Discovery of new pesticide candidates from nature: design, synthesis and bioactivity research of rutaecarpine derivatives.

Background: The invasion of viruses and fungi can cause pathological changes in the normal growth of plants and is an important factor in causing plant infectious diseases. These pathogenic microorganisms can also secrete toxic metabolites, affecting crop quality and posing a threat to human health. In this work, we selected the natural product rutaecarpine as the lead compound to achieve the total synthesis and structural derivation. The antiphytoviral activities of these compounds were systematically studied using tobacco mosaic virus (TMV) as the tested strain, and the structure-activity relationships were summarized.

Result: The anti TMV activities of compounds 5a, 5n, 6b, and 7c are significantly higher than that of commercial antiviral agent ningnanmycin. We chose 5n for further antiviral mechanism research, and the results showed that it can directly act on viral particles. The molecular docking results further confirmed the interaction of compound 5n and coat protein (CP). These compounds also exhibited broad-spectrum fungicidal activities against eight plant pathogens. Especially compounds 5j and 5p have significant anti-fungal activities (EC: 5j, 1.76 μg mL; 5p, 1.59 μg mL) and can be further studied as leads for plant-based anti-fungal agents.

Conclusion: The natural product rutaecarpine and its derivatives were synthesized, and evaluated for their anti-TMV and fungicidal activities. Compounds 5n and 5p with good activities emerged as new antiviral and anti-fungal candidates, respectively. This study provides important information for the research and development of the novel antiviral and fungicidal agents based on rutaecarpine derivatives. © 2024 Society of Chemical Industry.