategy was exploited in the synthesis of PA probes bearing fluorescent and photoaffinity tags as well as a bifunctional probe containing both a photoaffinity moiety and an azide as a secondary handle for purification purposes. To discern the ability of these PA analogues to mimic the natural lipid in protein binding properties, each compound was incorporated into vesicles for binding studies using a known PA receptor, the C2 domain of PKCα. In these studies, each compound exhibited binding properties that were comparable to those of synthetic PA, indicating their viability as probes for effectively studying the activities of PA in cellular processes. PMID:19668861

  7. Eco-friendly synthesis, physicochemical studies, biological assay and molecular docking of steroidal oxime-ethers

    Science.gov (United States)

    Alam, Mahboob; Lee, Dong-Ung

    2015-01-01

    The aim of this study was to report the synthesis of biologically active compounds; 7-(2′-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85-93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay. The binding capabilities of a compound 6 exhibiting good antibacterial potential were assessed on the basis of molecular docking studies and four types of three-dimensional molecular field descriptors. Moreover the structure-antimicrobial activity relationships were studied using some physicochemical and quantum-chemical parameters with GAMESS interface as well as WebMO Job Manager by using the basic level of theory. Hence, this synthetic approach is believed to provide a better scope for the synthesis of steroidal oxime-ether analogues and will be a more practical alternative to the presently existing procedures. Moreover, detailed in silico docking studies suggested the plausible mechanism of steroidal oxime-ethers as effective antimicrobial agents. PMID:27330525

  8. Synthesis of [13C6]-labelled phenethylamine derivatives for drug quantification in biological samples.

    Science.gov (United States)

    Karlsen, Morten; Liu, HuiLing; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bård Helge

    2014-05-15

    The availability of high-quality (13)C-labelled internal standards will improve accurate quantification of narcotics and drugs in biological samples. Thus, the synthesis of 10 [(13)C6]-labelled phenethylamine derivatives, namely amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, 4-methoxyamphetamine, 4-methoxymethamphetamine, 3,5-dimethoxyphenethylamine 4-bromo-2,5-dimethoxyphenethylamine and 2,5-dimethoxy-4-iodophenethylamine, have been undertaken. [(13)C6]-Phenol proved to be an excellent starting material for making (13)C-labelled narcotic substances in the phenethylamine class, and a developed Stille-type coupling enabled an efficient synthesis of the 3,4-methylenedioxy and 4-methoxy derivatives. The pros and cons of alternative routes and transformations are also discussed. The [(13)C6]-labelled compounds are intended for use as internal standards in forensic analysis, health sciences and metabolomics studies by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. Copyright © 2014 John Wiley & Sons, Ltd.

  9. Biological Synthesis of Silver Nanoparticles by Cell-Free Extract of Spirulina platensis

    Directory of Open Access Journals (Sweden)

    Gaurav Sharma

    2015-01-01

    Full Text Available The present study explores biological synthesis of silver nanoparticles (AgNPs using the cell-free extract of Spirulina platensis. Biosynthesised AgNPs were characterised by UV-Vis spectroscopy, SEM, TEM, and FTIR analysis and finally evaluated for antibacterial activity. Extracellular synthesis using aqueous extract of S. platensis showed the formation of well scattered, highly stable, spherical AgNPs with an average size of 30–50 nm. The size and morphology of the nanoparticles were confirmed by SEM and TEM analysis. FTIR and UV-Vis spectra showed that biomolecules, proteins and peptides, are mainly responsible for the formation and stabilisation of AgNPs. Furthermore, the synthesised nanoparticles exhibited high antibacterial activity against pathogenic Gram-negative, that is, Escherichia coli, MTCC-9721; Proteus vulgaris, MTCC-7299; Klebsiella pneumoniae, MTCC-9751, and Gram-positive, that is, Staphylococcus aureus, MTCC-9542; S. epidermidis, MTCC-2639; Bacillus cereus, MTCC-9017, bacteria. The AgNPs had shown maximum zone of inhibition (ZOI that is 31.3±1.11 in P. vulgaris. Use of such a microalgal system provides a simple, cost-effective alternative template for the biosynthesis of nanomaterials of silver in a large scale that could be of great use in biomedical applications.

  10. Design of convergent pierce electron gun of accelerator for radiation sterilization by the method of synthesis

    International Nuclear Information System (INIS)

    Kong Xiaoxiao; Li Quanfeng

    2003-01-01

    A synthesis technique for the preliminary design of convergent Pierce electron guns is introduced briefly which has a series of advantages over the traditional methods. A thermal cathode electron gun used in the accelerator for radiation sterilization with the synthesis method is redesigned, and the validity of this method is proved. Based on the preliminary design parameters given by the synthesis method, a simulating calculation program, EGUN, was used in the numerical figure design of the focusing electrode and the anode. The final results can meet the engineering requirement as the current being 1A, the normalized emittance being less than 4 mm·mrad, and the final current density showing uniformity

  11. Enabling Lean Design Through Computer Aided Synthesis: The Injection Moulding Cooling Case

    NARCIS (Netherlands)

    Jauregui Becker, Juan Manuel; Wits, Wessel Willems

    2015-01-01

    This paper explores the application of Computer Aided Synthesis (CAS) to support the implementation of Set-Based Concurrent Engineering (SBCE) and Just In Time Decision Making (JIT-DM), which are considered as two of the cornerstones of the Lean Design method. Computer Aided Synthesis refers to a

  12. Synthesis of new Schiff bases as materials for the design of ...

    African Journals Online (AJOL)

    Synthesis of new Schiff bases as materials for the design of photovoltaics cells. ... We describe the synthesis of new organic Schiff bases chromophores 5 containing a rhodanine-3- acetic as electron accepteur moiety. Imines 3 were obtained by a condensation reaction from a lead molecule, the aminothiazolinethione 1 with ...

  13. Integration of thermodynamic insights and MINLP optimisation for the synthesis, design and analysis of process flowsheets

    DEFF Research Database (Denmark)

    Hostrup, Martin; Gani, Rafiqul; Kravanja, Zdravko

    1999-01-01

    This paper presents an integrated approach to the solution of process synthesis, design and analysis problems. Integration is achieved by combining two different techniques, synthesis based on thermodynamic insights and structural optimization together with a simulation engine and a properties pr...

  14. A Hierarchical Biology Concept Framework: A Tool for Course Design

    OpenAIRE

    Khodor, Julia; Halme, Dina Gould; Walker, Graham C.

    2004-01-01

    A typical undergraduate biology curriculum covers a very large number of concepts and details. We describe the development of a Biology Concept Framework (BCF) as a possible way to organize this material to enhance teaching and learning. Our BCF is hierarchical, places details in context, nests related concepts, and articulates concepts that are inherently obvious to experts but often difficult ...

  15. Finite-Element Model-Based Design Synthesis of Axial Flux PMBLDC Motors

    DEFF Research Database (Denmark)

    Fasil, Muhammed; Mijatovic, Nenad; Jensen, Bogi Bech

    2016-01-01

    of a unique solution. The designer can later select a design, based on comparing parameters of the designs, which are critical to the application that the motor will be used. The presented approach makes it easier to define constraints for a design synthesis problem. A detailed description of the setting up...

  16. Insulin-like Growth Factor 1 Analogs Clicked in the C Domain: Chemical Synthesis and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Macháčková, Kateřina; Collinsová, Michaela; Chrudinová, Martina; Selicharová, Irena; Pícha, Jan; Buděšínský, Miloš; Vaněk, Václav; Žáková, Lenka; Brzozowski, A. M.; Jiráček, Jiří

    2017-01-01

    Roč. 60, č. 24 (2017), s. 10105-10117 ISSN 0022-2623 Institutional support: RVO:61388963 Keywords : IGF-1 * receptor * synthesis * triazole Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 6.259, year: 2016 http://pubs.acs.org/doi/full/10.1021/acs.jmedchem.7b01331

  17. Design and synthesis of multidentate ligands via metal promoted C ...

    Indian Academy of Sciences (India)

    Unknown

    and can be controlled by the proper selection of the mediator complex. The two ... are important as these provide facile synthesis of many novel molecules that are ..... and the Council of Scientific and Industrial Research, New Delhi is gratefully.

  18. ‘PROTEIN SYNTHESIS GAME’: UTILIZING GAME-BASED APPROACH FOR IMPROVING COMMUNICATIVE SKILLS IN A-LEVELS BIOLOGY CLASS

    Directory of Open Access Journals (Sweden)

    Mohd Adlan Ramly

    2017-12-01

    Full Text Available This experimental paper seeks to elucidate the usage of the card game ‘Protein Synthesis Game’ as a student’s learning tool in studying the Biology topic of protein synthesis during an A-Level course. A total of 24 experimental students in 3 induced groups and 24 controlled students in controlled groups were involved in the experiment which began with a pretest on the topic of Protein Synthesis, followed by the experimentation, and ended with a post-test administered after the incubation period. Results indicate that students have better facilitative communicative engagement in learning protein synthesis when playing the game as compared to studying the topic from a book. The data suggests that such communicative engagement may lead to a successful meaningful learning on the students’ part.

  19. Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

    Science.gov (United States)

    Sarmiento, Viviana; Ramirez-Sanchez, Israel; Moreno-Ulloa, Aldo; Romero-Perez, Diego; Chávez, Daniel; Ortiz, Miguel; Najera, Nayelli; Correa-Basurto, Jose; Villarreal, Francisco; Ceballos, Guillermo

    2018-02-15

    To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Opuntia ficus indica peel derived pectin mediated hydroxyapatite nanoparticles: synthesis, spectral characterization, biological and antimicrobial activities.

    Science.gov (United States)

    Gopi, D; Kanimozhi, K; Kavitha, L

    2015-04-15

    In the present study, we have adapted a facile and efficient green route for the synthesis of HAP nanoparticles using pectin as a template which was extracted from the peel of prickly pear (Opuntia ficus indica) fruits. The concentration of pectin plays a major role in the behavior of crystallinity, purity, morphology as well as biological property of the as-synthesized HAP nanoparticles. The extracted pectin and the as-synthesized nanoparticles were characterized by various analytical techniques. The in vitro apatite formation on the surface of the as-synthesized nanoparticles in simulated body fluid (SBF) for various days showed an enhanced bioactivity. Also, the antimicrobial activity was investigated using various microorganisms. All the results revealed the formation of pure, low crystalline and discrete granular like HAP nanoparticles of size around 25 nm with enhanced biological and antimicrobial activities. Hence the as-synthesized nanoparticles can act as a better bone regenerating material in the field of biomedicine. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Synthesis, Characterization and Biological Studies of 99mTc and 188Re Peptides

    Science.gov (United States)

    Sanders, Vanessa

    Radiopharmaceuticals are very powerful diagnostic tools for evaluation of a host of medical conditions. These drugs are labeled with radioactive isotopes, which are utilized to create pictures of areas of interest through absorption of the drug. They are currently in high demand due to their ability to image areas that traditional imaging devices cannot. The radioisotope 99mTc, with a half-life of 6.01 hours and a 140 keV gamma emission, is central to many radiopharmaceutical compounds. This isotope is easily obtained from a 99Mo-99mTc generator, through beta decay and column chromatography separations. Very little technetium, less than 6 ng, is needed to label the pharmaceuticals for use in-vivo. Another radioisotope 188Re is also important due to its ability to be used for therapy while being tracked throughout the body. Radiotherapy gives radiopharmaceuticals a huge advantage by their ability to destroy rapidly growing cells. One of the main reasons there is interest in rhenium pharmaceuticals is the chemical similarity between it and technetium. The 188Re isotope also has a considerably short half-life of approximately 17 hours and has emission energy of 155 keV. The 188Re isotope is separated from 188W-188Re generator, analogously to the 99Mo-99mTc generator. The ligand used in this work is a pentapepetide macrocyclic ligand. This ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for imaging and therapeutic in vivo agents. Ligands are chosen based on their in-situ biological behavior, and are used in the complexation with technetium and rhenium. Understanding and exploiting technetium and rhenium chemistry can provide insight into the reaction mechanisms and coordination chemistry of these compounds. The exploration of various oxidation states as a function of the ligands used and the reaction conditions can help develop novel radiopharmaceuticals. The investigations of the manipulation of oxidation states

  2. Low Power Design with High-Level Power Estimation and Power-Aware Synthesis

    CERN Document Server

    Ahuja, Sumit; Shukla, Sandeep Kumar

    2012-01-01

    Low-power ASIC/FPGA based designs are important due to the need for extended battery life, reduced form factor, and lower packaging and cooling costs for electronic devices. These products require fast turnaround time because of the increasing demand for handheld electronic devices such as cell-phones, PDAs and high performance machines for data centers. To achieve short time to market, design flows must facilitate a much shortened time-to-product requirement. High-level modeling, architectural exploration and direct synthesis of design from high level description enable this design process. This book presents novel research techniques, algorithms,methodologies and experimental results for high level power estimation and power aware high-level synthesis. Readers will learn to apply such techniques to enable design flows resulting in shorter time to market and successful low power ASIC/FPGA design. Integrates power estimation and reduction for high level synthesis, with low-power, high-level design; Shows spec...

  3. AC Calorimetric Design for Dynamic of Biological Materials

    OpenAIRE

    Shigeo Imaizumi

    2006-01-01

    We developed a new AC calorimeter for the measurement of dynamic specific heat capacity in liquids, including aqueous suspensions of biological materials. This method has several advantages. The first is that a high-resolution measurement of heat capacity, inmillidegrees, can be performed as a function of temperature, even with a very small sample. Therefore, AC calorimeter is a powerful tool to study critical behavior a tphase transition in biological materials. The second advantage is that ...

  4. Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

    Science.gov (United States)

    Young, Eric; Alper, Hal

    2010-01-01

    The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research. PMID:20150964

  5. Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

    Directory of Open Access Journals (Sweden)

    Eric Young

    2010-01-01

    Full Text Available The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1 the process units and associated streams of the central dogma, (2 the intrinsic regulatory mechanisms, and (3 the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

  6. Synthetic biology: tools to design, build, and optimize cellular processes.

    Science.gov (United States)

    Young, Eric; Alper, Hal

    2010-01-01

    The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

  7. An integrated knowledge-based framework for synthesis and design of enterprise-wide processing networks

    DEFF Research Database (Denmark)

    Sin, Gürkan

    material, product portfolio and process technology selection for a given market scenario, their sustainability metrics and risk of investment under market uncertainties enabling risk-aware decision making. The framework is highlighted with successful applications for soybean oil processing (food technology......, the synthesis and design of processing networks is a complex and multidisciplinary problem, which involves many strategic and tactical decisions at business (considering financial criteria, market competition, supply chain network, etc) and engineering levels (considering synthesis, design and optimization...

  8. Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine

    OpenAIRE

    Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

    2016-01-01

    Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity ...

  9. "Intelligent" design of molecular materials: Understanding the concepts of design in supramolecular synthesis of network solids

    Science.gov (United States)

    Moulton, Brian D.

    This work endeavors to delineate modern paradigms for crystal engineering, i.e. the design and supramolecular synthesis of functional molecular materials. Paradigms predicated on an understanding of the geometry of polygons and polyhedra are developed. The primary focus is on structural determination by single crystal X-ray crystallography, structural interpretation using a suite of graphical visualization and molecular modeling software, and on the importance of proper graphical representation in the presentation and explanation of crystal structures. A detailed analysis of a selected series of crystal structures is presented. The reduction of these molecular networks to schematic representations that illustrate their fundamental connectivity facilitates the understanding of otherwise complex supramolecular solids. Circuit symbols and Schlafli notation are used to describe the network topologies, which enables networks of different composition and metrics to be easily compared. This reveals that molecular orientations in the crystals and networks are commensurate with networks that can be derived from spherical close packed lattices. The development of a logical design strategy for a new class of materials based on our understanding of the chemical composition and topology of these networks is described. The synthesis and crystal structure of a series of new materials generated by exploitation of this design strategy is presented, in addition to a detailed analysis of the topology of these materials and their relationship to a 'parent' structure. In summary, this dissertation demonstrates that molecular polygons can self-assemble at their vertexes to produce molecular architectures and crystal structures that are consistent with long established geometric dogma. The design strategy represents a potentially broad ranging approach to the design of nanoporous structures from a wide range of chemical components that are based on molecular shape rather than chemical

  10. Achieving More Sustainable Designs through a Process Synthesis-Intensification Framework

    DEFF Research Database (Denmark)

    Babi, Deenesh Kavi; Woodley, John; Gani, Rafiqul

    2014-01-01

    More sustainable process designs refer to design alternatives that correspond to lowervalues of a set of targeted performance criteria. In this paper, a multi-level frameworkfor process synthesis-intensification that leads to more sustainable process designs ispresented. At the highest level of a...

  11. Design experiment for Topo synthesis by using two process

    International Nuclear Information System (INIS)

    Meddour, L.; Loulou, M.; Megherbi, M.

    1997-02-01

    The main objectif of this work is the optimization of an organophosphorus compound synthesis. In this context, We have realized TO PO synthesis by means of two process: one based on POCL3, and the other on P CL3. To make in evidence the effects of three parameters (temperature, time and molar ratio from reactifs) it is necessary to carry eight experiences '23' factorial based on all the possible combinaisons of the minimum an d maximum values for the considerated parameters in their respectives variation ran ges

  12. Design and synthesis of mixed oxides nanoparticles for biofuel applications

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Senniang [Iowa State Univ., Ames, IA (United States)

    2010-05-15

    The work in this dissertation presents the synthesis of two mixed metal oxides for biofuel applications and NMR characterization of silica materials. In the chapter 2, high catalytic efficiency of calcium silicate is synthesized for transesterfication of soybean oil to biodisels. Chapter 3 describes the synthesis of a new Rh based catalyst on mesoporous manganese oxides. The new catalyst is found to have higher activity and selectivity towards ethanol. Chapter 4 demonstrates the applications of solid-state Si NMR in the silica materials.

  13. Biological Differences between Hanwoo longissimus dorsi and semimembranosus Muscles in Collagen Synthesis of Fibroblasts.

    Science.gov (United States)

    Subramaniyan, Sivakumar Allur; Hwang, Inho

    2017-01-01

    Variations in physical toughness between muscles and animals are a function of growth rate and extend of collagen type I and III. The current study was designed to investigate the ability of growth rate, collagen concentration, collagen synthesizing and degrading genes on two different fibroblast cells derived from Hanwoo m. longissimus dorsi (LD) and semimembranosus (SM) muscles. Fibroblast cell survival time was determined for understanding about the characteristics of proliferation rate between the two fibroblasts. We examined the collagen concentration and protein expression of collagen type I and III between the two fibroblasts. The mRNA expression of collagen synthesis and collagen degrading genes to elucidate the molecular mechanisms on toughness and tenderness through collagen production between the two fibroblast cells. From our results the growth rate, collagen content and protein expression of collagen type I and III were significantly higher in SM than LD muscle fibroblast. The mRNA expressions of collagen synthesized genes were increased whereas the collagen degrading genes were decreased in SM than LD muscle. Results from confocal microscopical investigation showed increased fluorescence of collagen type I and III appearing stronger in SM than LD muscle fibroblast. These results implied that the locomotion muscle had higher fibroblast growth rate, leads to produce more collagen, and cause tougher than positional muscle. This in vitro study mirrored that background toughness of various muscles in live animal is likely associated with fibroblast growth pattern, collagen synthesis and its gene expression.

  14. Synthesis, physical-chemical and biological properties of 7-benzyl-3-methyl-8-thioxanthine derivatives

    Directory of Open Access Journals (Sweden)

    D. H. Ivanchenko

    2017-12-01

    Full Text Available Introduction . Interest to the problem of creating new effective antimicrobial agents among xanthine derivatives does not decrease. Primarily, this is due to the increasing of microbial resistance to conventional antimicrobial agents and the emergence of their new strains. In recent years interest to the therapeutic use of antioxidants in the treatment of diseases associated with oxidative stress has increased. The aim of this work is to elaborate simple laboratory methods of 7-benzyl-3-methyl-8-thioxanthine derivatives synthesis, unspecified in scientific papers earlier, and to study their physical, chemical and biological properties. Materials and methods. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS. Study of antimicrobial and antifungal activity of synthesized compounds has been performed by two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds. Results. Under short-time heating up of the initial 7-benzyl-3-methyl-8-thioxanthine with alkyl, alkenyl, benzyl halides or heteroalkylchlorides in a water-propanol-2 mixture in the presence of an equimolar amount of sodium hydroxide leads to the formation of 8-S-substituted of 7-benzyl-3-methylxanthines. Structure of synthesized compounds was definitely proved by NMR-spectroscopy. We conducted primary screening research of antimicrobial activity of 7-benzyl-3-methyl-8-thioxanthine derivatives, which revealed moderate and weak activity in concentrations 50-100 mcg/ml. Most of the obtained compounds showed a

  15. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    International Nuclear Information System (INIS)

    Passos, E.D.; Queiroz, A.A.A. de

    2014-01-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and Discussion: The techniques SEM and EPF

  16. Procedure for developing biological input for the design, location, or modification of water-intake structures

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, D.A.; McKenzie, D.H.

    1981-12-01

    To minimize adverse impact on aquatic ecosystems resulting from the operation of water intake structures, design engineers must have relevant information on the behavior, physiology and ecology of local fish and shellfish. Identification of stimulus/response relationships and the environmental factors that influence them is the first step in incorporating biological information in the design, location or modification of water intake structures. A procedure is presented in this document for providing biological input to engineers who are designing, locating or modifying a water intake structure. The authors discuss sources of stimuli at water intakes, historical approaches in assessing potential/actual impact and review biological information needed for intake design.

  17. Perspective: Toward "synthesis by design": Exploring atomic correlations during inorganic materials synthesis

    Science.gov (United States)

    Soderholm, L.; Mitchell, J. F.

    2016-05-01

    Synthesis of inorganic extended solids is a critical starting point from which real-world functional materials and their consequent technologies originate. However, unlike the rich mechanistic foundation of organic synthesis, with its underlying rules of assembly (e.g., functional groups and their reactivities), the synthesis of inorganic materials lacks an underpinning of such robust organizing principles. In the latter case, any such rules must account for the diversity of chemical species and bonding motifs inherent to inorganic materials and the potential impact of mass transport on kinetics, among other considerations. Without such assembly rules, there is less understanding, less predictive power, and ultimately less control of properties. Despite such hurdles, developing a mechanistic understanding for synthesis of inorganic extended solids would dramatically impact the range of new material discoveries and resulting new functionalities, warranting a broad call to explore what is possible. Here we discuss our recent approaches toward a mechanistic framework for the synthesis of bulk inorganic extended solids, in which either embryonic atomic correlations or fully developed phases in solutions or melts can be identified and tracked during product selection and crystallization. The approach hinges on the application of high-energy x-rays, with their penetrating power and large Q-range, to explore reaction pathways in situ. We illustrate this process using two examples: directed assembly of Zr clusters in aqueous solution and total phase awareness during crystallization from K-Cu-S melts. These examples provide a glimpse of what we see as a larger vision, in which large scale simulations, data-driven science, and in situ studies of atomic correlations combine to accelerate materials discovery and synthesis, based on the assembly of well-defined, prenucleated atomic correlations.

  18. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Science.gov (United States)

    2015-12-01

    yield stability. Transgenic approach plays an important role in crop improvement. Currently, transgenes are randomly inserted into maize genome...Improve Microbial Biofuel Production - Mary Dunlop, University of Vermont 2:30-3:00 PM Targeted Integration of Genes into the Maize Genome Facilitated...highlights gaps in the present understanding of M13 biology. Understanding the subtleties of regulation will be important for maximally ex- ploiting the

  19. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2014

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, Christopher [Massachusetts Institute of Technology

    2014-07-01

    SEED2014 focused on advances in the science and technology emerging from the field of synthetic biology. We broadly define this as technologies that accelerate the process of genetic engineering. It highlighted new tool development, as well as the application of these tools to diverse problems in biotechnology, including therapeutics, industrial chemicals and fuels, natural products, and agriculture. Systems spanned from in vitro experiments and viruses, through diverse bacteria, to eukaryotes (yeast, mammalian cells, plants).

  20. Synthesis and properties of ZnFe2O4 replica with biological hierarchical structure

    International Nuclear Information System (INIS)

    Liu, Hongyan; Guo, Yiping; Zhang, Yangyang; Wu, Fen; Liu, Yun; Zhang, Di

    2013-01-01

    Highlights: • ZFO replica with hierarchical structure was synthesized from butterfly wings. • Biotemplate has a significant impact on the properties of ZFO material. • Our method opens up new avenues for the synthesis of spinel ferrites. -- Abstract: ZnFe 2 O 4 replica with biological hierarchical structure was synthesized from Papilio paris by a sol–gel method followed by calcination. The crystallographic structure and morphology of the obtained samples were characterized by X-ray diffraction, field-emission scanning electron microscope, and transmittance electron microscope. The results showed that the hierarchical structures were retained in the ZFO replica of spinel structure. The magnetic behavior of such novel products was measured by a vibrating sample magnetometer. A superparamagnetism-like behavior was observed due to nanostructuration size effects. In addition, the ZFO replica with “quasi-honeycomb-like structure” showed a much higher specific capacitance of 279.4 F g −1 at 10 mV s −1 in comparison with ZFO powder of 137.3 F g −1 , attributing to the significantly increased surface area. These results demonstrated that ZFO replica is a promising candidate for novel magnetic devices and supercapacitors

  1. Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4.

    Science.gov (United States)

    Ty, Nancy; Pontikis, Renée; Chabot, Guy G; Devillers, Emmanuelle; Quentin, Lionel; Bourg, Stéphane; Florent, Jean-Claude

    2013-03-01

    To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (-)-1b, (-)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities. Copyright © 2013. Published by Elsevier Ltd.

  2. Synthesis, characterization, and biological activity of a new palladium(II) complex with deoxyalliin

    Energy Technology Data Exchange (ETDEWEB)

    Corbi, P.P.; Massabni, A.C. [Inst. de Quimica - UNESP, Dept., Dept. de Quimica Geral e Inoganica, Araraquara (Brazil)]. E-mail: pedrocorbi@yahoo.com; Moreira, A.G. [Inst. de Quimica - UNESP, Dept. de Quimica Geral e Inoganica, Araraquara (Brazil); Faculdade de Medicina de Ribeirao Preto - USP, Dept. de Bioquimica e Imunologia, Ribeirao Preto (Brazil); Medrano, F.J. [Laboratorio Nacional de Luz Sincrotron - LNLS, Campinas (Brazil); Jasiulionis, M.G. [Escola Paulista de Medicina - UNIFESP, Dept. de Micro-Imuno-Parasitologia, Sao Paulo (Brazil); Costa-Neto, C.M. [Faculdade de Medicina de Ribeirao Preto - USP, Dept. de Bioquimica e Imunologia, Ribeirao Preto (Brazil)

    2005-02-15

    Synthesis, characterization, and biological activity of a new water-soluble Pd(II)-deoxyalliin (S-allyl-L-cysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C{sub 6}H{sub 10}NO{sub 2}S){sub 2}]. {sup 13}C NMR, {sup 1}H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1. (author)

  3. Synthesis, characterization and biological behavior of some Schiff's and Mannich base derivatives of Lamotrigine

    Directory of Open Access Journals (Sweden)

    A.A. Kulkarni

    2017-02-01

    Full Text Available A series of various Schiff's and Mannich base derivatives (N1–2 & ND1–6 of Lamotrigine with isatin and substituted isatin were synthesized to get more potent anticonvulsant agents. The starting material for the synthesis of various new Schiff's and Mannich base derivatives was isatin (1H-indole- 2, 3-dione which in turn was prepared from substituted isonitrosoacetanilide using aniline. Lamotrigine reacts with isatin & substituted isatin gave Schiff's bases (N1–2 which on reaction with various secondary amines (dimethylamine, diethylamine, morpholine produced Mannich bases (ND1–6. The structures of newly synthesized compounds were characterized by using TLC, UV, FT-IR, 1HNMR and studied for their anticonvulsant activity. Anticonvulsant activity of all the derivatives was evaluated by MES method using phenobarbitone sodium & Lamotrigine as standard drugs and % reduction of time spent by animals in extension, flexion, clonus, and stupor phase were noted. Compounds ND-4 and ND-6 showed significant anticonvulsant activity when compared with that of standard drugs. The remaining all compounds show moderate activity. Biological activity data of the synthesized derivatives revealed that, the synthesized derivatives are good anticonvulsant agents as compared to Lamotrigine.

  4. Synthesis, crystal structure and biological activity of 2-hydroxyethylammonium salt of p-aminobenzoic acid.

    Directory of Open Access Journals (Sweden)

    Manuela E Crisan

    Full Text Available p-Aminobenzoic acid (pABA plays important roles in a wide variety of metabolic processes. Herein we report the synthesis, theoretical calculations, crystallographic investigation, and in vitro determination of the biological activity and phytotoxicity of the pABA salt, 2-hydroxyethylammonium p-aminobenzoate (HEA-pABA. The ability of neutral and anionic forms of pABA to interact with TIR1 pocket was investigated by calculation of molecular electrostatic potential maps on the accessible surface area, docking experiments, Molecular Dynamics and Quantum Mechanics/Molecular Mechanics calculations. The docking study of the folate precursor pABA, its anionic form and natural auxin (indole-3-acetic acid, IAA with the auxin receptor TIR1 revealed a similar binding mode in the active site. The phytotoxic evaluation of HEA-pABA, pABA and 2-hydroxyethylamine (HEA was performed on the model plant Arabidopsis thaliana ecotype Col 0 at five different concentrations. HEA-pABA and pABA acted as potential auxin-like regulators of root development in Arabidopsis thaliana (0.1 and 0.2 mM and displayed an agravitropic root response at high concentration (2 mM. This study suggests that HEA-pABA and pABA might be considered as potential new regulators of plant growth.

  5. Synthesis, Biological Evaluation, and Molecular Modeling Studies of New Oxadiazole-Stilbene Hybrids against Phytopathogenic Fungi

    Science.gov (United States)

    Jian, Weilin; He, Daohang; Song, Shaoyun

    2016-08-01

    Natural stilbenes (especially resveratrol) play important roles in plant protection by acting as both constitutive and inducible defenses. However, their exogenous applications on crops as fungicidal agents are challenged by their oxidative degradation and limited availability. In this study, a new class of resveratrol-inspired oxadiazole-stilbene hybrids was synthesized via Wittig-Horner reaction. Bioassay results indicated that some of the compounds exhibited potent fungicidal activity against Botrytis cinerea in vitro. Among these stilbene hybrids, compounds 11 showed promising inhibitory activity with the EC50 value of 144.6 μg/mL, which was superior to that of resveratrol (315.6 μg/mL). Remarkably, the considerably abnormal mycelial morphology was observed in the presence of compound 11. The inhibitory profile was further proposed by homology modeling and molecular docking studies, which showed the possible interaction of resveratrol and oxadiazole-stilbene hybrids with the cytochrome P450-dependent sterol 14α-demethylase from B. cinerea (BcCYP51) for the first time. Taken together, these results would provide new insights into the fungicidal mechanism of stilbenes, as well as an important clue for biology-oriented synthesis of stilbene hybrids with improved bioactivity against plant pathogenic fungi in crop protection.

  6. Gold nanoparticles synthesis and biological activity estimation in vitro and in vivo.

    Science.gov (United States)

    Rieznichenko, L S; Dybkova, S M; Gruzina, T G; Ulberg, Z R; Todor, I N; Lukyanova, N Yu; Shpyleva, S I; Chekhun, V F

    2012-01-01

    The aim of the work was the synthesis of gold nanoparticles (GNP) of different sizes and the estimation of their biological activity in vitro and in vivo. Water dispersions of gold nanoparticles of different sizes have been synthesized by Davis method and characterized by laser-correlation spectroscopy and transmission electron microscopy methods. The GNP interaction with tumor cells has been visualized by confocal microscopy method. The enzyme activity was determined by standard biochemical methods. GNP distribution and content in organs and tissues have been determined via atomic-absorption spectrometry method; genotoxic influence has been estimated by "Comet-assay" method. The GNP size-dependent accumulation in cultured U937 tumor cells and their ability to modulate U937 cell membrane Na(+),K(+)-АТР-ase activity value has been revealed in vitro. Using in vivo model of Guerin carcinoma it has been shown that GNP possess high affinity to tumor cells. Our results indicate the perspectives of use of the synthesized GNP water dispersions for cancer diagnostics and treatment. It's necessary to take into account a size-dependent biosafety level of nanoparticles.

  7. Functionalized polypyrrole film: synthesis, characterization, and potential applications in chemical and biological sensors.

    Science.gov (United States)

    Dong, Hua; Cao, Xiaodong; Li, Chang Ming

    2009-07-01

    In this paper, we report the synthesis of a carboxyl-functionalized polypyrrole derivative, a poly(pyrrole-N-propanoic acid) (PPPA) film, by electrochemical polymerization, and the investigation of its basic properties via traditional characterization techniques such as confocal-Raman, FTIR, SEM, AFM, UV-vis, fluorescence microscopy, and contact-angle measurements. The experimental data show that the as-prepared PPPA film exhibits a hydrophilic nanoporous structure, abundant -COOH functional groups in the polymer backbone, and high fluorescent emission under laser excitation. On the basis of these unique properties, further experiments were conducted to demonstrate three potential applications of the PPPA film in chemical and biological sensors: a permeable and permselective membrane, a membrane with specific recognition sites for biomolecule immobilization, and a fluorescent conjugated polymer for amplification of fluorescence quenching. Specifically, the permeability and permselectivity of ion species through the PPPA film are detected by means of rotating-disk-electrode voltammetry; the specific recognition sites on the film surface are confirmed with protein immobilization, and the amplification of fluorescence quenching is measured by the addition of a quenching agent with fluorescence microscopy. The results are in good agreement with our expectations.

  8. Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging.

    Science.gov (United States)

    Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R

    2013-01-16

    Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

  9. High-temperature Ionization-induced Synthesis of Biologically Relevant Molecules in the Protosolar Nebula

    Science.gov (United States)

    Bekaert, David V.; Derenne, Sylvie; Tissandier, Laurent; Marrocchi, Yves; Charnoz, Sebastien; Anquetil, Christelle; Marty, Bernard

    2018-06-01

    Biologically relevant molecules (hereafter biomolecules) have been commonly observed in extraterrestrial samples, but the mechanisms accounting for their synthesis in space are not well understood. While electron-driven production of organic solids from gas mixtures reminiscent of the photosphere of the protosolar nebula (PSN; i.e., dominated by CO–N2–H2) successfully reproduced key specific features of the chondritic insoluble organic matter (e.g., elementary and isotopic signatures of chondritic noble gases), the molecular diversity of organic materials has never been investigated. Here, we report that a large range of biomolecules detected in meteorites and comets can be synthesized under conditions typical of the irradiated gas phase of the PSN at temperatures = 800 K. Our results suggest that organic materials—including biomolecules—produced within the photosphere would have been widely dispersed in the protoplanetary disk through turbulent diffusion, providing a mechanism for the distribution of organic meteoritic precursors prior to any thermal/photoprocessing and subsequent modification by secondary parent body processes. Using a numerical model of dust transport in a turbulent disk, we propose that organic materials produced in the photosphere of the disk would likely be associated with small dust particles, which are coupled to the motion of gas within the disk and therefore preferentially lofted into the upper layers of the disk where organosynthesis occurs.

  10. Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates

    Science.gov (United States)

    Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

    2015-04-01

    This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

  11. The Total Synthesis Problem of linear multivariable control. II - Unity feedback and the design morphism

    Science.gov (United States)

    Sain, M. K.; Antsaklis, P. J.; Gejji, R. R.; Wyman, B. F.; Peczkowski, J. L.

    1981-01-01

    Zames (1981) has observed that there is, in general, no 'separation principle' to guarantee optimality of a division between control law design and filtering of plant uncertainty. Peczkowski and Sain (1978) have solved a model matching problem using transfer functions. Taking into consideration this investigation, Peczkowski et al. (1979) proposed the Total Synthesis Problem (TSP), wherein both the command/output-response and command/control-response are to be synthesized, subject to the plant constraint. The TSP concept can be subdivided into a Nominal Design Problem (NDP), which is not dependent upon specific controller structures, and a Feedback Synthesis Problem (FSP), which is. Gejji (1980) found that NDP was characterized in terms of the plant structural matrices and a single, 'good' transfer function matrix. Sain et al. (1981) have extended this NDP work. The present investigation is concerned with a study of FSP for the unity feedback case. NDP, together with feedback synthesis, is understood as a Total Synthesis Problem.

  12. Synthesis, Crystal Structure and Biological Activities of Novel Anthranilic(Isophthalic) Acid Esters

    Institute of Scientific and Technical Information of China (English)

    YAN Tao; YU Guan-ping; LIU Peng-fei; XIONG Li-xia; YU Shu-jing; LI Zheng-ming

    2012-01-01

    In search of environmentally benign insecticides with high activity,low toxicity and low resistance,a series of novel anthranilic(isophthalic) acid esters was designed and synthesized based on the structure of ryanodine modulating agent.All the compounds were characterized by 1H NMR spectra,elemental analysis or high resolution mass spectrometry(HRMS).The preliminary results of biological activity assessment indicate that some of the title compounds exhibit certain but unremarkable insecticidal activity against Mythimna separata Walker at 200 mg/L and fungicidal activities against five funguses at 50 mg/L.

  13. Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

    Directory of Open Access Journals (Sweden)

    Burkhard Koenig

    2011-01-01

    Full Text Available N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.

  14. [Synthesis and biological activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone analogs. 1. Substitution at the S atom].

    Science.gov (United States)

    Schulze, W; Gutsche, W; Wohlrabe, K; Fleck, W; Tresselt, D

    1985-08-01

    The synthesis of S-substituted derivatives of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone is described. The obtained 1,4-benzoquinone-guanylhydrazone-S-alkyl (resp. aralkyl)-isothiosemicarbazones, in comparison with the unsubstituted standard compound, showed a significantly decreased biological activity against the murine leukemias L 1210 and P 388 as well as against the growth of several kinds of bacteria. Therefore the S-substitution seems not to be useful for reaching a maximum activity.

  15. Total Synthesis of Natural Products of Microbial Origins(Recent Topics of the Agricultunal Biological Science in Tohoku University)

    OpenAIRE

    Hiromasa, KIYOTA; Shigefumi, KUWAHARA; Laboratory of Applied Bioorganic Chemistry, Division of Bioscience & Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University; Laboratory of Applied Bioorganic Chemistry, Division of Bioscience & Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University

    2008-01-01

    Microorganisms are an important rich source of secondary metabolites, which could be useful leads to valuable agrochemicals and/or medicinal drugs. This mini-review describes our recent achievements on the total synthesis of biologically active natural products of microbial origins: pteridic acids A and B (strong plant growth promoters), epoxyquinols A and B (anti-angiogenic compounds), communiols A-F, G, and H, and macrotetrolide α (antibiotics), pyricuol and tabtoxinine-β-lactam (phytotoxin...

  16. Synthesis, chemical and biological properties of the new mono- and bis-derivatives of imidazoles

    Directory of Open Access Journals (Sweden)

    E. V. Welchinska

    2014-12-01

    Full Text Available The aim of research. The problem of finding effective antitumour medical preparation with low toxicity is an important issue of medical and pharmaceutical chemistry. Knowledge of cancer cell features and its metabolism enables to predict the direction of chemical and biological research, to conduct a targeted synthesis of potential drugs, and to assess their applicability in oncological practice as antitumor agents. The purpose of work is to explain preformed heterocycles as purines, its synthesis and investigation of chemical and biological properties. After construction of the potential active structures we proposed the new method of original derivatives synthesis which are received on the base of imidazole, from one side, and fluorocontaining common anesthetic halothane (2-bromo-1,1,1-trifluoro-2-chloroethane from other side. Molecular complex of more perspective biologically active bis-imidazole with antitumour bacterial lectine has been received. With the purpose to synthesize potential antitumour compounds on the base of halothane and imidazole, new convenient methods for the preparation of original heterocyclic derivatives of imidazole have been described. The structure and composition of synthesized compound has been confirmed by the methods of elemental analysis, IR- and NMRІН-spectra. Materials and methods. The majority of the absolute organic solvents (benzene, dimethylformamide, ethyl ester employed in the present studies were distilled before their use. Organic solvents were dried over anhydrous magnesium sulfate or metallic sodium. Gas-liquid chromatography was carried out by Perkin Elmer chromatograph with UV-detector ("Perkin", Germany. IR spectra were recorded in a UR-20 spectrometer ("Charles Ceise Hena", Germany. The 1HNMR spectra were recorded in DMSO-d6 on a 200 MHz BrakerWP-200 ("Braker", Switzerland or Varian T-60 spectrometer ("Varian", USA. Investigation of critical toxicity of new compounds was carried out at

  17. Synthesis of C-di-saccharidic compounds by radical cyclisation. Study of biological, structural and dynamic properties

    International Nuclear Information System (INIS)

    Rubinstenn, Gilles

    1996-01-01

    The synthesis of carbohydrate mimics and particularly of C-disaccharides, molecules in which the inter-glycosidic oxygen atom has been replaced by a methylene group, has become, this past two decades, an important challenge in organic chemistry. In the first chapter we present the synthesis of C-disaccharides from the neutral series by a silaketal tethering. The key step of this C-glycosylation is a radical macro-cyclisation. This strategy is applied to the synthesis of two analogues of natural, biologically active, products, the lactose and the Lewis x tri-saccharide. The biological activity of this mimetics is then evaluated. A new tethering strategy, based on the use of phosphorus III compounds, is applied, in the second chapter, to the building of C-disaccharides of the 2'-amino 2'- deoxy series. The third chapter deals with the structural and dynamics study of the C-glycosides prepared in chapter 1 by Nuclear Magnetic Resonance. A new methodology, studying the dipolar relaxation along an effective field, generated through an off-resonance RF field, allowed the precise measurement of longitudinal and transverse cross-relaxation rates. Structural and dynamics parameter thus derived are used as restraints for molecular modeling. The results of this study are then compared to those of the biological tests. (author) [fr

  18. The design of trickling biological periwinkle shells filter for closed ...

    African Journals Online (AJOL)

    ... and economics of biofilter in reirculating aquaculture systems using local material ... The system with the designed biofilter served as the treatment system, while the ... The selected system recirculation rate was 10 times per hour, while the ...

  19. Multivariable feedback design: concepts for a classical/modern synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, J C; Stein, G

    1980-01-01

    A practical design perspective on multivariable feedback control problems is presented. The basic issue - feedback design in the face of uncertainites - is reviewed and known SISO statements and constraints of the design problem to MIMO cases are generalized. Two major MIMO design approaches are then evaluated in the context of these results.

  20. Computer-aided design of biological circuits using TinkerCell.

    Science.gov (United States)

    Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

    2010-01-01

    Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. © 2010 Landes Bioscience

  1. Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

    Directory of Open Access Journals (Sweden)

    Valentina Onnis

    2016-04-01

    Full Text Available The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N′-(4-arylidene-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210, human T-cell leukemia (CEM, human cervix carcinoma (HeLa and human pancreas carcinoma cells (Mia Paca-2. A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC50 values in the low micromolar range.

  2. Biotechnology by Design: An Introductory Level, Project-Based, Synthetic Biology Laboratory Program for Undergraduate Students†

    OpenAIRE

    Beach, Dale L.; Alvarez, Consuelo J.

    2015-01-01

    Synthetic biology offers an ideal opportunity to promote undergraduate laboratory courses with research-style projects, immersing students in an inquiry-based program that enhances the experience of the scientific process. We designed a semester-long, project-based laboratory curriculum using synthetic biology principles to develop a novel sensory device. Students develop subject matter knowledge of molecular genetics and practical skills relevant to molecular biology, recombinant DNA techniq...

  3. Biological shield design for a 10 MeV Rhodotron

    International Nuclear Information System (INIS)

    Khalafi, H.; Ghane, A.; Safaei Arshi, S.; Tabakh, F.

    2012-01-01

    Highlights: ► We evaluate the produced radiations of the Rhodotron-TT200 and their attenuation to the permitted level. ► We apply analytical calculations to determine the shield material and thickness. ► We simulate the Rhodotron accelerator and its shielding using MCNPX code to make sure of results accuracy. -- Abstract: Radiation field of the Rhodotron-TT200 electron accelerator is determined in this study. Regarding the interactions of electron with matter, the produced radiations and their attenuation to the permitted level (i.e. 0.01 mrem/h) are evaluated and calculated. For this purpose analytical calculations are applied to determine the biological shield material and thickness. In order to make sure of results accuracy, Rhodotron accelerator and its shielding are simulated using MCNPX code and the results of analytical calculations and MCNPX code are compared with the experimental ones.

  4. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    Energy Technology Data Exchange (ETDEWEB)

    Passos, E.D.; Queiroz, A.A.A. de [Universidade Federal de Itajuba (UNIFEI), MG (Brazil)

    2014-07-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and

  5. Procafd: Computer Aided Tool for Synthesis-Design & Analysis of Chemical Process Flowsheets

    DEFF Research Database (Denmark)

    Kumar Tula, Anjan; Eden, Mario R.; Gani, Rafiqul

    2015-01-01

    and emission to the surrounding and many more. In terms of approaches to solve the synthesis-design problem three major lines of attack have emerged: (a) the knowledge based approach [1] which relies on engineering knowledge & problem insights, (b) the optimization approach [2] which relies on the use...... of mathematical programming techniques, (c) hybrid approach which combine two or more approaches. D’Anterroches [3] proposed a group contribution based hybrid approach to solve the synthesis-design problem where, chemical process flowsheets could be synthesized in the same way as atoms or groups of atoms...... parameters for the operations of the high ranked flowsheets are established through reverse engineering approaches based on driving forces available for each operation. In the final stage, rigorous simulation is performed to validate the synthesis-design. Note that since the flowsheet is synthesized...

  6. Integrated Business and Engineering Framework for Synthesis and Design of Enterprise-Wide Processing Networks

    DEFF Research Database (Denmark)

    Quaglia, Alberto; Sarup, Bent; Sin, Gürkan

    2012-01-01

    The synthesis and design of processing networks is a complex and multidisciplinary problem, which involves many strategic and tactical decisions at business (considering financial criteria, market competition, supply chain network, etc) and engineering levels (considering synthesis, design...... and optimisation of production technology, R&D, etc), all of which have a deep impact on the profitability of processing industries. In this study, an integrated business and engineering framework for synthesis and design of processing networks is presented. The framework employs a systematic approach to manage...... the complexity while solving simultaneously both the business and the engineering aspects of problems, allowing at the same time, comparison of a large number of alternatives at their optimal points. The results identify the optimal raw material, the product portfolio and select the process technology...

  7. Programming biological operating systems: genome design, assembly and activation.

    Science.gov (United States)

    Gibson, Daniel G

    2014-05-01

    The DNA technologies developed over the past 20 years for reading and writing the genetic code converged when the first synthetic cell was created 4 years ago. An outcome of this work has been an extraordinary set of tools for synthesizing, assembling, engineering and transplanting whole bacterial genomes. Technical progress, options and applications for bacterial genome design, assembly and activation are discussed.

  8. Extracellular synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 and their biological applications.

    Science.gov (United States)

    Singh, Priyanka; Singh, Hina; Kim, Yeon Ju; Mathiyalagan, Ramya; Wang, Chao; Yang, Deok Chun

    2016-05-01

    The present study highlights the microbial synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 strain, in an efficient way. The synthesized nanoparticles were characterized by ultraviolet-visible spectrophotometry, which displayed maximum absorbance at 424nm and 531nm for silver and gold nanoparticles, respectively. The spherical shape of nanoparticles was characterized by field emission transmission electron microscopy. The energy dispersive X-ray spectroscopy and elemental mapping were displayed the purity and maximum elemental distribution of silver and gold elements in the respective nanoproducts. The X-ray diffraction spectroscopy results demonstrate the crystalline nature of synthesized nanoparticles. The particle size analysis demonstrate the nanoparticles distribution with respect to intensity, volume and number of nanoparticles. For biological applications, the silver nanoparticles have been explored in terms of MIC and MBC against pathogenic microorganisms such as Vibrio parahaemolyticus, Escherichia coli, Salmonella enterica, Bacillus anthracis, Bacillus cereus and Staphylococcus aureus. Moreover, the silver nanoparticles in combination with commercial antibiotics, such as vancomycin, rifampicin, oleandomycin, penicillin G, novobiocin, and lincomycin have been explored for the enhancement of antibacterial activity and the obtained results showed that 3μg concentration of silver nanoparticles sufficiently enhance the antimicrobial efficacy of commercial antibiotics against pathogenic microorganism. Furthermore, the silver nanoparticles potential has been reconnoitered for the biofilm inhibition by S. aureus, Pseudomonas aeruginosa and E. coli and the results revealed sufficient activity at 6μg concentration. In addition, gold nanoparticles have been applied for catalytic activity, for the reduction of 4-nitrophenol to 4-aminophenol using sodium borohydride and positive results were attained. Copyright © 2016 Elsevier Inc. All

  9. Development of the Neuron Assessment for Measuring Biology Students' Use of Experimental Design Concepts and Representations

    Science.gov (United States)

    Dasgupta, Annwesa P.; Anderson, Trevor R.; Pelaez, Nancy J.

    2016-01-01

    Researchers, instructors, and funding bodies in biology education are unanimous about the importance of developing students' competence in experimental design. Despite this, only limited measures are available for assessing such competence development, especially in the areas of molecular and cellular biology. Also, existing assessments do not…

  10. Digital learning material for experimental design and model building in molecular biology

    NARCIS (Netherlands)

    Aegerter-Wilmsen, T.

    2005-01-01

    Designing experimental approaches is a major cognitive skill in molecular biology research, and building models, including quantitative ones, is a cognitive skill which is rapidly gaining importance. Since molecular biology education at university level is aimed at educating future researchers, we

  11. Design and Synthesis of Novel Fluorine-containing Acrylates

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A series of novel fluorine-containing acrylates 6a-6g were synthesized via the condensation of ethyl cyanoacetate and trifluoroacetic anhydride, followed by chloridization and the coupling reaction with amines. These new compounds exhibited some biological activity as preliminary bioassay indicated. A plausible reaction mechanism was outlined and discussed.

  12. Design and Biological Evaluation of Antifouling Dihydrostilbene Oxime Hybrids.

    Science.gov (United States)

    Moodie, Lindon W K; Cervin, Gunnar; Trepos, Rozenn; Labriere, Christophe; Hellio, Claire; Pavia, Henrik; Svenson, Johan

    2018-04-01

    By combining the recently reported repelling natural dihydrostilbene scaffold with an oxime moiety found in many marine antifoulants, a library of nine antifouling hybrid compounds was developed and biologically evaluated. The prepared compounds were shown to display a low antifouling effect against marine bacteria but a high potency against the attachment and growth of microalgae down to MIC values of 0.01 μg/mL for the most potent hybrid. The mode of action can be characterized as repelling via a reversible non-toxic biostatic mechanism. Barnacle cyprid larval settlement was also inhibited at low μg/mL concentrations with low levels or no toxicity observed. Several of the prepared compounds performed better than many reported antifouling marine natural products. While several of the prepared compounds are highly active as antifoulants, no apparent synergy is observed by incorporating the oxime functionality into the dihydrostilbene scaffold. This observation is discussed in light of recently reported literature data on related marine natural antifoulants and antifouling hybrids as a potentially general strategy for generation of improved antifoulants.

  13. Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

    Directory of Open Access Journals (Sweden)

    Thilo Focken

    2014-08-01

    Full Text Available A review of the synthesis of natural products and bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be summarized, as well as an overview of the synthesis of the employed phosphonamide reagents.

  14. Biologically active perspective synthesis of heteroannulated 8-nitroquinolines with green chemistry approach.

    Science.gov (United States)

    Arasakumar, Thangaraj; Mathusalini, Sadasivam; Gopalan, Subashini; Shyamsivappan, Selvaraj; Ata, Athar; Mohan, Palathurai Subramaniam

    2017-04-01

    A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Design Approach of Biologically-Inspired Musculoskeletal Humanoids

    Directory of Open Access Journals (Sweden)

    Yuto Nakanishi

    2013-04-01

    Full Text Available In order to realize more natural and various motions like humans, humanlike musculoskeletal tendon-driven humanoids have been studied. Especially, it is very challenging to design musculoskeletal body structure which consists of complicated bones, redundant powerful and flexible muscles, and large number of distributed sensors. In addition, it is very challenging to reveal humanlike intelligence to manage these complicated musculoskeletal body structure. This paper sums up life-sized musculoskeletal humanoids Kenta, Kotaro, Kenzoh and Kenshiro which we have developed so far, and describes key technologies to develop and control these robots.

  16. Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

    Science.gov (United States)

    Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

    2013-07-01

    A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The influence of heat exchanger design on the synthesis of heat exchanger networks

    Directory of Open Access Journals (Sweden)

    Liporace F.S.

    2000-01-01

    Full Text Available Heat exchanger network (HEN synthesis has been traditionally performed without accounting for a more detailed unit design, which is important since the final HEN may require unfeasible units. Recently, publications on this matter have appeared, as well as softwares that simultaneously perform synthesis and units design. However, these publications do not clearly show the influence of the new added features on the final HEN. Hence, this work aims at showing that units' design can strongly affect the final HEN. Improvements on heat transfer area and total annual cost estimations, which influence the HEN structural evolution, are the main responsible for that. It is also shown the influence of some design bounds settings, which can indicate an unfeasible unit design and, therefore, the need for a new match search or the maintenance of a loop. An example reported in the literature is used to illustrate the discussion.

  18. Guided synthesis of accumulative solutions for the conceptual design of an efficient stove working with biomass

    International Nuclear Information System (INIS)

    Álvarez Cabrales, Alexis; Gaskins Espinosa, Benjamín Gabriel; Pérez Rodríguez, Roberto; Simeón Monet, Rolando Esteban

    2014-01-01

    The conceptual design is closely related to a product functional structure and the search of solution principles for its definition. This work exposes an accumulative method for the traceability of the functional structure that implements the guided conceptual synthesis of solutions in the preliminary analysis of this designing process stage. The method constitutes a contribution to Pahls and Beitzs classic design model. In it, the functional information system is manipulated, providing the designer with a help so that he can examine the different solutions that are obtained, giving him the possibility of selecting the most convenient one. The guided analysis of the accumulative solutions synthesis is illustrated by means of the conceptual design of an efficient stove working with biomass. (author)

  19. Designer genes. Recombinant antibody fragments for biological imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A.M.; Yazaki, P.J. [Beckman Research Institute of the City of Hope, Duarte, CA (United States). Dept. of Molecular Biology

    2000-09-01

    and expression, combined with novel specificities that will arise form advances in genomic and combinatorial approaches to target discovery, will usher in a new era of recombinant antibodies for biological imaging.

  20. Designer genes. Recombinant antibody fragments for biological imaging

    International Nuclear Information System (INIS)

    Wu, A.M.; Yazaki, P.J.

    2000-01-01

    expression, combined with novel specificities that will arise form advances in genomic and combinatorial approaches to target discovery, will usher in a new era of recombinant antibodies for biological imaging

  1. Genome-scale metabolic models as platforms for strain design and biological discovery.

    Science.gov (United States)

    Mienda, Bashir Sajo

    2017-07-01

    Genome-scale metabolic models (GEMs) have been developed and used in guiding systems' metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models.

  2. Rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid

    DEFF Research Database (Denmark)

    Bunch, Lennart; Liljefors, Tommy; Greenwood, Jeremy R

    2003-01-01

    conformationally restricted (S)-glutamic acid (Glu) analogue intended as a mimic of the folded Glu conformation. The synthesis of 1 was completed in its racemic form in eight steps from commercially available starting materials. As a key step, the first facially selective hydroboration of a 5-methylidene[2......The design and synthesis of conformationally restricted analogues of alpha-amino acids is an often used strategy in medicinal chemistry research. Here we present the rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid (1), a novel...... studies on native 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) (IC(50) > 300 microM, [(3)H]AMPA) or kainic acid (IC(50) > 160 microM, [(3)H]kainic acid) receptors nor in binding studies on the cloned iGluR5,6 subtypes (IC(50) > 300 microM, [(3)H]kainic acid)....

  3. Computational protein design-the next generation tool to expand synthetic biology applications.

    Science.gov (United States)

    Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

    2018-05-02

    One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology. Here, we review efforts to increase the capabilities of synthetic biology using computational protein design. We focus primarily on computationally designed proteins not only validated in vitro, but also shown to modulate different activities in living cells. Efforts made to validate computational designs in cells can illustrate both the challenges and opportunities in the intersection of protein design and synthetic biology. We also highlight protein design approaches, which although not validated as conveyors of new cellular function in situ, may have rapid and innovative applications in synthetic biology. We foresee that in the near-future, computational protein design will vastly expand the functional capabilities of synthetic cells. Copyright © 2018. Published by Elsevier Ltd.

  4. Sharing Structure and Function in Biological Design with SBOL 2.0.

    Science.gov (United States)

    Roehner, Nicholas; Beal, Jacob; Clancy, Kevin; Bartley, Bryan; Misirli, Goksel; Grünberg, Raik; Oberortner, Ernst; Pocock, Matthew; Bissell, Michael; Madsen, Curtis; Nguyen, Tramy; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Densmore, Douglas; Gennari, John H; Wipat, Anil; Sauro, Herbert M; Myers, Chris J

    2016-06-17

    The Synthetic Biology Open Language (SBOL) is a standard that enables collaborative engineering of biological systems across different institutions and tools. SBOL is developed through careful consideration of recent synthetic biology trends, real use cases, and consensus among leading researchers in the field and members of commercial biotechnology enterprises. We demonstrate and discuss how a set of SBOL-enabled software tools can form an integrated, cross-organizational workflow to recapitulate the design of one of the largest published genetic circuits to date, a 4-input AND sensor. This design encompasses the structural components of the system, such as its DNA, RNA, small molecules, and proteins, as well as the interactions between these components that determine the system's behavior/function. The demonstrated workflow and resulting circuit design illustrate the utility of SBOL 2.0 in automating the exchange of structural and functional specifications for genetic parts, devices, and the biological systems in which they operate.

  5. Synthesis and biological incorporation of icons into macromolecules for NMR study. Final report, June 1, 1977--May 31, 1978

    International Nuclear Information System (INIS)

    Grant, D.M.; Horton, W.J.

    1978-01-01

    Carbon-13 enrichment synthesis and incorporation into three important biological systems have been carried out to provide materials for carbon-13 magnetic resonance studies. These systems include antibody-labeled haptens, labeled t-RNA and 5S-RNA molecules, and pyridoxal-5'-phosphate-labeled substrate mixtures. The synthesis phase of the work has been completed in all three cases, and the NMR studies completed on all but the antibody-hapten system which is still in process having been absorbed into other supported projects. Publications are now in preparation for the RNA and pyridoxal work. Preliminary results on the antibody-haptens work are encouraging as signals of antibody absorbed haptens have been observed but the results are still not yet conclusive

  6. Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase.

    Science.gov (United States)

    Rota, Paola; Cirillo, Federica; Piccoli, Marco; Gregorio, Antonio; Tettamanti, Guido; Allevi, Pietro; Anastasia, Luigi

    2015-10-05

    Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP-Neu5Ac congeners and their anti-GM3-synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3-synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. An Automated Analysis-Synthesis Package for Design Optimization ...

    African Journals Online (AJOL)

    90 standards is developed for the design optimization of framed structures - continuous beams, plane and space trusses and rigid frames, grids and composite truss-rigid frames. The package will enable the structural engineer to effectively and ...

  8. Photonic band gap materials: design, synthesis, and applications

    International Nuclear Information System (INIS)

    John, S.

    2000-01-01

    Full text: Unlike semiconductors which facilitate the coherent propagation of electrons, photonic band gap (PBG) materials execute their novel functions through the coherent localization of photons. I review and discuss our recent synthesis of a large scale three-dimensional silicon photonic crystal with a complete photonic band gap near 1.5 microns. When a PBG material is doped with impurity atoms which have an electronic transition that lies within the gap, spontaneous emission of light from the atom is inhibited. Inside the gap, the photon forms a bound state to the atom. Outside the gap, radiative dynamics in the colored vacuum is highly non Markovian. I discuss the influence of these memory effects on laser action. When spontaneous emission is absent, the next order radiative effect (resonance dipole dipole interaction between atoms) must be incorporated leading to anomalous nonlinear optical effects which occur at a much lower threshold than in ordinary vacuum. I describe the collective switching of two-level atoms near a photonic band edge, by external laser field, from a passive state to one exhibiting population inversion. This effect is forbidden in ordinary vacuum. However, in the context of a PBG material, this effect may be utilized for an all-optical transistor. Finally, I discuss the prospects for a phase sensitive, single atom quantum memory device, onto which information may be written by an external laser pulse

  9. Synthesis, structure combined with conformational analysis, biological activities and docking studies of bis benzylidene cyclohexanone derivatives

    Directory of Open Access Journals (Sweden)

    Gehad Lotfy

    2017-07-01

    Full Text Available We report the synthesis and biological evaluation of bis benzylidne cyclohexanone derivatives 2,6-di(4-fluorobenzylidenecyclohexanone 3a and (2E,6E‐2,6‐bis({[4‐(trifluoromethylphenyl]methylidene}cyclohexanone 3b. Compound 3b crystallized in the monoclinic space group P21/n with unit cell parameters a = 29.3527(12 Å, b = 8.3147(3 Å, c = 32.7452(14 Å, β = 112.437(2°, and V = 7386.8(5 Å3, Z = 16, and Rint = 0.072 at T = 100 K. The asymmetric unit contains four independent molecules, each of which has slight differences in the bond lengths and angles. One non-classical C11D–H11F⋯F3A hydrogen bond connects the molecules. Density functional theory was used to optimize the structures and calculate the natural charges, dipole moments, frontier molecular orbitals, and NMR and UV–Vis spectroscopic properties, which are discussed and compared with the experimental data. The synthetic derivatives were evaluated for α-glucosidase inhibitory activity, and we found that compound 3a (IC50 = 96.3 ± 0.51 μM is a potent α-glucosidase inhibitor, showing superior activity to the standard drug acarbose (IC50 = 841 ± 1.73 μM. Compound 3b (IC50 = 7.92 ± 1.3 μg/mL was found to be a potent antileishmanial compound, especially compared to the antileishmanial drugs pentamidine (IC50 = 5.09 ± 0.04 μM and amphotericine B (IC50 = 0.29 ± 0.05 μg/mL. In addition, 3a and 3b have cytotoxic effects against PC3 (prostate cancer, HeLa (cervical cancer, and MCF-3 (breast cancer cell lines. Docking study for compounds activity was performed with Openeye software in order to understanding their pose of interaction in the target receptors.

  10. Bio-templated CdSe quantum dots green synthesis in the functional protein, lysozyme, and biological activity investigation

    International Nuclear Information System (INIS)

    Wang, Qisui; Li, Song; Liu, Peng; Min, Xinmin

    2012-01-01

    Bifunctional fluorescence (CdSe Quantum Dots) – protein (Lysozyme) nanocomposites were synthesized at room temperature by a protein-directed, solution-phase, green-synthetic method. Fluorescence (FL) and absorption spectra showed that CdSe QDs were prepared successfully with Lyz. The average particle size and crystalline structure of QDs were investigated by high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD), respectively. With attenuated total reflection-fourier transform infrared (ATR-FTIR) spectra and thermogravimetric (TG) analysis, it was confirmed that there is interaction between QDs and amide I, amide II groups in Lyz. FL polarization was measured and FL imaging was done to monitor whether QDs could be responsible for possible changes in the conformation and activity of Lyz. Interestingly, the results showed Lyz still retain the biological activity after formation of QDs, but the secondary structure of the Lyz was changed. And the advantage of this synthesis method is producing excellent fluorescent QDs with specifically biological function. -- Highlights: ► Lysozyme-directed green synthesis of CdSe quantum dots. ► Lysozyme still retain the biological activity after formation of CdSe. ► The method is the production of fluorescent QDs with highly specific and functions.

  11. One-pot synthesis of water soluble iron nanoparticles using rationally-designed peptides and ligand release.

    Science.gov (United States)

    Papst, Stefanie; Cheong, Soshan; Banholzer, Moritz J; Brimble, Margaret A; Williams, David E; Tilley, Richard D

    2013-05-18

    Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.

  12. Design and evaluation of a gesture driven wavefield synthesis auditory game

    DEFF Research Database (Denmark)

    Grani, Francesco; Paisa, Razvan; Banas, Jan Stian

    2016-01-01

    An auditory game has been developed as a part of research in Wavefield Synthesis. In order to design and implement this game, a number of technologies have been incorporated in the development process. By pairing motion capture with a WiiMote new dimension of movement input was achieved. We present...... an evaluation study where the game was assessed....

  13. Phenomena-based Process Synthesis and Design to achieve Process Intensification

    DEFF Research Database (Denmark)

    Lutze, Philip; Babi, Deenesh Kavi; Woodley, John

    2012-01-01

    at the lowest level of aggregation: phenomena. Therefore, in this paper, a phenomena-based synthesis/design methodology is presented. Using this methodology, a systematic identification of necessary and desirable (integrated) phenomena as well as generation and screening of phenomena-based flowsheet options...

  14. Design, synthesis, and characterization of novel fine-particle, unsupported catalysts for coal liquefaction

    Energy Technology Data Exchange (ETDEWEB)

    Klein, M.T.

    1991-12-30

    The purpose of this work is to investigate the kinetics-assisted design, synthesis and characterization of fme-pardcle, unsupported catalysts for coal liquefaction. The goal is to develop a fundamental understanding of coal catalysis and catalysts that will, in turn, allow for the specification of a novel optimal catalyst for coal liquefaction.

  15. Design and synthesis of multipurpose batch plant using a robust scheduling platform

    CSIR Research Space (South Africa)

    Seid, ER

    2013-10-01

    Full Text Available & Engineering Chemistry Research October 2012/ Vol. 52(46) Design and Synthesis of Multipurpose Batch Plants Using a Robust Scheduling Platform Esmael R. Seid † and Thokozani Majozi *†‡ † Department of Chemical Engineering, University of Pretoria...

  16. Design and validation of general biology learning program based on scientific inquiry skills

    Science.gov (United States)

    Cahyani, R.; Mardiana, D.; Noviantoro, N.

    2018-03-01

    Scientific inquiry is highly recommended to teach science. The reality in the schools and colleges is that many educators still have not implemented inquiry learning because of their lack of understanding. The study aims to1) analyze students’ difficulties in learning General Biology, 2) design General Biology learning program based on multimedia-assisted scientific inquiry learning, and 3) validate the proposed design. The method used was Research and Development. The subjects of the study were 27 pre-service students of general elementary school/Islamic elementary schools. The workflow of program design includes identifying learning difficulties of General Biology, designing course programs, and designing instruments and assessment rubrics. The program design is made for four lecture sessions. Validation of all learning tools were performed by expert judge. The results showed that: 1) there are some problems identified in General Biology lectures; 2) the designed products include learning programs, multimedia characteristics, worksheet characteristics, and, scientific attitudes; and 3) expert validation shows that all program designs are valid and can be used with minor revisions. The first section in your paper.

  17. The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs.

    Science.gov (United States)

    Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Pocock, Matthew; Flanagan, Keith; Hallinan, Jennifer; Wipat, Anil

    2016-06-17

    Recently, synthetic biologists have developed the Synthetic Biology Open Language (SBOL), a data exchange standard for descriptions of genetic parts, devices, modules, and systems. The goals of this standard are to allow scientists to exchange designs of biological parts and systems, to facilitate the storage of genetic designs in repositories, and to facilitate the description of genetic designs in publications. In order to achieve these goals, the development of an infrastructure to store, retrieve, and exchange SBOL data is necessary. To address this problem, we have developed the SBOL Stack, a Resource Description Framework (RDF) database specifically designed for the storage, integration, and publication of SBOL data. This database allows users to define a library of synthetic parts and designs as a service, to share SBOL data with collaborators, and to store designs of biological systems locally. The database also allows external data sources to be integrated by mapping them to the SBOL data model. The SBOL Stack includes two Web interfaces: the SBOL Stack API and SynBioHub. While the former is designed for developers, the latter allows users to upload new SBOL biological designs, download SBOL documents, search by keyword, and visualize SBOL data. Since the SBOL Stack is based on semantic Web technology, the inherent distributed querying functionality of RDF databases can be used to allow different SBOL stack databases to be queried simultaneously, and therefore, data can be shared between different institutes, centers, or other users.

  18. Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design.

    Science.gov (United States)

    Raman, Ritu; Bashir, Rashid

    2017-10-01

    The discipline of biological design has a relatively short history, but has undergone very rapid expansion and development over that time. This Progress Report outlines the evolution of this field from biomimicry to biofabrication to biohybrid systems' design, showcasing how each subfield incorporates bioinspired dynamic adaptation into engineered systems. Ethical implications of biological design are discussed, with an emphasis on establishing responsible practices for engineering non-natural or hypernatural functional behaviors in biohybrid systems. This report concludes with recommendations for implementing biological design into educational curricula, ensuring effective and responsible practices for the next generation of engineers and scientists. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Design, Synthesis, and Antifouling Activity of Glucosamine-Based Isocyanides.

    Science.gov (United States)

    Umezawa, Taiki; Hasegawa, Yuki; Novita, Ira S; Suzuki, Junya; Morozumi, Tatsuya; Nogata, Yasuyuki; Yoshimura, Erina; Matsuda, Fuyuhiko

    2017-06-29

    Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Organotin compounds were utilized since the 1960s as an antifouling material; however, the use of such compounds was later banned by the International Maritime Organization (IMO) due to their high toxicity toward marine organisms, resulting in masculinization and imposex. Since the ban, there have been extensive efforts to develop environmentally benign antifoulants. Natural antifouling products obtained from marine creatures have been the subject of considerable attention due to their potent antifouling activity and low toxicity. These antifouling compounds often contain isocyano groups, which are well known to have natural antifouling properties. On the basis of our previous total synthesis of natural isocyanoterpenoids, we envisaged the installation of an isocyano functional group onto glucosamine to produce an environmentally friendly antifouling material. This paper describes an effective synthetic method for various glucosamine-based isocyanides and evaluation of their antifouling activity and toxicity against cypris larvae of the barnacle Amphibalanus amphitrite . Glucosamine isocyanides with an ether functionality at the anomeric position exhibited potent antifouling activity, with EC 50 values below 1 μg/mL, without detectable toxicity even at a high concentration of 10 μg/mL. Two isocyanides had EC 50 values of 0.23 and 0.25 μg/mL, comparable to that of CuSO₄, which is used as a fouling inhibitor (EC 50 = 0.27 μg/mL).

  20. A focus on polarity: Investigating the role of orientation cues in mediating student performance on mRNA synthesis tasks in an introductory cell and molecular biology course.

    Science.gov (United States)

    Olimpo, Jeffrey T; Quijas, Daniel A; Quintana, Anita M

    2017-11-01

    The central dogma has served as a foundational model for information flow, exchange, and storage in the biological sciences for several decades. Despite its continued importance, however, recent research suggests that novices in the domain possess several misconceptions regarding the aforementioned processes, including those pertaining specifically to the formation of messenger ribonucleic acid (mRNA) transcripts. In the present study, we sought to expand upon these observations through exploration of the influence of orientation cues on students' aptitude at synthesizing mRNAs from provided deoxyribonucleic acid (DNA) template strands. Data indicated that participants (n = 45) were proficient at solving tasks of this nature when the DNA template strand and the mRNA molecule were represented in an antiparallel orientation. In contrast, participants' performance decreased significantly on items in which the mRNA was depicted in a parallel orientation relative to the DNA template strand. Furthermore, participants' Grade Point Average, self-reported confidence in understanding the transcriptional process, and spatial ability were found to mediate their performance on the mRNA synthesis tasks. Collectively, these data reaffirm the need for future research and pedagogical interventions designed to enhance students' comprehension of the central dogma in a manner that makes transparent its relevance to real-world scientific phenomena. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):501-508, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  1. Design and synthesis of reactive separation systems. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, M.F.

    1992-12-31

    During the last decade there has been a rapid upturn in interest in reactive distillation. The chemical process industry recognizes the favorable economics of carrying out reaction simultaneously with distillation for certain classes of reacting systems, and many new processes have been built based on this technology. Interest is also increasing by academics and software vendors. Systematic design methods for reactive distillation systems have only recently begun to emerge. In this report we survey the available design techniques and point out the contributions made by our group at the University of Massachusetts.

  2. Synthesis and in vitro biological evaluation of new pyrazole chalcones and heterocyclic diamides as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Sankappa Rai U.

    2015-05-01

    Full Text Available Synthesis and characterization of new heterocyclic pyrazole chalcones (4a–e and diamide (6a–e derivatives are described. Pyrazole chalcones were synthesized by the reaction of pyrazole aldehydes and suitable aromatic ketones. Diamides were synthesized by the reaction of phthalic acid and amines. Newly synthesized compounds were characterized by spectral studies and their biological activity was assessed in vitro using MCF-7 (human breast adenocarcinoma and HeLa (human cervical tumor cells cell lines. Few of the synthesized molecules inhibited the growth of the human breast cancer cell lines and human cervical tumor cell lines at low micromolar to nanomolar concentrations.

  3. Systematic process synthesis and design methods for cost effective waste minimization

    International Nuclear Information System (INIS)

    Biegler, L.T.; Grossman, I.E.; Westerberg, A.W.

    1995-01-01

    We present progress on our work to develop synthesis methods to aid in the design of cost effective approaches to waste minimization. Work continues to combine the approaches of Douglas and coworkers and of Grossmann and coworkers on a hierarchical approach where bounding information allows it to fit within a mixed integer programming approach. We continue work on the synthesis of reactors and of flexible separation processes. In the first instance, we strive for methods we can use to reduce the production of potential pollutants, while in the second we look for ways to recover and recycle solvents

  4. Systematic process synthesis and design methods for cost effective waste minimization

    Energy Technology Data Exchange (ETDEWEB)

    Biegler, L.T.; Grossman, I.E.; Westerberg, A.W. [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    1995-12-31

    We present progress on our work to develop synthesis methods to aid in the design of cost effective approaches to waste minimization. Work continues to combine the approaches of Douglas and coworkers and of Grossmann and coworkers on a hierarchical approach where bounding information allows it to fit within a mixed integer programming approach. We continue work on the synthesis of reactors and of flexible separation processes. In the first instance, we strive for methods we can use to reduce the production of potential pollutants, while in the second we look for ways to recover and recycle solvents.

  5. Structural higher education reform - design and evaluation: synthesis report

    NARCIS (Netherlands)

    File, Jonathan M.; Huisman, Jeroen; de Boer, Harry F.; Seeber, Marco; Vukasovic, Martina; Westerheijden, Donald F.

    2016-01-01

    This study analyses how different types of system-level (or ‘landscape’) structural reforms in higher education have been designed and implemented in selected higher education systems. In the 12 case studies that form the core of the project, the researchers examine reforms aimed at: - Increasing

  6. AN AUTOMATED ANALYSIS-SYNTHESIS PACKAGE FOR DESIGN ...

    African Journals Online (AJOL)

    continuous beams, plane and space trusses and rigidframes, grids and composite truss- rigid frames. The package ... equilibrium conditions and the general expression that forms the basis for the stiffness method for multiple ... Given preassigned parameters and loading conditions, find the vector of design variables. X = {X, ...

  7. Quinazoline derivatives: synthesis and bioactivities

    OpenAIRE

    Wang, Dan; Gao, Feng

    2013-01-01

    Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. This review summarizes the recent advances in the synthesis and biological activities investigations of quinazoline derivatives. According to the main method the authors adopted in their research design, those synthetic methods were divided into five main classifications, including Aza-reaction, Microwave-assisted reaction, Metal-mediated reac...

  8. A Behavioral Synthesis Frontend to the Haste/TiDE Design Flow

    DEFF Research Database (Denmark)

    Nielsen, Sune Fallgaard; Sparsø, Jens; Jensen, Jonas Braband

    2009-01-01

    This paper presents a complete design tool which performs automatic behavioral synthesis of asynchronous circuits (resource sharing, scheduling and binding). The tool targets a traditional control-datapath-style template architecture. Within the limitations set by this template architecture...... and a controller. The tool may be seen as an add-on to the Haste/TiDE tool flow, and it can be used to automatically optimize parts of a design and to quickly xplore alternative optimizations. The paper outlines the design flow, explains key elements of the design tool, and presents a number of benchmark results....

  9. Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

    Science.gov (United States)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

    The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

  10. Convergent and sequential synthesis designs: implications for conducting and reporting systematic reviews of qualitative and quantitative evidence.

    Science.gov (United States)

    Hong, Quan Nha; Pluye, Pierre; Bujold, Mathieu; Wassef, Maggy

    2017-03-23

    Systematic reviews of qualitative and quantitative evidence can provide a rich understanding of complex phenomena. This type of review is increasingly popular, has been used to provide a landscape of existing knowledge, and addresses the types of questions not usually covered in reviews relying solely on either quantitative or qualitative evidence. Although several typologies of synthesis designs have been developed, none have been tested on a large sample of reviews. The aim of this review of reviews was to identify and develop a typology of synthesis designs and methods that have been used and to propose strategies for synthesizing qualitative and quantitative evidence. A review of systematic reviews combining qualitative and quantitative evidence was performed. Six databases were searched from inception to December 2014. Reviews were included if they were systematic reviews combining qualitative and quantitative evidence. The included reviews were analyzed according to three concepts of synthesis processes: (a) synthesis methods, (b) sequence of data synthesis, and (c) integration of data and synthesis results. A total of 459 reviews were included. The analysis of this literature highlighted a lack of transparency in reporting how evidence was synthesized and a lack of consistency in the terminology used. Two main types of synthesis designs were identified: convergent and sequential synthesis designs. Within the convergent synthesis design, three subtypes were found: (a) data-based convergent synthesis design, where qualitative and quantitative evidence is analyzed together using the same synthesis method, (b) results-based convergent synthesis design, where qualitative and quantitative evidence is analyzed separately using different synthesis methods and results of both syntheses are integrated during a final synthesis, and (c) parallel-results convergent synthesis design consisting of independent syntheses of qualitative and quantitative evidence and an

  11. Design and Synthesis of Novel Discotic Liquid Crystals

    Science.gov (United States)

    Kayal, Himadri Sekhar

    Columnar mesophases of discotic liquid crystals (DLCs) have attracted much attention as organic semiconductors and have been tested as active materials in light-emitting diodes, photovoltaic solar cells, and field-effect transistors. However, devices based on DLCs have shown lower performance than devices based on polymeric and small molecule glass semiconductors, despite their superior charge conducting and advantages self-organizing properties. Most DLCs also require relatively complex processing conditions for the preparation of electronic devices, which is another significant disadvantage. Consequently, new types of DLCs are sought-after to overcome these limitations and described in this thesis are new types of discotic materials and their synthesis. Chapters 2 and 3 describe star-shaped discotic molecules for donor-acceptor columnar structures and as novel flexible core discotic molecules. Presented are the first examples of star-shaped heptamers of donor and acceptor discotic molecules which have six hexaalkoxy triphenylene ligands and a hexaazatriphenylene hexacarboxylate core or a hexaazatriphenylene hexaamide core. The hexaazatriphenylene cores were chosen because of their electron deficient character while the hexaalkoxy triphenylenes are known to be electron rich. Envisioned is the formation of super-columns in which the heptamers stack on top of each other and generate a material with electron acceptor and electron donor channels separated by aliphatic chains. This is an important difference to previously reported donor-acceptor star-shaped structures that were connected via conjugated linkers and do not form separate columnar stacks. Star-shaped DLCs based on small aromatic groups linked together by short flexible spacers may represent a novel type of discotic core structure that does not require peripheral flexible chains. Softening of the core by the spacer group is expected to sufficiently lower melting points and not interfere with the columnar

  12. From the "Modern Synthesis" to cybernetics: Ivan Ivanovich Schmalhausen (1884-1963) and his research program for a synthesis of evolutionary and developmental biology.

    Science.gov (United States)

    Levit, Georgy S; Hossfeld, Uwe; Olsson, Lennart

    2006-03-15

    Ivan I. Schmalhausen was one of the central figures in the Russian development of the "Modern Synthesis" in evolutionary biology. He is widely cited internationally even today. Schmalhausen developed the main principles of his theory facing the danger of death in the totalitarian Soviet Union. His great services to evolutionary and theoretical biology are indisputable. However, the received view of Schmalhausen's contributions to evolutionary biology makes an unbiased reading of his texts difficult. Here we show that taking all of his works into consideration (including those only available in Russian) paints a much more dynamic and exciting picture of what he tried to achieve. Schmalhausen pioneered the integration of a developmental perspective into evolutionary thinking. A main tool for achieving this was his approach to living objects as complex multi-level self-regulating systems. Schmalhausen put enormous effort into bringing this idea into fruition during the final stages of his career by combining evolutionary theory with cybernetics. His results and ideas remain thought-provoking, and his texts are of more than just historical interest. Copyright 2006 Wiley-Liss, Inc.

  13. Design, Synthesis and Antifungal Activity of Psoralen Derivatives

    Directory of Open Access Journals (Sweden)

    Xiang Yu

    2017-10-01

    Full Text Available A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by 1H-NMR spectroscopy, high resolution mass spectra (EI-MS, IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Botrytis cinerea, Alternaria solani, Gibberella zeae, Cucumber anthrax, and Alternaria leaf spot at 100 μg/mL, and some of the designed compounds exhibited potential antifungal activities. Compound 3a (67.9% exhibited higher activity than the control Osthole (66.1% against Botrytis cinerea. Furthermore, compound 4b (62.4% represented equivalent antifungal activity as Osthole (69.5% against Rhizoctonia solani. The structure-activity relationship (SAR study demonstrates that linear furanocoumarin moiety has an important effect on the antifungal activity, promoting the idea of the coumarin ring as a framework that might be exploited in the future.

  14. Building biological foundries for next-generation synthetic biology.

    Science.gov (United States)

    Chao, Ran; Yuan, YongBo; Zhao, HuiMin

    2015-07-01

    Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.

  15. Synthesis and biological evaluation of novel conjugates of camptothecin and 5-Flurouracil as cytotoxic agents

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Liu, E-mail: yqliu@lzu.edu.c [Lanzhou Jiaotong University (China). Environmental and Municipal Engineering School; Chun-Yan Zhaob; Ying-Qian Liu [Lanzhou University (China). School of Pharmacy

    2011-07-01

    A series of novel conjugates of camptothecin and 5-fluorouracil were first synthesized and their cytotoxic activities against two human tumor cell lines (SGC-7901 and A-549) as well as in vitro pharmacokinetic determination of lactone stability were studied. Among these compounds, most tested conjugates showed comparable or superior cytotoxic activities to 2, but less potent compared with 1. Particularly, conjugates 10b and 10d were highly active against A-549 with IC{sub 50} values of 0.45 and 0.38 {mu}mol L{sup -1}, respectively. Also, the in vitro pharmacokinetic determination of lactone levels of representative compound 10b showed that the biological life span of their lactone forms in human and mouse plasma significantly increased compared with their mother compound 1. Quantitative structure-activity relationship (QSAR) method was then applied for developing linear models to predict the cytotoxic activities of these derivatives that have not yet been synthesized or experimentally tested. In addition, molecular docking was used to clarify the binding mode of these derivatives to human DNA topoisomerase I. The important hydrogen-bonding interactions were observed between these derivatives and their receptor. The results from molecular modeling and QSAR study can guide the design of novel conjugates with higher antitumor activity. (author)

  16. Comparing novelty of designs from biological-inspiration with those from brainstorming

    DEFF Research Database (Denmark)

    Keshwani, Sonal; Lenau, Torben Anker; Ahmed-Kristensen, Saeema

    2017-01-01

    This research aims to understand the significance of biological-analogies in fostering novelty by comparing biological-analogies with other design methods for idea generation. Among other design methods, brainstorming was chosen here as benchmark. Four studies were conducted to compare: (i......) the levels of abstraction at which concepts were ideated using biological inspiration (represented using biocards) with that using traditional brainstorming; and (ii) the novelty of concepts produced by using these two design methods. Concepts produced in these studies were evaluated for levels...... of abstraction at which they were ideated, average novelty, and proportion of high-novelty concepts. Results suggest that concepts generated using biocards were ideated at higher abstraction levels than those using brainstorming, but neither were at the highest abstraction levels. The average novelty of concepts...

  17. Radiolabelled neurotensin analogues. I. Solid phase synthesis and biological characterization of [Trp11]-neurotensin precursor of an ionidated ligand

    International Nuclear Information System (INIS)

    Labbe-Jullie, C.; Granier, C.; Van Rietschoten, J.; Kitabgi, P.; Vincent, J.P.

    1983-01-01

    In order to generate highly labelled neurotensin analogues, synthesis has been performed of two types of precursors, one for iodination and one for tritiation. Iodination of native neurotensin occurs on both tyrosines in position 3 and 11 and thus affects greatly its binding capacities. Synthesis and chemical characterization of [Trp 11 ]-neurotensin are described which can be iodinated without loss of activity. Synthesis was by solid phase procedure on an experimental support, Pab-resin, α-(4-chloromethylphenylacetamido)-benzyl copoly (styrene 1 per cent divinylbenzene). The homogeneity of [Trp 11 ]-neurotensin was assessed by amino acid analysis, high voltage paper electrophoresis and high pressure liquid chromatography. Iodination by the lactoperoxydase method gave iodo-[Trp 11 ]-neurotensin iodinated on the Tyr 3 . Compared to neurotensin, potency of [Trp 11 ]-neurotensin and of iodo-[Trp 11 ]-neurotensin in competitive inhibition of tritiated neurotensin binding to rat brain synaptic membranes was respectively 93 per cent and 80 per cent, but in the biological test on the contractility of isolated longitudinal smooth muscle strips of guinea pig the relative activity for the two analogues was of 10 per cent [fr

  18. From bricolage to BioBricks™: Synthetic biology and rational design.

    Science.gov (United States)

    Lewens, Tim

    2013-12-01

    Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Metal Organic Frameworks: Explorations and Design Strategies for MOF Synthesis

    KAUST Repository

    AbdulHalim, Rasha

    2016-11-27

    Metal-Organic Frameworks (MOFs) represent an emerging new class of functional crystalline solid-state materials. In the early discovery of this now rapidly growing class of materials significant challenges were often encountered. However, MOFs today, with its vast structural modularity, reflected by the huge library of the available chemical building blocks, and exceptional controlled porosity, stand as the most promising candidate to address many of the overbearing societal challenges pertaining to energy and environmental sustainability. A variety of design strategies have been enumerated in the literature which rely on the use of predesigned building blocks paving the way towards potentially more predictable structures. The two major design strategies presented in this work are the molecular building block (MBB) and supermolecular building block (SBB) -based approaches for the rationale assembly of functional MOF materials with the desired structural features. In this context, we targeted two highly connected MOF platforms, namely rht-MOF and shp-MOF. These two MOF platforms are classified based on their topology, defined as the underlying connectivity of their respective net, as edge transitive binodal nets; shp being (4,12)-connected net and rht being (3,24)-connected net. These highly connected nets were deliberately targeted due to the limited number of possible nets for connecting their associated basic building units. Two highly porous materials were designed and successfully constructed; namely Y-shp-MOF-5 and rht-MOF-10. The Y-shp-MOF-5 features a phenomenal water stability with an exquisite behavior when exposed to water, positioning this microporous material as the best adsorbent for moisture control applications. The shp-MOF platform proved to be modular to ligand functionalization and thus imparting significant behavioral changes when hydrophilic and hydrophobic functionalized ligands were introduced on the resultant MOF. On the other hand, rht

  20. Design, Synthesis and Insecticidal Activity of Novel Phenylurea Derivatives

    Directory of Open Access Journals (Sweden)

    Jialong Sun

    2015-03-01

    Full Text Available 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.

  1. The Synthesis Approach to Analysing Educational Design Dataset: Application of Three Scaffolds to a Learning by Design Task for Postgraduate Education Students

    Science.gov (United States)

    Thompson, Kate; Carvalho, Lucila; Aditomo, Anindito; Dimitriadis, Yannis; Dyke, Gregory; Evans, Michael A.; Khosronejad, Maryam; Martinez-Maldonado, Roberto; Reimann, Peter; Wardak, Dewa

    2015-01-01

    The aims of the Synthesis and Scaffolding Project were to understand: the role of specific scaffolds in relation to the activity of learners, and the activity of learners during a collaborative design task from multiple perspectives, through the collection and analysis of multiple streams of data and the adoption of a synthesis approach to the…

  2. Synthesis and biological evaluation of new salicylate macrolactones from anacardic acids

    International Nuclear Information System (INIS)

    Logrado, Lucio P.L.; Santos, Maria Lucilia dos; Silveira, Damaris; Romeiro, Luiz A.S.; Moraes, Manoel O. de; Cavalcanti, Bruno C.; Costa-Lotufo, Leticia V.; Pessoa, Claudia do O

    2005-01-01

    In connection with our ongoing investigation in the search for new bioactive compounds using non-isoprenoid phenolic lipids from Anacardium occidentale as starting material, we describe the synthesis and cytotoxicity screening of some novel salicylate macrolactones prepared from anacardic acids, the major constituents of natural cashew nut-shell liquid (CNSL). (author)

  3. Synthesis and biological evaluation of 3,6-dialkylsubstituted-[1,2,4 ...

    Indian Academy of Sciences (India)

    VIJAYENDAR VENEPALLY

    2018-02-16

    Feb 16, 2018 ... A series of 3,6-dialkyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole (10) analogues were ... Cytotoxicity data revealed that most of the tested compounds revealed cytotoxic ...... jary B 2003 Synthesis characterization and anticancer.

  4. Materials-by-design: computation, synthesis, and characterization from atoms to structures

    Science.gov (United States)

    Yeo, Jingjie; Jung, Gang Seob; Martín-Martínez, Francisco J.; Ling, Shengjie; Gu, Grace X.; Qin, Zhao; Buehler, Markus J.

    2018-05-01

    In the 50 years that succeeded Richard Feynman’s exposition of the idea that there is ‘plenty of room at the bottom’ for manipulating individual atoms for the synthesis and manufacturing processing of materials, the materials-by-design paradigm is being developed gradually through synergistic integration of experimental material synthesis and characterization with predictive computational modeling and optimization. This paper reviews how this paradigm creates the possibility to develop materials according to specific, rational designs from the molecular to the macroscopic scale. We discuss promising techniques in experimental small-scale material synthesis and large-scale fabrication methods to manipulate atomistic or macroscale structures, which can be designed by computational modeling. These include recombinant protein technology to produce peptides and proteins with tailored sequences encoded by recombinant DNA, self-assembly processes induced by conformational transition of proteins, additive manufacturing for designing complex structures, and qualitative and quantitative characterization of materials at different length scales. We describe important material characterization techniques using numerous methods of spectroscopy and microscopy. We detail numerous multi-scale computational modeling techniques that complements these experimental techniques: DFT at the atomistic scale; fully atomistic and coarse-grain molecular dynamics at the molecular to mesoscale; continuum modeling at the macroscale. Additionally, we present case studies that utilize experimental and computational approaches in an integrated manner to broaden our understanding of the properties of two-dimensional materials and materials based on silk and silk-elastin-like proteins.

  5. Design and Synthesis of Archaea-Inspired Tetraether Lipids

    Science.gov (United States)

    Koyanagi, Takaoki

    Maintaining the correct ion homeostasis across membranes is a major challenge in both nature and artificial systems. Archaea, have evolved to solve membrane permeability problems to survive in extreme environments by incorporating unique structural features found in their lipid. Specifically, inclusion of phytanyl side chains, ether glycerol linkages, tethering of lipids, cycloalkanes, and different polar lipid headgroups into their lipid membrane are believed to contribute to membrane stability. We sought to gain a better understanding of the functional benefits attributed to these structural features to membrane stability to design a new class of synthetic Archaea inspired lipid membranes that can be used to overcome limitations (i.e. unstable in serum environment, high background leakage, and prone to hydrolysis) found in current lipid based technologies. Leakage experiments revealed liposomes made from GMGTPC (glycerol monoalkyl glycerol tetraether lipid with phosphatidylcholine headgroup) demonstrated a two order magnitude reduction in membrane leakage to small ions when compared with liposomes made from EggPC. Additionally, liposomes composed of GMGTPC-CH (cyclohexane integrated) lipid displayed an additional 40% decrease in membrane leakage to small ions when compared with liposomes made from GMGTPC lipids. Furthermore, leakage experiments revealed a higher degree of tolerance to headgroup modifications to membrane leakage for liposomes made from GMGT lipid analogs when compared with liposomes made from POPC. After designing an optimal tetraether lipid scaffold that incorporates key Archaeal structural features for membrane leakage, we explored to integrate strategies employed by eukaryotes to improve membrane properties (i.e. addition of cholesterol). Liposomes made from the hybrid lipid, GcGTPC-CH, displayed a five-fold decrease in membrane leakage when compared with liposomes made from GMGTPC-CH, while maintaining functional membrane properties similar to

  6. Simulation, design and proof-of-concept of a two-stage continuous hydrothermal flow synthesis reactor for synthesis of functionalized nano-sized inorganic composite materials

    DEFF Research Database (Denmark)

    Zielke, Philipp; Xu, Yu; Simonsen, Søren Bredmose

    2016-01-01

    Computational fluid dynamics simulations were employed to evaluate several mixer geometries for a novel two-stage continuous hydrothermal flow synthesis reactor. The addition of a second stage holds the promise of allowing the synthesis of functionalized nano-materials as for example core-shell...... or decorated particles. Based on the simulation results, a reactor system employing a confined jet mixer in the first and a counter-flow mixer in the second stage was designed and built. The two-stage functionality and synthesis capacity is shown on the example of single- and two-stage syntheses of pure...... and mixed-phase NiO and YSZ particles....

  7. Synthesis and biological evaluation of structurally simplified noscapine analogues as microtubule binding agents

    Czech Academy of Sciences Publication Activity Database

    Ghaly, P.E.; Churchill, C.D.M.; Abou El-Magd, R.M.; Hájková, Zuzana; Dráber, Pavel; West, F.G.; Tuszyński, J.A.

    2017-01-01

    Roč. 95, č. 6 (2017), s. 649-655 ISSN 0008-4042 R&D Projects: GA ČR GA15-22194S Institutional support: RVO:68378050 Keywords : noscapine * microtubule * tubulin * cytotoxicity * microtubule dynamics * docking Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 1.080, year: 2016

  8. Design, Synthesis and Antitumor Evaluation of Novel Pyrazolopyrimidines and Pyrazoloquinazolines

    Directory of Open Access Journals (Sweden)

    Mohamed El-Naggar

    2018-05-01

    Full Text Available A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a–u and N-aryl-pyrazolo[1,5-a]quinazolines 25a–c were designed and synthesized via the reaction of 5-aminopyrazoles 11a–c with enaminones 12a–g or 19, respectively. The new compounds were screened for their in vitro antitumor activity toward liver (HepG-2 and breast (MCF-7 human cancer cells using 3-[4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide MTT assay. From the results, it was found that all compounds showed dose-dependent cytotoxic activities against both HepG-2 and MCF-7 cells. Two compounds 18o and 18a were selected for further investigations. Cell cycle analysis of liver (HepG-2 cells treated with 18o and breast (MCF-7 cells treated with 18a showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining.

  9. Design, Synthesis and Fungicidal Activities of Some Novel Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Xue-Ru Liu

    2014-09-01

    Full Text Available In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS, and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank Donk, Fusarium oxysporum (S-chl f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27–32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.

  10. Design, synthesis and fungicidal evaluation of novel pyraclostrobin analogues.

    Science.gov (United States)

    Wang, Lili; Zhao, Shuangshuang; Kong, Xiaotian; Cao, Lingling; Tian, Sheng; Ye, Yonghao; Qiao, Chunhua

    2018-02-15

    A series of novel pyraclostrobin derivatives were designed and prepared as antifungal agents. Their antifungal activities were tested in vitro with five important phytopathogenic fungi, namely, Batrylis cinerea, Phytophthora capsici, Fusarium sulphureum, Gloeosporium pestis and Sclerotinia sclerotiorum using the mycelium growth inhibition method. Among these compounds, 5s displayed IC 50 value of 0.57 μg/mL against Batrylis cinerea and 5k-II displayed IC 50 value of 0.43 μg/mL against Sclerotinia sclerotiorum, which were close to that of the positive control pyraclostrobin (0.18 μg/mL and 0.15 μg/mL). Other compounds 5f, 5k-II, 5j, 5m and 5s also exhibited strong antifungal activity. Further enzymatic assay demonstrated compound 5s inhibited porcine bc 1 complex with IC 50 value of 0.95 μM. The statistical results from an integrated computational pipeline demonstrated the predicted total binding free energy for compound 5s is the highest. Consequently, compound 5s with the biphenyl-4-methoxyl side chain could serve as a new motif as inhibitors of bc 1 complex and deserve to be further investigated. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Design and synthesis of a novel cationic thiolated polymer.

    Science.gov (United States)

    Rahmat, Deni; Sakloetsakun, Duangkamon; Shahnaz, Gul; Perera, Glen; Kaindl, Reinhard; Bernkop-Schnürch, Andreas

    2011-06-15

    The purpose of this study was to design and characterize a novel cationic thiolated polymer. In this regard a hydroxyethylcellulose-cysteamine conjugate (HEC-cysteamine) was synthesized. Oxidative ring opening with periodate and reductive amination with cysteamine were performed in order to immobilize free thiol groups to HEC. The resulting HEC-cysteamine displayed 2035 ± 162 μmol immobilized free thiol groups and 185 ± 64 μmol disulfide bonds per gram of polymer being soluble in both acidic and basic conditions. Unlike the unmodified HEC, in case of HEC-cysteamine, a three-fold increase in the viscosity was observed when equal volumes of the polymer were mixed with mucin solution. Tablets based on HEC-cysteamine remained attached on freshly excised porcine mucosa for 8 0h and displayed increased disintegration time of 2h. Swelling behavior of HEC-cysteamine tablets in 0.1M phosphate buffer pH 6.8 indicated swelling ratio of 19 within 8h. In contrast, tablets comprising unmodified HEC detached from the mucosa within few seconds and immediately disintegrated. In addition, they did not exhibit swelling behavior. The transport of rhodamine 123 across freshly excised rat intestine enhanced by a value of approximately 1.6-fold (p-value = 0.0024) in the presence of 0.5% (m/v) HEC-cysteamine as compared to buffer control. Result from cytotoxicity test of HEC-cysteamine applied to Caco-2 cells in concentration of 0.5% (m/v) revealed 82.4 ± 4.60% cell viability. According to these results, HEC-cysteamine seems to be a promising polymer for various pharmaceutical applications especially for intestinal drug delivery. Copyright © 2011. Published by Elsevier B.V.

  12. Application of CAPEC Lipid Property Databases in the Synthesis and Design of Biorefinery Networks

    DEFF Research Database (Denmark)

    Bertran, Maria-Ona; Cunico, Larissa; Gani, Rafiqul

    Petroleum is currently the primary raw material for the production of fuels and chemicals. Consequently, our society is highly dependent on fossil non-renewable resources. However, renewable raw materials are recently receiving increasing interest for the production of chemicals and fuels, so a n...... of biorefinery networks. The objective of this work is to show the application of databases of physical and thermodynamic properties of lipid components to the synthesis and design of biorefinery networks.......]. The wide variety and complex nature of components in biorefineries poses a challenge with respect to the synthesis and design of these types of processes. Whereas physical and thermodynamic property data or models for petroleum-based processes are widely available, most data and models for biobased...

  13. Fault tree synthesis for software design analysis of PLC based safety-critical systems

    International Nuclear Information System (INIS)

    Koo, S. R.; Cho, C. H.; Seong, P. H.

    2006-01-01

    As a software verification and validation should be performed for the development of PLC based safety-critical systems, a software safety analysis is also considered in line with entire software life cycle. In this paper, we propose a technique of software safety analysis in the design phase. Among various software hazard analysis techniques, fault tree analysis is most widely used for the safety analysis of nuclear power plant systems. Fault tree analysis also has the most intuitive notation and makes both qualitative and quantitative analyses possible. To analyze the design phase more effectively, we propose a technique of fault tree synthesis, along with a universal fault tree template for the architecture modules of nuclear software. Consequently, we can analyze the safety of software on the basis of fault tree synthesis. (authors)

  14. Traditional Versus Online Biology Courses: Connecting Course Design and Student Learning in an Online Setting.

    Science.gov (United States)

    Biel, Rachel; Brame, Cynthia J

    2016-12-01

    Online courses are a large and growing part of the undergraduate education landscape, but many biology instructors are skeptical about the effectiveness of online instruction. We reviewed studies comparing the effectiveness of online and face-to-face (F2F) undergraduate biology courses. Five studies compared student performance in multiple course sections at community colleges, while eight were smaller scale and compared student performance in particular biology courses at a variety of types of institutions. Of the larger-scale studies, two found that students in F2F sections outperformed students in online sections, and three found no significant difference; it should be noted, however, that these studies reported little information about course design. Of the eight smaller scale studies, six found no significant difference in student performance between the F2F and online sections, while two found that the online sections outperformed the F2F sections. In alignment with general findings about online teaching and learning, these results suggest that well-designed online biology courses can be effective at promoting student learning. Three recommendations for effective online instruction in biology are given: the inclusion of an online orientation to acclimate students to the online classroom; student-instructor and student-student interactions facilitated through synchronous and asynchronous communication; and elements that prompt student reflection and self-assessment. We conclude that well-designed online biology courses can be as effective as their traditional counterparts, but that more research is needed to elucidate specific course elements and structures that can maximize online students' learning of key biology skills and concepts.

  15. Traditional Versus Online Biology Courses: Connecting Course Design and Student Learning in an Online Setting

    Directory of Open Access Journals (Sweden)

    Rachel Biel

    2016-12-01

    Full Text Available Online courses are a large and growing part of the undergraduate education landscape, but many biology instructors are skeptical about the effectiveness of online instruction. We reviewed studies comparing the effectiveness of online and face-to-face (F2F undergraduate biology courses. Five studies compared student performance in multiple course sections at community colleges, while eight were smaller scale and compared student performance in particular biology courses at a variety of types of institutions. Of the larger-scale studies, two found that students in F2F sections outperformed students in online sections, and three found no significant difference; it should be noted, however, that these studies reported little information about course design. Of the eight smaller scale studies, six found no significant difference in student performance between the F2F and online sections, while two found that the online sections outperformed the F2F sections. In alignment with general findings about online teaching and learning, these results suggest that well-designed online biology courses can be effective at promoting student learning. Three recommendations for effective online instruction in biology are given: the inclusion of an online orientation to acclimate students to the online classroom; student-instructor and student-student interactions facilitated through synchronous and asynchronous communication; and elements that prompt student reflection and self-assessment. We conclude that well-designed online biology courses can be as effective as their traditional counterparts, but that more research is needed to elucidate specific course elements and structures that can maximize online students’ learning of key biology skills and concepts.

  16. Development of biological criteria for the design of advanced hydropower turbines

    Energy Technology Data Exchange (ETDEWEB)

    Cada, Glenn F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Coutant, Charles C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Whitney, Richard R. [Leavenworth, WA (United States)

    1997-03-01

    A review of the literature related to turbine-passage injury mechanisms suggests the following biological criteria should be considered in the design of new turbines: (1) pressure; (2) cavitation; (3) shear and turbulence; and (4) mechanical injury. Based on the study’s review of fish behavior in relation to hydropower facilities, it provides a number of recommendations to guide both turbine design and additional research.

  17. Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

    Directory of Open Access Journals (Sweden)

    Mathieu L. Lepage

    2015-05-01

    Full Text Available The synthesis and photophysical properties of the first examples of iminosugar clusters based on a BODIPY or a pyrene core are reported. The tri- and tetravalent systems designed as molecular probes and synthesized by way of Cu(I-catalysed azide–alkyne cycloadditions are fluorescent analogues of potent pharmacological chaperones/correctors recently reported in the field of Gaucher disease and cystic fibrosis, two rare genetic diseases caused by protein misfolding.

  18. Designing and evaluating a context-based lesson sequence promoting conceptual coherence in biology

    NARCIS (Netherlands)

    Ummels, M. H J; Kamp, M. J A; De Kroon, H.; Boersma, K. Th|info:eu-repo/dai/nl/073043141

    2015-01-01

    Context-based education, in which students deal with biological concepts in a meaningful way, is showing promise in promoting the development of students conceptual coherence. However, literature gives little guidance about how this kind of education should be designed. Therefore, our study aims at

  19. Synthesis and biology of cyclic imine toxins, an emerging class of potent, globally distributed marine toxins.

    Science.gov (United States)

    Stivala, Craig E; Benoit, Evelyne; Aráoz, Rómulo; Servent, Denis; Novikov, Alexei; Molgó, Jordi; Zakarian, Armen

    2015-03-01

    From a small group of exotic compounds isolated only two decades ago, Cyclic Imine (CI) toxins have become a major class of marine toxins with global distribution. Their distinct chemical structure, biological mechanism of action, and intricate chemistry ensures that CI toxins will continue to be the subject of fascinating fundamental studies in the broad fields of chemistry, chemical biology, and toxicology. The worldwide occurrence of potent CI toxins in marine environments, their accumulation in shellfish, and chemical stability are important considerations in assessing risk factors for human health. This review article aims to provide an account of chemistry, biology, and toxicology of CI toxins from their discovery to the present day.

  20. Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK.

    Directory of Open Access Journals (Sweden)

    Mike Bührmann

    Full Text Available In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography.

  1. Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

    Directory of Open Access Journals (Sweden)

    Igor O. Shmarakov

    2014-10-01

    Full Text Available Aiming to reduce the potential in vivo hepato-and nephrotoxicity of Ag/Au bimetallic nanoparticles (NPs stabilized by sodium dodecyl sulphate (SDS, an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp as a reducing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5–15 nm sized were able to form stable aggregates with an average size of 370–450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical parameters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application.

  2. Microfluidic Synthesis and Biological Evaluation of Photothermal Biodegradable Copper Sulfide Nanoparticles.

    Science.gov (United States)

    Ortiz de Solorzano, Isabel; Prieto, Martín; Mendoza, Gracia; Alejo, Teresa; Irusta, Silvia; Sebastian, Victor; Arruebo, Manuel

    2016-08-24

    The continuous synthesis of biodegradable photothermal copper sulfide nanoparticles has been carried out with the aid of a microfluidic platform. A comparative physicochemical characterization of the resulting products from the microreactor and from a conventional batch reactor has been performed. The microreactor is able to operate in a continuous manner and with a 4-fold reduction in the synthesis times compared to that of the conventional batch reactor producing nanoparticles with the same physicochemical requirements. Biodegradation subproducts obtained under simulated physiological conditions have been identified, and a complete cytotoxicological analysis on different cell lines was performed. The photothermal effect of those nanomaterials has been demonstrated in vitro as well as their ability to generate reactive oxygen species.

  3. Synthesis of novel aryl brassinosteroids through alkene cross-metathesis and preliminary biological study

    Czech Academy of Sciences Publication Activity Database

    Kořínková, Petra; Bazgier, V.; Oklešťková, Jana; Rárová, L.; Strnad, Miroslav; Kvasnica, Miroslav

    2017-01-01

    Roč. 127, NOV (2017), s. 46-55 ISSN 0039-128X R&D Projects: GA ČR GJ15-08202Y; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Brassinosteroids * BRI1 receptor kinase * Cross-metathesis * Molecular docking * Organic synthesis * Plant bioassays Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.282, year: 2016

  4. Some chemical synthesis of 14C labelled compounds of pharmaceutical or biological interest

    International Nuclear Information System (INIS)

    Pichat, I.; Baret, C.; Audinot, M.; Herbert, M.; Lambin, J.

    1955-01-01

    The recent discovery of the tuberculostatic properties of the hydrazide of isonicotinic acid (so-called 'Isoniazide', 'Rimifon') has raised considerably its interest, as for metabolic studies which it is more interesting to have it labelled with 14 C. We describe in this report the chemical synthesis of 14 C carboxyl labelled isoniazide which were done in the pyridine ring to highlight his metabolic function on the Koch's bacillus. (M.B.)

  5. Some chemical synthesis of {sup 14}C labelled compounds of pharmaceutical or biological interest

    Energy Technology Data Exchange (ETDEWEB)

    Pichat, I; Baret, C; Audinot, M; Herbert, M; Lambin, J [Commissariat a l' Energie Atomique, Lab. du Fort de Chatillon, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1955-07-01

    The recent discovery of the tuberculostatic properties of the hydrazide of isonicotinic acid (so-called 'Isoniazide', 'Rimifon') has raised considerably its interest, as for metabolic studies which it is more interesting to have it labelled with {sup 14}C. We describe in this report the chemical synthesis of {sup 14}C carboxyl labelled isoniazide which were done in the pyridine ring to highlight his metabolic function on the Koch's bacillus. (M.B.)

  6. Novel modified purine bases and nucleosides: new methodologies of synthesis and biological activity

    Czech Academy of Sciences Publication Activity Database

    Hocek, Michal

    -, č. 49 (2005), s. 29-30 ISSN 0261-3166. [International Symposium on Nucleic Acids Chemistry /4./. Fukuoka, 20.09.2005-22.09.2005] R&D Projects: GA ČR(CZ) GA203/03/0035; GA MŠk(CZ) 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : purines * nucleosides * synthesis Subject RIV: CC - Organic Chemistry

  7. Dimeric ligands for GPCRs involved in human reproduction : synthesis and biological evaluation

    NARCIS (Netherlands)

    Bonger, Kimberly Michelle

    2008-01-01

    Dimeric ligands for G-protein coupled receptors that are involved in human reproduction, namely the gonadotropin releasing hormone receptor, the luteinizing hormone receptor and the follicle-stimulating hormone receptor, were synthesized and biologically evaluated.

  8. Work Design Influences: A Synthesis of Multi-Level Factors that Affect The Design of Work

    OpenAIRE

    Parker, Sharon; Van den Broeck, Anja; Holman, David

    2017-01-01

    High quality work design is a key determinant of employee well-being, positive work attitudes, and job/organizational performance. Yet many job incumbents continue to experience deskilled and demotivating work. We argue that there is a need to understand better where work designs come from. We review research that investigates the factors that influence work design, noting that this research is only a small fragment of the work design literature. The research base is also rather disparate, sp...

  9. Mixed-Methods Design in Biology Education Research: Approach and Uses

    Science.gov (United States)

    Warfa, Abdi-Rizak M.

    2016-01-01

    Educational research often requires mixing different research methodologies to strengthen findings, better contextualize or explain results, or minimize the weaknesses of a single method. This article provides practical guidelines on how to conduct such research in biology education, with a focus on mixed-methods research (MMR) that uses both quantitative and qualitative inquiries. Specifically, the paper provides an overview of mixed-methods design typologies most relevant in biology education research. It also discusses common methodological issues that may arise in mixed-methods studies and ways to address them. The paper concludes with recommendations on how to report and write about MMR. PMID:27856556

  10. Designing a 'neotissue' using the principles of biology, chemistry and engineering.

    Science.gov (United States)

    Nannaparaju, Madhusudhan; Oragui, Emeka; Khan, Wasim S

    2012-01-01

    The traditional methods of treating musculoskeletal injuries and disorders are not completely effective and have several limitations. Tissue engineering involves using the principles of biology, chemistry and engineering to design a 'neotissue' that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. In this review we provide an overview of the biology of common musculoskeletal tissue and discuss their common pathologies. We also describe the commonly used stem cells, scaffolds and bioreactors and evaluate their role in issue engineering.

  11. Hardware synthesis from DDL. [Digital Design Language for computer aided design and test of LSI

    Science.gov (United States)

    Shah, A. M.; Shiva, S. G.

    1981-01-01

    The details of the digital systems can be conveniently input into the design automation system by means of Hardware Description Languages (HDL). The Computer Aided Design and Test (CADAT) system at NASA MSFC is used for the LSI design. The Digital Design Language (DDL) has been selected as HDL for the CADAT System. DDL translator output can be used for the hardware implementation of the digital design. This paper addresses problems of selecting the standard cells from the CADAT standard cell library to realize the logic implied by the DDL description of the system.

  12. A novel gait-based synthesis procedure for the design of 4-bar exoskeleton with natural trajectories

    Directory of Open Access Journals (Sweden)

    Ramanpreet Singh

    2018-01-01

    The Translational Potential of this Article: Many hospitals and individuals have used the immobile and portable rehabilitation devices. These devices involve mechanisms, and the design of mechanism plays a vital role in the functioning of these devices; therefore, we have developed a new synthesis procedure for the design of the mechanism. Besides synthesis procedure, a mechanism is developed that can be used in the rehabilitation devices, bipeds, exoskeletons, etc., to benefit the society.

  13. Cu(II AND Zn(II COMPLEX COMPOUNDS WITH BIGUANIDES AROMATIC DERIVATIVES. SYNTHESIS, CHARACTERIZATION, BIOLOGICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Ticuţa Negreanu-Pîrjol

    2011-05-01

    Full Text Available In this paper we report the synthesis, physical-chemical characterization and antimicrobial activity of some new complex compounds of hetero-aromatic biguanides ligands, chlorhexidine base (CHX and chlorhexidine diacetate (CHXac2 with metallic ions Cu(II and Zn(II, in different molar ratio. The synthesized complexes were characterized by elemental chemical analysis and differential thermal analysis. The stereochemistry of the metallic ions was determined by infrared spectra, UV-Vis, EPR spectroscopy and magnetic susceptibility in the aim to establish the complexes structures. The biological activity of the new complex compounds was identified in solid technique by measuring minimum inhibition diameter of bacterial and fungal culture, against three standard pathogen strains, Escherichia coli ATCC 25922, Staphilococcus aureus ATCC 25923 and Candida albicans ATCC 10231. The results show an increased specific antimicrobial activity for the complexes chlorhexidine:Cu(II 1:1 and 1:2 compared with the one of the Zn(II complexes.

  14. Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.

    Science.gov (United States)

    Menezes, Carla M S; Rivera, Gildardo; Alves, Marina A; do Amaral, Daniel N; Thibaut, Jean Pierre B; Noël, François; Barreiro, Eliezer J; Lima, Lídia M

    2012-06-01

    The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. © 2012 John Wiley & Sons A/S.

  15. Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Margherita De Rosa

    2015-12-01

    Full Text Available The synthesis and the biological activity of novel semi-synthetic β-lactam compounds containing an azetidinone moiety joined to the amino-nitrogen of the (+-6-aminopenicillanic acid (6-APA as new antibacterial agents is reported. The synthesized compounds were screened for their in vitro antimicrobial activity against a panel of Gram positive and Gram negative pathogens and environmental bacteria. Tested compounds displayed good antimicrobial activity against all tested Gram positive bacteria and for Staphylococcus aureus and Staphylococcus epidermidis antimicrobial activity resulted higher than that of the reference antibiotic. Additionally, in vitro cytotoxic screening was also carried out indicating that the compounds do not cause a cell vitality reduction effective at concentration next to and above those shown to be antimicrobial.

  16. Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation.

    Science.gov (United States)

    De Rosa, Margherita; Vigliotta, Giovanni; Palma, Giuseppe; Saturnino, Carmela; Soriente, Annunziata

    2015-12-10

    The synthesis and the biological activity of novel semi-synthetic β-lactam compounds containing an azetidinone moiety joined to the amino-nitrogen of the (+)-6-aminopenicillanic acid (6-APA) as new antibacterial agents is reported. The synthesized compounds were screened for their in vitro antimicrobial activity against a panel of Gram positive and Gram negative pathogens and environmental bacteria. Tested compounds displayed good antimicrobial activity against all tested Gram positive bacteria and for Staphylococcus aureus and Staphylococcus epidermidis antimicrobial activity resulted higher than that of the reference antibiotic. Additionally, in vitro cytotoxic screening was also carried out indicating that the compounds do not cause a cell vitality reduction effective at concentration next to and above those shown to be antimicrobial.

  17. Phase-assisted synthesis and DNA unpacking evaluation of biologically inspired metallo nanocomplexes using peptide as unique building block.

    Science.gov (United States)

    Raman, N; Sudharsan, S

    2011-12-01

    The goal of nanomaterials' surface modification using a biomaterial is to preserve the materials' bulk properties while modifying only their surface to possess desired recognition and specificity. Here, we have developed a phase-assisted, modified Brust-Schiffrin methodological synthesis of metallo nanocomplexes anchored by a peptide, N,N'-(1,3-propylene)-bis-hippuricamide. The spectral, thermal and morphological characterizations assure the formation of nanocomplexes. Therapeutic behavior of all the nanocomplexes has been well sighted by evaluating their DNA unpacking skills. In addition, we demonstrate their biological inspiration by targeting few bacterial and fungal strains. The in vitro antimicrobial investigation reports that all the nanocomplexes disrupt microbial cell walls/membranes efficiently and inhibit the growth of microbes. These sorts of nanocomplexes synthesized in large quantities and at low cost, deliver versatile biomedical applications, and can be used to treat various diseases which may often cause high mortality. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Fast Synthesis of Gibbsite Nanoplates and Process Optimization using Box-Behnken Experimental Design

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xin; Zhang, Xianwen; Graham, Trenton R.; Pearce, Carolyn I.; Mehdi, Beata L.; N' Diaye, Alpha T.; Kerisit, Sebastien N.; Browning, Nigel D.; Clark, Sue B.; Rosso, Kevin M.

    2017-10-26

    Developing the ability to synthesize compositionally and morphologically well-defined gibbsite particles at the nanoscale with high yield is an ongoing need that has not yet achieved the level of rational design. Here we report optimization of a clean inorganic synthesis route based on statistical experimental design examining the influence of Al(OH)3 gel precursor concentration, pH, and aging time at temperature. At 80 oC, the optimum synthesis conditions of gel concentration at 0.5 M, pH at 9.2, and time at 72 h maximized the reaction yield up to ~87%. The resulting gibbsite product is composed of highly uniform euhedral hexagonal nanoplates within a basal plane diameter range of 200-400 nm. The independent roles of key system variables in the growth mechanism are considered. On the basis of these optimized experimental conditions, the synthesis procedure, which is both cost-effective and environmentally friendly, has the potential for mass production scale-up of high quality gibbsite material for various fundamental research and industrial applications.

  19. Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents.

    Science.gov (United States)

    Mabkhot, Yahia N; Alharbi, Mohammed M; Al-Showiman, Salim S; Ghabbour, Hazem A; Kheder, Nabila A; Soliman, Saied M; Frey, Wolfgang

    2018-05-11

    The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

  20. Synthesis of biotinyl derivatives of peptide hormones and other biological materials

    International Nuclear Information System (INIS)

    Finn, F.M.; Hofmann, K.H.

    1985-01-01

    Methods for the preparation of biotinylated ligands for the avidin-biotin system are described. Also described are procedures for modifying and labelling avidin and for assessing the rate of dissociation of biotin derivatives from avidin. The most widely used procedure for introducing biotin into other molecules involves acylation with N-hydroxysuccinimido-biotinate. Experimental details are given for the synthesis of dethiobiotin, iminobiotin, and biotinylated ligands in which a 6-aminohexanoic acid spacer is interposed between the biotin or biotin derivative and the insulin molecule. The syntheses of biotinylated corticotropins are presented only in principle

  1. Biological evaluation and simple method for the synthesis of tetrahydrobenzo[a]xanthenes-11-one derivatives

    Directory of Open Access Journals (Sweden)

    Ali Akbari

    2017-01-01

    Full Text Available A simple method for the synthesis of Tetrahydrobenzo[a]xanthenes-11-one derivatives in the presence of BF3.SiO2, and its antibacterial activity was assessed against Pseudomonas syringae, Xanthomonas citi and Pectobacterium carotovorum. The structure of the isolated compounds has been determined by means of 1H/13C NMR and FT-IR spectroscopy. The reactions were carried out in water at room temperature for 5 h. This method has some advantages such as good to excellent yield, mild reaction condition, ease of operation and workup, high product purity and green process.

  2. Polycyclic Aromatic Compounds as Anticancer Agents: Synthesis and Biological Evaluation of Methoxy Dibenzofluorene Derivatives

    Directory of Open Access Journals (Sweden)

    Bimal Krishna Banik

    2014-08-01

    Full Text Available Synthesis of a new methoxy dibenzofluorene through alkylation, cyclodehydration and aromatization in a one-pot operation is achieved for the first time. Using this hydrocarbon, a few derivatives are prepared through aromatic nitration, catalytic hydrogenation, coupling reaction with a side chain and reduction. The benzylic position of this hydrocarbon with the side chain is oxidized and reduced. Some of these derivatives have demonstrated excellent antitumor activities in vitro. This study confirms antitumor activity depends on the structures of the molecules.

  3. Replacement of the double bond of antitubulin chalcones with triazoles and tetrazoles: Synthesis and biological evaluation.

    Science.gov (United States)

    Mesenzani, Ornella; Massarotti, Alberto; Giustiniano, Mariateresa; Pirali, Tracey; Bevilacqua, Valentina; Caldarelli, Antonio; Canonico, Pierluigi; Sorba, Giovanni; Novellino, Ettore; Genazzani, Armando A; Tron, Gian Cesare

    2011-01-15

    In the chalcone scaffold, it is thought that the double bond is an important structural linker but it is likely not essential for the interaction with tubulin. Yet, it may be a potential site of metabolic degradation and interaction with biological nucleophiles. In this letter, we have replaced this olefinic portion of chalcones with two metabolically stable and chemically inert heterocyclic rings, namely triazole or tetrazole. Yet, our biologic data suggest that, unlike in other antitubulinic structures, the olephinic ring might not be merely a structural linker. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Synthesis, Physical Characterization and Biological Activity of Some Schiff Base Complexes

    Directory of Open Access Journals (Sweden)

    R. Rajavel

    2008-01-01

    Full Text Available Structural modification of organic molecule has considerable biological relevance. Further, coordination of a biomolecules to the metal ions significantly alters the effectiveness of the biomolecules. In view of the antimicrobial activity ligand [bis-(2-aminobenzaldehyde] malonoyl dihydrazone], metal complexes with Cu(II, Ni(II, Zn(II and oxovanadium(IV have been synthesized and found to be potential antimicrobial agents. An attempt is also made to correlate the biological activities with geometry of the complexes. The complexes have been characterized by elemental analysis, molar conductance, spectra and cyclicvoltammetric measurements. The structural assessment of the complexes has been carried out based on electronic, infrared and molar conductivity values.

  5. Design and Synthesis of New Peptidomimetics as Potential Inhibitors of MurE.

    Science.gov (United States)

    Zivec, Matej; Turk, Samo; Blanot, Didier; Gobec, Stanislav

    2011-03-01

    With the continuing emergence and spread of multidrug-resistant bacteria, there is an urgent need for the development of new antimicrobial agents. One possible source of new antibacterial targets is the biosynthesis of the bacterial cell-wall peptidoglycan. The assembly of the peptide stem is carried out by four essential enzymes, known as the Mur ligases (MurC, D, E and F). We have designed and synthesised a focused library of compounds as potential inhibitors of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE) from Staphylococcus aureus. This was achieved using two approaches: (i) synthesis of transition-state analogues based on the methyleneamino core; and (ii) synthesis of MurE reaction product analogues. Two methyleneamino-based compounds are identified as initial hits for inhibitors of MurE.

  6. Computer-aided Framework for Synthesis, Design and Retrofit of Wastewater Treatment Plants

    DEFF Research Database (Denmark)

    Bozkurt, Hande

    Water is used for several purposes in houses and industrial applications, which results in the generation of considerable amounts of wastewater. Wastewater should be handled appropriately which is required from legal, environmental as well as economic and societal perspectives. Wastewater treatment...... be formulated as a process synthesis challenge in the sense that a new taskcan be added to the existing treatment line or one or several existing processes can be changed as a result of the emerging needs. Existing plants need retrofitting due to a number of reasons such as: change in the wastewater flow...... plant (WWTP) design is a formidable challenge. One of the key steps involved is the process synthesis - defined as the selection of treatment processes as a combination of unit operations and processes to create the process flow diagram.As a consequence of the emerging technological developments...

  7. Hierarchical modeling and robust synthesis for the preliminary design of large scale complex systems

    Science.gov (United States)

    Koch, Patrick Nathan

    Large-scale complex systems are characterized by multiple interacting subsystems and the analysis of multiple disciplines. The design and development of such systems inevitably requires the resolution of multiple conflicting objectives. The size of complex systems, however, prohibits the development of comprehensive system models, and thus these systems must be partitioned into their constituent parts. Because simultaneous solution of individual subsystem models is often not manageable iteration is inevitable and often excessive. In this dissertation these issues are addressed through the development of a method for hierarchical robust preliminary design exploration to facilitate concurrent system and subsystem design exploration, for the concurrent generation of robust system and subsystem specifications for the preliminary design of multi-level, multi-objective, large-scale complex systems. This method is developed through the integration and expansion of current design techniques: (1) Hierarchical partitioning and modeling techniques for partitioning large-scale complex systems into more tractable parts, and allowing integration of subproblems for system synthesis, (2) Statistical experimentation and approximation techniques for increasing both the efficiency and the comprehensiveness of preliminary design exploration, and (3) Noise modeling techniques for implementing robust preliminary design when approximate models are employed. The method developed and associated approaches are illustrated through their application to the preliminary design of a commercial turbofan turbine propulsion system; the turbofan system-level problem is partitioned into engine cycle and configuration design and a compressor module is integrated for more detailed subsystem-level design exploration, improving system evaluation.

  8. Synthesis and Preliminary Biological Evaluations of Fluorescent or 149Promethium Labeled Trastuzumab-Polyethylenimine

    Directory of Open Access Journals (Sweden)

    Jonathan Fitzsimmons

    2015-12-01

    Full Text Available Background: Radioimmunotherapy utilize a targeting antibody coupled to a therapeutic isotope to target and treat a tumor or disease. In this study we examine the synthesis and cell binding of a polymer scaffold containing a radiotherapeutic isotope and a targeting antibody. Methods: The multistep synthesis of a fluorescent or 149Promethium-labeled Trastuzumab-polyethyleneimine (PEI, Trastuzumab, or PEI is described. In vitro uptake, internalization and/or the binding affinity to the Her2/neu expressing human breast adenocarcinoma SKBr3 cells was investigated with the labeled compounds. Results: Fluorescent-labeled Trastuzumab-PEI was internalized more into cells at 2 and 18 h than fluorescent-labeled Trastuzumab or PEI. The fluorescent-labeled Trastuzumab was concentrated on the cell surface at 2 and 18 h and the labeled PEI had minimal uptake. DOTA-PEI was prepared and contained an average of 16 chelates per PEI; the compound was radio-labeled with 149Promethium and conjugated to Trastuzumab. The purified 149Pm-DOTA-PEI-Trastuzumab had a radiochemical purity of 96.7% and a specific activity of 0.118 TBq/g. The compound demonstrated a dissociation constant for the Her2/neu receptor of 20.30 ± 6.91 nM. Conclusion: The results indicate the DOTA-PEI-Trastuzumab compound has potential as a targeted therapeutic carrier, and future in vivo studies should be performed.

  9. Synthesis and biological evaluation of flexible and conformationally constrained LpxC inhibitors

    DEFF Research Database (Denmark)

    Löppenberg, Marius; Müller, Hannes; Pulina, Carla

    2013-01-01

    , conformationally constrained C-glycosidic as well as open chained hydroxamic acids with a defined stereochemistry were prepared. Diversity was introduced by performing C–C coupling reactions like the Sonogashira and Suzuki cross-coupling reactions. The biological evaluation of the synthesized compounds revealed...

  10. Synthesis, characterization and functionalization of silicon nanoparticle based hybrid nanomaterials for photovoltaic and biological applications

    Science.gov (United States)

    Xu, Zejing

    Silicon nanoparticles are attractive candidates for biological, photovoltaic and energy storage applications due to their size dependent optoelectronic properties. These include tunable light emission, high brightness, and stability against photo-bleaching relative to organic dyes (see Chapter 1). The preparation and characterization of silicon nanoparticle based hybrid nanomaterials and their relevance to photovoltaic and biological applications are described. The surface-passivated silicon nanoparticles were produced in one step from the reactive high-energy ball milling (RHEBM) of silicon wafers with various organic ligands. The surface structure and optical properties of the passivated silicon nanoparticles were systematically characterized. Fast approaches for purifying and at the same time size separating the silicon nanoparticles using a gravity GPC column were developed. The hydrodynamic diameter and size distribution of these size-separated silicon nanoparticles were determined using GPC and Diffusion Ordered NMR Spectroscopy (DOSY) as fast, reliable alternative approaches to TEM. Water soluble silicon nanoparticles were synthesized by grafting PEG polymers onto functionalized silicon nanoparticles with distal alkyne or azide moieties. The surface-functionalized silicon nanoparticles were produced from the reactive high-energy ball milling (RHEBM) of silicon wafers with a mixture of either 5-chloro-1-pentyne in 1-pentyne or 1,7 octadiyne in 1-hexyne to afford air and water stable chloroalkyl or alkynyl terminated nanoparticles, respectively. Nanoparticles with the ω-chloroalkyl substituents were easily converted to ω-azidoalkyl groups through the reaction of the silicon nanoparticles with sodium azide in DMF. The azido terminated nanoparticles were then grafted with monoalkynyl-PEG polymers using a copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction to afford core-shell silicon nanoparticles with a covalently attached PEG shell. Covalently

  11. A design concept of parallel elasticity extracted from biological muscles for engineered actuators.

    Science.gov (United States)

    Chen, Jie; Jin, Hongzhe; Iida, Fumiya; Zhao, Jie

    2016-08-23

    Series elastic actuation that takes inspiration from biological muscle-tendon units has been extensively studied and used to address the challenges (e.g. energy efficiency, robustness) existing in purely stiff robots. However, there also exists another form of passive property in biological actuation, parallel elasticity within muscles themselves, and our knowledge of it is limited: for example, there is still no general design strategy for the elasticity profile. When we look at nature, on the other hand, there seems a universal agreement in biological systems: experimental evidence has suggested that a concave-upward elasticity behaviour is exhibited within the muscles of animals. Seeking to draw possible design clues for elasticity in parallel with actuators, we use a simplified joint model to investigate the mechanisms behind this biologically universal preference of muscles. Actuation of the model is identified from general biological joints and further reduced with a specific focus on muscle elasticity aspects, for the sake of easy implementation. By examining various elasticity scenarios, one without elasticity and three with elasticity of different profiles, we find that parallel elasticity generally exerts contradictory influences on energy efficiency and disturbance rejection, due to the mechanical impedance shift thus caused. The trade-off analysis between them also reveals that concave parallel elasticity is able to achieve a more advantageous balance than linear and convex ones. It is expected that the results could contribute to our further understanding of muscle elasticity and provide a theoretical guideline on how to properly design parallel elasticity behaviours for engineering systems such as artificial actuators and robotic joints.

  12. On Designing Multicore-Aware Simulators for Systems Biology Endowed with OnLine Statistics

    Directory of Open Access Journals (Sweden)

    Marco Aldinucci

    2014-01-01

    Full Text Available The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  13. On designing multicore-aware simulators for systems biology endowed with OnLine statistics.

    Science.gov (United States)

    Aldinucci, Marco; Calcagno, Cristina; Coppo, Mario; Damiani, Ferruccio; Drocco, Maurizio; Sciacca, Eva; Spinella, Salvatore; Torquati, Massimo; Troina, Angelo

    2014-01-01

    The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big) data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  14. Modular design of synthetic gene circuits with biological parts and pools.

    Science.gov (United States)

    Marchisio, Mario Andrea

    2015-01-01

    Synthetic gene circuits can be designed in an electronic fashion by displaying their basic components-Standard Biological Parts and Pools of molecules-on the computer screen and connecting them with hypothetical wires. This procedure, achieved by our add-on for the software ProMoT, was successfully applied to bacterial circuits. Recently, we have extended this design-methodology to eukaryotic cells. Here, highly complex components such as promoters and Pools of mRNA contain hundreds of species and reactions whose calculation demands a rule-based modeling approach. We showed how to build such complex modules via the joint employment of the software BioNetGen (rule-based modeling) and ProMoT (modularization). In this chapter, we illustrate how to utilize our computational tool for synthetic biology with the in silico implementation of a simple eukaryotic gene circuit that performs the logic AND operation.

  15. Toward Developing Made-to-Order Metal-Organic Frameworks: Design, Synthesis and Applications

    KAUST Repository

    Ashri, Lubna Y.

    2016-05-26

    Synthesis of materials with certain properties for targeted applications is an ongoing challenge in materials science. One of the most interesting classes of solid-state materials that have been recently introduced with the potential to address this is metal-organic frameworks (MOFs). MOFs chemistry offers a higher degree of control over materials to be synthesized utilizing various new design strategies, such as the molecular building blocks (MBBs) and the supermolecular building layers (SBLs) approaches. Depending on using predetermined building blocks, these strategies permit the synthesis of MOFs with targeted topologies and enable fine tuning of their properties. This study examines a number of aspects of the design and synthesis of MOFs while exploring their possible utilization in two diverse fields related to energy and pharmaceutical applications. Concerning MOFs design and synthesis, the work presented here explores the rational design of various MOFs with predicted topologies and tunable cavities constructed by pillaring pre-targeted 2-periodic SBLs using the ligand-to-axial and six-connected axial-to-axial pillaring strategies. The effect of expanding the confined spaces in prepared MOFs or modifying their functionalities, while preserving the underlying network topology, was investigated. Additionally, The MBBs approach was employed to discover new modular polynuclear rare earth (RE)-MBBs in the presence of different angular polytopic ligands containing carboxylate and nitrogen moieties with the aid of a modulator. The goal was to assess the diverse possible coordination modes and construct highly-connected nets for utility in the design of new MOFs and enhance the predictability of structural outcomes. The effect of adjusting ligands’ length-to-width ratio on the prepared MOFs was also evaluated. As a result, the reaction conditions amenable for reliable formation of the unprecedented octadecanuclear, octanuclear and double tetranuclear RE-MBBs were

  16. Hibiscus latent Fort Pierce virus in Brazil and synthesis of its biologically active full-length cDNA clone.

    Science.gov (United States)

    Gao, Ruimin; Niu, Shengniao; Dai, Weifang; Kitajima, Elliot; Wong, Sek-Man

    2016-10-01

    A Brazilian isolate of Hibiscus latent Fort Pierce virus (HLFPV-BR) was firstly found in a hibiscus plant in Limeira, SP, Brazil. RACE PCR was carried out to obtain the full-length sequences of HLFPV-BR which is 6453 nucleotides and has more than 99.15 % of complete genomic RNA nucleotide sequence identity with that of HLFPV Japanese isolate. The genomic structure of HLFPV-BR is similar to other tobamoviruses. It includes a 5' untranslated region (UTR), followed by open reading frames encoding for a 128-kDa protein and a 188-kDa readthrough protein, a 38-kDa movement protein, 18-kDa coat protein, and a 3' UTR. Interestingly, the unique feature of poly(A) tract is also found within its 3'-UTR. Furthermore, from the total RNA extracted from the local lesions of HLFPV-BR-infected Chenopodium quinoa leaves, a biologically active, full-length cDNA clone encompassing the genome of HLFPV-BR was amplified and placed adjacent to a T7 RNA polymerase promoter. The capped in vitro transcripts from the cloned cDNA were infectious when mechanically inoculated into C. quinoa and Nicotiana benthamiana plants. This is the first report of the presence of an isolate of HLFPV in Brazil and the successful synthesis of a biologically active HLFPV-BR full-length cDNA clone.

  17. Synthesis, formulation of nucleo-equipment and biological studies of the 99m Tc-MAG3

    International Nuclear Information System (INIS)

    Reyes H, L.; Lezama C, J.; Ferro F, G.

    1991-10-01

    Technetium-99m-mercaptoacetyl glycylglycylglycine ( 99m Tc-MAG 3 ) is introduced to replace o-iodohippurate (OIH) for renal function studies. In this paper we present the synthesis, labelling and biological evaluation of 99m Tc- MAG 3 prepared in our laboratory. The precursor s-benzoyl-mercaptoacetyl glycyl glycylglycine (Bz-MAG 3 ) was synthesized by condensation of glycylglycylglycine with chloroacetyl chloride to obtain chloroacetyl glycylglycylglycine and this product was condensate with sodium thiobenzoate. The Bz-MAG 3 was characterized by IR and NMR. The labelling with 99m Tc was carried out at pH 9.0 using stannous chloride as a reducing agent with heating to boiling for 15 min. The benzoyl group is lost in this step, forming 99m Tc-MAG 3 complex with radiochemical purity of 99%. The biodistribution properties were evaluated in mice and a rapid renal extraction was apparent at the 10 minutes value (51.65% of the injected dose). The radiotracer was administered to 5 patients showing a good biological behavior. Based on these results, the 99m Tc-MAG 3 is expected to have widespread clinical utility in Mexico. (Author)

  18. Biological assessment of the advanced turbine design at Wanapum Dam, 2005

    Energy Technology Data Exchange (ETDEWEB)

    Dauble, D. D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Deng, Z. D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Richmond, M. C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moursund, R. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carlson, T. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rakowski, C. L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Duncan, J. P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2007-08-01

    Three studies were conducted to evaluate the biological performance of an advanced design turbine installed at Unit 8 of Wanapum Dam on the Columbia River in 2005 versus a conventional Kaplan turbine, Unit 9. The studies included an evaluation of blade-strike using deterministic and probabilistic models, integrated analysis of the response of the Sensor Fish to sever hydraulic events within the turbine system, and a novel dye technique to measure injury to juvenile salmonids in the field.

  19. Combined Model of Intrinsic and Extrinsic Variability for Computational Network Design with Application to Synthetic Biology

    Science.gov (United States)

    Toni, Tina; Tidor, Bruce

    2013-01-01

    Biological systems are inherently variable, with their dynamics influenced by intrinsic and extrinsic sources. These systems are often only partially characterized, with large uncertainties about specific sources of extrinsic variability and biochemical properties. Moreover, it is not yet well understood how different sources of variability combine and affect biological systems in concert. To successfully design biomedical therapies or synthetic circuits with robust performance, it is crucial to account for uncertainty and effects of variability. Here we introduce an efficient modeling and simulation framework to study systems that are simultaneously subject to multiple sources of variability, and apply it to make design decisions on small genetic networks that play a role of basic design elements of synthetic circuits. Specifically, the framework was used to explore the effect of transcriptional and post-transcriptional autoregulation on fluctuations in protein expression in simple genetic networks. We found that autoregulation could either suppress or increase the output variability, depending on specific noise sources and network parameters. We showed that transcriptional autoregulation was more successful than post-transcriptional in suppressing variability across a wide range of intrinsic and extrinsic magnitudes and sources. We derived the following design principles to guide the design of circuits that best suppress variability: (i) high protein cooperativity and low miRNA cooperativity, (ii) imperfect complementarity between miRNA and mRNA was preferred to perfect complementarity, and (iii) correlated expression of mRNA and miRNA – for example, on the same transcript – was best for suppression of protein variability. Results further showed that correlations in kinetic parameters between cells affected the ability to suppress variability, and that variability in transient states did not necessarily follow the same principles as variability in the steady

  20. Modified Polyacrylic Acid-Zinc Composites: Synthesis, Characterization and Biological Activity

    Directory of Open Access Journals (Sweden)

    Mohammed Rafi Shaik

    2016-02-01

    Full Text Available Polyacrylic acid (PAA is an important industrial chemical, which has been extensively applied in various fields, including for several biomedical purposes. In this study, we report the synthesis and modification of this polymer with various phenol imides, such as succinimide, phthalimide and 1,8-naphthalimide. The as-synthesized derivatives were used to prepare polymer metal composites by the reaction with Zn+2. These composites were characterized by using various techniques, including NMR, FT-IR, TGA, SEM and DSC. The as-prepared PAA-based composites were further evaluated for their anti-microbial properties against various pathogens, which include both Gram-positive and Gram-negative bacteria and different fungal strains. The synthesized composites have displayed considerable biocidal properties, ranging from mild to moderate activities against different strains tested.

  1. Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

    Science.gov (United States)

    Chen, Fei; Shao, Kejing; Zhu, Bao; Jiang, Mengjun

    2016-05-15

    A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Synthesis, Characterization, and Biological Activity of Nickel (II and Palladium (II Complex with Pyrrolidine Dithiocarbamate (PDTC

    Directory of Open Access Journals (Sweden)

    Sk Imadul Islam

    2016-01-01

    Full Text Available The synthesis of square planar Ni(II and Pd(II complexes with pyrrolidine dithiocarbamate (PDTC was characterized by elemental, physiochemical, and spectroscopic methods. Two complexes were prepared by the reaction of nickel acetate and palladium acetate with pyrrolidine dithiocarbamate (PDTC in 1 : 2 molar ratio. The bovine serum albumin (BSA interaction with complexes was examined by absorption and fluorescence spectroscopic techniques at pH 7.4. All the spectral data suggest that coordination of the pyrrolidine dithiocarbamate (PDTC takes place through the two sulphur atoms in a symmetrical bidentate fashion. All the synthesized compounds were screened for their antimicrobial activity against some species of pathogenic bacteria (Escherichia coli, Vibrio cholerae, Streptococcus pneumonia, and Bacillus cereus. It has been observed that complexes have higher activity than the free ligand.

  3. Synthesis on Biology and Uranium Mineralization of Rabau Hulu Sector Kalan, Kalimantan Barat

    International Nuclear Information System (INIS)

    Bambang-Soetopo; Retno-Witjahyanti; Yanu-Wusana

    2004-01-01

    The results of previous research on Rabau Hulu sector consist of geology, geophysics and drilling data show that the area prospect for finding U mineralization. Goal of this synthesis is to know geological and U mineralization of Rabau sector in order to develop further followup program. In general geology the area consists of biotite micro quartzite, muscovite micro quartzite, muscovite quartzite, leopard quartzite, horn fels and granite. The directions of stratification is NE-SW of the dipping is NW. Prominent fault is NE-SW sinistral fault, NNE-SSW and NW-SE dextral fault. Uranium mineralization as a uraninite fill in the space between minerals and fractures system ENE-WSW, its associated with pyrite, pyrrhotite, chalcopyrite, molybdenite, sphalerite, magnetite, tourmaline and quartz. With radiometric anomalies values are about 1.000-15.000 c/s. Uranium mineralization process is connected with the granite intrusion as the hydrothermal magnetic process. (author)

  4. Synthesis, biological activity and computational studies of novel azo-compounds

    International Nuclear Information System (INIS)

    Ashraf, J.; Murtaza, S.; Mughal, E.U.; Sadiq, A.

    2017-01-01

    In the present protocol, we report the synthesis and characterization of some novel azo-compounds starting from 4-methoxyaniline and 4-aminophenazone, which were diazotized at low temperature. 4-nitrophenol, 2-aminobenzoic acid, benzamide, 4-aminobenzoic acid, resorcinol, o-bromonitrobenzene and 2-nitroaniline were used as active aromatic coupling compounds for the second step. The synthesized compounds were investigated for their potential antibacterial activities by using disc diffusion method against Escherichia coli, Shigellasonnei, Streptococcus pyrogenes, Staphylococcus aureus and Neisseria gonorrhoeae strains. They were also subjected to antioxidant activities by using DPPH method. Results revealed that the compounds of 4-methoxyaniline and 4-aminophenazone showed good antibacterial activity against all strains, where as some azo-compounds have moderate to good antioxidant activities. Furthermore, these compounds were studied by computational analysis. (author)

  5. Thiophenyl-substituted triazolyl-thione L-alanine: asymmetric synthesis, aggregation and biological properties.

    Science.gov (United States)

    Saghyan, Ashot S; Simonyan, Hayarpi M; Petrosyan, Satenik G; Geolchanyan, Arpine V; Roviello, Giovanni N; Musumeci, Domenica; Roviello, Valentina

    2014-10-01

    In this work, we report the asymmetric synthesis and characterization of an artificial amino acid based on triazolyl-thione L-alanine, which was modified with a thiophenyl-substituted moiety, as well as in vitro studies of its nucleic acid-binding ability. We found, by dynamic light scattering studies, that the synthetic amino acid was able to form supramolecular aggregates having a hydrodynamic diameter higher than 200 nm. Furthermore, we demonstrated, by UV and CD experiments, that the heteroaromatic amino acid, whose enzymatic stability was demonstrated by HPLC analysis also after 24 h of incubation in human serum, was able to bind a RNA complex, which is a feature of biomedical interest in view of innovative antiviral strategies based on modulation of RNA-RNA molecular recognition.

  6. Synthesis and biological activity of sulfur compounds showing structural analogy with combretastatin A-4

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Edson dos A. dos; Prado, Paulo C.; Carvalho, Wanderley R. de; Lima, Ricardo V. de; Beatriz, Adilson; Lima, Denis P. de, E-mail: denis.lima@ufms.br [Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Departamento de Quimica; Hamel, Ernest [Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD (United States); Dyba, Marzena A. [Basic Science Program , SAIC-Frederick, Inc., Structural Biophysics Laboratory National Cancer Institute, Frederick, MD (United States); Albuquerque, Sergio [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Ciencias Farmaceuticas

    2013-09-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904),and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15). (author)

  7. Synthesis, spectroscopic, biological activity and thermal characterization of ceftazidime with transition metals

    Science.gov (United States)

    Masoud, Mamdouh S.; Ali, Alaa E.; Elasala, Gehan S.; Kolkaila, Sherif A.

    2018-03-01

    Synthesis, physicochemical characterization and thermal analysis of ceftazidime complexes with transition metals (Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)) were discussed. It's obtained that ceftazidime act as bidentate ligand. From magnetic measurement and spectral data, octahedral structures were proposed for all complexes except for cobalt, nickel and mercury had tetrahedral structural. Hyper chemistry program confirmed binding sites of ceftazidime. Ceftazidime complexes show higher activity than ceftazidime for some strains. From TG and DTA curves the thermal decomposition mechanisms of ceftazidime and their metal complexes were suggested. The thermal decomposition of the complexes ended with the formation of metal oxides as a final product except in case of Hg complex.

  8. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    Science.gov (United States)

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively).

  9. Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents.

    Directory of Open Access Journals (Sweden)

    Anna Gliszczyńska

    Full Text Available The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59-87% and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts. The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2.

  10. Synthesis and biological evaluation of boronated polyglycerol dendrimers as potential agent for neutron capture therapy

    International Nuclear Information System (INIS)

    Silva, Gerald S.; Camillo, Maria A.P.; Higa, Olga Z.; Pugliesi, Reynaldo; Fermamdes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

    In this work, the polyglycerol dendrimer (PGLD) generation 5 was used to obtain a boronated macromolecule for boron neutron capture therapy. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography, nuclear magnetic resonance ( 1 H-NMR, 13 C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (M w /M n = 1.05) and a degree of branching of 0.82, which characterize the polymer dendritic structure. Quantitative neutron capture radiography was used to investigate the boron-10 enrichment of the polyglycerol dendrimer. The in vitro cytotoxicity to Chinese hamster ovary cells of 10 B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

  11. Selenium-Doped Hydroxyapatite Nanocrystals–Synthesis, Physicochemical Properties and Biological Significance

    Directory of Open Access Journals (Sweden)

    Kamil Pajor

    2018-04-01

    Full Text Available Hydroxyapatites (HAs, as materials with a similar structure to bone minerals, play a key role in biomaterials engineering. They have been applied as bone substitute materials and as coatings for metallic implants, which facilitates their osseointegration. One of the beneficial characteristics of HA, when used to create biocompatible materials with improved physicochemical or biological properties, is its capacity for ionic substitution. The aim of the study was to present the current state of knowledge about HAs containing selenate ions IV or VI. The enrichment of HAs with selenium aims to create a material with advantageous effects on bone tissue metabolism, as well as having anticancer and antibacterial activity. The work is devoted to both methods of obtaining Se-HA and an evaluation of its chemical structure and physicochemical properties. In addition, the biological activity of such materials in vitro and in vivo is discussed.

  12. Recent Progress in Synthesis and Functionalization of Multimodal Fluorescent-Magnetic Nanoparticles for Biological Applications

    Directory of Open Access Journals (Sweden)

    Raquel Serrano García

    2018-01-01

    Full Text Available There is a great interest in the development of new nanomaterials for multimodal imaging applications in biology and medicine. Multimodal fluorescent-magnetic based nanomaterials deserve particular attention as they can be used as diagnostic and drug delivery tools, which could facilitate the diagnosis and treatment of cancer and many other diseases. This review focuses on the recent developments of magnetic-fluorescent nanocomposites and their biomedical applications. The recent advances in synthetic strategies and approaches for the preparation of fluorescent-magnetic nanocomposites are presented. The main biomedical uses of multimodal fluorescent-magnetic nanomaterials, including biological imaging, cancer therapy and drug delivery, are discussed, and prospects of this field are outlined.

  13. Supporting cognition in systems biology analysis: findings on users' processes and design implications.

    Science.gov (United States)

    Mirel, Barbara

    2009-02-13

    Current usability studies of bioinformatics tools suggest that tools for exploratory analysis support some tasks related to finding relationships of interest but not the deep causal insights necessary for formulating plausible and credible hypotheses. To better understand design requirements for gaining these causal insights in systems biology analyses a longitudinal field study of 15 biomedical researchers was conducted. Researchers interacted with the same protein-protein interaction tools to discover possible disease mechanisms for further experimentation. Findings reveal patterns in scientists' exploratory and explanatory analysis and reveal that tools positively supported a number of well-structured query and analysis tasks. But for several of scientists' more complex, higher order ways of knowing and reasoning the tools did not offer adequate support. Results show that for a better fit with scientists' cognition for exploratory analysis systems biology tools need to better match scientists' processes for validating, for making a transition from classification to model-based reasoning, and for engaging in causal mental modelling. As the next great frontier in bioinformatics usability, tool designs for exploratory systems biology analysis need to move beyond the successes already achieved in supporting formulaic query and analysis tasks and now reduce current mismatches with several of scientists' higher order analytical practices. The implications of results for tool designs are discussed.

  14. Synthesis and preliminary biological evaluation of a compound library of triazolylcyclitols.

    Science.gov (United States)

    Carrau, Gonzalo; Drewes, Carine C; Shimada, Ana Lúcia B; Bertucci, Ana; Farsky, Sandra H P; Stefani, Helio A; Gonzalez, David

    2013-07-15

    A small library of compounds was prepared by a combination of toluene dioxygenase (TDO)-catalyzed enzymatic dihydroxylation and copper(I)-catalyzed Hüisgen cycloaddition. Some compounds were obtained by coupling an alkyne and a conduritol derivative, while more complex structures were obtained by a double Hüisgen reaction of a dialkyne and two molecules of the cyclitol. The compounds were fully characterized and subjected to preliminary biological screening. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Building Design Guidelines of Interior Architecture for Bio safety Levels of Biology Laboratories

    International Nuclear Information System (INIS)

    ElDib, A.A.

    2014-01-01

    This paper discusses the pivotal role of the Interior Architecture As one of the scientific disciplines minute to complete the Architectural Sciences, which relied upon the achievement and development of facilities containing scientific research laboratories, in terms of planning and design, particularly those containing biological laboratories using radioactive materials, adding to that, the application of the materials or raw materials commensurate with each discipline of laboratory and its work nature, and by the discussion the processing of design techniques and requirements of interior architecture dealing with Research Laboratory for electronic circuits an their applications with the making of its prototypes

  16. Green Synthesis of Ultraviolet Absorber 2-Ethylhexyl Salicylate: Experimental Design and Artificial Neural Network Modeling

    Directory of Open Access Journals (Sweden)

    Shang-Ming Huang

    2017-11-01

    Full Text Available 2-Ethylhexyl salicylate, an ultraviolet filter, is widely used to protect skin against sunlight-induced harmful effects in the cosmetic industry. In this study, the green synthesis of 2-ethylhexyl salicylate using immobilized lipase through a solvent-free and reduced pressure evaporation system was investigated. A Box–Behnken design was employed to develop an artificial neural network (ANN model. The parameters for an optimal architecture of an ANN were set out: a quick propagation algorithm, a hyperbolic tangent transfer function, 10,000 iterations, and six nodes within the hidden layer. The best-fitting performance of the ANN was determined by the coefficient of determination and the root-mean-square error between the correlation of predicted and experimental data, indicating that the ANN displayed excellent data-fitting properties. Finally, the experimental conditions of synthesis were well established with the optimal parameters to obtain a high conversion of 2-ethylhexyl salicylate. In conclusion, this study efficiently replaces the traditional solvents with a green process for the synthesis of 2-ethylhexyl salicylate to avoid environmental contamination, and this process is well-modeled by a methodological ANN for optimization, which might be a benefit for industrial production.

  17. Ultra-Structure database design methodology for managing systems biology data and analyses

    Directory of Open Access Journals (Sweden)

    Hemminger Bradley M

    2009-08-01

    Full Text Available Abstract Background Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping. Results We transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research. Conclusion We find

  18. The biological shield of a high-intensity spallation source: a monte Carlo design study

    International Nuclear Information System (INIS)

    Koprivnikar, I.; Schachinger, E.

    2004-01-01

    The design of high-intensity spallation sources requires the best possible estimates for the biological shield. The applicability of three-dimensional Monte Carlo simulation in the design of the biological shield of a spallation source will be discussed. In order to achieve reasonable computing times along with acceptable accuracy, biasing techniques are to be employed and it was the main purpose of this work to develop a strategy for an effective Monte Carlo simulation in shielding design. The most prominent MC computer codes, namely MCNPX and FLUKA99, have been applied to the same model spallation source (the European Spallation Source) and on the basis of the derived strategies, the design and characteristics of the target station shield are discussed. It is also the purpose of the paper to demonstrate the application of the developed strategy for the design of beam lines with their shielding using as an example the target-moderator-reflector complex of the ESS as the primary particle source. (author)

  19. VisBOL: Web-Based Tools for Synthetic Biology Design Visualization.

    Science.gov (United States)

    McLaughlin, James Alastair; Pocock, Matthew; Mısırlı, Göksel; Madsen, Curtis; Wipat, Anil

    2016-08-19

    VisBOL is a Web-based application that allows the rendering of genetic circuit designs, enabling synthetic biologists to visually convey designs in SBOL visual format. VisBOL designs can be exported to formats including PNG and SVG images to be embedded in Web pages, presentations and publications. The VisBOL tool enables the automated generation of visualizations from designs specified using the Synthetic Biology Open Language (SBOL) version 2.0, as well as a range of well-known bioinformatics formats including GenBank and Pigeoncad notation. VisBOL is provided both as a user accessible Web site and as an open-source (BSD) JavaScript library that can be used to embed diagrams within other content and software.

  20. Systemic design methodologies for electrical energy systems analysis, synthesis and management

    CERN Document Server

    Roboam, Xavier

    2012-01-01

    This book proposes systemic design methodologies applied to electrical energy systems, in particular analysis and system management, modeling and sizing tools. It includes 8 chapters: after an introduction to the systemic approach (history, basics & fundamental issues, index terms) for designing energy systems, this book presents two different graphical formalisms especially dedicated to multidisciplinary devices modeling, synthesis and analysis: Bond Graph and COG/EMR. Other systemic analysis approaches for quality and stability of systems, as well as for safety and robustness analysis tools are also proposed. One chapter is dedicated to energy management and another is focused on Monte Carlo algorithms for electrical systems and networks sizing. The aim of this book is to summarize design methodologies based in particular on a systemic viewpoint, by considering the system as a whole. These methods and tools are proposed by the most important French research laboratories, which have many scientific partn...

  1. Exploration of dual supply voltage logic synthesis in state-of-the-art ASIC design flows

    Directory of Open Access Journals (Sweden)

    T. Mahnke

    2003-01-01

    Full Text Available Dual supply voltage scaling (DSVS for logiclevel power optimization at the has increasingly attracted attention over the last few years. However, mainly due to the fact that the most widely used design tools do not support this new technique, it has still not become an integral part of real-world design flows. In this paper, a novel logic synthesis methodology that enables DSVS while relying entirely on standard tools is presented. The key to this methodology is a suitably modeled dual supply voltage (DSV standard cell library. A basic evaluation of the methodology has been carried out on a number of MCNC benchmark circuits. In all these experiments, the results of state-of-the-art powerdriven single supply voltage (SSV logic synthesis have been used as references in order to determine the true additional benefit of DSVS. Compared with the results of SSV power optimization, additional power reductions of 10% on average have been achieved. The results prove the feasibility of the new approach and reveal its greater efficiency in comparison with a well-known dedicated DSVS algorithm. Finally, the methodology has been applied to an embedded microcontroller core in order to further explore the potentials and limitations of DSVS in an existing industrial design environment.

  2. Simulation-Optimization Framework for Synthesis and Design of Natural Gas Downstream Utilization Networks

    Directory of Open Access Journals (Sweden)

    Saad A. Al-Sobhi

    2018-02-01

    Full Text Available Many potential diversification and conversion options are available for utilization of natural gas resources, and several design configurations and technology choices exist for conversion of natural gas to value-added products. Therefore, a detailed mathematical model is desirable for selection of optimal configuration and operating mode among the various options available. In this study, we present a simulation-optimization framework for the optimal selection of economic and environmentally sustainable pathways for natural gas downstream utilization networks by optimizing process design and operational decisions. The main processes (e.g., LNG, GTL, and methanol production, along with different design alternatives in terms of flow-sheeting for each main processing unit (namely syngas preparation, liquefaction, N2 rejection, hydrogen, FT synthesis, methanol synthesis, FT upgrade, and methanol upgrade units, are used for superstructure development. These processes are simulated using ASPEN Plus V7.3 to determine the yields of different processing units under various operating modes. The model has been applied to maximize total profit of the natural gas utilization system with penalties for environmental impact, represented by CO2eq emission obtained using ASPEN Plus for each flowsheet configuration and operating mode options. The performance of the proposed modeling framework is demonstrated using a case study.

  3. Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

    Directory of Open Access Journals (Sweden)

    Eliezer J. Barreiro

    2012-11-01

    Full Text Available In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1, a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637 and 14g (LASSBio-1639 were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2 at concentrations of 10 mM.

  4. Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.

    Science.gov (United States)

    de Miranda, Amanda Silva; Bispo Júnior, Walfrido; da Silva, Yolanda Karla Cupertino; Alexandre-Moreira, Magna Suzana; Castro, Rosane de Paula; Sabino, José Ricardo; Lião, Luciano Morais; Lima, Lídia Moreira; Barreiro, Eliezer J

    2012-11-28

    In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.

  5. Design of distributed systems of hydrolithosphere processes management. A synthesis of distributed management systems

    Science.gov (United States)

    Pershin, I. M.; Pervukhin, D. A.; Ilyushin, Y. V.; Afanaseva, O. V.

    2017-10-01

    The paper considers an important problem of designing distributed systems of hydrolithosphere processes management. The control actions on the hydrolithosphere processes under consideration are implemented by a set of extractive wells. The article shows the method of defining the approximation links for description of the dynamic characteristics of hydrolithosphere processes. The structure of distributed regulators, used in the management systems by the considered processes, is presented. The paper analyses the results of the synthesis of the distributed management system and the results of modelling the closed-loop control system by the parameters of the hydrolithosphere process.

  6. Design, synthesis, and characterization of fluorine-free PAGs for 193-nm lithography

    Science.gov (United States)

    Liu, Sen; Glodde, Martin; Varanasi, Pushkara R.

    2010-04-01

    Photoacid generators (PAGs) are a key component in chemically amplified resists used in photolithography. Perfluorooctanesulfonates (PFOS) and other perfluoroalkylsulfonates (PFAS) have been well adopted as PAGs in 193 nm photoresist. Recently, concerns have been raised about their environmental impact due to their chemical persistency, bioaccumulation and toxicity. It is a general interest to find environmentally benign PAGs that are free of fluorine atoms. Here we describe the design, synthesis and characterization of a series of novel fluorine-free onium salts as PAGs for 193 nm photoresists. These PAGs demonstrated desirable physical and lithography properties when compared with PFAS-based PAGs for both dry and immersion exposures.

  7. Zeolite-like metal–organic frameworks (ZMOFs): design, synthesis, and properties

    KAUST Repository

    Eddaoudi, Mohamed; Sava, Dorina F.; Eubank, Jarrod F.; Adil, Karim; Guillerm, Vincent

    2014-01-01

    This review highlights various design and synthesis approaches toward the construction of ZMOFs, which are metal–organic frameworks (MOFs) with topologies and, in some cases, features akin to traditional inorganic zeolites. The interest in this unique subset of MOFs is correlated with their exceptional characteristics arising from the periodic pore systems and distinctive cage-like cavities, in conjunction with modular intra- and/or extra-framework components, which ultimately allow for tailoring of the pore size, pore shape, and/or properties towards specific applications.

  8. Zeolite-like metal–organic frameworks (ZMOFs): design, synthesis, and properties

    KAUST Repository

    Eddaoudi, Mohamed

    2014-10-24

    This review highlights various design and synthesis approaches toward the construction of ZMOFs, which are metal–organic frameworks (MOFs) with topologies and, in some cases, features akin to traditional inorganic zeolites. The interest in this unique subset of MOFs is correlated with their exceptional characteristics arising from the periodic pore systems and distinctive cage-like cavities, in conjunction with modular intra- and/or extra-framework components, which ultimately allow for tailoring of the pore size, pore shape, and/or properties towards specific applications.

  9. Design, Specification, and Synthesis of Aircraft Electric Power Systems Control Logic

    Science.gov (United States)

    Xu, Huan

    Cyber-physical systems integrate computation, networking, and physical processes. Substantial research challenges exist in the design and verification of such large-scale, distributed sensing, actuation, and control systems. Rapidly improving technology and recent advances in control theory, networked systems, and computer science give us the opportunity to drastically improve our approach to integrated flow of information and cooperative behavior. Current systems rely on text-based specifications and manual design. Using new technology advances, we can create easier, more efficient, and cheaper ways of developing these control systems. This thesis will focus on design considerations for system topologies, ways to formally and automatically specify requirements, and methods to synthesize reactive control protocols, all within the context of an aircraft electric power system as a representative application area. This thesis consists of three complementary parts: synthesis, specification, and design. The first section focuses on the synthesis of central and distributed reactive controllers for an aircraft elec- tric power system. This approach incorporates methodologies from computer science and control. The resulting controllers are correct by construction with respect to system requirements, which are formulated using the specification language of linear temporal logic (LTL). The second section addresses how to formally specify requirements and introduces a domain-specific language for electric power systems. A software tool automatically converts high-level requirements into LTL and synthesizes a controller. The final sections focus on design space exploration. A design methodology is proposed that uses mixed-integer linear programming to obtain candidate topologies, which are then used to synthesize controllers. The discrete-time control logic is then verified in real-time by two methods: hardware and simulation. Finally, the problem of partial observability and

  10. Hierarchically nanostructured hydroxyapatite: hydrothermal synthesis, morphology control, growth mechanism, and biological activity

    Science.gov (United States)

    Ma, Ming-Guo

    2012-01-01

    Hierarchically nanosized hydroxyapatite (HA) with flower-like structure assembled from nanosheets consisting of nanorod building blocks was successfully synthesized by using CaCl2, NaH2PO4, and potassium sodium tartrate via a hydrothermal method at 200°C for 24 hours. The effects of heating time and heating temperature on the products were investigated. As a chelating ligand and template molecule, the potassium sodium tartrate plays a key role in the formation of hierarchically nanostructured HA. On the basis of experimental results, a possible mechanism based on soft-template and self-assembly was proposed for the formation and growth of the hierarchically nanostructured HA. Cytotoxicity experiments indicated that the hierarchically nanostructured HA had good biocompatibility. It was shown by in-vitro experiments that mesenchymal stem cells could attach to the hierarchically nanostructured HA after being cultured for 48 hours. Objective The purpose of this study was to develop facile and effective methods for the synthesis of novel hydroxyapatite (HA) with hierarchical nanostructures assembled from independent and discrete nanobuilding blocks. Methods A simple hydrothermal approach was applied to synthesize HA by using CaCl2, NaH2PO4, and potassium sodium tartrate at 200°C for 24 hours. The cell cytotoxicity of the hierarchically nanostructured HA was tested by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results HA displayed the flower-like structure assembled from nanosheets consisting of nanorod building blocks. The potassium sodium tartrate was used as a chelating ligand, inducing the formation and self-assembly of HA nanorods. The heating time and heating temperature influenced the aggregation and morphology of HA. The cell viability did not decrease with the increasing concentration of hierarchically nanostructured HA added. Conclusion A novel, simple and reliable hydrothermal route had been developed for the synthesis of

  11. Hierarchically nanostructured hydroxyapatite: hydrothermal synthesis, morphology control, growth mechanism, and biological activity

    Directory of Open Access Journals (Sweden)

    Ma MG

    2012-04-01

    Full Text Available Ming-Guo MaInstitute of Biomass Chemistry and Technology, College of Materials Science and Technology, Beijing Forestry University, Beijing, People's Republic of ChinaAbstract: Hierarchically nanosized hydroxyapatite (HA with flower-like structure assembled from nanosheets consisting of nanorod building blocks was successfully synthesized by using CaCl2, NaH2PO4, and potassium sodium tartrate via a hydrothermal method at 200°C for 24 hours. The effects of heating time and heating temperature on the products were investigated. As a chelating ligand and template molecule, the potassium sodium tartrate plays a key role in the formation of hierarchically nanostructured HA. On the basis of experimental results, a possible mechanism based on soft-template and self-assembly was proposed for the formation and growth of the hierarchically nanostructured HA. Cytotoxicity experiments indicated that the hierarchically nanostructured HA had good biocompatibility. It was shown by in-vitro experiments that mesenchymal stem cells could attach to the hierarchically nanostructured HA after being cultured for 48 hours.Objective: The purpose of this study was to develop facile and effective methods for the synthesis of novel hydroxyapatite (HA with hierarchical nanostructures assembled from independent and discrete nanobuilding blocks.Methods: A simple hydrothermal approach was applied to synthesize HA by using CaCl2, NaH2PO4, and potassium sodium tartrate at 200°C for 24 hours. The cell cytotoxicity of the hierarchically nanostructured HA was tested by MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay.Results: HA displayed the flower-like structure assembled from nanosheets consisting of nanorod building blocks. The potassium sodium tartrate was used as a chelating ligand, inducing the formation and self-assembly of HA nanorods. The heating time and heating temperature influenced the aggregation and morphology of HA. The cell viability did

  12. Synthesis and Characterization of Rhodamine B-ethylenediamine-hyaluronan Acid as Potential Biological Functional Materials

    Science.gov (United States)

    Li, Y. L.; Wang, W. X.; Wang, Y.; Zhang, W. B.; Gong, H. M.; Liu, M. X.

    2018-05-01

    The purpose of this study is to synthesize and characterize fluorescent polymers, rhodamine B-ethylenediamine-hyaluronan acid (RhB-EA-HA). RhB-EA-HA was successfully synthesized by ester ammonolysis reaction and amidation reaction. Moreover, the structural properties of RhB-EA-HA were characterized by 1H-NMR spectra, UV-vis spectrometry and Fourier transform infrared spectroscopy (FT-IR). RhB-EA-HA can be grafted on the surface of silica nanomaterials, which may be potential biological functional materials for drug delivery system.

  13. Synthesis of 1-indanones with a broad range of biological activity

    Directory of Open Access Journals (Sweden)

    Marika Turek

    2017-03-01

    Full Text Available This comprehensive review describes methods for the preparation of 1-indanones published in original and patent literature from 1926 to 2017. More than 100 synthetic methods utilizing carboxylic acids, esters, diesters, acid chlorides, ketones, alkynes, alcohols etc. as starting materials, have been performed. This review also covers the most important studies on the biological activity of 1-indanones and their derivatives which are potent antiviral, anti-inflammatory, analgesic, antimalarial, antibacterial and anticancer compounds. Moreover, they can be used in the treatment of neurodegenerative diseases and as effective insecticides, fungicides and herbicides.

  14. Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity.

    Science.gov (United States)

    Mbaba, Mziyanda; Mabhula, Amanda N; Boel, Natasha; Edkins, Adrienne L; Isaacs, Michelle; Hoppe, Heinrich C; Khanye, Setshaba D

    2017-07-01

    A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity compared to organic analogues 5a-b and 5e-f. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Synthesis and biological evaluation of trans-3-phenyl-1-indanamines as potential norepinephrine transporter imaging agents

    International Nuclear Information System (INIS)

    McConathy, Jonathan; Owens, Michael J.; Kilts, Clinton D.; Malveaux, Eugene J.; Votaw, John R.; Nemeroff, Charles B.; Goodman, Mark M.

    2005-01-01

    The development of radioligands suitable for studying the central nervous system (CNS) norepinephrine transporter (NET) in vivo will provide important new tools for examining the pathophysiology and pharmacotherapy of a variety of neuropsychiatric disorders including major depression. Towards this end, a series of trans-3-phenyl-1-indanamine derivatives were prepared and evaluated in vitro. The biological properties of the most promising compound, [ 11 C]3-BrPA, were investigated in rat biodistribution and nonhuman primate PET studies. Despite high in vitro affinity for the human NET, the uptake of [ 11 C]3-BrPA in the brain and the heart was not displaceable with pharmacological doses of NET antagonists

  16. 'What-if' design: a synthesis method in the design process

    NARCIS (Netherlands)

    Lutters, Diederick; Vaneker, Thomas H.J.; van Houten, Frederikus J.A.M.

    2004-01-01

    In integrating functions, information and control in the design and engineering cycle, the information content acts as a facilitator, whereas the processes involved actually effectuate the results of the development cycle. As combining processes in an effective and efficient manner becomes

  17. Industrial scale gene synthesis.

    Science.gov (United States)

    Notka, Frank; Liss, Michael; Wagner, Ralf

    2011-01-01

    The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Properties of alternative microbial hosts used in synthetic biology: towards the design of a modular chassis

    Science.gov (United States)

    Kim, Juhyun; Salvador, Manuel; Saunders, Elizabeth; González, Jaime; Avignone-Rossa, Claudio

    2016-01-01

    The chassis is the cellular host used as a recipient of engineered biological systems in synthetic biology. They are required to propagate the genetic information and to express the genes encoded in it. Despite being an essential element for the appropriate function of genetic circuits, the chassis is rarely considered in their design phase. Consequently, the circuits are transferred to model organisms commonly used in the laboratory, such as Escherichia coli, that may be suboptimal for a required function. In this review, we discuss some of the properties desirable in a versatile chassis and summarize some examples of alternative hosts for synthetic biology amenable for engineering. These properties include a suitable life style, a robust cell wall, good knowledge of its regulatory network as well as of the interplay of the host components with the exogenous circuits, and the possibility of developing whole-cell models and tuneable metabolic fluxes that could allow a better distribution of cellular resources (metabolites, ATP, nucleotides, amino acids, transcriptional and translational machinery). We highlight Pseudomonas putida, widely used in many different biotechnological applications as a prominent organism for synthetic biology due to its metabolic diversity, robustness and ease of manipulation. PMID:27903818

  19. Mixed-Methods Design in Biology Education Research: Approach and Uses.

    Science.gov (United States)

    Warfa, Abdi-Rizak M

    Educational research often requires mixing different research methodologies to strengthen findings, better contextualize or explain results, or minimize the weaknesses of a single method. This article provides practical guidelines on how to conduct such research in biology education, with a focus on mixed-methods research (MMR) that uses both quantitative and qualitative inquiries. Specifically, the paper provides an overview of mixed-methods design typologies most relevant in biology education research. It also discusses common methodological issues that may arise in mixed-methods studies and ways to address them. The paper concludes with recommendations on how to report and write about MMR. © 2016 L. A.-R. M. Warfa. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  20. Coriandrum sativum mediated synthesis of silver nanoparticles and evaluation of their biological characteristics

    Science.gov (United States)

    Senthilkumar, N.; Aravindhan, V.; Ruckmani, K.; Vetha Potheher, I.

    2018-05-01

    Silver (Ag) nanoparticles (NPs) were prepared by percolated green synthesis method using Coriandrum sativum leaf, root, seed and stem extracts and reported its antibacterial activity. The synthesized Ag NPs were confirmed by UV–visible Spectroscopy, Powder x-ray Diffraction (PXRD), Fourier Transform Infra Red (FT-IR) Spectroscopy analyzes. The Maximum absorbance observed around 400–450 nm reveal the characteristic absorbance of Ag NPs. The Dynamic Light Scattering (DLS) analysis shows the stability of synthesized NPs with average size varying from 35 to 53 nm and also zeta potential stability varying from ‑20 to ‑30 mV. The cubic structure, crystalline nature and purity of the material was confirmed by powder x-ray diffraction studies. FT-IR spectrum shows the presence of various functional groups in the resultant material. The Field Emission Scanning Electron Microscopy (FESEM) image shows the surface morphology of the synthesized NPs and the Energy Dispersive x-ray Analysis (EDAX) confirms the presence of silver metal ions. The Coriandrum sativum aqueous extract exhibited excellent antimicrobial activity against Klebsiella pneumoniae (Gram -ve) bacteria. Numerous studies have been made previously in our field of study but optimization has not been carried out by both extract (different parts like leaf, root, seed and stem) and without addition of any external source such as chemicals, heat etc.