United States Department of Agriculture, Agricultural Research Service, University, MS 38677, USA.
Pest Manag Sci. 2012 Apr;68(4):519-28. doi: 10.1002/ps.2332. Epub 2012 Jan 9.
Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry.
杂草继续对所有已知的除草作用模式产生抗药性，但近 20 年来，还没有一种具有新靶标的除草剂实现商业化。所谓的“新化学物质”只是属于新化学类别的分子，它们的作用机制与较老的除草剂相同（例如原卟啉原氧化酶抑制剂嘧啶二酮 saflufenacil 或针对非常长链脂肪酸延长酶的磺酰异噁唑啉除草剂 pyroxasulfone）。因此，管理杂草的工具，特别是那些能够控制抗除草剂杂草的工具，正在迅速减少。迫切需要真正创新的除草剂类别，这些类别探索化学空间，并与以前未被旧有效成分利用的靶标位点相互作用。本综述提出了一种以天然产物为中心的除草剂发现方法的基本原理，该方法利用了这些生物活性化合物提供的结构多样性和创造力。扩展高通量筛选的自然过程（在很长一段时间内对许多潜在靶标位点测试大量化合物）塑造了天然产物的进化，这一过程往往会产生与特定靶标位点相互作用的分子。正如本综述所示，天然和合成植物毒素的作用模式通常很少重叠，应该更加重视应用已被证明对制药行业有益的方法来解决农业化学工业中的问题。
