Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-09-15T15:28:18Z No. of bitstreams: 1 Dissertação Caline Gomes Ferraz.pdf: 5892044 bytes, checksum: c69c009c9c27a1226b6cad92dfad11f6 (MD5) / Approved for entry into archive by Vanessa Reis (vanessa.jamile@ufba.br) on 2016-09-15T15:42:14Z (GMT) No. of bitstreams: 1 Dissertação Caline Gomes Ferraz.pdf: 5892044 bytes, checksum: c69c009c9c27a1226b6cad92dfad11f6 (MD5) / Made available in DSpace on 2016-09-15T15:42:14Z (GMT). No. of bitstreams: 1 Dissertação Caline Gomes Ferraz.pdf: 5892044 bytes, checksum: c69c009c9c27a1226b6cad92dfad11f6 (MD5) / Capes / O presente trabalho relata o estudo fotoquímico do extrato hexânico do caule de Clusia burle-marxii (Clusiaceae). O espécime foi coletado nas proximidades da Cachoeira do Fraga no município de Rio de Contas, Chapada Diamantina, Bahia. Do extrato hexânico do caule possibilitou o isolamento, identificação e determinação de algumas classes de metabólitos. Foram isolados dois triterpenos, quatro esteróides, dez benzofenonas e dez ésteres graxos. Estas substâncias foram obtidas por processos de fracionamento em coluna cromatográfica e cromatografia em camada delgada preparativa. Os triterpenos (Friedelina e Friedelinol), os esteróides (β- Sitosterol, Estigmast-5-eno-3β,7β-diol, Estigmast-5-eno-3β,7α-diol, Estigmast-7-en- 3β-ol-6-ona) e a benzofenona (Nemorosonol) foram identificadas por analises de RMN de 1H e RMN de 13 C, DEPT e por comparação com os dados descritos na literatura. Este procedimento foi usado para determinação estrutural do esteróide inédito Estigmast-7- en- 3β-ol-6-ona. Os ésteres graxos (Tetradeconoato de metila, Pentadeconoato de metila, Hexadecanoato de metila, Heptadecanoato de metila, Octadenoato de metila, Nonadeconoato de metila, Eicosanoato de metila e Docosonoato de metila) foram identificados após analise de EM. Para determinação estrutural da benzofenona inédita foram utlilizadas as técnicas de RMN de 1H e RMN de 13C, DEPT, HMBC, HSQC. / The present work described the phytochemistry study the wood hexane extracts studies of specie Clusia burle-marxii. The specie was collected nearby Cachoeira do Fraga in the Rio de Contas, Chapada Diamantina, Bahia, Brazil. The wood hexane extracts allowed the isolations, identification and structural determination of some metabolites class. Two triterpenes, four steroids, ten benzophenones, ten fatty esters. These substances were obtained by fractionation through preparative thin layer chromatographyc and chromatographyc column. The triterpenes ( Friedeline and Friedelinol), the steroids (β- Sitosterol, Stigmast-5-ene- 3β,7β-diol, Stigmast-5-ene-3β,7α-diol, and the benzophenone (Nemorosonol) were identified by 1H NMR and 13C NMR, DEPT analysis and comparson with the data from literature. This same procedure was used in the novel steroid Stigmast-7-en- 3β-ol-6- ona structural determination. The fatty esters (methyl tetradecanoate, methyl pentadecanoate, methyl hexadecanoate, methyl heptadecanoate, methyl octadecanoate, methyl nonadecanoate, methyl eicisanoate and methyl docosanoate) were identified by MS analysis. The structural determination of the new benzophenone was performed by NMR spectrocopyc techniques (1H NMR and 13C NMR, DEPT, HMBC, HMQC).

L'artémisinine (ART) est un composé antipaludique majeur très actif sur les souches multi-résistantes de Plasmodium falciparum. Cependant, son application clinique est limitée par sa faible solubilité en milieu aqueux et sa faible biodisponibilité par voie orale. La mise en œuvre de cyclodextrines (CDs) bioestérifiées et de dérivés amphiphiles polyoxyéthylénés permet de viser deux objectifs : i) d'une part d'améliorer la concentration aqueuse d'ART à travers son association aux vecteurs colloïdaux de CDs modifiées et ii) d'autre part d'améliorer sa biodisponibilité et son efficacité thérapeutique à travers la décoration de la surface des vecteurs. La décoration surfacique est sensée augmenter le temps de circulation sanguine des nanovecteurs de manière à maintenir des doses plasmatiques efficaces d'ART sur une longue période, suite à une administration intraveineuse. Des suspensions colloïdales stables suffisamment chargées d'ART ont été mises au point permettant de palier le problème d'insolubilité en milieu aqueux de la molécule active et donc d'envisager son administration par voie parentérale. Les essais de lyodisponibilité indiquent que l'ART est libérée des nanosystèmes pendant une période de 4 jours pour les nanoréservoirs et de 11 jours pour les nanosphères. En plus des caractérisations physico-chimiques et pharmacotechniques, les potentialités des nanoparticules décorées en surface ont été évaluées et comparées au cours de tests biologiques. In vitro, l'ART mise en forme a montré une bonne efficacité sur des souches plasmodiales choloroquino-sensibles (3D7) et chloroquino-résistantes (K1) avec des CI50 très faibles de l'ordre de 3 à 6 ng/mL. Le concept de co-nano-assemblage de dérivés amphiphiles de γ-CD-C10 bioestérifiée et de polyéthylène glycol (PEG) dans les conditions de nanoprécipitation semble être une approche intéressante pour conférer des propriétés de furtivité aux nano-systèmes de γ-CD-C10. En effet, les études in vitro mettent en évidence une diminution significativement de la phagocytose par les cellules macrophagiques et/ou de l'adsorption des protéines du complément sérique à la surface des nanoparticules de γ-CD-C10 décorées par le polysorbate 80, le stéarate de PEG1500, et le DMPE-mPEG2000. In vivo, nous observons une augmentation du temps de circulation sanguine des nanoréservoirs γ-CD-C10/polysorbate 80 et des nanosphères γ-CD-C10/DMPE-mPEG2000. Enfin, les études de pharmacocinétique réalisées chez le rat montrent que les paramètres pharmacocinétiques de l'ART sont améliorés lorsqu'elle est associée aux deux systèmes nanoparticulaires précédents. En effet, des valeurs de clairance plasmatique très faibles et de temps de demi-vie plasmatique longs (3 et 5 heures, respectivement) de l'ART ont été enregistrées avec ces deux formulations. Ces formes vectorisées d'ART mises au point ouvrent de perspectives intéressantes pour la prise en charge thérapeutiques des crises de paludisme sévère. / Artemisinin (ART), an endoperoxide sesquiterpene lactone antimalarial drug isolated from a Chinese medicinal herb (Artemisia annua), has a fast action against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, making it very effective in the treatment of multidrug-resistant malaria. However, its poor aqueous solubility, short half-life, and high first-pass metabolism limit its use in therapeutics. The purpose of the present study was to investigate the potential of self-assembled bio-transesterified CD-based nanocarriers as ART delivery systems for an intravenous route. The objective of our study was twofold: (i) to improve the ART dosage through its association with CD esters-based nanocarriers, (ii) to ensure a sufficient blood circulation time of the nanocarriers through their surface decoration, which is a prerequisite to reach infected erythrocytes after systemic administration. Stable colloidal suspensions with good ART association rate were developed to solve the problem of insolubility in aqueous medium of the active molecule and therefore consider its parenteral administration. The γ-CD-C 10 based nanospheres showed a significant sustained release profile of ART extended up to 4 days for nanosphères and 11 days for nanoreservoirs. In addition to the physicochemical characterizations, the potential of nanoparticles decorated on the surface were evaluated and compared in biological tests. The results from this study indicate that ART-loaded nanosystems, mainly PEGylated ones exhibit satisfactory in vitro activity against Chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum with very low IC50 of the order of 3 to 6 ng / mL. The concept of co-assembly of nano-amphiphilic derivatives of γ-CD-C10 bioestérifiée and polyethylene glycol (PEG) under conditions of nanoprecipitation seems to be an interesting approach to impart stealth nano-systems-γ-CD C10. Indeed, in vitro studies show a significant decrease in phagocytosis by macrophages and/or adsorption of serum complement proteins on the surface of nanoparticles of γ-CD-C10 decorated by polysorbate 80, PEG1500 stearate, and mPEG2000-DMPE. In vivo, we observed an increase in blood circulation time of nanoreservoirs γ-CD-C10/polysorbate 80 and nanospheres γ-CD-C10/DMPE-mPEG2000. Finally, pharmacokinetic studies in rats show that the pharmacokinetics of ART are enhanced when combined with previous two nanoparticle systems. Indeed, values of plasma clearance and very low time of long plasma half-life (3 to 5 hours, respectively) of ART were recorded with both formulations. These colloidal forms of ART developed open up interesting prospects for the therapeutic treatment of severe malaria.

Emulsões são sistemas dispersos constituídos de pelo menos duas fases líquidas imiscíveis e um agente emulsificante para estabilização das mesmas. a fase dispersa destesw sistemas é conhecida como fase interna e o meio dispersante como fase externa, porém, são sistemas termodinamicamente instáveis. A presença de cirstais líquidos aumenta a estabilidade destas dispersões e além de alterar a viscosidade. São capazes de promover o encapsulamento de ativos, permitindo liberação sustentada, bem como a proteção dos fármacos foto- e termosensíveis. O óleo de girassol é uma interessante fase oleosa em uma emulsão, pois possui proprie3dades cicatrizantes devido à alta concentração de ácido linoléico e propriedades antioxidantes devido à presença de polifenóis e vitamina E Possuemaplicações em diferentes áreas como: cosméticos, alimentos, veículos de medicamentos e outros. Assim, os objetivos deste estudo foram desenvolver emulsões estáveis contendo cristais líquidos a partir da mistura de óleo de girassol (Helianthus annus L.) e mineral (vaselina líquida), caracterizá-las e avaliar a influência de diferentes ésteres graxos na formação dos cristais líquidos. As formulações foram desenvolvidas utilizando o método de diagrama e pseudo-diagrama ternário, a partir dos quais foram selecionadas duas formulações que demonstraram se estáveis e apresentaram cristais líquidos durante todo o teste de estabilidade acelerada. As mesmas foram aditivadas com extrato glicólico de polifenois e ésteres graxos e permaneceram estáveis com cristal líquido. A caracterização reológica observou-se fluxo pseudo-plástico e tixotrópico, ideal para produtos farmacêuticos e cosméticos. O óleo de girassol apresentou atividade antioxidante mesmo quando aquecidos para o processo de emulsificação pelo método do radical DPPH·. As cadeias carbônicas dos ésteres graxos utilizados em produtos cosméticos podem influenciar na formação e manutenção dos cristais líquidos. Por meio dos testes in vivo observou-se que as formulações desenvolvidas promoveram aumento prolongado da hidratação da pele e não foram observados sinais de irritação cutânea. / Emulsions are dispersed systems consisting of at least two immiscible liquid phases and an emulsifying agent to stabilize them. The dispersed phase of these systems is known as the internal phase and the dispersing environ is the external phase, which are, however, thermodynamically unstable systems. The presence of liquid crystals increases the stability of these dispersions and also change the viscosity. They are able to promote the encapsulation of active, allowing sustained release as well as the protection of photo-and thermo-sensitive drugs. Sunflower oil is an interesting phase in an oily emulsion, because it has healing properties due to the high concentration of linoleic acid, and antioxidant properties due to the presence of polyphenols and vitamin E. They have applications in different areas such as cosmetics, food, medicines and other vehicles. The objectives of this study were to develop stable emulsions containing liquid crystals from a mixture of sunflower oil (Helianthus annus L.) and mineral (mineral oil), characterize them and evaluate the influence of different fatty esters in the formation of liquid crystals. The formulations were developed using the method of diagram and ternary pseudo-diagram, from which we selected two formulations that have been demonstrated stable and presented as liquid crystals throughout the accelerated stability test. They were doped with polyphenols glycolic extracts and acid esters, and have been kept stable with liquid crystal. At the rheological characterization was observed pseudo-plastic flow and thixotropic, ideal for pharmaceuticals and cosmetics. Sunflower oil showed antioxidant activity even when heated to the emulsification process by the radical DPPHo method. The carbon chains of fatty esters used in cosmetics can influence the formation and maintenance of liquid crystals. In vivo tests showed that the formulations developed promoted prolonged increase in skin hydration and were not seen signs of skin irritation.

Emulsões são sistemas dispersos constituídos de pelo menos duas fases líquidas imiscíveis e um agente emulsificante para estabilização das mesmas. a fase dispersa destesw sistemas é conhecida como fase interna e o meio dispersante como fase externa, porém, são sistemas termodinamicamente instáveis. A presença de cirstais líquidos aumenta a estabilidade destas dispersões e além de alterar a viscosidade. São capazes de promover o encapsulamento de ativos, permitindo liberação sustentada, bem como a proteção dos fármacos foto- e termosensíveis. O óleo de girassol é uma interessante fase oleosa em uma emulsão, pois possui proprie3dades cicatrizantes devido à alta concentração de ácido linoléico e propriedades antioxidantes devido à presença de polifenóis e vitamina E Possuemaplicações em diferentes áreas como: cosméticos, alimentos, veículos de medicamentos e outros. Assim, os objetivos deste estudo foram desenvolver emulsões estáveis contendo cristais líquidos a partir da mistura de óleo de girassol (Helianthus annus L.) e mineral (vaselina líquida), caracterizá-las e avaliar a influência de diferentes ésteres graxos na formação dos cristais líquidos. As formulações foram desenvolvidas utilizando o método de diagrama e pseudo-diagrama ternário, a partir dos quais foram selecionadas duas formulações que demonstraram se estáveis e apresentaram cristais líquidos durante todo o teste de estabilidade acelerada. As mesmas foram aditivadas com extrato glicólico de polifenois e ésteres graxos e permaneceram estáveis com cristal líquido. A caracterização reológica observou-se fluxo pseudo-plástico e tixotrópico, ideal para produtos farmacêuticos e cosméticos. O óleo de girassol apresentou atividade antioxidante mesmo quando aquecidos para o processo de emulsificação pelo método do radical DPPH·. As cadeias carbônicas dos ésteres graxos utilizados em produtos cosméticos podem influenciar na formação e manutenção dos cristais líquidos. Por meio dos testes in vivo observou-se que as formulações desenvolvidas promoveram aumento prolongado da hidratação da pele e não foram observados sinais de irritação cutânea. / Emulsions are dispersed systems consisting of at least two immiscible liquid phases and an emulsifying agent to stabilize them. The dispersed phase of these systems is known as the internal phase and the dispersing environ is the external phase, which are, however, thermodynamically unstable systems. The presence of liquid crystals increases the stability of these dispersions and also change the viscosity. They are able to promote the encapsulation of active, allowing sustained release as well as the protection of photo-and thermo-sensitive drugs. Sunflower oil is an interesting phase in an oily emulsion, because it has healing properties due to the high concentration of linoleic acid, and antioxidant properties due to the presence of polyphenols and vitamin E. They have applications in different areas such as cosmetics, food, medicines and other vehicles. The objectives of this study were to develop stable emulsions containing liquid crystals from a mixture of sunflower oil (Helianthus annus L.) and mineral (mineral oil), characterize them and evaluate the influence of different fatty esters in the formation of liquid crystals. The formulations were developed using the method of diagram and ternary pseudo-diagram, from which we selected two formulations that have been demonstrated stable and presented as liquid crystals throughout the accelerated stability test. They were doped with polyphenols glycolic extracts and acid esters, and have been kept stable with liquid crystal. At the rheological characterization was observed pseudo-plastic flow and thixotropic, ideal for pharmaceuticals and cosmetics. Sunflower oil showed antioxidant activity even when heated to the emulsification process by the radical DPPHo method. The carbon chains of fatty esters used in cosmetics can influence the formation and maintenance of liquid crystals. In vivo tests showed that the formulations developed promoted prolonged increase in skin hydration and were not seen signs of skin irritation.

L'utilisation de matières premières renouvelables issues de la biomasse a récemment trouvé un regain d'intérêt pour des raisons économiques et écologiques. Les triglycérides issus d'oléagineux, les terpènes extraits de plantes, et les dérivés phénoliques contenus dans la lignine représentent de grandes familles de molécules naturelles qui offrent un potentiel important pour l'accès à des produits à haute valeur ajoutée. Dans ce contexte, des transformations par catalyse homogène offrent des perspectives intéressantes dans le cadre d'une chimie verte et durable. La métathèse des oléfines en présence de catalyseurs commerciaux du ruthénium a permis d'accéder à de nouveaux terpènes fonctionnalisés par métathèse croisée avec des oléfines fonctionnelles pauvres en électron. L'application de la même réaction de métathèse à des dérivés de l'eugénol en contrôlant en même temps la position de la double liaison terminale dans ces substrats a permis l'accès à de nouveaux dérivés allyliques du phénol par métathèse croisée avec des acrylates, l'acrylonitrile et les acrylamides. Enfin une cascade réactionnelle mettant en jeu la métathèse croisée de dérivés d'esters gras, de terpènes et de l'eugénol insaturés avec des chlorures allyliques suivie d'une réaction d'élimination a conduit à une méthode générale de formation de diènes conjugués terminaux. Ces réactions séquentielles en un seul pot permettent de diminuer les quantités de déchets générés pendant les traitements intermédiaires. Ces transformations catalytiques de ressources renouvelables ont été réalisées dans des solvants ''verts'' tels que des dialkyl carbonates ou en absence de solvant, leur permettant ainsi de répondre à plusieurs critères de la chimie verte. / The utilization of renewable feedstocks arising from biomass has recently found a renewed interest for economic and ecological reasons. Triglycerides arising from oil seeds, terpenes extracted from plants, and phenolic derivatives found in lignin represent important families of natural molecules with important potential for the access to high added value products. In this context, homogeneous catalytic transformations offer interesting perspectives towards green and sustainable chemistry. Olefin metathesis in the presence of commercially available ruthenium catalysts has given access to new functionalized terpenes using cross metathesis with electron deficient alkenes. The same type of reaction applied to eugenol derivatives controlling at the same time the position of their terminal double bond has provided access to new allylic derivatives of phenol by using acrylates, acrylonitrile and acrylamides as cross metathesis partners. Finally a cascade reaction involving cross metathesis of fatty ester, terpene and eugenol derivatives with allylic chlorides followed by an elimination reaction has led to a general method for the synthesis of terminal conjugated dienes. These sequential reactions in one pot allow decreasing the amount of wastes, which are usually generated during intermediate treatments. The reported catalytic transformations of renewable resources have been carried out in green solvents such as dialkyl carbonates or without solvent under neat conditions, and thus fulfill several criteria of green chemistry.