Études phytochimiques du lichen Nephroma laevigatum et de ses champignons endolichéniques. Évaluation des activités antiprolifératives et anti-biofilms.

Abstract : Antibiotics resistance or increase of difficulty to treat for current diseases with commercially available compounds has obligated researchers to find new sources of active molecules. Lichens produce various biologically active compounds due to the great diversity of their ecosystem. Thus, they represent a promising source of bioactive compounds. Chemical profiling of Nephroma laevigatum was performed. LC-MS/MS analysis with molecular network approach allowed understanding chemical diversity of this lichen and four different compounds were isolated and identified by NMR and tested for their antiproliferative activity. However, lichen resources are limited, which limits their use. In addition, lichen thalli are an ecological niche for other microorganisms and a wide reservoir for access to bioactive molecules. Cultivation of endolichenic fungi was undertaken. Thus, 46 strains were isolated and identified by DNA barcoding (primers ITS4 and ITS5). The isolated fungi belong to genus Nemania, Daldinia, Peziza and Coniochaeta. Biological investigation was carried out on six selected strains belonging to two species (Nemania aenea var. aureolatum and N. serpens). So, two strains distinguished by their antiproliferative and anti-biofilm activities. Further chemical and biological studies of these strains (Gir_20 N. aenea var. aureolatum and Cor_08 N. serpens) were subsequently performed and eight different compounds were isolated and identified by 1D and 2D NMR. Study of effect of the extracts on the human cancer lines HT-29, HCT116, PC-3 and DU145 made it possible to highlight morphological changes at the cellular level. Analyses of the expression of pro- and anti-apoptotic protein markers as well as DNA fragmentation demonstrate the induction of apoptosis. LC-MS/MS chemical profiling of these strains was performed and compared with molecular network approach, to visualize chemical diversity between the two species of endolichenic fungi.
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Aurélie Lagarde. Études phytochimiques du lichen Nephroma laevigatum et de ses champignons endolichéniques. Évaluation des activités antiprolifératives et anti-biofilms.. Chimie organique. Université de Limoges, 2017. Français. ⟨NNT : 2017LIMO0099⟩. ⟨tel-01740326⟩

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