%0 Journal Article
%T Cyprocide selectively kills nematodes via cytochrome P450 bioactivation.
%A Knox J
%A Burns AR
%A Cooke B
%A Cammalleri SR
%A Kitner M
%A Ching J
%A Castelli JMP
%A Puumala E
%A Snider J
%A Koury E
%A Collins JB
%A Geissah S
%A Dowling JJ
%A Andersen EC
%A Stagljar I
%A Cowen LE
%A Lautens M
%A Zasada I
%A Roy PJ
%J Nat Commun
%V 15
%N 1
%D 2024 Jul 2
%M 38956039
%F 17.694
%R 10.1038/s41467-024-49738-4
%X 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.