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Docteur DALI YAHIA Mustapha Kamel
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Introduction : The search for new active molecules against Plasmodium falciparum in particular remains a major health challenge for academic pharmaceutical research, as the pharmaceutical industries are slow to develop new therapies, mainly for economic reasons. Plants have always played an important role in the discovery of major drugs such as quinine and artemisinin. It is estimated that only 1% of the known plant species have been the subject of pharmacological studies. So there are potentially many natural active ingredients to be discovered. Objectives : Our work aims mainly to valorize an original bioresource from the extreme south of Algeria by demonstrating the therapeutic potential of six species belonging to aromatic Asteraceae relatively abundant. The second objective consists to try - through a bioguided phytochemical investigation - to find from extracts of these same plant species, which bioactive metabolites can open new paths to the treatment of malaria. Materials and methods : The choice of these species is based on a chemotaxonomic criterion and the sampling concerned only the aerial parts of the plants ; the collection area being the center of the Ahaggar Cultural Park about forty kilometers north-east of Tamanrasset. After an in vitro biological screening for antiparasitic activity, evaluated on three strains of protozoa (Plasmodium falciparum, Leishmania infantum and Trypanosoma brucei ssp. brucei), four crude extracts are retained (Artemisia campestris ssp. glutinosa, Artemisia judaica ssp. sahariensis, Pentzia monodiana and Pulicaria incisa) to be subjected for an original LC-MS technique for detecting metabolites able to link to the heminic part of hemoglobin. In parallel to this highly relevant process in the investigation of molecules that can prevent the degradation of the heme by Plasmodium, we have considered a UPLC-MSbased dereplication approach which, using a database of known natural products , can be both precise and especially fast in establishing a metabolite profile for a given extract. Preparative chromatography techniques (CPC, CC flash, HPLC) were also used for a more complete phytochemical study of Pentzia monodiana. Results : The interpretation of the NMR spectra of the compounds isolated from the P. monodiana extract confirmed the identity of these presumed metabolites during our dereplicationprocedure; this is the case of two methoxyflavones, 3'-O-methylupatorine and artemetin which showed increased affinity for the heme. Similarly, the extracts of the two subspecies of Artemisia gave very significant antiplasmodial activities, partly due to derivatives of the hydroxyacetophenone, of which a chemical structure was determined by NMR. Myrciaphenone A - a hydroxyacetophenone glucoside - is probably present in the extract of Pulicaria incisa; the latter’s antiparasitic activity could be assigned to this biomolecule. Conclusion : At the end of this study, we were able to highlight the pharmacological potential of the few aromatic Asteraceae present at the level of the Cultural Park of the Ahaggar through : - A demonstration of bioactive compounds known and mentioned in the scientific literature; some of them were reported for the first time for P. monodiana. The dereplication approach has proved to be particularly appropriate here. - An in vitro biological screening and in particular the heme fixation test, which gave us enough positive results. Key words : CPC, Heme-binding test, Natural products, NMR, Pentzia, Plasmodium, UPLC-MS.