Thesis (Ph. D.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 220-232). Also available on the World Wide Web.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

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As part of an International Cooperative Biodiversity Group (ICBG) program and a collaborative research project with the Natural Products Discovery Institute, twenty plant extracts were investigated for their antiproliferative and antimalarial activities. Bioassay guided fractionation of thirteen extracts led to the identification of three new antiproliferative compounds, ethyl leptaulosides A-C (5.1-5.3), six new antiplasmodial compounds, apoplanesiacarpan A and B (2.4-2.5), (±)-rhodomyrtosone F (3.1), (±)-calliviminone C (3.2), 3α-angeloyloxy-15-hydroxylabda-7,13-dien-16,15-olid-18-oic acid (4.1), 3α-angeloyloxy-15-methoxylabda-7,13-dien-16,15-olid-18-oic acid (4.2), and twenty-six known compounds. The structures of these compounds were elucidated by using a combination of 1D (1H and 13C) and 2D NMR spectroscopy, mass spectrometry, UV, IR, CD, optical rotation, and chemical modifications. Compounds 5.1 and 5.2 showed moderate antiproliferative activity against the A2780 human ovarian cancer cell line assay with IC50 values of 3 uM and 10 uM, respectively. Compound 3.1 showed potent antiplasmodial activity with an IC50 value of 100 nM, while compounds 3.2 and 4.1 showed moderate antiplasmodial activity with IC50 values of 4 uM and 10 uM, respectively. The other compounds had IC50 values larger than 20 ug/mL, and were thus either inactive or only weakly active. / Ph. D.

O estudo fitoquímico do extrato etanólico de caules adultos de Araucaria angustifólia resultou no isolamento e identificação da vanilina, p-hidroxibenzaldeído, coniferaldeído, dois isoflavonóides (cabreuvina e irisolidona), quatro lignanas (pinoresinol, eudesmina, lariciresinol e 9\'-O-acetato de lariciresinol) e β-sitosterol. Foi desenvolvido um protocolo para a obtenção de calos, a partir de caules de plântulas estioladas, dos quais foram isolados e caracterizados mistura de isômeros E e Z do p-cumarato de octadecila e do ferulato de octadecila. / Phytochemical investigations carried out on ethanolic extract from woods of Araucaria angustifolia resulted on the isolation and identification of vanillin, p-hydroxybenzaldehyde, coniferaldehyde; two isoflavones (cabreuvine and irisolidone); four lignans (pinoresinol, eudesmine, lariciresinol and 9\'-O-lariciresinolacetate), and β-sitosterol. Its callus culture was showed to accumulate mixtures of isomers E and Z of octadecyl p-cumarate and of octadecyl ferulate.

This research is focused on finding new secondary metabolites from bacterial sources through genome mining, allowing the study of unknown molecules that could be potential candidates for use as drugs against microbial infections, cancer, and immune diseases. Bioprospection was conducted through targeted environmental sampling, unusual environments exploration and molecular and computational biology. In the first project, an environmental DNA (eDNA) fosmid library from urban soil samples was built and arrayed for the presence of potential gene clusters. In total, 7% of the library was positive for the presence of secondary metabolite pathways. Sequencing revealed genetic similarity with other organisms that belong to urban areas, showing adaptation of the microbiota to anthropogenic environments. The second project focuses on the heterologous expression of a lantipeptide from a bacterial isolate from an urban environment. Using a Multigene Expression System (MES), different components of the biosynthetic pathway were cloned and expressed. We were able to successfully express the genes responsible for lantipeptide tailoring but the lantipeptide portion of the pathway was not obtained with the methods used. The last project examined cave bacterial secondary metabolite production and organism diversity to determine the relationship between the microbiome and to retrieve potential active natural compounds. Through sequence analysis and LC-ESI-HRMS, several metabolites were detected and their potential role for the cave microbiome could be established.