Discovery of Cryptolepine and Its Derivatives as Novel Antiviral Agents

Based on the widespread utilization of aliphatic amines in pesticide research and development, a series of cryptolepine derivatives containing aliphatic amine moieties were designed and synthesized, and their antiviral activities were evaluated for the first time. The bioassay results indicated that most of these derivatives exhibited activity against the tobacco mosaic virus. Derivative <b>6k</b> demonstrated <i>in vivo</i> inactivation, curative, and protection activities of 57.9 ± 4.6, 51.7 ± 3.6, and 49.8 ± 3.1% at 500 mg/L, respectively, which were comparable to those of the commercial antiviral drug ningnanmycin (57.1 ± 3.9, 56.1 ± 4.2, and 59.8 ± 3.7%, respectively) at the same concentration. The antiviral mechanism study revealed that compound <b>6k</b> could influence rod TMV assembly by promoting the aggregation and fragmentation of TMV coat proteins. Molecular docking analysis suggested that compared to natural products, derivative <b>6k</b> exhibited more hydrogen bonding interactions with the target protein, resulting in a stronger binding affinity and consequently higher activity. Additionally, a field trial was conducted on compound <b>6k</b>, and the result indicated that <b>6k</b> demonstrated good control efficacy in the field. Furthermore, compounds <b>6f</b> and <b>6aa</b> exhibited good <i>in vivo</i> control efficacy against <i>Rhizoctonia solani</i> at 400 mg/L.