Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Feb. 6, 2008). Includes bibliographical references (p. 142-161).

No description available.

Thesis (M.Sc. (Organic Chemistry))--Mahidol University, 1983.

Modern manufacturing processes assume efficient utilization and recycling of natural resources whenever possible. Over the past decade paper recycling has progressed from 33.5% in 1990 to just above 48% in 2002.1 Indeed, for certain select grades, (newspaper and old corrugated containers) greater than 70% is currently being recycled. In contrast, mixed office waste and colored directory papers are often underutilized. A major difficulty in recycling these grades of paper is the problems associated with decolorizing the dyes present in the paper.2 Of the commonly used paper dyes, the stilbene dye Direct Yellow 113 and methine dye Basazol 46L are notorious4 for poor bleachability with the commonly used chemical bleaching agents including chlorine dioxide, oxygen, hydrogen peroxide and sodium dithionite. The ability of white-rot fungi to decolorize colored effluents containing textile dyes is currently the subject of intensive research efforts. The secreted enzymes involved in dye decolorization include manganese peroxidase, lignin peroxidase and laccase. Laccase, a lignolytic enzyme, has also been studied for many years for the biobleaching of wood pulps. The ability of laccase to delignify pulp is greatly enhanced by the addition of small molecule mediators such as 2-2´ azinobis (3-ethylbenzthiazoline-6-sulfonate) (ABTS) and 1-hydroxybenzotriazole (HBT). This research project focused on applying laccase combined with a mediator to decolorize C.I. Direct Yellow 11 and Basazol 46L. Three mediators were tested: ABTS, HBT and violuric acid. Laccase/ABTS was most effective with 60% of the color being removed. The level of color removal was maintained at 60% even when ABTS concentration was lowered from 5 mM to 0.01 mM. When laccase/1 mM ABTS was applied to Direct Yellow 11 in solution, the majority of color loss occurred within 60 minutes. The ability of soybean (SBP) and horseradish (HRP) peroxidases and laccase to decolorize Direct Yellow 11 and Basazol 46L in solution was also examined. The results demonstrated that these two recalcitrant dyes could be effectively decolorized by enzymatic treatments by horseradish peroxidase, soybean peroxidase, and laccase with ABTS as mediator. SBP is effective from pH 4.5 to 8.5. The stilbene dye Direct Yellow 11 responded to both SBP and laccase/ABTS. For the methine dye Basazol 46L, SBP was a more effective treatment than HRP or laccase/ABTS. Basazol 46L responded quickly to SBP treatment with 74% reduction in signal intensity within 5 minutes. To evaluate the effectiveness of laccase/ABTS treatment, pulp dyed with Direct Yellow 11 and three commercial colored pulps were subjected to seven different bleaching treatments. These treatments consisted of 1)laccase/ABTS; 2)laccase/ABTS followed by alkaline extraction; 3)laccase/ABTS followed by bleaching with sodium dithionite; 4)oxygen bleaching; 5)oxygen bleaching followed by dithionite treatment; 6)alkaline hydrogen peroxide bleaching; and 7)alkaline peroxide bleaching followed by dithionite treatment. The best results were obtained by including reductive bleaching with sodium dithionite. For Direct Yellow 11 dyed pulp, laccase/ABTS followed by dithionite yield comparable reduction in color to oxygen or peroxide followed by dithionite.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Sept. 16, 2009). Includes bibliographical references (p. 87-96).

Stilbene containing polymers are a group of interesting and versatile polymers. The pendent phenyl ring along the polymer backbone can impart unusual rigidity to the polymer backbone due to steric repulsion. By functionalizing stilbene, a variety of functional groups and ionic groups can be precisely placed along the polymer chain with tunable charge density. Therefore, stilbene containing polymers are potentially rod-like polyelectrolytes with controllable charges and charge density. They are the basis of a novel group of rigid synthetic polyelectrolytes and can be used for furthering our knowledge of rigid polyelectrolytes. A novel series of methyl substituted stilbenes were synthesized and copolymerized with maleic anhydride. A conversion-time study was undertaken to understand the methyl substituent effect on copolymerization rates. Methyl substituted stilbene-maleic anhydride copolymer compositions were determined by quantitative ¹³C 1D NMR. SEC measurements showed the weight average molecular weights of these copolymers vary from 3 000 to over 1 000 000 g/mol. No glass transition temperature or crystalline melting temperature was observed between 0 °C and 250 °C by DSC. TGA showed that these polymers have 5% weight loss around 290 °C. Precursors to a polycation and a polyanion based on functionalized stilbenes and maleimides have been prepared: poly(di-t-butyl-(E)-4,4′-stilbenedicarboxylate-co- N-(4-(t-butoxycarbonyl)phenyl)maleimide) and poly(N,N,Nâ ,Nâ -tetraalkyl-4,4′-di- aminostilbenes-co-N-4-(N′,N′-dimethylaminophenyl)-maleimide). These copolymer precursors were characterized by ¹H NMR, SEC, TGA, and DSC. The ¹H NMR spectrum indicated the rigidity of copolymer backbones. SEC measurements showed the weight average molecular weights of these copolymers vary from 5 000 to 11 700 g/mol. No glass transition temperature or crystalline melting temperature was observed between 0 °C and 175 °C by DSC for poly(di-t-butyl-(E)-4,4′-stilbenedicarboxylate-co-N-(4-(t-butoxy- carbonyl)phenyl)maleimide). TGA showed that this polymer has 5% weight loss around 210 °C and 26% weight loss on the first stage of decomposition which corresponds to elimination of t-butyl functional group in the copolymer. The homopolymerization of EMS-III via free radical polymerization, anionic polymerization and cationic polymerization was attempted. However, no polymer was obtained from any of these polymerization methods. In anionic polymerization, the solution changed to red upon the addition of the initiator sec-bu-Li, indicating the successful addition of the sec-bu-Li to EMS-III. However, the initiated monomer did not propagate to form homopolymer. / Master of Science

Les processus neuro-inflammatoires sont observés dans de nombreux troubles neurodégénératifs. Les cellules microgliales étant les principales cellules immunitaires du système nerveux central, plusieurs recherches ont été menées afin de déterminer des molécules possédant des propriétés anti-inflammatoires au niveau de ces cellules. Une famille de polyphénols, les stilbènes (des dérivés du resvératrol), présentent des activités anti-inflammatoires au niveau périphérique et central. Dans notre étude, nous avons premièrement évalué les propriétés anti-inflammatoires de 25 stilbènes en déterminant leur capacité à inhiber la libération de NO dans un modèle de cellules microgliales BV-2 activées par le LPS. Dix stilbènes inhibent significativement cette production avec des IC50 comprises entre 3,9 ± 0,7 et 23,4 ±1,0 µM. Parmi ces composés, 1 monomère (moracine M) et 2 tétramères du resvératrol (vitisines A et B) diminuent la synthèse d’iNOS, enzyme responsable à la libération de NO, au niveau transcriptionnel et traductionnel. Nous avons ensuite mis en évidence que la moracine M inhibe la phosphorylation d’ERK1/2 et JNK (deux MAPK) et d’Akt (la voie PI3K/Akt) dans des cellules BV-2 activées. Ces enzymes étant impliquées dans la signalisation de la réponse inflammatoire, elles induisent la production de plusieurs médiateurs inflammatoires. La moracine M inhibe significativement la production de certains d'entre eux (NO, TNF-α, IL-1β et PGE2). Ce stilbène attenue également la synthèse de la protéine de mPGEs-1 (enzyme impliquée à la production de PGE2). Ainsi, la moracine M pourrait être un candidat potentiel pour prévenir l’inflammation impliquée dans les maladies neurodégénératives. / Chronic neuro-inflammatory processes observed in many neurodegenerative disorders. Microglia are the main immune cells of the central nervous system. Many studies have been conducted to find molecules with anti-inflammatory properties in the central nervous system. A family of polyphénols, Stilbenoids (resveratrol derivatives), showed anti-inflammatory effects in peripheral and central levels.In this study, we have first evaluated anti-inflammatory effects of 25 stilbenes for their potential to inhibit NO release by LPS-activated BV-2 microglial cells. Ten stilbenes significantly reduced LPS-induced NO production with IC50 ranging from 3.9 ± 0.7 to 23.4 ±1.0 µM. Among these molecules 1 monomer (moracin M) and two tetramers (vitisins A and B) attenuated the expression of iNOS, a responsible enzyme for NO release on transcriptional and translational levels. Then, we have demonstrated that moracin M inhibits ERK1/2 and JNK phosphorylation of MAPK pathway and Akt phosphorylation of PI3K/Akt pathway, two signaling pathways involved in the inflammatory response in activated BV-2 cells. Indeed, the activation of these pathways leads to the production of several inflammatory mediators. We have shown that moracin M significantly inhibits the production of certain mediators such as NO, TNF-α, IL-1β and PGE2. This stilbene reduces the synthesis of mPGES-1 protein (an enzyme involved in the production of PGE2). In conclusion, we suggest that moracine M could be a potential candidate prevents the inflammation which involved in the progress of neurodegenerative diseases.

Stilbenoids possess a wide range of biological properties such as, anticancer, antiplatelet aggregation, antiestrogenic, antibacterial, antifungal and antiatherogenic, etc. Owing to these therapeutic values, a great deal of attention attracted in the synthesis of derivatives of stilbenes. During the course of the study, G6 a novel stilbenoid was discovered, through high throughput screening, to be a potent inhibitor of mutated JAK2-V617F. The mutated JAK2 variant has been implicated in various myeloproliferative disorders (MPDs) including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) has been targeted by therapeutics. Chapter 2 describes the synthesis of analogs of the stilbenoid G6 and N-substituted stilbenes bisoxazines by utilizing Mcmurry reaction and Mannich condensation methods. The main emphasis of this work is to develop novel stilbenoids as inhibitors of JAK2-V617F mutated Jak2 enzyme in Human erythroleukemia cells (HEL) since this mutation is discovered in the majority of patients with myeloproliferative disorders (MPDs). Using Mcmurry reaction, five novel trans-hydroxystilbenes have been synthesized from carbonyl compounds. Subsequently using Mannich coupling with five secondary amines and five primary amines, 25 novel stilbenoids and 9 novel N-substituted stilbene bisoxazines have been synthesized. In HEL cell assay, 8 stilbenoid analogues have been identified as potent inhibitors of Jak2 enzyme. Chapter 3 describes the modification of ketamine structurally for the synthesis of novel analogues to study for their agonist activity at GABAA receptors and antagonist activity at NMDA receptors. Ligand gated ion channels like GABAA and NMDA receptors are membrane-embedded proteins at synaptic cleft which controls intercommunication among neurons and plays an important role in motor control activity, learning. GABAA receptors are responsible for inhibitory action potentials while NMDA receptors are responsible for excitory action potentials. Ketamine, known as dissociative anesthetic, produces profound analgesia at low doses to a unique cardiovascular stimulation and a cataleptic state at higher doses with dose dependent side effects like vivid dreams, disruptions of cognitive functions. The main emphasis of this work is the synthesis of novel analogues of ketamine by transforming carbonyl group in ketamine to imine functionality with small to bulkier groups and to identify an analogue of ketamine which is highly potent in its activity at the both GABAA and NMDA receptors and improved clinical actions. Studies of analogues activity against GABAA subtypes α6Β2δ, α1Β2γ2 receptors and NMDA subtypes NR1/2A, NR1/2B, NR1/2D receptors have been described. Chapter 4 describes the formal synthesis of (±)-Rolipram and the chemoenzymatic synthesis of -aryl--lactone, a Rolipram analogue. The key steps, Pd catalyzed arylation of diethylmalonate and the efficient use of selective acylation of 1, 3-diol entails the formal synthesis of (±)-Rolipram. The regioselective deacylation of Β-aryl-1, 4-diacetate by lipase Pseudomonas Sepacia entails the formation of Β-aryl-γ-lactone. The efficient use of various methods including halogen exchange, Heck arylation of diethylmaleate and lactonization for the synthesis of Β-aryl-γ-lactone have been discussed. The present work provides an efficient and general route to γ-lactones.

Submitted by (edna.saturno@ufrpe.br) on 2016-06-13T14:10:30Z No. of bitstreams: 1 Ellen Cordeiro Bento da Silva.pdf: 1569026 bytes, checksum: 6366a64f83b2fc475c8cead9d8dc65aa (MD5) / Made available in DSpace on 2016-06-13T14:10:30Z (GMT). No. of bitstreams: 1 Ellen Cordeiro Bento da Silva.pdf: 1569026 bytes, checksum: 6366a64f83b2fc475c8cead9d8dc65aa (MD5) Previous issue date: 2014-02-26 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / It was aim to evaluate the effect of different concentrations of phenolic antioxidants on freezability of goats sperm, as well as their action during centrifugation in continuous Percoll density gradients and after selected semen freezing. Six goat semen pools were used for each of the three experiments. In the first two experiments, each semen pool was processed and diluted in the skimmed milk based extender (7 % glycerol), with or without antioxidants, according to experiment and experimental group [1 Experiment: 0, 15, 25, 50, 75 or 100 μM catechin or epigallocatechin gallate (EGCG); Experiment 2: 0, 15, 25, 50, 75 or 100 μM resveratrol or quercetin]. In Experiment 3, each semen pool was centrifugated in continuous Percoll density gradients and frozen (with or without antioxidants) according to experimental groups (NS=non selected; S= selected; SC75= selected with 75 μM catechin; SE100= selected with 100 μM EGCG; SQ25=selected with 25 μM quercetin; SR25=selected with 25 μM resveratrol; SR75=selected with 75 μM resveratrol). In Experiment 1, immediately after thawing, the straight linear velocity (VSL) and average path velocity (VAP) were greater (P<0.05) in 15 μM catechin than in 50 and 100 μM; wobble (WOB) was higher (P<0.05) in catechin 0, 15 and 25 μM than in 100 μM; beat cross frequency (BCF) was higher (P<0.05) in 75 and 100 μM catechin than in 0 μM. Progressive motility (PM) was greater (P<0.05) with 0 and 15 μM EGCG than with 50 and 75 μM; and linearity (LIN) was higher with 0 μM EGCG than with 100 μM. In Experiment 2 WOB was higher (P<0.05) in 0 and 25 μM resveratrol or 0 μM quercetin than 100 μM, immediately after thawing. In Experiment 3, immediately after sexing, PM, LIN, straightness (STR) and WOB from sexed groups were higher (P<0.05) than those from NS; SC75, VSL was higher (P<0.05) in SR25 and SR75 than in NS; amplitude of lateral movement of the head (ALH) was higher (P<0.05) in the NS than in other groups. SQ25 reduced (P<0.05) the mitochondrial membrane potential, compared to other groups. After thawing, PM, LIN, WOB, VSL and VAP were higher (P<0.05) in sexed groups than in NS, except to SE100 and SQ25; SC75 had greater (P<0.05) STR than NS; ALH was lower (P<0.05) in S, SC75, SR25 and SR75 than in NS; BCF was lower (P<0.05) in S than in NS; plasma membrane integrity was higher (P<0.05) in sexed groups than in NS, except to SE100; the percentage of intact and not dead cells was greater (P<0.05) in sexed groups than in NS. We concluded that, under the experimental conditions used, high concentrations (50 to 100 μM) of catechin inhibit the kinematics of frozen goat sperm in transitory way, and that resveratrol does not have any influence on goat semen freezability. Moreover, sex selection in continuous Percoll density gradients is feasible methodology to goats and compatible with freezing process; independent of antioxidant therapy used. / Objetivou-se avaliar o efeito de diferentes concentrações de antioxidantes fenólicos sobre a congelabilidade de espermatozoides caprinos, bem como a ação destes durante a centrifugação em gradientes contínuos de densidade de Percoll e após congelação do sêmen selecionado. Foram utilizados seis pools de sêmen caprino por experimento. Nos dois primeiros experimentos cada pool de sêmen foi processado e diluído em meio à base de leite desnatado (7% glicerol), acrescido ou não de antioxidantes, de acordo com o experimento e o grupo experimental [Experimento 1: 0, 15, 25, 50, 75 ou 100 μM de catequina ou de epigalocatequina galato (EGCG); Experimento 2: 0, 15, 25, 50, 75 ou 100 μM de resveratrol ou de quercetina]. No terceiro experimento, cada pool de sêmen foi centrifugado em gradiente contínuo de densidade de Percoll e congelado, de acordo com o grupo experimental (NS=não selecionado; S=selecionado; SC75=selecionado com 75 μM de catequina; SE100=selecionado com 100 μM de EGCG; SQ25=selecionado com 25 μM de quercetina; SR25=selecionado com 25 μM de resveratrol; SR75=selecionado com 75 μM de resveratrol). No Experimento 1, imediatamente após a descongelação, as velocidades linear progressiva (VSL) e média da trajetória (VAP) foram superiores (P<0,05) no grupo tratado com 15 μM de catequina do que com 50 e 100 μM; a oscilação (WOB) foi maior (P<0,05) com 0, 15 e 25 μM de catequina do que com 100 μM; e o batimento flagelar cruzado (BCF) foi maior (P<0,05) com 75 e 100 μM de catequina do que com 0 μM. A motilidade progressiva (MP) foi maior (P<0,05) com 0 e 15 μM de EGCG do que com 50 e 75 μM e a linearidade (LIN) foi maior (P<0,05) com 0 μM de EGCG do que com 100 μM. No Experimento 2, a WOB foi maior (P<0,05) com 0 e 25 μM de resveratrol ou 0 μM de quercetina do que com 100 μM, imediatamente após a descongelação. Para o Experimento 3, a MP, LIN, retilinearidade (STR) e WOB dos grupos selecionados em gradientes de Percoll foram maiores (P<0,05) do que as do NS; nos grupos SC75, SR25 e SR75 a VSL foi maior (P<0,05) do que no NS; a amplitude de deslocamento lateral de cabeça (ALH) foi maior (P<0,05) no grupo NS do que nos demais e o SQ25 reduziu (P<0,05) o potencial de membrana mitocondrial, em relação aos demais grupos. Após descongelação do sêmen, a MP, LIN, WOB, VSL e VAP foram maiores (P<0,05) nos grupos selecionados do que no NS, com exceção do SE100 e SQ25; o SC75 teve maior (P<0,05) STR do que o NS; a ALH foi menor (P<0,05) nos grupos S, SC75, SR25 e SR75 do que no NS; e o BCF foi menor no S do que no NS. A integridade de membrana plasmática foi maior (P<0,5) nos grupos selecionados do que no NS, com exceção do SE100; a porcentagem de células intactas e de não mortas foi maior (P<0,05) nos grupos selecionados do que no NS. Conclui-se que altas concentrações (50 a 100 μM) de catequina e EGCG inibem a cinética de espermatozoides congelados de caprinos, em caráter transitório, e que o resveratrol e a quercetina não têm qualquer influência sobre a congelabilidade do sêmen caprino. Por outro lado, a seleção de espermatozoides em gradientes contínuos de densidade de Percoll é uma metodologia viável para a espécie caprina e compatível com o processo de congelação; independente da terapian antioxidante usada.

Ce travail porte sur la mise au point et l’étude d’un nouveau système de culture in vitro permettant une production efficace de dérivés de t-resvératrol. Pour cela, des lignées de racines transformées de Vitis vinifera L. ont été établies, stabilisées et criblées. Le faible taux de croissance a été amélioré par criblage de différents milieux de cultures et différentes concentrations en saccharose, montrant une préférence pour le milieu ½ SH avec 2% (p/v) de saccharose. Les cinétiques de croissance et de production de stilbènes ont ensuite été évaluées dans ces conditions. Nous avons mis en évidence une production basale de stilbènes par les racines, bien que celles-ci soient aussi fortement inductibles par des traitements d’élicitation par du méthyl jasmonate et des cyclodextrines. Dans ces conditions, les racines transformées de vigne ont montré une forte capacité de production et d’excrétion de différents stilbènes. Un profilage phytochimique des racines et de leur milieu de culture a été réalisé par CPC-RMN et LC-MS pour illustrer cette diversité. En parallèle des études sur un modèle simplifié, les cultures de cellules en suspension ont été réalisées pour rechercher des transporteurs candidats pour l’excrétion active du t-resvératrol vers son lieu d’action. Une approche de protéomique globale de la membrane plasmique par iTRAQ a permis de cibler des candidats de type ABC transporteurs, qui ont ensuite été caractérisés par des approches d’étude de l’expression de leurs transcrits. Ensemble, ces résultats soutiennent l’intérêt de cet outil pour l’étude du métabolisme ainsi que pour la bioproduction de stilbènes. / This work aims at the setting up and the study of a new in vitro culture for a cost-effective production of highly pure resveratrol derivatives. To answer that need, hairy root lines of Vitis vinifera L. were established, stabilized and screened. Their low growth rate was improved by testing various culture media and different sucrose concentrations. The best growth rate was obtained with ½ SH medium with 2% (w/v) sucrose. The growth and stilbene production kinetics were assessed in these conditions. A constitutive production of stilbenes was observed in roots, though they showed a strong response to eliciting treatments such as methyl jasmonate and cyclodextrines. In these conditions, the hairy roots yielded high stilbene production in terms of concentrations as well as diversity. The diversity of the stilbenes obtained has been described by biochemical profiling of both root and their culture medium extracts using CPC-NMR and LC-MS. Together with the study of hairy roots, we used cell suspensions cultures as a simplified model to study the excretion of t-resveratrol. Candidate transporters have been screened for using a global plasma membrane proteomic approach based of iTRAQ. ABC G transporters were pointed out as promising candidates and were further characterized by studying their gene expression. Together, these results support the interest of grapevine hairy root cultures for the study of stilbenes metabolism and their bioproduction.