Indole-based natural product for plant protection: Discovery of alkaloid barrettin and its derivatives as novel antiviral and antifungal agents.

The extensive use of highly toxic and residual pesticides has a significant negative impact on agricultural production and the ecological environment. The development of new green antiviral agents has become a major demand for ensuring the development of green ecological agriculture. Indole alkaloids are widely present in nature and have diverse biological activities. In this work, we achieved efficient synthesis of indole alkaloid barettin. A series of barettin derivatives were designed, synthesized, and systematically investigated for their antiviral and fungicidal activities. Most of these compounds demonstrated superior antiviral activities against tobacco mosaic virus (TMV) comparing to the commercial antiviral agent ribavirin. Among them, compounds 14d, 14f, 16d, and 17b exhibited more potent antiviral effects (IC values: 186-220 μg/mL) than ningnanmycin (IC values: 232 μg/mL), emerging as novel antiviral candidates. Compound 17b was selected for further antiviral mechanism investigation. The results revealed that it can inhibit viral assembly by interacting with the TMV coat protein (CP). Molecular docking studies further confirmed that these compounds can interact with CP through hydrogen bonding. Additionally, several compounds exhibited significant fungicidal activities, making them promising candidates for further development of novel antifungal agents. This study provides valuable insights into the application of barettin alkaloids in plant protection.