Malaria is a major public health problem worldwide, with almost 600,000 deaths per year, most of them children under the age of 5. The treatment of this disease, caused mostly by the Plasmodium falciparum parasite, has been the main focus of our team’s work for many years. The successive resistance of this parasite to antimalarial drugs means that the therapeutic arsenal must be constantly renewed. In this context, we are looking at resistance to the artemisinin family (the main antimalarial drugs used), which is currently emerging in Africa, where 90% of malaria deaths are concentrated.

Our work has already led to the selection of the first artemisinin-resistant laboratory strain (F32-ART), to the demonstration that resistant parasites enter quiescence (or dormancy) during treatment, and to the identification of the pfk13 gene polymorphism as a molecular marker for this resistance.

We have recently demonstrated the involvement of redox, epigenetic and biochemical mechanisms in parasite resistance to artemisinins. We are continuing to explore the changes that occur in resistant parasites in order to identify relevant therapeutic targets for the design of drug candidates capable of eliminating artemisinin-resistant parasites.

In this context, we have designed and synthesised several families of molecules with good antimalarial activity. These molecules are often composed of several ‘fragments’, each with its own activity, so as to act simultaneously on several parasite targets (‘hybrid molecules’). This makes it possible to optimise antimalarial activity, particularly against resistant parasites.

Among these compounds, emoquine is the 2025 molecule of the year!ces composés, l’émoquine est la molécule de l’année 2025 !

A publication reporting the synthesis and antimalarial activity of emoquine-1 was published in 2025 in The Journal of Medicinal Chemistry (article).

This hybrid molecule, containing an emodin fragment coupled to a 4-aminoquinoline via a carefully chosen linker, is highly active against multi-resistant Plasmodium falciparum, including artemisinin-resistant Plasmodium falciparum. It is also active at low oral doses in an in vivo model. These characteristics make it an ideal drug candidate for combating malaria that is resistant to current first-line therapies.

The acquisition of drug resistance capacity by malaria parasites is a process that depends on many factors, both exogenous, such as drug quality (storage conditions, counterfeiting) and compliance, and endogenous (genetic background, compensatory mechanisms, parasite fitness). To date, none of the compounds used to treat malaria has escaped this problem.

Understanding the mechanisms associated with the selection of artemisinin resistance will open up new avenues both for monitoring the emergence of resistance and for the development of drug candidates that will enable this phenomenon to be avoided. The aim of all this work is to propose new diagnostic and therapeutic tools for combating these resistant parasites.

There is currently no effective medication for Alzheimer’s disease. This neurodegenerative disease is characterised by a loss of endogenous copper regulation, which accumulates in amyloid plaques in the brains of patients (six times more than in healthy brains). This phenomenon is responsible for the overproduction of hydroxyl radicals (ROS) which induce neuronal death and, consequently, the loss of cognitive functions. We have synthesised a series of molecules containing an 8-aminoquinoline motif and a diamine side chain (called TDMQ), capable of specifically chelating Cu(II) in a square planar environment. These drug candidates effectively inhibit episodic memory loss in a mouse model mimicking the early stages of Alzheimer’s disease.

A compound in this family, TDMQ20, is also active against Wilson’s disease, a genetic disorder characterised by a toxic accumulation of copper in the liver. In mice, TDMQ20 is more effective than the drugs currently used clinically or in development, in reducing the hepatic load of copper and facilitating its biliary excretion. Unlike reference products, TDMQ20 is not acutely or chronically toxic in mice.Un composé de cette famille, la TDMQ20 est également actif contre la maladie de Wilson, pathologie génétique caractérisée par une accumulation toxique de cuivre dans le foie. Chez la souris, la TDMQ20 est plus efficace que les médicaments actuellement utilisés en clinique ou en développement, pour diminuer la charge hépatique de cuivre et faciliter son excrétion biliaire. Contrairement aux produits de référence, la TDMQ20 ne présente aucune toxicité aigüe ou chronique chez la souris.