School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, College of Life Science, Huzhou University, Huzhou 313000, China.
J Agric Food Chem. 2024 Sep 25;72(38):20831-20841. doi: 10.1021/acs.jafc.4c03976. Epub 2024 Sep 16.
This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: , , , and . The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that had the best antifungal effect against , and its EC value was up to μg/mL. In addition, an in vivo activity test showed that the protective effect of on apples was 82.2% at 200 μg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound affected the morphology of mycelia. The compound was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound can be used as a candidate lead compound for further structural optimization and development.
本研究采用 Fischer 吲哚合成方法，以异卡波肼为指导，继续构建新型类药性化学实体，得到了四个系列的衍生物： 、 、 、 。进一步评价了这些衍生物对植物病原菌的抗菌活性。结果表明， 对 具有最佳的抗真菌效果，其 EC 值高达 μg/mL。此外，体内活性试验表明，化合物 在 200μg/mL 时对苹果的保护效果为 82.2%，优于嘧啶胺（45.4%）。同时，通过扫描电子显微镜和透射电子显微镜发现，该化合物会影响菌丝的形态。通过 PI 和 ROS 染色发现，化合物 会破坏细胞膜。通过细胞内容物泄漏等实验发现，化合物 改变了细胞膜的通透性，导致细胞内物质泄漏。根据上述研究，化合物 可作为进一步结构优化和开发的候选先导化合物。
