Design, synthesis, and biological evaluation of novel derivatives of marine natural product ammosamide B

BACKGROUNDPlant diseases caused by plant viruses and pathogens seriously affect crop yield and quality, making prevention and control extremely difficult and posing a serious threat to human health. Marine alkaloids have novel structures and diverse biological activities, which are an important source of the development of new pesticides. In this work, ammosamide alkaloids were selected as the parent structure. A series of derivatives based on the chlorinated pyrrolo[4,3,2-de]quinoline were synthesized and evaluated for their antiviral and fungicidal activities.RESULTAmmosamide B was efficiently synthesized from commercially available 6-chloroisatin in seven steps with an overall yield of 18.5%. A series of pyrrolo[4,3,2-de]quinoline derivatives were synthesized and evaluated for their antiviral and fungicidal activities. Most of these compounds were demonstrated to have higher antiviral activities than ribavirin. Particularly, compounds 7, 8a, 11, and 13a exhibited higher inhibitory activities against tobacco mosaic virus (TMV) and potato virus Y (PVY) than ningnanmycin. Antiviral mechanism research revealed that compound 13a can inhibit the assembly of TMV particles by interfering with the formation of the 20S coat protein (CP) disk. We further validated the interaction between this type of compound and TMV CP through molecular docking. This type of compounds also exhibits broad-spectrum inhibitory effects against eight common plant fungi, especially Physalospora piricola.CONCLUSIONAn improved method for synthesis of ammosamide B and its derivatives from commercially available 6-chloroisatin was explored. Systematic structural modifications based on ammosamide alkaloids were carried out and the structure-activity relationship of anti-TMV activity was summarized. Compound 13a, exhibiting excellent antiviral activity, has emerged as a new candidate for antiviral agents. The current work provides a valuable reference for exploring the potential applications of ammosamide derivatives in plant protection. (c) 2025 Society of Chemical Industry.