Diverse Plant-Parasitic Nematodes are Selectively Killed by Oxadiazole Thioether Pro-Nematicides

Knox, J.; Burns, A. R.; Cooke, B.; Cammalleri, S. R.; Kitner, M.; Ching, J.; Castelli, J. M. P.; Puumala, E.; Snider, J.; Koury, E.; Collins, J. B.; Andersen, E. C.; Stagljar, I.; Cowen, L.; Lautens, M.; Zasada, I.; Roy, P.

doi:10.1101/2023.09.14.557801

bioRxiv · 10.1101/2023.09.14.557801

Diverse Plant-Parasitic Nematodes are Selectively Killed by Oxadiazole Thioether Pro-Nematicides

Knox, J.·Burns, A. R.·Cooke, B.·Cammalleri, S. R.·Kitner, M.·Ching, J.·Castelli, J. M. P.·Puumala, E.·Snider, J.·Koury, E.·Collins, J. B.·Andersen, E. C.·Stagljar, I.·Cowen, L.·Lautens, M.·Zasada, I.·Roy, P.

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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 diverse plant-parasitic nematodes. Cyprocide is bioactivated into a lethal reactive electrophilic metabolite by specific nematode cytochrome P450 enzymes. Because Cyprocide fails to kill non-target organisms, we infer 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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Knox, J., Burns, A. R., Cooke, B., Cammalleri, S. R., Kitner, M., Ching, J., Castelli, J. M. P., Puumala, E., Snider, J., Koury, E., Collins, J. B., Andersen, E. C., Stagljar, I., Cowen, L., Lautens, M., Zasada, I., Roy, P.. 2023-09-17. Diverse Plant-Parasitic Nematodes are Selectively Killed by Oxadiazole Thioether Pro-Nematicides. https://doi.org/10.1101/2023.09.14.557801

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