Novel nematicidal agents to improve crop production

该提案旨在资助开发一种用于作物保护的新型杀线虫剂。植物寄生线虫（PPN）对作物的破坏是对各地良好生产的一个主要威胁。在全球范围内，PPN估计每年造成3500亿美元的作物损失。在某些情况下，PPN使作物产量减少80%以上。随着全球气温的上升，PPN对作物的侵染率将增加，更多的PPN物种将成为加拿大农业的新威胁。显然，PPN对全球粮食安全构成严重威胁。 虽然健全的农业实践，生物制剂和转基因生物可以减少PPN侵扰，但4000多种不同的PPN物种找到了规避这些创新的方法。因此，小分子杀线虫剂对于PPN控制策略至关重要。对环境毒性和人类安全的担忧无疑促使限制和禁止许多有效的杀线虫剂，包括熏蒸剂甲基溴和神经毒性有机磷酸酯和氨基甲酸酯。法规限制了可用的杀线虫剂的数量，使得对几种PPN物种不再有可靠的控制选择，包括寄生在加拿大马铃薯、洋葱、番茄、葡萄和其他作物上的北方根结线虫。显然需要开发新的、安全和有效的化学工具来控制PPN。 罗伊实验室发现了一类新的不饱和咪唑并噻唑化合物（UIC），它们在温室植物感染性测试中对PPN有效。UIC对PPN具有选择性，对植物、人类细胞和小鼠等非靶生物无明显影响。我们从这个系列的主要候选人是同样有效的，或优于商业杀线虫剂阻断PPN感染，但有更大的选择性PPN的整体。我们已申请临时专利，涵盖UIC对抗PPN的效用。 在这里，我们请求I2I第一阶段资金来合成额外的UIC类似物，对PPN进行更大规模的温室试验，并对各种其他非靶生物进行额外的毒性试验。这笔资金是从UIC开发可销售的杀线虫剂的关键。

This proposal seeks to fund the development of a novel nematicidal agent for crop protection. A major threat to good production everywhere is crop destruction by plant parasitic nematodes (PPNs). Globally, PPNs are estimated to cause $350 billion in crop losses every year. In some cases, PPNs reduce crop yield by over 80%. As global temperatures rise, the rate of crop infestation by PPNs will increase and additional PPN species will become new threats to Canadian agriculture. Clearly, PPNs pose a serious threat to global food security. Although sound agricultural practices, biologicals, and GMOs can reduce PPN infestation, the more than 4000 different PPN species find ways to circumvent these innovations. Small molecule nematicides have consequently been essential for PPN control strategies. Concerns over environmental toxicity and human safety have justifiably prompted restrictions and bans on many effective nematicides, including the fumigant methyl bromide, and neurotoxic organophosphates and carbamates. Regulations have limited the number of available nematicides such that there are no longer reliable control options for several PPN species, including Meloidogyne hapla that parasitizes Canadian potatoes, onion, tomatoes, grapes and other crops. There is a clear need to develop new, safe and effective chemical tools to control PPNs. The Roy Lab has discovered a new class of unsaturated imidazothiazole compounds (UICs) that are effective against PPNs in greenhouse-based plant infectivity tests. The UICs are selective for PPNs, demonstrating no obvious effects on non-target organisms such as plants, human cells, and mice. Our lead candidate from this series is equally effective as, or better than, commercial nematicides at blocking PPN infection, but has greater selectivity for PPNs overall. We have filed a provisional patent covering the utility of the UICs against PPNs. Here, we request I2I Phase I funding to synthesize additional UIC analogs, carry out larger-scale greenhouse assays against PPNs, and perform additional toxicity tests with a variety of other non-target organisms. This funding is key to developing a marketable nematicide from the UICs.