Constituants chimiques de trois plantes médicinales camerounaises de la famille des Loranthaceae: Globimetula dinklagei (Engler) Van Tieghem, Tapinanthus bangwensis Engler & Krause et Phragmanthera capitata (Sprengel) S. Balle Structures- Transformations

Abstract

The works described in this thesis are part of the research theme of Laboratory 260, managed by Professor Nkengfack. It aims to search molecules from plant of the Cameroonian flora endowed of antitumor and antimicrobial activity.The study of three medicinal plants, Globimetula dinklagei, Tapinanthus bangwensis,Phragmanthera capitata, all belonging to the Loranthaceae family, more precisely the isolation, the purification, the characterisation, the chemical transformations and the biological activities of some secondary metabolites from those plants are the object of this thesis. Those plants were selected on the basis of their therapeutical value notably their uses in traditional folk medicine for the treatment of several diseases such as cholera and cancer.Thus, from these three plants, thirty five compounds were isolated, using liquid phase chromatographic methods, twenty six of which were entirely characterized. Among them, there are ten new pentacyclic triterpene derivatives, three of which are lupan-type named globimetulin A-C; five belongs to oleanane-type, bangwaoleanene A-E whereas two are ursane-type designated bangwaursene A-B. Of the sixteen remaining known compounds, there are ten pentacyclic triterpenes derivatives (friedelin, friedelan-3-ol, 28-hydroxyfriedelin, 3-O-β-D-glucopyranosyl-α-amyrin, 3β-acetoxy-β-amyrin, 3β-acetoxy-urs-12-en-11-one, 3β acetoxy-11α-hydroxyurs-12-ene, 3β acetoxy-11α,12α-oxidotaraxerol, lup-20(29)-en 7β,15α-diol-3β-palmitate, 28-hydroxy-3-O-β-D-glucopyranosyl-α-amyrin); one flavonoid glycoside (8-C-β-D-glucopyranosyl-apigenin), one gallic acid derivative (4-hydroxy-3,5-dimethoxybenzoïc acid); one bicyclic compound ((1R,5S,7S)-7-[2-(4-hydroxyphenyl)ethyl]-2,6-dioxabicyclo[3.3.1]nonan-3-one) and 3 carbohydrates (2-deoxyribose, myo-inisitol, sorbitol). The structures of all these compounds were elucidated from the detailed analysis of their spectral data including one and two dimensional proton and carbon 13 NMR techniques (COSY, HSQC, HMBC) in conjunction with mass spectrometry (FAB, ESI) and by comparison of the spectral data of these compounds with those reported in the literature. Globimetulin A, containing a terminal double bond and an ester function in its structure was subjected to some chemical transformations including epoxydation, ozonolysis and a Grignard reaction, reaction products obtained were characterized. Some of these compounds were evaluated for their cytotoxic and antimicrobial activities. The results obtained showed that globimetulin B and 28-hydroxy-3-O-β-D glucopyranosyl-α-amyrin present a noticeable antitumoral activity toward four cancer cell lines (MCF-7, HeLa, Caco-2, A549) with GI50 varying between 5.61 and 16.57 µg/mL; while bangwaursene B is active toward Gram positive bacteria (Staphylococus aureus) and Gram negative bacteria (Escherichia coli).