Design, Synthesis,\nand Antimicrobial Activity Evaluation\nof Novel Isocryptolepine Derivatives against Phytopathogenic Fungi\nand Bacteria

This research adopted the Fischer indole synthesis method\nto continue\nconstructing a novel drug-like chemical entity based on the guidance\nof isocryptolepine and obtained four series of derivatives: <b>Y</b>, <b>Da</b>, <b>Db</b>, and <b>Dc</b>.\nThe antimicrobial activity of these derivatives against plant pathogens\nwas further evaluated. The results showed that <b>Dc-2</b> had\nthe best antifungal effect against Botrytis cinerea, and its EC<sub>50</sub> value was up to <b>1.29</b> μg/mL.\nIn addition, an in vivo activity test showed that the protective effect\nof <b>Dc-2</b> on apples was 82.2% at 200 μg/mL, which\nwas better than that of Pyrimethanil (45.4%). Meanwhile, it was found\nby scanning electron microscopy and transmission electron microscopy\nthat the compound <b>Dc-2</b> affected the morphology of mycelia.\nThe compound <b>Dc-2</b> was found to damage the cell membrane\nby PI and ROS staining. Through experiments such as leakage of cell\ncontents, it was found that the compound <b>Dc-2</b> changed\nthe permeability of the cell membrane and caused the leakage of substances\nin the cell. According to the above studies, compound <b>Dc-2</b> can be used as a candidate lead compound for further structural\noptimization and development.