Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Mar 21

Thesis (Ph. D.)--University of Wisconsin--Madison, 2007. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Canterbury, 2006. / Typescript (photocopy). Includes bibliographical references (leaves 285-305). Also available via the World Wide Web.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 158-177).

Licentiatavhandling (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 2 uppsatser.

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Orientadores: João Ernesto de Carvalho, Mary Ann Foglio / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-18T04:00:21Z (GMT). No. of bitstreams: 1 Pais_ViniciusAndradeArce_M.pdf: 3917209 bytes, checksum: 81f3730bcb96d1f985bbe7ac68e8c8cf (MD5) Previous issue date: 2011 / Resumo: O câncer é um conjunto de mais de 100 doenças diferentes que afligem a população mundial e caracteriza-se pela perda de função celular e ausência de diferenciação, além da proliferação descontrolada. Somente no Brasil, estima-se que foram registrados 489.270 novos casos de câncer em 2010. O Brasil é o país com a maior diversidade genética vegetal do mundo, representando uma das mais ricas fontes de materiais farmacologicamente ativos. Os extratos de plantas medicinais e seus compostos derivados são conhecidos por serem efetivos agentes contra vários tipos de cânceres. Estima-se que 60% das drogas antitumorais sejam de origem vegetal. A partir da coleta aleatória realizada no projeto BIOPROSPECTA-FAPESP (04/15410-0), foram selecionadas 10 espécies que apresentaram efeitos antiproliferativos. Dessas espécies, 5 foram novamente coletadas, sendo elas: Miconia latecrenata (DC.)Naudin, Mollinedia schottiana (Spreng.)Perkins, Boehmeria caudata Sw., Boehmeria cylindrica Sw. e Acnistus arborescens. Foram preparados extratos diclorometânicos (EBD) e etanólicos (EBE) das folhas destas espécies os quais foram avaliados quanto à atividade antiproliferativa in vitro, em linhagens de células tumorais humanas. Todos os extratos apresentaram pelo menos efeito citostático no teste in vitro à exceção daqueles obtidos de Mollinedia schottiana. A partir desses resultados e da disponibilidade de material vegetal, foram selecionados para dar continuidade ao estudo Boehmeria caudata e a B. cylindrica. Assim, por existir dados referentes a alcalóides com efeitos citostáticos descritos na literatura, realizou-se extração ácido-base dos dois espécimes, onde se isolou alcalóides de polaridades diferentes. Os alcalóides isolados, e suas frações neutras, das duas plantas, EBAEN e EBCA, para Boehmeria cylindrica e FALCBC e FAENBC para Boehmeria caudata, foram encaminhados a testes in vitro, onde apenas os alcalóides da espécie B. caudata, retornou resultados positivos. O EBD de Boehmeria cylindrica e os extratos EBE e EBD de Boehmeria caudata, juntamente com a fração FALCBC foram submetidos a testes in vivo, utilizando o modelo do Tumor Sólido de Ehrlich. O EBD de Boehmeria cylindrica e de Boehmeria caudata apresentaram resultados significativos ( p<0,05) diminuindo a progressão tumoral.Os EBDs de B. cylindrica e de B. caudata apresentaram redução significativa (p<0,05) na progressão tumoral. Por outro lado, o EBE de B. caudata e a fração FALCBC não apresentaram atividade no teste in vivo, sugerindo que em função da maior polaridade dos compostos presentes nessas amostras, essas substâncias que apresentaram atividade antiproliferativa in vitro foram metabolizadas e excretadas antes de atingirem seus sítios de ação no modelo in vivo. Concluindo, as espécies estudadas apresentaram significativa atividade antitumoral, corroborando com os relatos existentes de estudos de atividade antitumoral para outras espécies do gênero Boehmeria, e indicando o potencial do gênero para o desenvolvimento de uma droga anticâncer / Abstract: Cancer is a group of 100 different diseases that afflict the world's population and is characterized by loss of cell function, due to absence of differentiation, in addition to uncontrolled proliferation. In Brazil alone, an estimated 489,270 new cancer cases were reported in 2010. Brazil is the country with the greatest plant genetic diversity of the world, representing one of the richest sources of pharmacologically active materials. Extracts of medicinal plants and their derived compounds are known to be effective agents against several types of cancers. It is estimated that 60% of anticancer drugs are of plant origin. Based on the random collection performed in the project BIOprospecTA-FAPESP (04/15410-0), 10 species that had significant anti-proliferative effects, were selected. From these, five were collected again, as follows: Miconia latecrenata (DC.)Naudin, Mollinedia schottiana (Spreng.)Perkins, Boehmeria caudata Sw., Boehmeria cylindrica Sw. and Acnistus arborescens. These species were submitted for extraction process, resulting in dichloromethane and ethanolic extracts, subsequently which was evaluated with in vitro tests of human tumor cell lines. All of them showed cytocidal or cytostatic effects with in vitro assays, except for Mollinedia schottiana that produced no positive results. The available specimens with positive results were selected to continue the study; they are Boehmeria caudata and Boehmeria cylindrica. Thus, since data of alkaloids with cytostatic effects have been described in the literature, an acid-base extraction was made of the two specimens, where alkaloids of different polarities were isolated. Isolated alkaloids, and the respective neutral fractions of the two plants, EBAEN and EBCA for Boehmeria cylindrica, FALCBC and FAENBC for Boehmeria caudata, were used in in vitro assays, where only the alkaloids from B. caudata, gave positive results. The DBE of Boehmeria cylindrica and the extracts, EBE and DBE of Boehmeria caudata, along with the FALCBC fraction were tested in vivo using the solid Ehrlich's tumor model. The DBE of Boehmeria cylindrica and of Boehmeria caudata showed significant results (p <0.05), decreasing tumor progression. The brute ethanol extract of Boehmeria caudata, along with its fraction, FALCBC, showed no anti-proliferative activity. The genus Boehmeria was subject to several studies for different species, indicating a potential of the genus for the discovery of a new anticancer drug. The species studied showed significant antitumor activity. The negative results of the alkaloidal fraction and the EBE of Boehmeria caudata in in vivo tests, do not invalidate its potential because these samples were possibly metabolized and excreted before reaching their action sites, probably due to the polarity of these substances / Mestrado / Biologia Celular / Mestre em Biologia Celular e Estrutural

Ph.D. (Chemistry) / Alchornea species (Euphorbiaceae) have been used in traditional medicine across Africa and are well known to display broad spectrum biological activities including anti‐microbial, antiinflammatory and anti‐cancer activities. This project is aimed at discovering bioactive compounds for anti‐microbial and anti‐cancer therapy from plants of the Alchornea species and developing suitable nanocarrier drug delivery systems (DDS) as drug or compound transporters using gold nanoparticles and natural polymers. The plant material (roots, stems and leaves) was collected in bulk from an uncultivated farmland of the Elounden Mount, in the Yaoundé central region of Cameroon. The extracts were prepared using solvents of varying polarity in order to extract a wide range of phytochemicals. The extracts of A. cordifolia, A. floribunda and A. laxiflora as well as those isolated compounds that were sufficiently pure, were screened for antibacterial activity against four Gram‐positive bacteria (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus and S. saprophyticus) and four Gram‐negative bacteria (Escherichia coli, Klebsiella pneumonia, Moraxella catarrhalis and Proteus mirabilis), as well as antimycobacterial activity (Mycobacterium aurum and M. smegmatis). The anti‐cancer properties were similarly tested against SNO oesophageal cancer, breast cancer (MDA‐MB‐231 and MCF‐7), and leukemia HL‐60 cell lines. The antimicrobial activities were evaluated using the micro‐dilution assay while the anticancer activity was evaluated by means of cell viability (MTT assay, Alamar blue, trypan blue and an ATP assays). The isolation of compounds and synthesis of derivatives were performed by exhaustive chromatographic techniques and suitable organic reactions. The structures of the compounds were determined by means of spectroscopic methods (FT‐IR, MS, 1D and 2D NMR). Three compounds (AC3.1, AC2.4 and 3HB) were used to synthesize DDS and were characterized using UV‐Vis, FT‐IR, TEM, SEM, XRD, EDS, DLS and zeta potential.

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