Marine Natural Product for Pesticide Candidate: Pulmonarin Alkaloids as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents

Abstract

Plant diseases are seriously endangering agricultural production. The emergence of drug resistance has brought great challenges to the prevention and control of plant diseases. There is an urgent need for the emergence of new drug candidates. In this work, we achieved the efficient synthesis of pulmonarins A and B in 64% and 59% overall yield, respectively. Pulmonarins A and B were found to have good antiviral activities against tobacco mosaic virus (TMV) for the first time. A series of pulmonarin derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities systematically. Most compounds displayed higher anti-TMV activities than commercial ribavirin. Compounds 6a, 6c, and 6n with better inactivation effects than ningnanmycin emerged as new antiviral candidates. We selected 6c for further antiviral mechanism research, which revealed that it could inhibit virus assembly by interacting with TMV coat protein (CP). The molecular docking results further confirmed that these compounds could interact with CP through hydrogen bonding. These compounds also displayed broad spectrum fungicidal activities. Especially compound 6u with prominent antifungal activity emerged as a new fungicidal candidate for further research. The current work provides a reference for understanding the application of pulmonarin alkaloids in plant protection.

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

“…Among these chemicals, alkaloids were the main small molecule in Indigo Naturalis [40,41]. Alkaloids has been proven to exhibit antiviral e cacy and inhibit LPS induced in ammation [42,43].…”

Screening of Marine Bioactive Antimicrobial Compounds for Plant Pathogens

“…However, the molecular docking is only a prediction, therefore, the interaction between the compound and the target requires further biological strategies to verify it. Through a computer-simulated molecular docking method, it was predicted that two pulmonarin derivatives compounds 6a (4) and 6b (5) could interact with the TMV coat protein (CP), so it can be inferred that compounds 4 and 5 (Figure 2) may inhibit the assembly of TMV particles [104].…”

“…Wang's lab has done a lot of work in this area [104,126,152]. In 2014, they fully synthesized penicimonoterpene (±) (62) (Figure 7) for the first time using a Reformatsky reaction, which started from the 6-methylhept-5-en-2-one precursor compound and the yield of the entire synthesis process was 25-85% through a four-step reaction [126].…”

“…The activity of these derivatives against the plant pathogenic virus TMV was significantly improved compared with pre-modification [152]. Recently, they have effectively synthesized the compounds 4 and 5 (pulmonarins A and B, Figure 2) through a total synthesis method, with yields as high as 64% and 59%, respectively [104]. In addition, compounds 4 and 5 have high resistance to TMV [104].…”

“…Recently, they have effectively synthesized the compounds 4 and 5 (pulmonarins A and B, Figure 2) through a total synthesis method, with yields as high as 64% and 59%, respectively [104]. In addition, compounds 4 and 5 have high resistance to TMV [104]. These results all indicate that chemical synthesis can greatly increase the yield and activity of active compounds, making it possible for these compounds to be applied on a large scale in agriculture.…”