Article Dans Une Revue Journal of Medicinal Chemistry Année : 2025

Emoquine-1: A Hybrid Molecule Efficient against Multidrug-Resistant Plasmodium Parasites, Including the Artemisinin-Resistant Quiescent Stage, and Also Active In Vivo

Benoît Witkowski

Résumé

To challenge the multidrug resistance of Plasmodium falciparum malaria parasites, new hybrid compounds were synthesized and evaluated against laboratory strains and multidrug-resistant clinical isolates. Among these hybrids, emoquine-1 was the most active on proliferative P. falciparum, with IC50 values in the range of 20–55 nM and a high selectivity index with respect to mammalian cells. This drug retained its activity on several multiresistant field isolates from Cambodia and Guiana, exhibited no cross-resistance to artemisinin, and is also very active against the quiescent stage of the artemisinin-resistant parasites, three features that constitute the gold standard for new antimalarial drugs. In vivo, emoquine-1 is active against Plasmodium vinckei petteri at 25 mg/kg/d per os and by the intraperitoneal route at 1–5 mg/kg/d, with total cure at 10 mg/kg/d, making emoquine-1 an ideal candidate to fight Plasmodium parasites resistant to artemisinin-based combination therapies (ACTs) with a capacity to eliminate persistent parasites.

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hal-04931161 , version 1 (05-02-2025)

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Youzhi Li, Michel Nguyen, Marion Laurent, Sharon Wein, Lucie Paloque, et al.. Emoquine-1: A Hybrid Molecule Efficient against Multidrug-Resistant Plasmodium Parasites, Including the Artemisinin-Resistant Quiescent Stage, and Also Active In Vivo. Journal of Medicinal Chemistry, 2025, 68 (3), pp.3559-3571. ⟨10.1021/acs.jmedchem.4c02702⟩. ⟨hal-04931161⟩
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