gibbilimbol-b and Chagas-Disease

Topics: Chagas Disease; Drug Design; Humans; Multivariate Analysis; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma cruzi

Leishmaniasis and Chagas disease are parasitic protozoan infections that affect the poorest population in the world, causing high mortality and morbidity. As a result of highly toxic and long-duration treatments, novel, safe and more efficacious drugs are essential. In this work, the methanol (MeOH) extract from the leaves of Piper malacophyllum (Piperaceae) was fractioned to afford one alkenylphenol, which was characterized as 4-[(3'E)-decenyl]phenol (gibbilimbol B) by spectroscopic methods. Anti-protozoan in vitro assays demonstrated for the first time that Leishmania (L.) infantum chagasi was susceptible to gibbilimbol B, with an in vitro EC(50) of 23 μg/mL against axenic promastigotes and an EC(50) of 22 μg/mL against intracellular amastigotes. Gibbilimbol B was also tested for anti-trypanosomal activity (Trypanosoma cruzi) and showed an EC(50) value of 17 μg/mL against trypomastigotes. To evaluate the cytotoxic parameters, this alkenylphenol was tested in vitro against NCTC cells, showing a CC(50) of 59 μg/mL and absent hemolytic activity at the highest concentration of 75 μg/mL. Using the fluorescent probe SYTOX Green suggested that the alkenylphenol disrupted the Leishmania plasma membrane upon initial incubation. Further drug design studies aiming at derivatives could be a promising tool for the development of new therapeutic agents for leishmaniasis and Chagas disease.

Topics: Animals; Antiprotozoal Agents; Biological Assay; Cell Survival; Chagas Disease; Clone Cells; Cricetinae; Erythrocytes; Female; Leishmania infantum; Leishmaniasis, Visceral; Macrophages, Peritoneal; Mesocricetus; Mice; Mice, Inbred BALB C; Phenols; Piper; Trypanosoma cruzi