Contribution à l’étude phytochimique de deux plantes endémiques de l’île de la Réunion, Vernonia fimbrillifera et Monimia rotundifolia, et de leur potentiel antiplasmodial

ABSTRACTAs natural products represent more than 60 % of active substances on the pharmaceutical market, our research group, the Laboratory of Pharmacognosy (ULg), decided to collaborate with Reunion Island University for the discovery of new antiplasmodial metabolites from plants. A large screening of several plants from this volcanic island highlighted the promising in vitro antiplasmodial activity of Vernonia fimbrillifera Less. (Compositae) and Monimia rotundifolia Thouars (Monimiaceae). As such, the aim of this thesis will focus on the phytochemical and pharmacological investigation of these two endemic species from La Réunion. A bioactivity-guided fractionation was carried out on the leaf extract from Vernonia fimbrillifera. Three sesquiterpene lactones were isolated, namely 8-(4’-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8-[4’-hydroxymethacrylate)-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited in vitro antiplasmodial activity with IC50 values ≤ 5 µg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine their selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10). The study of M. rotundifolia leaves through the combination of several analytical techniques such as preparative HPLC, LC-MS/MS and LC-SPE-NMR/MS led to successfully characterize and elucidate the structure of four aporphine alkaloids (1-4) known as norboldine (1), boldine (2), laurotetanin (3) and N-methyllaurotetanin (4). In the course of our experiments, a mixture of laurotetanine and N-methyllaurotetanine was isolated through preparative HPLC analysis. They displayed moderate in vitro activity on P. falciparum with IC50 values = 15 µg/mL. On the other hand, HPLC-SPE-NMR/MS method was developed to identify aporphine alkaloids from M. rotundifolia leaves. This study demonstrated that this technique, combined with other methods (e.g. LC-MS/MS and HR-ESI-MS) is a powerful and useful tool for the identification of natural constituents, such as alkaloids, among rich crude plant extracts. To conclude, this work showed that Reunion Island’s unique flora needs to be promoted, valorized and preserved as a promising source of potential therapeutic substances.