Antitrypanosomal activity and effect in plasma membrane permeability of (−)-bornyl p-coumarate isolated from Piper cernuum (Piperaceae)

Abstract

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 IC50 values of 33.1, 31.8 and 45.9 μM, respectively, while compounds 1 and 4 were inactive (IC50 > 100 μM). On the other hand, compound 6 displayed an IC50 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.