Antiproliferative effect and ultrastructural alterations induced by 5-O-methylembelin on Trypanosoma cruzi

作者：Maria Spina Renata; Lozano Esteban; Andrea Barrera Patricia; Belen Aguero Maria; Tapia Alejandro; Egly Feresin Gabriela; Angel Sosa Miguel

来源：Phytomedicine, 2018, 46: 111-118.

DOI：10.1016/j.phymed.2018.04.032

• Embelin (EMB)
• 5-O-methylembelin (ME)
• 2,5-di-O-methylembelin (DME)
• Trypanosoma cruzi
• Chagas' disease

Background: Embelin (EMB), obtained from Oxalis erythrorhiza Gillies ex Hooker a Arnott (Oxalidaceae), was reported against Trypanosoma cruzi and Leishmania spp. Additionally, antiprotozoan activity against Plasmodium falciparum was reported for its methylated derivative (ME).
Purpose: To evaluate the potential anti-Trypanosoma cruzi activity of EMB, ME and 2,5-di-O-methylembelin (DME) and analyze the possible mechanism of action.
Study design/Methods: EMB was isolated by a chromatographic method from the air-dried ground whole plant. To evaluate the effects of methylation, ME and DME were synthesized and tested against T. cruzi epimastigotes and trypomastigotes. The most active compound ME was evaluated against amastigotes. Ultrastructural alterations, ROS generation and the effect on mitochondrial activity of ME were measured.
Results: Compounds inhibited the proliferation of epimastigotes. ME was also active against intracellular amastigotes. Mitochondrial alterations were observed by TEM. Additionally, ME modified the mitochondrial activity, and induced an increase in ROS levels. These evidences postulate the mitochondrion as a possible target of ME.
Conclusion: ME inhibited amastigotes proliferation, thus being a potential lead compound for the treatment of Chagas' disease.

• 出版日期2018-7-15
• 单位河北医科大学