The shikimate pathway is responsible for the biosynthesis of essential aromatic metabolites and, as such, its enzymes are targets for the design of potential antimicrobial and herbicidal agents. The enzyme 3-dehydroquinate dehydratase (dehydroquinase, DHQase) catalyses the conversion of 3-dehydroquinate to 3-dehydroshikimate, the third step of the shikimate pathway. There are two types of DHQase, unrelated structurally and mechanistically. Type I DHQase catalyses the rection by via a covalently attached imine intermediate. Type II DHQase catalyses the reaction by way of an enolate intermediate. This thesis describes the synthesis of a series of potential inhibitors of type II DHQase. Inhibitors with C and N at C-3 and with both sp2 and sp3 character at this position were prepared. A potential type I DHQase inhibitor was also prepared. The biological evaluation of these inhibitors against type II DHQases from Mycobacterium tuberculosis and Streptomyces coelicolor and type I DHQase from Salmonella typhi is described. Inhibitors were evaluated by spectrophotometric assay. However, this proved inappropriate for some inhibitors with the S. coelicolor enzyme. The development of an alternative 1H NMR assay and its application to the evaluation of S. coelicolor DHQase inhibitors is therefore also described. Some insights into the structure activity relationships of type II DHQases, obtained from the results of these studies, are discussed.

The shikimate pathway is responsible for the biosynthesis of essential aromatic metabolites and, as such, its enzymes are targets for the design of potential antimicrobial and herbicidal agents. The enzyme 3-dehydroquinate dehydratase (dehydroquinase, DHQase) catalyses the conversion of 3-dehydroquinate to 3-dehydroshikimate, the third step of the shikimate pathway. There are two types of DHQase, unrelated structurally and mechanistically. Type I DHQase catalyses the rection by via a covalently attached imine intermediate. Type II DHQase catalyses the reaction by way of an enolate intermediate. This thesis describes the synthesis of a series of potential inhibitors of type II DHQase. Inhibitors with C and N at C-3 and with both sp2 and sp3 character at this position were prepared. A potential type I DHQase inhibitor was also prepared. The biological evaluation of these inhibitors against type II DHQases from Mycobacterium tuberculosis and Streptomyces coelicolor and type I DHQase from Salmonella typhi is described. Inhibitors were evaluated by spectrophotometric assay. However, this proved inappropriate for some inhibitors with the S. coelicolor enzyme. The development of an alternative 1H NMR assay and its application to the evaluation of S. coelicolor DHQase inhibitors is therefore also described. Some insights into the structure activity relationships of type II DHQases, obtained from the results of these studies, are discussed.

Today we can easily find the most diverse kind of information about a particular medicinal plant, but without scientific basis, making their use a potential risk to health. Overall, the findings on the safety and efficacy are based on precarious evaluations and popular use. There is a need for qualified professionals to access, critical analyze and assign such information in a way that it could be easily understood, not only by health professionals, but also by the users of these products. One example of these plants used in popular medicine, but without scientific evidence, is Euphorbia tirucalli L., popularly known as Dog-Stick, Pencil tree, or more commonly as Aveloz. This plant has been used for the treatment of many diseases, such as microbial diseases, immunossupression problems, and even in the cancer treatment. However, some works reveal precisely the opposite, namely that the latex of Euphorbia tirucalli can cause immunosuppression, and often is associated to the appearance of Burkitt's Lymphoma, a type of cancer. Lupeol was isolated and identificated from hexane fraction by GC-MS for the first time for the plant, among other 3 hydrocarbons, 7 long chain fat acids, 2 steroids, and 3 compounds of the vegetal metabolism. A preliminary phytochemistry screening allowed to the visualization of the principal groups in the plant. Polyphenols and condensed tannins contents were determined in the crude extract and fractions. Ethyl ether and ethyl acetate fractions showed the greatest antioxidant activity in the DPPH test. Antimicrobial activity was observed mainly against Candida albicans, Candida glabrata and Saccharomyces cereviseae, as well as for the opportunist algae Prototheca zopfii. A preliminary study of toxicity using Artemia saline and acute oral toxicity in mice, indicate the plant as low toxicity. The latex of the E. tirucalli, even in small doses (1%) can cause in vitro inhibition over the human Acetylcholinesterase enzyme. A prominent in vitro inhibitory activity over human platelets aggregation was also observed. The effects of the extract of the plant over the blood cells in a culture medium using ex-vivo blood samples of male Wistar rats were evaluated. The results demonstrated that the extract caused thrombocytopenia, leucopenia and lymphopenia. / Atualmente podemos encontrar facilmente as mais diversas informações sobre uma determinada planta medicinal, mas que carecem de fundamento científico, tornando assim seu uso um potencial risco a saúde. Em geral, as conclusões sobre segurança e eficácia são baseadas em avaliações precárias do uso popular. Portanto, há necessidade de que profissionais qualificados possam, além de acessar tais informações, analisá-las criticamente para disponibilizá-las de forma que sejam facilmente compreendidas, não só por profissionais da saúde, mas também pelos usuários destes produtos. Um exemplo destas plantas utilizadas na medicina popular, mas sem comprovação científica, é a Euphorbia tirucalli L., conhecida popularmente como Graveto-do-cão, Árvore Lápis, ou mais comumente como Aveloz. Esta planta tem sido utilizada para o tratamento de inúmeras enfermidades, como afecções microbianas, problemas de imunossupressão, cicatrização de berrugas e até mesmo no tratamento do câncer. Entretanto, alguns trabalhos revelam justamente o contrário, ou seja, que o látex da Euphorbia tirucalli pode causar imunossupressão, e freqüentemente encontra-se associado ao aparecimento do Linfoma de Burkitt, que é um tipo de câncer. Foram isolados e identificados por cromatografia gasosa acoplada a espectrometria de massas, 03 hidrocarbonetos, 07 ácidos graxos de cadeia longa, 02 esteróides, 03 compostos do metabolismo vegetal e 01 triterpeno, não relatado até o momento, o qual foi isolado da fração hexânica e identificado como sendo o lupeol. Foi realizada uma análise fitoquímica preliminar, o que permitiu a visualização dos grupos de compostos presentes na planta. A quantidade de polifenóis e taninos condensados foi determinada na planta e suas frações. Realizou-se o teste de atividade antioxidante e com ele verificamos uma excelente atividade das frações éter etílico e acetato de etila. Analisou-se a atividade antimicrobiana da planta e obtivemos resultados excelentes para os fungos Candida albicans, Candida glabrata e Saccharomyces cereviseae, bem como para a alga oportunista Prototheca zopfii. Realizou-se um estudo de toxicidade sobre a Artemia salina e estudo de toxicidade oral aguda. Os resultados apontam a espécie como sendo não tóxica. O látex da E. tirucalli, mesmo em doses pequenas (1%) pode causar inibição (in vitro) a enzima Acetilcolinesterase Humana. Uma acentuada atividade inibitória sobre a agregação plaquetária foi observada. O extrato da planta sobre cultura de células sanguíneas de ratos Wistar (exvivo) causou diminuição do número de leucocitos, linfócito e plaquetas.

Dissertação(mestrado) - Universidade Federal do Rio Grande, Programa de Pós-Graduação em Engenharia e Ciência de Alimentos, Escola de Química e Alimentos, 2007. / Submitted by Caroline Silva (krol_bilhar@hotmail.com) on 2012-09-25T19:15:56Z No. of bitstreams: 1 dissertao vivian feddern.pdf: 798840 bytes, checksum: fb6b9cb9996dbbe1c8dcf944da2944b5 (MD5) / Approved for entry into archive by Bruna Vieira(bruninha_vieira@ibest.com.br) on 2012-11-06T18:24:30Z (GMT) No. of bitstreams: 1 dissertao vivian feddern.pdf: 798840 bytes, checksum: fb6b9cb9996dbbe1c8dcf944da2944b5 (MD5) / Made available in DSpace on 2012-11-06T18:24:30Z (GMT). No. of bitstreams: 1 dissertao vivian feddern.pdf: 798840 bytes, checksum: fb6b9cb9996dbbe1c8dcf944da2944b5 (MD5) Previous issue date: 2007 / As misturas à base de farelo de cereais, popularmente denominadas de multimisturas, vêm se destacando no combate a desnutrição infantil em comunidades de baixa renda, por serem um suplemento de baixo custo e por aportarem nutrientes como minerais, vitaminas e proteínas. Este trabalho objetivou avaliar a biodisponibilização de nutrientes em multimisturas através da alteração da composição e de um processo fermentativo. Para tal, foi realizada a caracterização físico-química e nutricional dos farelos de arroz fermentado e não fermentado e foram também elaboradas, caracterizadas físico-química e nutricionalmente e avaliadas biologicamente oito multimisturas que diferiram quanto ao tipo de farelo (trigo ou arroz); presença ou ausência de pó de folha de mandioca; submetidos ou não a processo fermentativo em estado sólido com Saccharomyces cerevisiae durante 6h a 30ºC. As multimisturas foram peletizadas constituindo as dietas que foram administradas em ratas da cepa Wistar/UFPEL, avaliadas pelo coeficiente de eficiência alimentar, razão de eficiência protéica, razão de eficiência líquida protéica e digestibilidades in vivo aparente e verdadeira. Foram realizados ainda testes bioquímicos como determinação de glicose sanguínea e cálcio plasmático nas ratas. Os resultados permitiram concluir que a fermentação do farelo de arroz ocasionou uma diminuição nos valores de pH, metionina disponível e carboidratos, proporcionando um aumento da acidez, dos açúcares redutores, cinzas e fibras. Os teores de cálcio, proteína e lipídios não foram alterados. As multimisturas com farelo de arroz apresentaram médias dos teores de lipídios (18,1%), cinzas (14,1%), fibras (7,8%), acidez (3,1%), digestibilidade in vitro (80,8%) mais elevadas do que as multimisturas com farelo de trigo, as quais, por sua vez, apresentaram teores de proteínas (14,5%), carboidratos (68,9%) e pH (7,8) maiores que as com farelo de arroz. A fermentação, em algumas multimisturas, ocasionou aumento nos conteúdos de proteínas, minerais, fibras e acidez, porém uma diminuição dos carboidratos, metionina disponível e pH. Com relação aos efeitos biológicos, a fermentação ocasionou aumento no coeficiente de eficácia alimentar na maioria das multimisturas, não influenciando o quociente de eficiência protéica, o quociente de eficiência líquida protéica, a digestibilidade in vivo ou in vitro, a glicemia e o cálcio plasmático. A presença da folha de mandioca não influenciou na composição físico-química das multimisturas, mas tendeu a apresentar melhores coeficientes de eficácia alimentar que as demais multimisturas. As multimisturas contendo farelo de trigo apresentaram valores de digestibilidade in vivo superiores às multimisturas com farelo de arroz. / The mixtures based on cereal brans, popularly denominated “multimisturas”, are standing out to combat infantile malnutrition in communities of low income, by being a low cost supplement and for containing nutrients, such as minerals, vitamins and proteins. In virtue of existence controversies on the real nutritional value of the “multimisturas”, this work aimed at evaluating the bioavailability of nutrients in “multimisturas” by altering the formulation and a fermentative process. Therefore, it was made the physical-chemical and nutritional characterization of fermented and not fermented rice bran, and it was also elaborated, characterized physical-chemical and nutritionally and biologically evaluated eight “multimisturas”, which differed from each other by the source of bran (rice or wheat bran), presence or not of cassava leaf powder and being or not submitted to a solid-state fermentation process with Saccharomyces cerevisiae during 6h at 30ºC. The “multimisturas” were manually made in pellets, constituting the diets, which were administered in female Wistar/UFPEL rats. The diets were evaluated by Food Efficiency Ratio (FER), Net Protein Ratio (NPR), Protein Efficiency Ratio (PER) and apparent and true in vivo digestibility. Biochemical tests as the blood glucose determination and plasmatic calcium in female Wistar/UFPEL rats were also realized. The results allowed concluding that the fermentation of the rice bran caused a decrease on pH, available methionine and carbohydrates, providing an increase of the acidity, reducing sugars, ashes and fibers. Calcium, protein and lipids contents were not altered. The “multimisturas” with rice bran presented averages of lipids (18,1%), ashes (14,1%), fibers (7,8%), acidity (3,1%), in vitro availability (80,8%) higher than the “multimisturas” with wheat bran, which presented proteins (14,5%), carbohydrates (68,9%) and pH (7,8) values higher than the “multimisturas” with rice bran. In some “multimisturas”, the fermentation caused an increase in proteins, fibers, acidity, but a decrease in carbohydrates, available methionine and pH. With relationship to the biological effects, the fermentation caused a FER increase in most of the “multimisturas”, not influencing PER, NPR, in vivo or in vitro digestibility, glycemia and plasmatic calcium. The presence of cassava leaf, didn't influence the physical-chemical composition of multimisturas, but it tended to present better FER that the other ones. The “multimisturas” containing wheat bran presented higher values of in vivo digestibility than those with rice bran.

Depuis une vingtaine d’années, l’utilisation massive des antibiotiques a provoqué l’apparition de souches bactériennes résistantes contre la plupart des familles d’antibiotiques disponibles sur le marché pharmaceutique. L’apparition de souches multirésistantes voire totorésistantes notamment dans le milieu hospitalier, pose de manière croissante des difficultés thérapeutiques et constitue un grave problème de santé publique. Lors de mon doctorat, deux approches ont été abordées.La première approche consiste à inhiber les enzymes DapF et MurE impliquées dans la voie de biosynthèse du peptidoglycane, composant principal de la paroi des cellules bactériennes. Nous avons donc préparé des acides aminés comportant des groupes fonctionnels triazolyle ou alcynyle, analogues stériquement contraints de l’acide 2,6-diaminopimélique (méso-DAP).La deuxième approche développée au laboratoire repose sur le développement d’adjuvants d’antibiotiques, permettant de cibler spécifiquement les protéines responsables des mécanismes de résistances (Histidines kinases, HKs). Ce travail a permis l’obtention de trente-trois molécules dérivées du thiophène, dont huit présentent une activité biologique contre trois HKs différentes (1,63 < CI50 (μM) < 243,9). De plus, sur les huit molécules biologiquement actives, deux ont présenté une inhibition de la croissance bactérienne contre des bactéries à gram-positif et/ou à gram-négatif (B. subtilis, S. aureus, B. anthracis, E. coli…) et une restaure la sensibilité de souches bactériennes (E. coli productrice de β-lactamases à spectre large (BLSE) et S. aureus résistant à la méticilline (SARM)) à l’antibiotique approprié (céfotaxime). / Over the two past decades, the massive use of antibiotics has led to the emergence of resistant bacterial strains against most families of antibiotics available on the pharmaceutical market. The emergence of multiresistant and totoresistant bacterial strains particularly in hospitals, which create increasing problem in the development of new therapeutics and constitutes serious public health threat problems. During my PhD, two approaches were discussed.The first approach of this project consist in targeting the DapF and MurE enzymes, which are implicated in the biochemical pathway for peptidoglycan biosynthesis, a key component of the bacterial cell wall. Consequently, we prepared amino acids derivatives with triazolyl and alkynyl groups, sterically hindered analogs of 2,6-diaminopimelic acid (meso-DAP).The second approach is the development of antibiotic adjuvants, to target specific proteins implicated in the development of bacterial resistance mechanisms (Histidine kinases, HKs). This work has enabled the development of thirty-three thiophene derivatives, eight of them have biological activity against three HKs (1.63 < IC50 (μM) < 243.9). In addition, among the eight molecules with biological activity, two of them present inhibition of bacterial growth (bactericide) against both gram-positive and/or gram-negative bacteria (B. subtilis, S. aureus, B. anthracis, E. coli…) and one of them restores the sensibility of bacterial strains (E. coli producing extended spectrum of β-lactamases (ESBL) and S. aureus resistant to methicillin (MRSA)) to the appropriate antibiotic (cefotaxim).

Ces travaux de thèse s’inscrivent dans un projet à long terme concernant le développement de nouveaux composés peptidomimétiques à motif oxaprolines et oxadiazine-3,6-diones présentant des activités biologiques ou des potentiels de structuration intéressants. En particulier, nous nous sommes attachés à synthétiser différents mimes du peptide Pro-Leu-Gly-NH2, un modulateur allostérique des récepteurs D2 de la dopamine. Ces dérivés ont présenté une activité sur des cellules du striatum supérieure en comparaison avec les valeurs obtenues avec le peptide de référence PLG. D’autre part, notre intérêt pour des structures de type oxadiazine-3,6-diones (Oxd), des motifs très peu décrits dans la littérature, nous a permis d’accéder à une librairie de 1,2,4- et d’1,2,5-Oxd, que nous avons par la suite insérée dans de courtes séquences peptidiques, valorisées comme mime potentiel de beta-turn. Enfin, au cours de ces travaux de doctorat, une nouvelle méthodologie de clivage chimiosélectif de groupements protecteurs a été développée. Cette stratégie originale, basée sur l’utilisation de MgI2 dans le THF sous irradiation micro-ondes, a permis de mettre en évidence de nouvelles orthogonalités telles que le maintien d’un groupement Fmoc lors d’un clivage d’un ester éthylique ou méthylique, ou encore de la résine de Merrifield. / This work is a part of a long-term project aiming to develop original oxaproline and oxadiazine-3,6-diones peptidomimetics with biological activities or potential folding properties. Especially, we proposed an access to various mimetics of the Pro-Leu-Gly-NH2 peptide (PLG), an allosteric modulator of the dopamine D2 receptor. The synthesized derivatives revealed to exhibit higher activity on striatum cells than the PLG initial reference.Moreover, our interest for the poorly described oxadiazine-3,6-diones (Oxd) scaffolds led us to access to a library of 1,2,4- and 1,2,5- Oxd, that we are able to efficiently insert into short peptide sequences with potential beta-turn inducing properties.Finally, during this Ph.D work, an unprecedented methodology for the chemoselective cleavage of protecting groups was developed. Using MgI2 in THF under microwave irradiations, this strategy highlighted novel orthogonalities such as the conservation of the Fmoc protecting group during ethyl or methyl ester deprotection, or even, during the Merrifield resin cleavage.

Biodegradable implants continue to be of interest in orthopaedics for their many potential applications. The magnesium (Mg) alloy WE43 is a biodegradable material with the CE mark approval for clinical application and today mostly used as screws for dental prosthesis. Additional to magnesium, WE43 contains rare earth elements (REEs) of around 7 wt%. These REEs are needed to give the material its mechanical properties and corrosion resistance. Although WE43 is a promising material thought to be used in a diverse number of orthopaedical applications, questions have risen regarding the potential long-term effects of these REEs on the body after the implant degrades. Additionally, with the global demand of REEs rising and a decreasing supply of these elements, there may also be a potential future problem regarding the availability of materials based on REEs. Therefore, new materials containing only elements naturally found in the body are of interest. One such material is the novel Mg-Ca alloy, X0. In this study, a biological comparison was made to answer the question whether the biological performance of X0 is comparable to the already CE approved WE43. Viability, proliferation, and differentiation of MC3T3-E1 (preosteoblast) cells combined with extracts from X0 and WE43, respectively were used. An additional experiment was conducted were X0 was tested against three different versions of WE43 and titanium. In summary, the X0 alloy performed similarly to WE43 in all testing. Both WE43 and X0 showed indications of being bioactive. This led to the conclusion that the X0 alloy showed promise for future use and being a viable alternative to WE43.

O ambiente marinho tem sido reconhecido como uma importante fonte de metabólitos secundários biologicamente ativos. Neste contexto, fungos endofíticos associados a algas ganharam importância nas últimas décadas, como alvos alternativos para a pesquisa de produtos naturais. O presente trabalho teve como o objetivo o estudo químico e biológico de duas linhagens de fungos endofíticos associados à alga vermelha Bostrychia radicans. Inicialmente foi realizada a triagem química e biológica (atividade antitumoral e antimicrobiana) dos extratos brutos das duas linhagens selecionadas, linhagens M20 (Hypocrea lixii) e M23 (Eutypella sp), obtidos a partir de cultivos em escala piloto, tanto variando-se os meios de cultivo e bem como períodos de crescimento. O extrato da linhagem M20 cultivada em arroz apresentou potencial citotóxico interessante quando submetido a ensaios utilizando células tumorais HCT-116. Ainda, após a análise química, esta linhagem foi selecionada para o cultivo em escala ampliada, visando o isolamento e elucidação estrutural dos metabólitos secundários presentes neste fungo. O estudo químico em escala ampliada da linhagem M20, espécie Hypocrea lixii, proporcionou o isolamento e identificação de quatro metabólitos: ácido 3-hidroxi-5-metóxi-6-metil-1,3-diidro-isobenzofurano-4- carboxílico (S1), 3,7-dimetóxi-6-metil-1-oxo-1,3-diidro-isobenzofurano-4-carbaldeído (S3), galactitol (S4), convolvulol (S5), além do isolamento de dois metabólitos que ainda não foram completamente elucidados, S2 e S6. Os metabólitos S1 e S3 são metabólitos inéditos como produtos naturais. Além disso, foi possível a identificação de 14 substâncias via cromatografia gasosa acoplada à espectrometria de massas (CG-EM), entre elas hidrocarbonetos, ácidos graxos, inclusive insaturados, aldeídos, aldeídos ?,?-insaturados e esteróide. As substâncias S1 e S4 foram submetidas à avaliação de atividade biológica (atividade antibacteriana, antifúngica, anticolinesterásica e antitumoral), porém nenhum resultado positivo foi constatado. Foi realizada avaliação da atividade tumoral das frações da linhagem M20, e as frações M20F e M20H apresentaram atividade citotóxica seletiva para linhagens de células tumorais. Em um segundo momento foi realizado o cultivo em escala ampliada da linhagem M23 (Eutypella sp) que proporcionou o isolamento da R-5-metilmeleína (S7). Dessa forma, o estudo químico de fungos endofíticos associados à alga Bostrychia radicans mostrou-se promissor na busca de novas estruturas químicas, visto que já foram isoladas e identificadas duas estruturas inéditas como produtos naturais. / The marine environment has been recognized as an important source of biologically active secondary metabolites. In this context, endophytic fungi associated with algae gained importance in recent decades, as alternative to natural products research targets. The present work had as goal the chemical and biological study of two strains of endophytic fungi associated with red algae Bostrychia radicans. The chemical and biological screening (antimicrobial and antitumor activity) of the crude extracts of two selected strains, M20 (Hypocrea lixii) and M23 (Eutypella sp), were obtained from pilot-scale cultivation, by means of culture media and growth period variation. The M20 strain extract, grown in rice, showed an interesting cytotoxic potential front HCT -116 tumor cells and after chemical analysis, this strain was selected for cultivation on a large scale, with the purpose of secondary metabolites isolation. Chemical studies of M20 species strain Hypocrea lixii, performed on an enlarged scale, afforded the isolation and identification of four metabolites: 3-hydroxy-5-methoxy-6- methyl-1,3-dihydro-isobenzofuran-4-carboxylic acid (S1), 3,7 dimethoxy-6-methyl-1-oxo- 1,3-dihydro-isobenzofuran-4-carbaldehyde (S3), galactitol (S4), convolvulol (S5), in addition the isolation of two metabolites which have not yet been fully elucidated, S2 and S6. The S1 and S3 metabolites are novel metabolites as natural products. Furthermore, it was possible to identify 14 compounds by gas chromatography coupled to mass spectrometry (GC-MS), including hydrocarbons, fatty acids, besides unsaturated ones, aldehydes, ?,?-unsaturated aldehydes and steroid. The S1 and S4 compounds were subjected to biological activity evaluation (antibacterial, antifungal, antitumor and acetylcholinesterase potential), but without any positive result. Assessment of tumor activity of fractions of the M20 strain was performed, and the M20F and M20H fractions showed selective cytotoxicity to tumor cell lines. In a second step, the M23 strain (Eutypella sp) was grown on a large scale, resulting in the R-5-metilmeleina (S7) isolation. Thus, the chemical study of endophytic fungi associated to Bostrychia radicans algae proved to be promising concerning the search for new chemical compounds discovery, since it yielded two new structures as natural products.

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-09-26T14:37:02Z No. of bitstreams: 2 dissertação final recorrigida-capa.pdf: 401652 bytes, checksum: 86330537bc26151925bb8c03de4f993a (MD5) Dissertação Versão Final.pdf: 2578250 bytes, checksum: 19ad7de8c52c85cf3e787b04c08ce9ef (MD5) / Approved for entry into archive by Vanessa Reis (vanessa.jamile@ufba.br) on 2016-09-26T15:02:14Z (GMT) No. of bitstreams: 2 dissertação final recorrigida-capa.pdf: 401652 bytes, checksum: 86330537bc26151925bb8c03de4f993a (MD5) Dissertação Versão Final.pdf: 2578250 bytes, checksum: 19ad7de8c52c85cf3e787b04c08ce9ef (MD5) / Made available in DSpace on 2016-09-26T15:02:14Z (GMT). No. of bitstreams: 2 dissertação final recorrigida-capa.pdf: 401652 bytes, checksum: 86330537bc26151925bb8c03de4f993a (MD5) Dissertação Versão Final.pdf: 2578250 bytes, checksum: 19ad7de8c52c85cf3e787b04c08ce9ef (MD5) / CAPES / O presente trabalho relata o estudo químico das sementes de Spondias tuberosa Arr. Cam., como aproveitamento de resíduos industrial. Spondias tuberosa, pertencente a família Anacardiaceae, é uma árvore endêmica do semi-árido brasileiro, cujos frutos conhecidos como umbu, são comercializados in natura ou em forma de polpa e suas raízes e folhas também podem ser utilizadas como alimento. O extrato metanólico bruto das sementes do umbu foi submetido à partição líquido- líquido e sua atividade citotóxica e antioxidante foi avaliada. O extrato hexânico obtido das sementes apresentou-se atóxico para o teste de letalidade de Artemia salina e os demais extratos foram moderadamente tóxicos. Em relação à atividade antioxidante, a fase AcOEt demonstrou ser a mais ativa, seguido da CHCl3. A partir de sucessivos fracionamentos cromatográfico da fase clorofórmica da sementes de Spondias tuberosa permitiu o isolamento de uma mistura de ácidos graxos que posteriormente foram submetidos à transesterificação obtendo-se onze ésteres metílicos, além de uma mistura de sitosterol e estigmasterol. Do fracionamento da fase acetato de etila foi isolado o 5-hidroximetil-2-furfural (5-HMF). Do extrato hexânico foi isolado uma mistura de triglicerídeos que foi submetido à reação de saponificação seguida de esterificação obtendo-se assim, uma composição química com nove ésteres metílicos. A elucidação estrutural das substâncias isoladas foi baseada na análise de dados de espectros de Massas, dos espectros de RMN de 1H e 13C, juntamente com a RMN de correlação (HMQC e HMBC) e comparação com dados da literatura. / This paper reports the chemical study of seeds of Spondias tuberosa Arr. Cam., As utilization of industrial waste. Spondias tuberosa, belonging to Anacardiaceae family, is an endemic tree from the Brazilian semi-arid region, known as umbu whose fruits are sold fresh or in the form of pulp and the leaves and roots can also be used as food. The crude extract from the seeds of umbu methanol was subjected to liquid- liquid partition and their cytotoxic and antioxidant activity was evaluated. The hexane extract obtained from the seeds showed up were nontoxic to moderately toxic lethality test of Artemia salina and other extracts. In relation to the antioxidant activity, the EtOAc phase was shown to be the most active, followed by CHCl3. From successive chromatographic fractionation of the chloroform phase seeds Spondias tuberosa allowed isolation of a mixture of fatty acids which were subsequently subjected to transesterification to give methyl esters eleven, and a mixture of sitosterol and stigmasterol. The fractionation of the ethyl acetate phase was isolated 5-hydroxymethyl-2-furfural (5-HMF). The hexane extract was isolated a mixture of triglycerides which was subjected to saponification reaction followed by esterification thereby obtaining a chemical composition with nine methyl ester. The structural elucidation of the isolated compounds was based on the analysis of spectral data Masses, the NMR spectra of 1H and 13C NMR along with the correlation (HMQC and HMBC) and comparison with literature data.

74 f. / Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2013-04-08T15:15:32Z No. of bitstreams: 1 Dissertação_JC Selva.pdf: 822691 bytes, checksum: e44864a244534144b43291b347e46945 (MD5) / Approved for entry into archive by Ana Hilda Fonseca(anahilda@ufba.br) on 2013-05-09T17:19:25Z (GMT) No. of bitstreams: 1 Dissertação_JC Selva.pdf: 822691 bytes, checksum: e44864a244534144b43291b347e46945 (MD5) / Made available in DSpace on 2013-05-09T17:19:25Z (GMT). No. of bitstreams: 1 Dissertação_JC Selva.pdf: 822691 bytes, checksum: e44864a244534144b43291b347e46945 (MD5) Previous issue date: 2010 / CAPES / O presente trabalho relata o estudo químico das cascas das raízes de Caesalpinia pyramidalis Tul., uma árvore pertencente a família Leguminosae endêmica da região da caatinga baiana cujas folhas são utilizadas na medicina popular como diurético e digestivo. O extrato metanólico bruto foi submetido à extração liquido-liquido e sua atividade citotóxica e antioxidante foram avaliadas. O extrato hexânico apresentou-se atóxico para o teste de letalidade de Artemia salina e os demais extratos foram moderadamente tóxicos. Em relação à atividade antioxidante, o extrato AcOEt foi o mais ativo, seguido do BuOH e MeOH. O fracionamento cromatográfico da fase hexânica permitiu o isolamento do lupeol, acacetina, um novo fenilpropanóide, ácido (E)-8-hidroxi-3,5-dimetoxicumarico, além de uma mistura de sitosterol e estigmasterol. Da fase metanólica foram isolados o mesmo fenilpropanóide encontrado na hexânica além de um novo biflavonóide, 7-hidroxi-4’-metoxiflavona-5α-2,4- dihidroxi-4’-metoxidihidrochalcona. A estrutura deste novo biflavonóide bem como das outras substâncias isoladas foram elucidadas a partir da análise dos dados de RMN 1H e 13C (BB e APT) juntamente com a RMN de correlação (HMQC e HMBC). / Salvador