Cyprocide selectively kills nematodes via cytochrome P450 bioactivation

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, James J. Dowling, Erik C. Andersen, Igor Stagljar, Leah E. Cowen, Mark Lautens, Inga Zasada and Peter J. Roy ()
Additional contact information
Jessica Knox: University of Toronto
Andrew R. Burns: University of Toronto
Brittany Cooke: University of Toronto
Savina R. Cammalleri: 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
Emily Puumala: University of Toronto
Jamie Snider: University of Toronto
Emily Koury: Northwestern University
J. B. Collins: Northwestern University
Salma Geissah: University of Toronto
James J. Dowling: University of Toronto
Erik C. Andersen: Johns Hopkins University
Igor Stagljar: University of Toronto
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

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49738-4

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