Toad Alkaloid for Pesticide Discovery: Dehydrobufotenine Derivatives as Novel Agents against Plant Virus and Fungi

Abstract

Plant viruses and fungi are a serious threat to food security and natural ecosystems. The efficient and environment-friendly control methods are urgently needed to help safeguard such resources. Here, we achieved the efficient synthesis of toad alkaloid dehydrobufotenine in eight steps with an overall yield of 8% from 5-methoxyindole. A series of dehydrobufotenine derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities systematically. It was found for the first time that these compounds have good anti-plant virus activities and anti-plant pathogen activities. The antiviral activities of 21 compounds were similar to or better than those of ribavirin. Compounds <b>12</b> and <b>17</b> displayed better antiviral activities than ningnanmycin which is perhaps the most effective anti-plant virus agent. The antiviral mechanism research study of <b>12</b> revealed that it could make 20S CP disk fusion and aggregation. Further molecular docking results showed that there are hydrogen bonds between compounds <b>12</b>, <b>17</b>, and tobacco mosaic virus CP. The docking results are consistent with the antiviral activity. These compounds also displayed broad-spectrum fungicidal activities against 14 kinds of fungi, especially for <i>Sclerotinia sclerotiorum</i>. In this work, the synthesis, structure optimization, structure-activity relationship studies, and mode of action research of dehydrobufotenine alkaloids were carried out. It provides a reference for the development of the anti-plant virus agent and anti-plant pathogen agent from toad alkaloids.