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Recherche de composés à activité antiplasmodiale à partir de la biodiversité malgache

Abstract : As part of the search for new compounds with antiplasmodial activity, two malagasy plants were studied: Pyrostria major (Rubiaceae) and Gonioma malagasy (Apocynaceae). The Ethyl acetate and alkaloidic extracts showed significant antiplasmodial activity against the chloroquine-resistant strain FcB1 during a preliminary screening. The phytochemical study of the leaves of P. major has led to the isolation of β-sitosterol together with eight new diarylheptanoid glucoside, described for the first time in a plant belonging to the Rubiaceae family. The antiplasmodial activity of the EtOAc extract of the leaves is probably due to the presence of β-sitosterol. This activity is due to the stomatocytogenic effect caused by this family of compound. The use of the "exciton chirality" has determined the absolute configuration of the natural diarylheptanoid glucoside. This structural study allowed us to obtain, two selective antiplasmodial and non-cytotoxic compounds, as well as potential antileishmanial and antitrypanosomal compounds. The study of the alkaloidic extract of G. malagasy led to the isolation of a novel chemical series, "The goniomedines." They are characterized by a bisindole backbone consisting of two monomers connected by a dihydropyran unit. Their absolute configurations were deduced following the comparison of experimental and theoretically calculated ECD spectra and through biogenetic considerations. Among these compounds, only one showed a significant antiplasmodial activity.
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Ahmed-Mehdi Beniddir. Recherche de composés à activité antiplasmodiale à partir de la biodiversité malgache. Sciences agricoles. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA114847⟩. ⟨tel-00796218⟩

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