International Research Organization for Advanced Science and Technology (IROAST), Kumamoto University, Kurokami 2-39-1, Kumamoto, 860-8555, Japan.
Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Kumamoto, 860-8555, Japan.
Sci Rep. 2021 Mar 23;11(1):6077. doi: 10.1038/s41598-021-85501-1.
The discovery and useful application of natural products can help improve human life. Chemicals that inhibit plant growth are broadly utilized as herbicides to control weeds. As various types of herbicides are required, the identification of compounds with novel modes of action is desirable. In the present study, we discovered a novel N-alkoxypyrrole compound, kumamonamide from Streptomyces werraensis MK493-CF1 and established a total synthesis procedure. Resulted in the bioactivity assays, we found that kumamonamic acid, a synthetic intermediate of kumamonamide, is a potential plant growth inhibitor. Further, we developed various derivatives of kumamonamic acid, including a kumamonamic acid nonyloxy derivative (KAND), which displayed high herbicidal activity without adverse effects on HeLa cell growth. We also detected that kumamonamic acid derivatives disturb plant microtubules; and additionally, that KAND affected actin filaments and induced cell death. These multifaceted effects differ from those of known microtubule inhibitors, suggesting a novel mode of action of kumamonamic acid, which represents an important lead for the development of new herbicides.
天然产物的发现和有效应用有助于改善人类生活。抑制植物生长的化学物质被广泛用作除草剂来控制杂草。由于需要各种类型的除草剂，因此希望鉴定具有新型作用模式的化合物。在本研究中，我们从链霉菌属 MK493-CF1 中发现了一种新型 N-烷氧基吡咯化合物，kumamonamide，并建立了全合成程序。在生物活性测定中，我们发现 kumamonamic acid 是 kumamonamide 的一种合成中间体，是一种潜在的植物生长抑制剂。此外，我们还开发了 kumamonamic acid 的各种衍生物，包括 kumamonamic acid nonyloxy 衍生物（KAND），它表现出高除草活性，而对 HeLa 细胞生长没有不良影响。我们还检测到 kumamonamic acid 衍生物会干扰植物微管；此外，KAND 还会影响肌动蛋白丝并诱导细胞死亡。这些多方面的作用与已知的微管抑制剂不同，表明 kumamonamic acid 具有新型作用模式，这为开发新的除草剂提供了重要的先导化合物。
