Abstract:
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, Ia, IIa, and IIIa, 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, Ia 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, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98-100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica 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.
摘要:
除草剂是管理杂草和促进粮食生产和可持续农业的有用工具。在这项研究中,我们报道了一类新型亲脂性嘧啶-联苯(PMB)除草剂的开发。首先,三个PMB,Ia,IIa,IIIa,通过支架跳跃策略合理设计,并确定抑制乙酰羟酸合酶(AHAS)。进行了计算模拟以研究PMBs对抗AHAS的效率的分子基础。有了合理的绑定模式,和最高的体外和体内效力,Ia被确定为较好的命中。此外,这些综合分析指导了18个新的PMB的设计,通过一步Suzuki-Miyaura交叉偶联反应合成。这些新的PMB,Iba-ic,与Ia相比,在草杂草的出苗后控制中更有效。有趣的是,在750gai/ha的情况下,其中6种PMB对控制杂草的抑制作用为98-100%。值得注意的是,在187.5gai/ha时,Ica对草类杂草的防治率≥80%。总的来说,我们全面而系统的调查表明,一类结构上不同的亲脂性PMB除草剂,将优异的除草活性与AHAS的新相互作用配对,在追求可持续的杂草控制解决方案方面,这是一个值得注意的发展。