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
  • Fonction : Auteur
  • PersonId : 751218
  • IdHAL : bwitkowski
Yan Liu
  • Fonction : Auteur correspondant
  • PersonId : 1031617

Connectez-vous pour contacter l'auteur

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.
Fichier sous embargo
Fichier sous embargo
0 5 2
Année Mois Jours
Avant la publication
jeudi 24 juillet 2025
Fichier sous embargo
jeudi 24 juillet 2025
Connectez-vous pour demander l'accès au fichier

Dates et versions

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

Licence

Identifiants

Citer

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, inPress, ⟨10.1021/acs.jmedchem.4c02702⟩. ⟨hal-04931161⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

More