Dados do Trabalho

Título

Anti-Trypanosoma cruzi activity of andrographolide, a diterpene isolated from the Brazilian plant Cymbopogon schoenanthus

Introdução

Trypanosoma cruzi, the etiologic agent of Chagas disease, affects 7-8 million people and is present mainly in developing countries. Due to the limited and toxic therapeutic options, new drugs are urgently needed. Natural prototypes have been the basis for more than 50% of FDA-approved drugs, including those from plants, which offer a wide variety of structurally complex metabolites with biological activities.

Objetivo (s)

To study in vitro the activity of andrographolide against Trypanosoma cruzi.

To determine in vitro the 50% inhibitory concentration (IC50) of andrographolide in extracellular trypomastigotes and intracellular amastigotes of Trypanosoma cruzi.
To determine in vitro the 50% cytotoxicity concentrations (CC50) of andrographolide in mammalian cells.
To determine the selectivity index.

Material e Métodos

In this work, by using bio-guided fractionation, we isolated the diterpene andrographolide, which was obtained from the leaves of the Brazilian plant Cymbopogon schoenanthus. The compound was chemically characterized by analysis of NMR and MS spectral data.

Resultados e Conclusão

When tested against the trypomastigotes of T. cruzi (Y strain), the compound killed 100% of the parasites at the highest tested concentration (100 µM), resulting in an IC50 value of 29.4 µM as determined by the colorimetric resazurin assay. Andrographolide was also tested against the intracellular amastigotes, using peritoneal macrophages as host cells. After 48h of treatment, the compound demonstrated an IC50 value of 2.9 µM. Benznidazole was used as a standard drug and showed IC50 values of 17.7 and 5.0 µM, respectively. To determine the selectivity index, andrographolide was tested against mammalian cells NCTC L929 cells and displayed a 50% cytotoxic concentration (CC50) of 92.8 µM by the colorimetric MTT assay. The selectivity index, given by the ration between the CC50 / IC50, resulted in a value of 32. Diterpenes have been shown interesting antiprotozoal activities. Our data, demonstrated for the first time the potential of andrographolide as a new hit compound against T. cruzi and it could be used as scaffold for the design of new drug candidates.

Palavras-chave

Trypanosoma cruzi, natural products, neglected tropical diseases, andrographolide, diterpene, new therapies.