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Cyprocide selectively kills nematodes via cytochrome P450 bioactivation

Author

Listed:
  • Jessica Knox

    (University of Toronto
    University of Toronto)

  • Andrew R. Burns

    (University of Toronto
    University of Toronto)

  • Brittany Cooke

    (University of Toronto
    University of Toronto)

  • Savina R. Cammalleri

    (University of Toronto
    University of Toronto)

  • Megan Kitner

    (Horticultural Crops Disease and Pest Management Research Unit)

  • Justin Ching

    (University of Toronto)

  • Jack M. P. Castelli

    (University of Toronto
    University of Toronto)

  • Emily Puumala

    (University of Toronto)

  • Jamie Snider

    (University of Toronto)

  • Emily Koury

    (Northwestern University)

  • J. B. Collins

    (Northwestern University)

  • Salma Geissah

    (University of Toronto
    The Hospital for Sick Children)

  • James J. Dowling

    (University of Toronto
    The Hospital for Sick Children)

  • Erik C. Andersen

    (Johns Hopkins University)

  • Igor Stagljar

    (University of Toronto
    University of Toronto
    University of Toronto
    Mediterranean Institute for Life Sciences)

  • Leah E. Cowen

    (University of Toronto)

  • Mark Lautens

    (University of Toronto)

  • Inga Zasada

    (Horticultural Crops Disease and Pest Management Research Unit)

  • Peter J. Roy

    (University of Toronto
    University of Toronto
    University of Toronto)

Abstract

Left unchecked, plant-parasitic nematodes have the potential to devastate crops globally. Highly effective but non-selective nematicides are justifiably being phased-out, leaving farmers with limited options for managing nematode infestation. Here, we report our discovery of a 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes. Cyprocide is bioactivated into a lethal reactive electrophilic metabolite by specific nematode cytochrome P450 enzymes. Cyprocide fails to kill organisms beyond nematodes, suggesting that the targeted lethality of this pro-nematicide derives from P450 substrate selectivity. Our findings demonstrate that Cyprocide is a selective nematicidal scaffold with broad-spectrum activity that holds the potential to help safeguard our global food supply.

Suggested Citation

  • Jessica Knox & Andrew R. Burns & Brittany Cooke & Savina R. Cammalleri & Megan Kitner & Justin Ching & Jack M. P. Castelli & Emily Puumala & Jamie Snider & Emily Koury & J. B. Collins & Salma Geissah , 2024. "Cyprocide selectively kills nematodes via cytochrome P450 bioactivation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49738-4
    DOI: 10.1038/s41467-024-49738-4
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    References listed on IDEAS

    as
    1. Andrew R. Burns & Genna M. Luciani & Gabriel Musso & Rachel Bagg & May Yeo & Yuqian Zhang & Luckshika Rajendran & John Glavin & Robert Hunter & Elizabeth Redman & Susan Stasiuk & Michael Schertzberg &, 2015. "Caenorhabditis elegans is a useful model for anthelmintic discovery," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    2. Andrew R. Burns & Rachel J. Baker & Megan Kitner & Jessica Knox & Brittany Cooke & Jonathan R. Volpatti & Aditya S. Vaidya & Emily Puumala & Bruna M. Palmeira & Elizabeth M. Redman & Jamie Snider & Sa, 2023. "Selective control of parasitic nematodes using bioactivated nematicides," Nature, Nature, vol. 618(7963), pages 102-109, June.
    Full references (including those not matched with items on IDEAS)

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