Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3-8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 +/- 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.

Automated summary

In this study, two new sesquiterpenes were isolated from Laggera pterodonta, along with six known eudesmane-type sesquiterpenes, and their inhibitory effect on acetylcholinesterase (AChE) was characterized. The results showed that these compounds had a dose-dependent inhibitory effect on AChE, with compound 5 exhibiting the highest inhibitory activity. Additionally, all compounds showed certain levels of toxicity on C. elegans and displayed good ADMET properties.