Through a continuing search for anticancer compounds as part of an International Cooperative Biodiversity Grant program, the extracts of two plants were selected for study on the basis of their cytotoxic activity. These extracts were further fractionated to yield four compounds. The structures of these compounds were elucidated with mass spectrometry and 1-D and 2-D NMR spectroscopy. The ethyl acetate extract of the twigs of Garcinia macrophylla from Suriname was weakly cytotoxic in the A2780 human ovarian cancer cell bioassay. The known benzophenone guttiferone A and a new guttiferone analog, named guttiferone G, were isolated from the extract and found to be responsible for the bioactivity. A known triterpene, friedelin, was also isolated from the extract and found to be inactive. The structure of guttiferone A was determined by comparison of its NMR data to those found in the literature. The structure of guttiferone G was determined by comparison to guttiferone A and through careful examination of both 1D and 2D NMR data. An extract of Bridelia tulasneana from Madagascar yielded one compound. It was identified as the known lignan deoxypodophyllotoxin and was responsible for the bioactivity. It was identified by a comparison of its spectral data to those found in the literature and those of an authentic sample. / Master of Science

The purpose of my research work was to assess a variety of Northern Thailand plants tissue extracts for antibacterial and anti-platelet aggregation activity. The Minimum Inhibitory Concentration assay method was used to assess antimicrobial activity of plant extracts, while the Zebrafish Platelet Aggregation Assay and the in vitro Whole Human Blood Impedance Aggregation Assay were used to study anti-platelet activity. Forty one plant extracts harvested from the tissues of 26 plants collected from Northern Thailand were assessed. Thirty-four plant extracts were found to have antibacterial activity against the Gram positive bacteria Staphylococcus aureus and/or Bacillus subtilis, while six plant extracts demonstrated activity against the Gram negative bacterium, Escherichia coli. Thirteen plant extracts exhibited anti-platelet aggregation activity better than the positive control. Two crude plant extracts, twigs from Garcinia sp. and twigs from Goniothalamus chilensis were selected for fractionation. Five of the 12 fractions showed anti-platelet activity. Four fractions (two from each plant extract) were selected for further sub-fractionation. Fourteen of 35 sub-fractions were selected for further testing of anti-platelet aggregation activity with 12 sub-fractions demonstrating positive antiplatelet activity. Positive sub-fractions were analyzed using liquid chromatography-mass spectrometry to determine their chemical properties. Three compounds that possessed anti-platelet activity were characterized by nuclear magnetic resonance. The compounds, all isolated from Garcinia sp., were identified as cambogin, isoxanthochymol and guttiferone F.

La guttiférone A , appartenant à la famille des PPAPs ou Acyle Phloroglucinol Polycycliques Polyprénylées, est une molécule extraite à partir d’un arbre tropicale, le Symphonia globulifera. Cette matière première est abondante et peut être facilement obtenue. De plus, elle présente de nombreuses activités biologiques, lui conférant un potentiel pharmacologique très intéressant. Trois approches ont été effectuées durant ces travaux. La première fût l’utilisation de microorganismes pour effectuer des biotransformations. L’utilisation de levures a permis de synthétiser la 3,16-oxy-guttiférone A, forme xanthone de la guttiférone. Le second axe a été d’utiliser des outils chimiques pour obtenir des dérivés de la guttiférone A. Dans un premier temps, une vingtaine d’analogues éther et ester du catéchol a été synthétisée, certains de ces composés ont montré un meilleur indice de sélectivité sur les parasites. Une synthèse sélective de xanthone par une réaction de couplage phénolique oxydatif a également été étudiée. Nous avons pu obtenir par cette approche la 3,16-oxy-guttiférone A, la 1,16-oxy-guttiférone A et la 1,12-oxy-guttiférone A. Ces réactions ont aussi donné accès à des dérivés xanthone hydroxylée jamais décrits dans la littérature. Enfin, un travail préliminaire de phytochimie sur les graines et feuilles du Symphonia globulifera a été réalisé, permettant d’isoler des analogues de la guttiférone A, la guttiférone C et D, ainsi que d’autres molécules comme des bisflavonoides et des xanthones. / Guttiferone A, belonging to the PPAPs family (Polycyclic Polyprenylated Acylphloroglucinols), is extracted from a tropical tree called Symphonia globulifera. This raw material is abundant and can be easily obtained. In addition, it has many biological activities, giving it a very interesting pharmacological potential. Three approaches were used in this work. The first was the use of microorganisms to perform biotransformations. The use of yeast allow the synthesis of 3,16-oxy-guttiférone A, a xanthone derivative of guttiferone A. The second theme was the use of chemical tools for guttiferone A derivation. First, twenty ether and ester catechol analogs were synthesized, some of these compounds showed a better selectivity index of parasites. Selective synthesis of xanthone by phenolic oxidative coupling reaction was also studied. We obtained by this approach the 3.16-oxy-guttiferone A, 1,16-oxy-guttiferone A and 1,12-oxy-guttiferone A. These reactions have also provided some hydroxylated xanthone never described before in the literature. Finally, preliminary phytochemical work on seeds and leaves of Symphonia globulifera lead to the isolation of guttiférone A analogues such as guttiférone C and D, as well as other molecules such as bisflavonoides and xanthones.