Nuclei of Bioassays, Biosynthesis and Ecophysiology of Natural Products (NuBBE), Department of Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, SP, 14801-970, Brazil; Department of Chemistry, Federal University of Technology - Paraná (UTFPR), Ponta Grossa, PR, 84017-220, Brazil.
Nuclei of Bioassays, Biosynthesis and Ecophysiology of Natural Products (NuBBE), Department of Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, SP, 14801-970, Brazil; Federal Institute of Education, Science and Technology of São Paulo (IFSP), Matão, SP, 15991-502, Brazil.
Exp Parasitol. 2023 Jul;250:108542. doi: 10.1016/j.exppara.2023.108542. Epub 2023 May 11.
Although new nematicides have appeared, the demand for new products less toxic and more efficient for the control of plant-parasitic nematodes are still high. Consequently, studies on natural secondary metabolites from plants, to develop new nematicides, have increased. In this work, nineteen extracts from eleven Brazilian plant species were screened for activity against Meloidogyne incognita. Among them, the extracts of Piterogyne nitens showed a potent nematostatic activity. The alkaloid fraction obtained from the ethanol extract of leaves of P. nitens was more active than the coming extract. Due to the promising activity from the alkaloid fraction, three isoprenylated guanidine alkaloids isolated from this fraction, galegine (1), pterogynidine (2), and pterogynine (3) were tested, showing similar activity to the alkaloid fraction, which was comparable to that of the positive control Temik at 250 μg/mL. At lower concentrations (125-50 μg/mL), compound 2 showed to be the most active one. As several nematicides act through inhibition of acetylcholinesterase (AChE), the guanidine alkaloids were also employed in two in vitro AChE assays. In both cases, compound 2 was more active than compounds 1 and 3. Its activity was considered moderated compared to the control (physostigmine). Compound 2 was selected for an in silico study with the electric eel (Electrophorus electricus) AChE, showing to bind mostly to the same site of physostigmine in the AChEs, pointing out that this could be the mechanism of action for this compound. These results suggested that the guanidine alkaloids 1,2 and 3 from P. nitens are promising for the development of new products to control M. incognita, especially guanidine 2, and encourage new investigations to confirm the mechanism of action, as well as to determine the structure-activity relationship of the guanidine alkaloids.
尽管出现了新的杀线虫剂，但人们仍然需要开发毒性更低、防治植物寄生线虫效果更好的新产品。因此，研究从植物中提取天然次生代谢产物以开发新型杀线虫剂的工作有所增加。在这项工作中，从 11 种巴西植物的 19 种提取物中筛选出对南方根结线虫（Meloidogyne incognita）有活性的物质。其中，Piterogyne nitens 的提取物表现出很强的线虫静止活性。从 P. nitens 叶乙醇提取物中获得的生物碱部分比原提取物更具活性。由于生物碱部分表现出有希望的活性，因此从该部分分离得到的三种异戊烯基胍类生物碱（galegine（1）、pterogynidine（2）和 pterogynine（3）进行了测试，它们的活性与生物碱部分相似，与阳性对照 Temik（250μg/mL）相当。在较低浓度（125-50μg/mL）下，化合物 2 显示出最强的活性。由于几种杀线虫剂通过抑制乙酰胆碱酯酶（AChE）起作用，因此胍类生物碱也被用于两种体外 AChE 测定中。在这两种情况下，化合物 2 都比化合物 1 和 3 更活跃。与对照物（毒扁豆碱）相比，其活性被认为是中等的。化合物 2 被选择用于电鳗（Electrophorus electricus）AChE 的计算机模拟研究，结果表明它主要与 AChE 中的毒扁豆碱结合在同一部位，这表明这可能是该化合物的作用机制。这些结果表明，P. nitens 中的胍类生物碱 1、2 和 3 具有开发防治南方根结线虫的新产品的潜力，特别是胍类生物碱 2，并鼓励进行新的研究以确认作用机制，以及确定胍类生物碱的构效关系。
