Li Jinliang, Li Fengchao, Wu Guoxing, Gui Furong, Li Hongmei, Xu Lili, Hao Xiaojiang, Zhao Yuhan, Ding Xiao, Qin Xiaoping
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, College of Plant Protection, Yunnan Agricultural University, Kunming, China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
Front Plant Sci. 2023 Feb 10;14:1074184. doi: 10.3389/fpls.2023.1074184. eCollection 2023.
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 , 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 . 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 .
植物源天然产物是农药发现的重要资源。乙酰胆碱酯酶（AChE）是一个经过充分验证的农药作用靶标，抑制AChE对昆虫具有致命性。最近的研究表明了各种倍半萜类化合物作为AChE抑制剂的潜力。然而，关于具有AChE抑制作用的桉叶烷型倍半萜的研究较少。因此，在本研究中，我们从[来源未明确]中分离出两种新的倍半萜，拉格兰宁A（1）和B（2），以及六种已知的桉叶烷型倍半萜（3 - 8），并对它们的结构及其对AChE的抑制作用进行了表征。结果表明，这些化合物对AChE具有一定的剂量依赖性抑制作用，其中化合物5的抑制效果最佳，IC50为437.33±8.33 mM。通过Lineweaver - Burk和Dixon图表明，化合物5对AChE活性的抑制是可逆的且具有竞争性。此外，所有化合物对[受试对象未明确]均表现出一定的毒性水平。同时，这些化合物具有良好的药物代谢动力学（ADMET）性质。这些结果对于发现新的靶向AChE的化合物具有重要意义，也丰富了[相关物种未明确]的生物活性谱。
