Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria

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: <b>Y</b>, <b>Da</b>, <b>Db</b>, and <b>Dc</b>. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that <b>Dc-2</b> had the best antifungal effect against <i>Botrytis cinerea</i>, and its EC₅₀ value was up to <b>1.29</b> μg/mL. In addition, an in vivo activity test showed that the protective effect of <b>Dc-2</b> 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 <b>Dc-2</b> affected the morphology of mycelia. The compound <b>Dc-2</b> 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 <b>Dc-2</b> changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound <b>Dc-2</b> can be used as a candidate lead compound for further structural optimization and development.