Planta Med 2013; 79 - PA18
DOI: 10.1055/s-0033-1351922

Soulamarin isolated from Calophyllum brasiliense (Clusiaceae) induces plasma membrane permeabilization of Trypanosoma cruzi and mytochondrial damage

JH Lago 1, A Rea 1, LG Silva 1, EG Pinto 2, JT Mesquita 3, AG Tempone 3
  • 1Universidade Federal de Sao Paulo (UNIFESP), Instituto de Ciencias Ambientais, Quimicas e Farmaceuticas, São Paulo, Brazil
  • 2Instituto Adolfo Lutz, Departamento de Parasitologia, Sao Paulo, Brazil Universidade de São Paulo, Instituto de Medicina Tropical, Sao Paulo, Brazil
  • 3Instituto Adolfo Lutz, Departamento de Parasitologia, Sao Paulo, Brazil

In the course of selection of novel drug candidates for Chaga's disease from Brazilian flora, we undertook the study of stem bark from Calophyllum brasiliense (Clusiaceae)1,2. After extraction, the MeOH extract was partitioned between MeOH:H2O and EtOAc. The organic phase displaying anti-Trypanosoma cruzi activity and was subjected to Sephadex LH-20 (MeOH), to yield nine fractions (A – I). Through bio-guided fractionation, the activity was detected at fraction C, which was subjected to silica gel column (hexane-EtOAc) resulting in four fractions (C1 – C4). Since the activity was detected in fraction C2, this material was purified using preparative TLC to afford soulamarin (Figure 1), a previously isolated coumarin from C. soulatrii 3. The structure of this compound was established on the basis of spectroscopic data, mainly NMR and MS. Soulamarin showed activity against trypomastigotes of T. cruzi with an IC50 value of 85.3 µg/mL and a similar IC50 value to benznidazole (114.6 µg/mL). No hemolytic activity could be detected up to 150 µg/mL. By using the fluorimetric vital dye SYTOX Green, soulamarin induced permeabilization of plasma membrane when compared to untreated group. Spectrofluorimetric data using MitoTracker Red, demonstrated that soulamarin also induced a strong depolarization of the mitochondrial membrane potential, reducing the fluorescence intensity by 97% when compared to untreated group. These data suggest that the lethal effects of soulamarin in T. cruzi involve damages to plasma membrane of the parasite, which may have contributed to the mitochondrial disturbance and cell death. Considering the unique mitochondrion of T. cruzi, secondary metabolites of plants as soulamarin may contribute as scaffolds for the design of novel and selective drug candidates for neglected diseases. Support: FAPESP and CNPq.

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