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Prodrugs oF antiparasitic RedOx-active compoundS

Project description

Antiparasitic prodrugs against tropical human and animal parasitic diseases

Malaria alone kills 600 000 people each year. Unfortunately, medicines are increasingly losing ground to drug-resistant parasites. Neglected tropical diseases, such as Chagas, leishmaniasis and schistosomiasis, are also major health concerns. The EIC-funded FeROS project aims to develop antiparasitic prodrugs, targeting four human parasitic diseases and potentially extending to animal health. The project will establish structure-activity relationships using in vitro and in vivo assays. It will also develop chemical tools to visualise the release of active metabolites in living parasites under reactive oxygen species conditions. The project focuses on the discovery of non-quinonoid chemotypes that can serve as precursors to 3-benzylmenadiones, which exhibit distinct antiparasitic profiles depending on their substitution patterns.

Objective

With 600,000 deaths per year, malaria remains the most devastating parasitic disease for humans. The efficiency of artemisinin-based combination therapy, the spearhead of malarial treatment, is now threatened by the development of drug resistant parasites displaying enhanced transmission potential to mosquitoes. Chagas disease, leishmaniasis and schistosomiasis are neglected tropical parasitic diseases that are considered as the greatest missed opportunities atop the priorities for WHO. The FeROS project is based on the discovery of promising non-quinonoid chemotypes as precursors of 3-benzylmenadiones, with specific antiparasitic profiles depending on the substitution pattern. FeROS will follow convergent and complementary objectives: (i) to develop innovative and specific antiparasitic prodrugs in specific series of optimized drug-candidates to reach total cures in infected animal models for four human parasitic diseases, (ii) to extend the concept to animal health, (iii) to draw structure-activity relationships in in vitro and in vivo parasite assays, (iv) to build innovative chemical tools to visualize the release of active principles under ROS fluxes, in living parasites upon drug treatment, (v) to decipher the molecular and cellular mechanisms that underlie prodrug antiparasitic activities and selectivity. FeROS is built on the multidisciplinary expertise of 7 laboratories from France, Belgium, Switzerland and USA. In an interdisciplinary approach, we will combine a large set of expertise, ranging from medicinal chemistry, physico(bio)chemistry, proteomics to parasite genetics and molecular and cellular parasitology to optimize the antiparasitic non-quinonoid prodrugs of 3-benzylmenadiones, to unravel their mode of action and take them to early clinical studies.

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Programme(s)

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Topic(s)

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Call for proposal

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(opens in new window) HORIZON-EIC-2025-PATHFINDEROPEN

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 310 395,00
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 368 432,50

Participants (4)

Partners (1)

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