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

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

  • J Med Chem. 2025 Feb 13;68(3):3559-3571. doi: 10.1021/acs.jmedchem.4c02702.
Youzhi Li 1 2,  Michel Nguyen 1 3,  Marion Laurent 1 3,  Sharon Wein 4,  Lucie Paloque 1 3,  Shivani Kessavdjee-Djouma 1,  Benoît Witkowski 5,  Lise Musset 6,  Jean-Michel Augereau 1 3,  Rachel Cerdan 4,  Anne Robert 1,  Yan Liu 2,  Bernard Meunier 1 2,  Françoise Benoit-Vical 1 3
Affiliations

Affiliations

  • 1 Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Inserm ERL 1289 MAAP, Université de Toulouse, 205 route de Narbonne, 31077 Toulouse cedex, France.
  • 2 School of Chemical Engineering and Light Industry, Higher Education Mega Center, Guangdong University of Technology, Guangzhou 510006, P. R. China.
  • 3 Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III - Paul Sabatier (UT3), 205 Route de Narbonne, 31077 Toulouse cedex, France.
  • 4 LPHI-Laboratory of Pathogens and Host Immunity, CNRS, INSERM, Université de Montpellier, Place Eugène Bataillon Bât 24, 34095 Montpellier cedex 5, France.
  • 5 Malaria Unit #5 Monivong bvd, Institut Pasteur du Cambodge, 120210 Phnom Penh, Cambodia.
  • 6 Laboratoire de Parasitologie, Centre National de Référence du Paludisme, Pôle Zones Endémiques, WHO Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, 97306 Cayenne cedex, French Guiana.
PMID: 39849946 DOI: 10.1021/acs.jmedchem.4c02702
Abstract

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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