Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
School of Physics, Zhejiang University, Hangzhou 310027, China.
Molecules. 2024 May 21;29(11):2409. doi: 10.3390/molecules29112409.
Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, , , and , were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki-Miyaura cross-coupling reaction. These new PMBs, , were more effective in post-emergence control of grass weeds compared with . Interestingly, six of the PMBs displayed 98-100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.
除草剂是管理杂草、促进粮食生产和可持续农业的有用工具。在这项研究中，我们报告了一类新型亲脂嘧啶联苯 (PMB) 除草剂的开发。首先，通过支架跳跃策略合理设计了三种 PMB， ， ，和 ，并确定它们抑制乙酰羟酸合酶 (AHAS)。进行了计算模拟以研究 PMB 对 AHAS 效率的分子基础。具有合理的结合模式和最高的体外和体内活性， 被鉴定为较好的命中物。此外，这些综合分析指导了十八种新型 PMB 的设计，这些 PMB 是通过一步 Suzuki-Miyaura 交叉偶联反应合成的。与 相比，这些新的 PMB， ，在芽后控制杂草方面更有效。有趣的是，在 750 g ai/ha 下，有 6 种 PMB 对杂草的抑制率达到 98-100%。值得注意的是， 以 187.5 g ai/ha 的剂量对杂草的控制率达到≥80%。总体而言，我们全面而系统的研究表明，一类结构独特的亲脂性 PMB 除草剂具有极好的除草活性，并与 AHAS 发生新的相互作用，代表了可持续杂草控制解决方案的重要发展。
