Thesis (Ph. D.)--University of California, San Diego, 1998. / Vita. Includes bibliographical references (p. 223-227).

Thesis (Ph. D.)--University of Canterbury, 2008. / Typescript (photocopy). "January 2008." Includes bibliographical references (leaves 201-215). Also available via the World Wide Web.

Thesis (Ph.D.) - University of Glasgow, 1993. / Ph.D. thesis submitted to the Faculty of Law and Financial Studies, Department of Accounting and Finance, University of Glasgow, 1993. Includes bibliographical references. Print version also available.

Thesis (M.Sc.)--University of Wollongong, 2004. / Typescript. Includes bibliographical references: leaf 121-148.

Thesis (Ph. D.)--Oregon State University, 2006. / Printout. Includes bibliographical references (leaves 223-233). Also available on the World Wide Web.

Thesis (Ph. D.)--University of Canterbury, 2006. / Typescript (photocopy). "February 2006." Includes bibliographical references. Also available via the World Wide Web.

Made available in DSpace on 2015-03-03T11:52:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-03-27Bitstream added on 2015-03-03T12:07:00Z : No. of bitstreams: 1 000796507_20160331.pdf: 2180495 bytes, checksum: 25429d969bb87ee08e7eadffef3f70c8 (MD5) Bitstreams deleted on 2016-04-01T11:49:40Z: 000796507_20160331.pdf,. Added 1 bitstream(s) on 2016-04-01T11:50:35Z : No. of bitstreams: 1 000796507.pdf: 21738804 bytes, checksum: 9cd0a111999a851d1e7097b315760950 (MD5) / As macroalgas Dichotomaria marginata e Padina gymnospora foram coletadas no litoral paulista e seus microrganismos associados, Penicillium citrinum (Dm1) e Penicillium chrysogenum (Pg1), respectivamente, foram isolados e identificados. Os microrganismos foram cultivados em arroz parboilizado estéril e as culturas obtidas foram extraídas com acetato de etila e submetidas a partição. A fração FMeCN de cada extrato foi submetida às técnicas cromatográficas a fim de isolar os metabólitos secundários. Os extratos das macroalgas foram submetidos a partição e as frações resultantes submetidas a estudo químico por CLAE-DAD, CLAE-DAD/EMIES e RMN 1H. A comparação dos perfis cromatográficos das frações obbtidas das macroalgas permitiu uma abordagem qualitativa dos constituintes por gerar informações sobre a composição química das macroalgas em estudo. Os ácidos graxos foram analisados nas frações apolares das macroalgas e microrganismos associados por CG-EM e resultou na identificação de 27 substâncias nas frações hexânicas das macroalgas, sendo 19 da D. marginata e 8 da P. gimnospora, enquanto para os microrganismos, 32 substâncias foram identificadas, sendo 16 de P. citrinum e 16 de P. chrysogenum. A fração em MeCN de P. citrinum forneceu 17 substâncias, sendo 4 alcaloides quinolizidínicos: citrinadina A (1), citrinadina B (2), 18- desidroxi-citrinadina B (3), chrisogenamida (4); 4 alcaloides quinolactínicos: quinolactinas A (11), B1/B2 (12), B (13) e D (14) e 9 policetídeos: dicitrinina A (5), 1,5-dihidroxi-2-metil-3-(1-metil-2-hidroxi)-propilbenzeno (6), esclerotinina A (7), descarboxidihidrocitrinona (8), 1-carboxi-8-hidroxi-6-metilxantona éster metílico (9), ácido linoléico (10), ácido italícico (15), citrinina (16), e 1,3,8-tri-hidroxi-6- (hidroximetil)antraceno-9,10-diona (17). Adicionalmente, 9 substâncias foram obtidas a partir de P. chrysogenum, sendo 3... / Macroalgae Dichotomaria marginata and Padina gymnospora were collected at Sao Paulo State shore and their associated microrganisms, Penicillium citrinum (Dm1) and Penicillium chrysogenum (Pg1), respectively, were isolated and identified. The microorganisms were cultivated in sterile parboilized rice and the resulting cultures were extracted with ethyl acetate and submitted to partitioning. Fraction FMeCN of each extract was submitted to chromatography aiming at the isolation of secondary metabolites. The macroalgae extracts were submitted to partitioning and the resulting fractions were analyzed by HPLC-DAD, HPLC-DAD-MS/ESI and 1H NMR. The chromatographic profile comparison for the resulting fractions from macroalgae allowed the qualitative assessment of the chemical constituents, and afforded information on the chemical composition of the macroalgae. Fatty acids were analysed in the low polarity fractions of the macroalgae and microrganisms extracts by GC-MS and resulted in the identification of 27 compounds from the hexane fractions of macroalgae, including 19, from D. marginata, and 8, from P. gimnospora, whereas 32 fatty acids were identified from the microorganisms, including 16 from P. citrinum and 16, from P. chrysogenum. Fraction in MeCN from P. citrinum afforded 17 compounds: 4 quinolizidine alkaloids: citrinadin A (1), citrinadin B (2), 18-dehydroxy-citrinadin B (3), chrysogenamide (4); 4 quinolactin alkaloids: quinolactins A (11), B1/B2 (12), B (13) and D (14), and 9 poliketides: dicitrinin A (5), 1,5-dihydroxy-2-methyl-3-(1-methyl-2-hydroxy)-propylbenzene (6), esclerotinin A (7), decarboxydihydrocitrinone (8), de 1-carboxy-8-hydroxy-6- methylxanthone methyl ester (9), linoleic acid (10), italicic acid (15), citrinin (16), e 1,3,8-trihydroxy-6-(hydroxymethyl)antracene-9,10-dione (17). Aditionally, 9 compounds were obtained from P. chrysogenum, 3 nucleotides: adenosine (18)...

Orientador: Lucia Maria Xavier Lopes / Banca: Conceição de Fátima Alves Olguim / Banca:Maria de Meneses Pereira / Resumo: O presente trabalho descreve o isolamento e a elucidação estrutural dos constuintes químicos de Aristolochia gigantea Mart. A. gigantea desenvolve um forte sistema subterrâneo de caules e raízes (tubérculos e rizomas). Os extratos etanólicos destas partes da planta foram submetidos a cromatografia (CC, CCDP e CLAE), resultando em doze e oito substâncias, respectivamente. Entre as quais, uma nova aristolactama, aristolactama 9-[O-b-glicopiranosil-O-(1 ׳׳® ׳ 2 )-b-glicopiranosídeo], e duas alcamidas, cis- e trans-N-p-coumaroil-3-O-metildopamina juntamente com as substâncias conhecidas alantoína, b-sitosterol, E-nerolidol, (+)-kobusina, (+)- eudesmina, cis- e trans-N-feruloiltiramina, trans-N-coumaroiltiramina, cis- e trans-Nferuloil- 3-O-metildopamina, aristolactama Ia 8-β-O-glicosídeo, aristolactama Ia N-β- glicosídeo, aristolactama IIIa e magnoflorina. Suas estruturas foram determinadas por análises espectroscópicas. Os efeitos dos extratos, da alantoína, (+)-kobusina e (+)-eudesmina na ação das fosfolipases e proteases dos venenos das serpentes Bothrops jararacussu e Crotalus durissus terrificus foram avaliados. A alantoína foi o inibidor mais eficiente das fosfolipases enquanto a (+)-eudesmina e os extratos apresentaram atividade inibitória moderada. Além disso, os extratos, a alantoína e a (+)-eudesmina mostraram atividade moderada para as proteases de Bothrops jararacussu enquanto a (+)-kobusina apresentou maior potencial inibitório. / Abstract: The present work describes the isolation and structural elucidation of the chemical constituents of Aristolochia gigantea Mart. A. gigantea develops a strong system of subterranean stems and roots (tuberous or rhizomatous roots). Ethanol extracts of these plant parts were subjected to chromatography (CC, TLC, and HPLC) to give twelve and eight compounds, respectively. Among which, a new aristolactam, aristolactam 9-O-b-D-glucopyranosyl-(1 ׳ 2→׳׳ )-b-D-glucoside, and two alkamides, cisand trans-N-p-coumaroyl-3-O-methyldopamine together with the known compounds allantoin, E-nerolidol, b-sitosterol, (+)-kobusin, (+)-eudesmin, cis- and trans-Nferuloyltyramine, trans-N-coumaroyltyramine, cis- and trans-N-feruloyl-3-Omethyldopamine, aristolactam Ia 8-b-O-glucoside, aristolactam Ia N-b-D-glucoside, aristolactam IIIa, and magnoflorine. Their structures were determined by spectroscopic analyses. Effects of extracts, allantoin, (+)-kobusin and (+)-eudesmin on action of phospholipases and proteases from venoms of the snakes Bothrops jararacussu and Crotalus durissus terrificus were evaluated. Allantoin was the most efficient inhibitor of phospholipases whereas (+)-eudesmin and the extracts showed moderate inhibitory activity. In addition, the extracts, allantoin, and (+)-eudesmin showed moderate activity on proteases from Bothrops jararacussu whereas (+)- kobusin showed the highest inhibitory potential. / Mestre

abstract: Throughout time, compounds from natural sources have provided humans with medicines, and recently become the structural inspiration for semisynthetic drugs. One arena that has benefited greatly from the use of these natural products is the discovery of novel antibacterial agents. Methicillin-resistant Staphylcoccus aureus (MRSA) continues to plague the United States as well as throughout the world, at least in part because of increasing antibiotic resistance. Therefore, scientists continue to scour natural products as potential leads, either directly or indirectly, for antibiotics to treat MRSA. The structure of the indole sesquiterpene, polyalthenol, was discovered in 1976 and recent work shows a 4µg/mL minimum inhibitory concentration (MIC) against a variety of strains of MRSA. Given the unique framework of this natural product and its biological activity against MRSA, the total synthesis becomes the next logical step. Presently a racemic synthesis has successfully afforded an indole ketone with the correct relative stereochemistry of polyalthenol, however, the completion of the total synthesis of polyalthenol presents several challenges. Herein, the work towards the synthesis is described in addition to the proposed completion of the synthesis. / Dissertation/Thesis / M.S. Applied Biological Sciences 2012

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-05-20T17:51:21Z No. of bitstreams: 1 Nanashara Coelho de Carvalho. Avaliação... 2013.pdf: 833577 bytes, checksum: 03372af4fb8e4842dea6880a1dee5c9a (MD5) / Made available in DSpace on 2014-05-20T17:51:21Z (GMT). No. of bitstreams: 1 Nanashara Coelho de Carvalho. Avaliação... 2013.pdf: 833577 bytes, checksum: 03372af4fb8e4842dea6880a1dee5c9a (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / O câncer é uma doença caracterizada pelo processo proliferativo descontrolado de células transformadas. Devido à possibilidade de metástase, o melanoma cutâneo é considerado um dos cânceres mais agressivos. Produtos naturais derivados de plantas e outros organismos têm sido utilizados como fonte para o desenvolvimento de quimioterápicos empregados no tratamento de diversos tipos de câncer, inclusive do melanoma. A própolis é um produto natural produzido por abelhas a partir de exudatos de brotos e botões florais, e apresenta uma composição química complexa que influência sua atividade biológica. O presente trabalho propõe a investigação da atividade antineoplásica do extrato etanólico da própolis G6 baiana (EEPG6), que apresenta uma composição química distinta de outras própolis, principalmente pela ausência de flavonóides. A citotoxicidade do EEPG6 frente a diferentes linhagens neoplásicas foi determinada através do modelo de incorporação de timidina tritiada. O padrão de morte celular e a influência das espécies reativas de oxigênio foram avaliados em células da linhagem B16-F10 após tratamento com a EEPG6. A eficácia da própolis G6 em reduzir o desenvolvimento neoplásico foi determinada em camundongos da linhagem C57Bl/6 portadores de melanoma subcutâneo. Os resultados encontrados demonstram uma atividade do EEPG6 frente a diferentes linhagens malignas, com valores de CI50 variando entre 13,2 μg/mL e 24,1 μg/mL. Através da dupla marcação com a anexina V e iodeto de propídio, e ensaio de ativação de caspase-3 foi possível determinar que o tratamento com o EEPG6 induz a morte celular por apoptose. Esses dados corroboram com o padrão morfológico de células, alteração do potencial transmembrânico mitocondrial, fragmentação do DNA e bloqueio do ciclo celular encontrados em células tratadas com a própolis G6 e que são alterações características da morte celular por apoptose. No modelo murino de melanoma subcutâneo, o tratamento com a EEPG6 na dose de 200 mg/kg foi capaz de inibir em cerca de 81,72% o peso médio dos tumores. Desse modo, a própolis G6 baiana revela-se como uma fonte de substâncias com potencial antineoplásico na terapia convencional. / Cancer is a disease process characterized by uncontrolled proliferation of transformed cells. Due to the possibility of metastasis, cutaneous melanoma is considered one of the most aggressive cancers. Natural products derived from plants and other organisms have been used as a source for the development of chemotherapeutic agents used in the treatment of various cancers, including melanoma. Propolis is a natural product produced by bees from exudates shoots and buds, and has a complex chemical composition that influence their biological activity. This study aims to investigate the anticancer activity of ethanol extract of G6 propolis from Bahia (EEPG6), which has a different chemical composition of other propolis, especially in the absence of flavonoids. The cytotoxicity of the EEPG6 against different neoplastic strains was determined using the model of tritiated thymidine incorporation. The pattern of cell death and the influence of reactive oxygen species were assessed in cell line B16-F10 after treatment with EEPG6. The effectiveness of propolis G6 in reducing neoplastic development was determined in mice of strain C57BL/6 bearing subcutaneous melanoma. The results demonstrate the EEP G6 activity against different strains malignant, with IC50 values ranging from 13.2 mg/mL and 24.1 mg/mL. Through the double staining with Annexin V and propidium iodide, and testing the activation of caspase-3 was determined that treatment with EEPG6 induces cell death by apoptosis. These data corroborate with the cell morphology, alteration of mitochondrial transmembrane potential, DNA fragmentation and cell cycle arrest found in cells treated with propolis G6 and changes which are characteristic of apoptotic cell death. In a murine model of subcutaneous melanoma, treatment with EEPG6 at a dose of 200 mg/kg was able to reduce the average weight of the tumors in about 81.72%. Thus, G6 propolis from Bahia appears as a source of potential anticancer substances in conventional therapy