Novel nematicidal agents to improve crop production

提高作物产量的新型杀线虫剂

• 批准号: 555963-2020
• 负责人: Roy, PeterPJ
• 金额: $ 4.37万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761225
• 关键词: Novel; nematicidal; agents; improve; crop

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.

这项提案旨在为开发一种用于作物保护的新型杀线虫剂提供资金。植物寄生线虫(PPN)对世界各地良好生产的主要威胁是对作物的破坏。据估计，在全球范围内，PPN每年造成3500亿美元的作物损失。在某些情况下，PPN会使作物减产80%以上。随着全球气温的上升，PPN对作物的侵害率将会增加，更多的PPN物种将成为对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。尽管良好的农业实践、生物制品和转基因生物可以减少PPN的侵扰，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PPN控制策略至关重要。出于对环境毒性和人类安全的担忧，有理由对许多有效的杀线虫剂进行限制和禁止，包括熏蒸剂甲基溴以及具有神经毒性的有机磷和氨基甲酸酯。法规限制了可用杀线虫剂的数量，因此对几种PPN物种不再有可靠的防治选择，包括寄生在加拿大土豆、洋葱、西红柿、葡萄和其他作物上的哈普拉根结线虫。显然有必要开发新的、安全和有效的化学工具来控制PPN。Roy实验室在温室植物感染性测试中发现了一类新的不饱和咪唑噻唑化合物(UICs)。UIC对PPN具有选择性，对植物、人类细胞和小鼠等非靶标生物没有明显影响。我们在这一系列中的主要候选药物在阻断PPN感染方面与商业杀线虫剂一样有效，甚至更好，但总体上对PPN具有更高的选择性。我们已经申请了一项临时专利，涵盖了UIC对PPN的效用。在此，我们申请I2I第一阶段资金，以合成更多的UIC类似物，针对PPN进行更大规模的温室试验，并对各种其他非靶标生物进行额外的毒性测试。这笔资金是从UIC开发一种适销对路的杀线虫药物的关键。