Terpenoid Plant Metabolites - Structural Characterization and Biological Importance

Sammanfattning: Popular Abstract in English The secondary metabolites found in plants represent an extremely rich and limitless source of novel chemical diversity for drug discovery. In fact, some of the most important drugs currently in use today are derived from plants and they were discovered as a result of the study of medicinal plants used in traditional medicine. In this context, Bolivia is one of the most biological diverse countries of the world maintaining vast intact humid and dry forest ecosystems, which are the habitat of more than 20,000 species of higher plants. Due to the biodiversity and individuality of each geographical region, the medicinal plant knowledge is unique to the ethnical group living and working in these regions and it is therefore essential to preserve them. The current renewed interest in natural products prompted us to study medicinal plants as source of bioactive compounds with anticancer or leishmanial activities. In this thesis, medicinal plants growing at high altitudes were collected in Cochabamba, Bolivia, and their ethanol crude extracts screened for leishmanicidal activity. Kaunia lasiophthalma, Trixis antimenorrhoea and Lantana balansae showed high or moderate activity and were therefore chosen for detailed phytochemical and biological studies. Kaunia lasiophthalma yielded two new eudesmane derivatives, a novel terpenoid, and several previously discovered sesquiterpenes and flavonoids. The anticancer activities of the isolated sesquiterpene lactones assayed in five brest-cancer cell lines was compared with the cytotoxicity in the normal-like epithelial cell line, MCF-10A. These biological results demostrate that all assayed compounds showed different levels of cytotoxicity and that the normal-like MCF-10A was the least sensitive to all compounds. Trixis antimenorrhoea was found to be rich in terpenoids and flavonoids, which are interesting groups of natural products that have shown to exhibit several biological properties including leishmanicidal activity. T. antimenorrohea produced two new natural products, a novel nortrixane and a trixanolide derivative. The low yield of the novel nortrixane prevented further studies of this compound, while the new trixanolide exhibited high activity towards the two strains of Leishmania parasite used in this study. The lupane-type triterpernes and the flavonoids displayed different levels of activity. From the bioactive extract of Lantana balansae several known secondary metabolites were isolated, structurally analyzed and their biological activity evaluated. As a result, the cyclopentenone fatty derivative and the two flavanones are new classes of secondary metabolites for the genus Lantana and flavonoids were found to be the major metabolites. The potent antileishmanial activity of 12 oxo-phytodienoic and flavonoids explain the significant activity of the crude extract of L. balansae. In addition, structure elucidation of three novel macrocyclic monoterpene O glycosides isolated from the medicinal plant Parkinsonia aculeata was established by NMR and MS techniques. In summary, this research project contributes to the chemical knowledge of these plant species and confirmes that medicinal plants are an important source of bioactive metabolites with anticancer or antileishmanial activities. Further studies to understand the molecular mechanisms governing their beneficial activity should be performed.