2. Academic Validation
  3. Cyprocide selectively kills nematodes via cytochrome P450 bioactivation

Cyprocide selectively kills nematodes via cytochrome P450 bioactivation

  • Nat Commun. 2024 Jul 2;15(1):5529. doi: 10.1038/s41467-024-49738-4.
Jessica Knox 1 2,  Andrew R Burns 1 2,  Brittany Cooke 1 2,  Savina R Cammalleri 1 2,  Megan Kitner 3,  Justin Ching 4,  Jack M P Castelli 1 2,  Emily Puumala 1,  Jamie Snider 2,  Emily Koury 5,  J B Collins 5,  Salma Geissah 1 6,  James J Dowling 1 6,  Erik C Andersen 7,  Igor Stagljar 1 2 8 9,  Leah E Cowen 1,  Mark Lautens 4,  Inga Zasada 3,  Peter J Roy 10 11 12
Affiliations

Affiliations

  • 1 Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • 2 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
  • 3 United States Department of Agriculture - Agricultural Research Service, Horticultural Crops Disease and Pest Management Research Unit, Corvallis, OR, USA.
  • 4 Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, ON, Canada.
  • 5 Molecular Biosciences, Northwestern University, Evanston, IL, USA.
  • 6 Division of Neurology and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • 7 Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
  • 8 Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
  • 9 Mediterranean Institute for Life Sciences, Meštrovićevo Šetalište 45, HR-21000, Split, Croatia.
  • 10 Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. peter.roy@utoronto.ca.
  • 11 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada. peter.roy@utoronto.ca.
  • 12 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. peter.roy@utoronto.ca.
PMID: 38956039 DOI: 10.1038/s41467-024-49738-4
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.

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