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A new class of anthelmintics effective against drug-resistant nematodes

Author

Listed:
  • Ronald Kaminsky

    (Novartis Centre de Recherche Santé Animale)

  • Pierre Ducray

    (Novartis Animal Health Inc.)

  • Martin Jung

    (Novartis Centre de Recherche Santé Animale)

  • Ralph Clover

    (Cambria Biosciences, Woburn, Massachusetts 01801, USA)

  • Lucien Rufener

    (Novartis Centre de Recherche Santé Animale
    Institute of Cell Biology, University of Bern)

  • Jacques Bouvier

    (Novartis Centre de Recherche Santé Animale)

  • Sandra Schorderet Weber

    (Novartis Centre de Recherche Santé Animale)

  • Andre Wenger

    (Novartis Centre de Recherche Santé Animale)

  • Susanne Wieland-Berghausen

    (Novartis Animal Health Inc.)

  • Thomas Goebel

    (Novartis Animal Health Inc.)

  • Noelle Gauvry

    (Novartis Animal Health Inc.)

  • François Pautrat

    (Novartis Animal Health Inc.)

  • Thomas Skripsky

    (Novartis Animal Health Inc.)

  • Olivier Froelich

    (Novartis Centre de Recherche Santé Animale)

  • Clarisse Komoin-Oka

    (Laboratoire Central Vétérinaire de Bingerville, BP 206, Lanada, Côte d’Ivoire)

  • Bethany Westlund

    (Cambria Biosciences, Woburn, Massachusetts 01801, USA)

  • Ann Sluder

    (Cambria Biosciences, Woburn, Massachusetts 01801, USA)

  • Pascal Mäser

    (Institute of Cell Biology, University of Bern)

Abstract

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics—the benzimidazoles, imidazothiazoles and macrocyclic lactones—has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.

Suggested Citation

  • Ronald Kaminsky & Pierre Ducray & Martin Jung & Ralph Clover & Lucien Rufener & Jacques Bouvier & Sandra Schorderet Weber & Andre Wenger & Susanne Wieland-Berghausen & Thomas Goebel & Noelle Gauvry & , 2008. "A new class of anthelmintics effective against drug-resistant nematodes," Nature, Nature, vol. 452(7184), pages 176-180, March.
    • Handle: RePEc:nat:nature:v:452:y:2008:i:7184:d:10.1038_nature06722
    DOI: 10.1038/nature06722
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    Cited by:

    1. Peter J Hotez & Bernard Pecoul, 2010. "“Manifesto” for Advancing the Control and Elimination of Neglected Tropical Diseases," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 4(5), pages 1-7, May.
    2. Eric R. Morgan & Johannes Charlier & Guy Hendrickx & Annibale Biggeri & Dolores Catalan & Georg Von Samson-Himmelstjerna & Janina Demeler & Elizabeth Müller & Jan Van Dijk & Fiona Kenyon & Philip Skuc, 2013. "Global Change and Helminth Infections in Grazing Ruminants in Europe: Impacts, Trends and Sustainable Solutions," Agriculture, MDPI, vol. 3(3), pages 1-19, August.
    3. Taylor Davie & Xènia Serrat & Lea Imhof & Jamie Snider & Igor Štagljar & Jennifer Keiser & Hiroyuki Hirano & Nobumoto Watanabe & Hiroyuki Osada & Andrew G. Fraser, 2024. "Identification of a family of species-selective complex I inhibitors as potential anthelmintics," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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