Approche phylogénétique
Projet en cours
Algues marines anti-Apicomplexes
Les parasites apicomplexes (Plasmodium, Toxoplasma …) sont issus d’une endosymbiose secondaire entre une cellule eucaryote ancestrale et une algue rouge. De cette endosymbiose, ceux-ci ont hérité d’un chloroplaste vestigial d’origine algale (Wilson et Williamson, 1997). L’analyse de la relation phylogénétique qui lie certaines macro-algues à Plasmodium (Baumeister et al., 2010 ; Biot et al., 2012) montre que ceux-ci partagent plusieurs voies biochimiques essentielles à la survie de Plasmodium (Marechal et Cesbrun-Delaw, 2001). Le laboratoire s’appuie sur ce lien phylogénétique pour rechercher dans les algues des modulateurs capables d’interférer avec ces voies communes chez le parasite.
Automatic differential analysis of NMR experiments in complex samples
Magnetic Resonance in Chemistry 2018, 56, 469-479
Abstract: Liquid state nuclear magnetic resonance (NMR) is a powerful tool for the analysis of complex mixtures of unknown molecules. This capacity has been used in many analytical approaches: metabolomics, identification of active compounds in natural extracts, and characterization of species, and such studies require the acquisition of many diverse NMR measurements on series of samples. Although acquisition can easily be performed automatically, the number of NMR experiments involved in these studies increases very rapidly, and this data avalanche requires to resort to automatic processing and analysis. We present here a program that allows the autonomous, unsupervised processing of a large corpus of 1D, 2D, and diffusion-ordered spectroscopy experiments from a series of samples acquired in different conditions. The program provides all the signal processing steps, as well as peak-picking and bucketing of 1D and 2D spectra, the programand its components are fully available. In an experiment mimicking the search of a bioactive species in a natural extract, we use it for the automatic detection of small amounts of artemisinin added to a series of plant
extracts and for the generation of the spectral fingerprint of this molecule. This program called Plasmodesma is a novel tool that should be useful to decipher complex mixtures, particularly in the discovery of biologically active natural products fromplants extracts but can also in drug discovery ormetabolomics studies
Automatised pharmacophoric deconvolution of plant extracts, application to Cinchona bark crude extract
Margueritte L, Duciel L, Bourjot M, Vonthron- Sénécheau C, Delsuc M-A
Faraday Discussions 2018
Abstract: We present a development of the Plasmodesma dereplication method. This method is based on the automatic acquisition of a standard set of NMR experiments from a medium size set of samples differing by their bioactivity. From this raw data, an analysis pipeline is run and the data is analysed by leveraging machine learning approaches in order to extract the spectral fingerprints of the active compounds. The optimal conditions for the analysis are determined, and tested on two different system, a synthetic sample where a single active molecule is to be isolated and characterized, and a complex bioactive matrix with synergetic interactions between the components. The method allows the identification of the active compounds and performs a pharmacophoric deconvolution. The program is made freely available on internet, with an interactive visualisation of the statistical analysis, at plasmodesma.igbmc.science
Eleganolone, a Diterpene from the French Marine Alga Bifurcaria bifurcata Inhibits Growth of the Human Pathogens Trypanosoma brucei and Plasmodium falciparum
Marine Drugs, 2013, 11(3):599-610
Abstract : Organic extracts of 20 species of French seaweed have been screened against Trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. These extracts have previously shown potent antiprotozoal activities in vitro against Plasmodium falciparum and Leishmania donovani. The selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian L6 cell line. The ethyl acetate extract of the brown seaweed, Bifurcaria bifurcata, showed strong trypanocidal activity with a mild selectivity index (IC50 = 0.53 µg/mL; selectivity index (SI) = 11.6). Bio-guided fractionation led to the isolation of eleganolone, the main diterpenoid isolated from this species. Eleganolone contributes only mildly to the trypanocidal activity of the ethyl acetate extract (IC50 = 45.0 µM, SI = 4.0). However, a selective activity against P. falciparum erythrocytic stages in vitro has been highlighted (IC50 = 7.9 µM, SI = 21.6).
Antiprotozoal activities of organic extracts from French marine seaweeds
Marine Drugs 2011, 9:922-933
Abstract : Abstract: Marine macrophytes contain a variety of biologically active compounds, some reported to have antiprotozoal activity in vitro. As a part of a screening program to search for new natural antiprotozoals, we screened hydroalcoholic and ethyl acetate extracts of 20 species of seaweeds from three phyla (Rhodophyta, Heterokontophyta and Chlorophyta), sampled along the Normandy (France) coast. We tested them in vitro against the protozoa responsible for three major endemic parasitic diseases: Plasmodium falciparum, Leishmania donovani and Trypanosoma cruzi. The selectivity of the extracts was also evaluated by testing on a mammalian cell line (L6 cells). Ethyl acetate extracts were more active than hydroalcoholic ones. Activity against T. cruzi and L. donovani was non-existent to average, but almost half the extracts showed good activity against P. falciparum. The ethyl acetate extract of Mastocarpus stellatus showed the best antiplasmodial activity as well as the best selectivity index (IC50 = 2.8 µg/mL; SI > 30). Interestingly, a red algae species, which shares phylogenetic origins with P. falciparum, showed the best antiplasmodial activity. This study is the first to report comparative antiprotozoal activity of French marine algae. Some of the species studied here have not previously been biologically evaluated.
X-ray structure of floridoside isolated from the marine red algae Dilsea carnosa
Carbohydrate Research, 2008, 343(15):2697-2698
Abstract : The natural floridoside (2-O-alpha-d-galactopyranosylglycerol) was isolated from Dilsea carnosa, and its structure has been determined by single-crystal X-ray diffraction analysis. The solved structure is in agreement with the previously solved crystal structure of floridoside [Simon-Colin, C.; Michaud, F.; Léger, J.-M.; Deslandes E. Carbohydr. Res.2003, 338, 2413-2416] and demonstrates for the first time the presence of floridoside in the red algae Dilsea carnosa.
