Affiliation:
1. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular y Facultad de Ciencias Exactas y Naturales (CONICET-UBA), 1428 Buenos Aires
2. Instituto Nacional de Parasitología “Dr. Mario Fatala Chabén,” 1063 Buenos Aires
3. Instituto de Química y Metabolismo del Fármaco y Facultad de Farmacia y Bioquímica (CONICET-UBA), 1113 Buenos Aires, Argentina
Abstract
ABSTRACT
The trypanocidal action of green tea catechins against two different developmental stages of
Trypanosoma cruzi
is reported for the first time. This activity was assayed with the nonproliferative bloodstream trypomastigote and with the intracellular replicative amastigote parasite forms. An ethyl acetate fraction from
Camellia sinensis
green tea leaves, which contains most of the polyphenolic compounds and the maximal trypanocidal activity, was obtained by fractionation of the aqueous extract with organic solvents. The active compounds present in this extract were further purified by LH-20 column chromatography and were identified by high-performance liquid chromatography analysis with a photo diode array detector and gas chromatography coupled to mass spectroscopy. The following flavan-3-ols derivatives, known as catechins, were identified: catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. The purified compounds lysed more than 50% of the parasites present in the blood of infected BALB/c mice at concentrations as low as 0.12 to 85 pM. The most active compounds were gallocatechin gallate and epigallocatechin gallate, with minimal bactericidal concentrations that inhibited 50% of isolates tested of 0.12 and 0.53 pM, respectively. The number of amastigotes in infected Vero cells decreased by 50% in the presence of each of these compounds at 100 nM. The effects of the catechins on the recombinant
T. cruzi
arginine kinase, a key enzyme in the energy metabolism of the parasite, were assayed. The activity of this enzyme was inhibited by about 50% by nanomolar concentrations of catechin gallate or gallocatechin gallate, whereas the other members of the group were less effective. On the basis of these results, we suggest that these compounds could be used to sterilize blood and, eventually, as therapeutic agents for Chagas' disease.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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