Aaptamine analogues as novel antiviral and fungicidal agents for crop protection

Overview

Crop diseases caused by plant viruses and fungi continue to threaten global agricultural productivity, and the limited number of effective, environmentally responsible agents makes the discovery of new antiviral and fungicidal compounds a pressing need. This project focuses on aaptamine, a marine natural product alkaloid that has been shown to outperform commercial benchmarks such as ribavirin in anti-tobacco mosaic virus (anti-TMV) activity and to deliver broad-spectrum inhibitory effects against 14 plant pathogens. The research team aims to design and synthesize a focused library of aaptamine analogues, evaluate their biological activities, establish structure–activity relationships (SARs), and investigate the underlying mechanisms of action, with the goal of producing pesticide candidates with novel modes of action.

Technical specifications

Core compound and synthesis:

• Aaptamine was synthesized from 6,7-dimethoxy-1-methylisoquinoline in five steps with a 47% overall yield, demonstrating a scalable and efficient route to the parent scaffold.
• A series of aaptamine analogues will be designed to simplify the core structure while improving antiviral and fungicidal potency.

Biological performance observed:

• Anti-TMV activity at 500 μg/mL: 45% inactivation, 42% curative, and 49% protective effect, exceeding ribavirin at 31%, 33%, and 35% respectively.
• At 50 μg/mL, aaptamine showed broad-spectrum inhibitory activity against 14 tested plant pathogens.

Research platform:

• A collaborative natural-source pesticide creation team with established antiviral and fungicidal testing platforms and mode-of-action evaluation capabilities.
• Planned SAR studies and mechanism research on the most promising optimized analogues to identify candidates with new mechanisms of action.

Technology readiness level

The parent compound aaptamine has been synthesized efficiently and validated against multiple plant viruses and fungal pathogens, with performance exceeding that of a commercial standard. The project is now entering the analogue design, synthesis, and SAR optimization phase, with further mechanism studies and candidate selection planned over a two-year timeframe. The team is actively seeking partners to provide additional virus model development capabilities and funding for key personnel to advance the program toward pesticide candidate nomination.