Elisabeth |
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Information |
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Laboratoire d'Innovation Moléculaire et Applications (LIMA) | ||
Team "bio(IN)organic & medicinal chemistry" | ||
Strasbourg | ||
0000-0001-7026-4034 | ||
This email address is being protected from spambots. You need JavaScript enabled to view it. | ||
http://lima.unistra.fr/cbm/ | ||
@redoxLCBM | ||
Scientific interests and projects |
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The spread of drug resistance in parasites jeopardises recent progress to fight malaria. Chagas’ disease and schistosomiasis are neglected tropical parasitic diseases that are considered as public health top priorities. The expertise of the research team in redox medicinal chemistry is applied to the synthesis of ‘subversive substrates’ of NAD(P)H-dependent oxidoreductases, with the aim to develop antiparasitic agents and to identify new therapeutic targets. Our interdisciplinary activity spans from the synthesis (inhibitors, redox-cyclers, metabolites, ratiometric fluorescent probes sensitive to pH and redox gradients, labelled tools for metabol- & proteo-omics) to enzymology and understanding of the mechanisms of action in living parasites. Among our recent major achievements, we showed that, depending on their chemical substitution pattern, 3-benzyl-menadione derivatives, displayed potent antiparasitic activities, both in vitro and in vivo, against Plasmodium spp., Trypanosoma cruzi, or Schistosoma mansoni worms, induced specific phenotypic effects, with no obvious sign of toxicity in mice and in G6PD-deficient red blood cells. Our efforts are focused on the optimization of three early leads: the antimalarial plasmodione, a fast acting and transmission blocking agent, the anti-Chagas cruzidione, and the antischistosomal schistodiones. The goal of future collaborative research in ParaFrap is to optimize both early leads and synergistic partners for each disease model, to improve their pharmacokinetic properties and respective antiparasitic activities, to identify the sensitive parasite stages, their modes of action, and to validate the antiparasitic properties of the optimized compounds in vivo and with field parasite isolates. Our overarching aim is i) to select drug-candidates ready for further clinical development, ii) to unravel the modes of action through physicochemical approaches describing the interactions of antiparasitic agents with relevant targets. |
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Top 5 publications of the last 5 years |
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1. Feng L., Lanfranchi D. A., Cotos-Munoz L., Cesar Rodo E., Ehrhardt K., Goetz, A.-A., Zimmerman H., Fenaille F., Blandin S., Davioud-Charvet E. (2018) Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation. Org. Biomol. Chem. 16, 2647 - 2665. doi: 10.1039/C8OB00227D 2. Krieg R., Jortzik E., Goetz A.-A., Blandin S., Wittlin S., Elhabiri M., Rahbari M., Nuryyeva S., Voigt K., Dahse H.-M., Brakhage A., Beckmann S., Quack T., Grevelding C. G., Pinkerton A. B., Schönecker B., Burrows J., Davioud-Charvet E.,Rahlfs S., Becker K. (2017) Arylmethylamino steroids as novel antiparasitic agents. Nat. Commun. 8:14478. Erratum : Nat Commun. 2019, 10:2997. doi:10.1038/s41467-019-11018-x 3. Ehrhardt, K., Deregnaucourt, C., Goetz, A.-A., Tzanova, T., Pradines, B., Adjalley, S. H., Blandin, S., Bagrel, D., Lanzer, M., Davioud-Charvet, E. (2016) The redox-cycler plasmodione is a fast acting antimalarial lead compound with pronounced activity against sexual and early asexual blood-stage parasites. Antimicrob. Agents Chemother. 60, 5146- 58. doi: 10.1128/AAC.02975-15 4. Cesar Rodo E., Feng L., Jida, M., Ehrhardt K., Bielitza M., Boilevin J., Lanzer M., Williams D. L., Lanfranchi, D. A., Davioud-Charvet, E. (2016) A platform of regioselective methodologies to access to polysubstituted 2-methyl-1,4-naphthoquinones derivatives: scope and limitations. Eur. J. Org. Chem. 11, 1982–1993. doi: 10.1002/ejoc.201600144 5. Bielitza, M., Belorgey, D., Ehrhardt, K., Johann, L., Lanfranchi, D. A., Gallo, V., Schwarzer, E., Mohring, F., Jortzik, E., Williams, D. L., Becker, K., Arese, P., Elhabiri, M., Davioud- Charvet E. (2015) Antimalarial NADPH-consuming redox-cyclers as superior G6PD deficiency copycats. Antioxid. Redox Signal. 22, 1337-51. 10.1089/ars.2014.6047 |
The York Biomedical Research Institute (YBRI) are hosting an online live seminar on Friday 24th May 1-2pm BST as part of their biomedical science seminar series. You are all welcome to attend - registration is required via the...
[Communiqué] Congratulations to Arthur Talman, IRD Research Leader in the MIVEGEC laboratory (Montpellier), who has been awarded an Advanced Grant from the European Research Council (ERC) for the project "TROJAN - Molecular mimicry and immune...
Ana Rita Gomes, a CNRS Research Associate at the Laboratory of Pathogens and Host Immunity in Montpellier, and former Postdoctoral fellow of the LabEx ParaFrap, has been awarded the prestigious CNRS Bronze Medal in 2023. This...
. PhD Opportunity, Tours, France Supervision Thesis Supervisor: Sonia LAMANDE; Co-Supervisor: Julie TOTTEY Project: FUNTIONAL CHARACTERISATION OF CYSTEINE CATHEPSINS IN THE APICOMPLEXAN PARASITE CRYPTOSPORIDIUM...
Senior PostDoc position : computational biologist, Paris, France The ParSig team (https://research.pasteur.fr/en/team/molecular-parasitology-and-signaling) at the Institut Pasteur in Paris seeks for a highly...
Researcher in Livestock Immunology for the Study of Animal Trypanosomoses Through a One Health approach, the Intertryp Joint Research Unit (Cirad-IRD) is developing research on interactions between hosts,...
Happy New Year 2024! To kick off this new scientific year, here is the ParaFrap webinar schedule. Since January 2021, ParaFrap has been organizing a series of webinars. This monthly event, held every 2nd Thursday of the month, aims to strengthen...
PostDoc position : functional analysis of P. falciparum early gametocyte proteins, Allschwil, Switzerland The Malaria Gene Regulation Lab of Till Voss is looking for a highly motivated and talented postdoc to...
The team of Dr. Mohamed-Ali Hakimi, in collaboration with Isabelle Coppens (Johns Hopkins University Bloomberg School of Public Health and Malaria Research Institute, Baltimore, MD, USA), has developed a new (epi)genetic method to produce in vitro...
Success for ParaFrap students at MPM2023 Parafrap students won numerous awards at the MPM 2023, Woods Hole USA, 17-21 September 2023. A warm congratulations to all ! Parul Sharma (2nd year PhD under the...
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