Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, 09972-270 São Paulo, Brazil.
Center of Natural Sciences and Humanities, Universidade Federal do ABC, 09210-580 Santo Andre, São Paulo, Brazil.
Bioorg Chem. 2019 Aug;89:103001. doi: 10.1016/j.bioorg.2019.103001. Epub 2019 May 20.
This work describes the isolation of six metabolites from leaves and branches of Piper cernuum (Piperaceae): (-)-cubebin (1), (-)-hinokinin (2), (-)-kusunokinin (3), trans-dehydroagarofuran (4), 11-hydroxi-4,5-secoeudesmane-4,5-dione (5), and (-)-bornyl p-coumarate (6). Antitrypanosomal activity and toxicity of purified compounds were performed in vitro against trypomastigote forms of Trypanosoma cruzi and NCTC cells, respectively. Compounds 2, 3 and 5 showed moderate activities with IC values of 33.1, 31.8 and 45.9 μM, respectively, while compounds 1 and 4 were inactive (IC > 100 μM). On the other hand, compound 6 displayed an IC value of 2.1 μM, a selectivity index (SI) of 18 and induced a considerable interference in the plasma membrane permeability (87%) in trypomastigotes of T. cruzi. Additionally, the lethal effect of compound 6 in T. cruzi could be associated to the plasma membrane permeability. Finally, experiments using scanning electron microscopy (SEM) confirmed the obtained results in which was possible to observe total alteration parasites topography after treatment with compound 6 in comparison to untreated parasites. These data indicated that the lethal action of compound 6 is directly related to structural disruption of the membrane.
(-)-胡椒堿（1）、(-)-胡椒烯（2）、(-)-胡荽烯（3）、反式去氢线呋喃（4）、11-羟基-4,5-表桉烷-4,5-二酮（5）和（-）柏木脑对香豆酸酯（6）。对纯化化合物的抗锥虫活性和毒性在体外分别针对 Trypanosoma cruzi 的锥虫形式和 NCTC 细胞进行了测试。化合物 2、3 和 5 表现出中等活性，IC 值分别为 33.1、31.8 和 45.9µM，而化合物 1 和 4 无活性（IC>100µM）。另一方面，化合物 6 的 IC 值为 2.1µM，选择性指数（SI）为 18，并在 T. cruzi 的锥虫中引起质膜通透性的相当大干扰（87%）。此外，化合物 6 对 T. cruzi 的致死作用可能与质膜通透性有关。最后，使用扫描电子显微镜（SEM）的实验证实了获得的结果，其中在与未处理的寄生虫相比，在用化合物 6 处理后可以观察到寄生虫总体形态的完全改变。这些数据表明，化合物 6 的致死作用与膜的结构破坏直接相关。
