Chagas disease is caused by the parasitic protozoan Trypanosoma cruzi. It has high mortality as well as morbidity rates and usually affects the poorer sections of the population. The development of new, less harmful and more effective drugs is a promising research target, since current standard treatments are highly toxic and administered for long periods. Fractioning of methanol (MeOH) extract of the stem bark of Calophyllum brasiliense (Clusiaceae) resulted in the isolation of the coumarin soulamarin, which was characterized by one- and two-dimensional ¹H- and ¹³C NMR spectroscopy as well as ESI mass spectrometry. All data obtained were consistent with a structure of 6-hydroxy-4-propyl-5-(3-hydroxy-2-methyl-1-oxobutyl)-6″,6″-dimethylpyrane-[2″,3″:8,7]-benzopyran-2-one for soulamarin. Colorimetric MTT assays showed that soulamarin induces trypanocidal effects, and is also active against trypomastigotes. Hemolytic activity tests showed that soulamarin is unable to induce any observable damage to erythrocytes (c_max. = 1,300 µM). The lethal action of soulamarin against T. cruzi was investigated by using amino(4-(6-(amino(iminio)methyl)-1H-indol-2-yl)phenyl)methaniminium chloride (SYTOX Green and 1H,5H,11H,15H-Xantheno[2,3,4-ij:5,6,7-i′j′]diquinolizin-18-ium, 9-[4-(chloromethyl)phenyl]-2,3,6,7,12,13,16,17-octahydro-chloride (MitoTracker Red) as fluorimetric probes. With the former, soulamarin showed dose-dependent permeability of the plasma membrane, relative to fully permeable Triton X-100-treated parasites. Spectrofluorimetric and fluorescence microscopy with the latter revealed that soulamarin also induced a strong depolarization (ca. 97%) of the mitochondrial membrane potential. These data demonstrate that the lethal action of soulamarin towards T. cruzi involves damages to the plasma membrane of the parasite and mitochondrial dysfunction without the additional generation of reactive oxygen species, which may have also contributed to the death of the parasites. Considering the unique mitochondrion of T. cruzi, secondary metabolites of plants affecting the bioenergetic system as soulamarin may contribute as scaffolds for the design of novel and selective drug candidates for neglected diseases, mainly Chagas disease. Chagas disease is a parasitic protozoan that affects the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. Natural products isolated from plants are commonly used as drug prototypes or precursors to treat parasitic diseases. As part of our investigation of bioactive compounds from Brazilian flora, the present study was undertaken in order to determine the antitrypanosomal effects of the soulamarin, a coumarin isolated from the stem bark of Callophyllum brasiliense (Clusiaceae), against Trypanossoma cruzi. This study moreover investigated the lethal action of soulamarin towards the parasite. Considering the obtained results, secondary metabolites of plants affecting the bioenergetic system as soulamarin may contribute as scaffolds for the design of novel and selective drug candidates for neglected diseases, mainly Chagas disease.

Schinus terebinthifolius Raddi and the Myracrodruon urundeuva Allemão were evaluated in rats and mice for antiulcer effects, as these two plants are widely used in Brazil for gastric ulcer treatment. Extracts of the plants showed a marked protective effect against gastric ulcerations induced by immobilization stress at low temperature in rats. They also showed an increase in the pH and volume of the gastric contents, and reduction in gastric hemorrhage in rats, and decrease in intestinal transit in mice, even at the low doses of 3.4 mg/kg (1/4 of the dose used by humans).Foram avaliados, em ratos e camundongos, os efeitos antiúlcera de duas plantas usadas popularmente no Brasil para o tratamento de males gástricos: a Schinus terebinthifolius Raddi (aroeira-da-praia) e a Myracrodruon urundeuva Allemão (aroeira-do-sertão). Os decoctos de ambas as plantas apresentaram um marcante efeito protetor da mucosa gástrica contra as ulcerações induzidas por estresse de imobilização em baixa temperatura em ratos. Ambas as plantas apresentaram, ainda: elevação do pH, do volume do conteúdo gástrico, redução das hemorragias gástricas e do trânsito intestinal em camundongos, mesmo em doses tão reduzidas quanto 3,4 mg/kg (1/4 da dose utilizada pelo homem).Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUNIFESP, Depto. de PsicobiologiaSciEL