Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side effects and limited efficacy at the chronic stage. Natural products provide a pool of diversity structures to lead the chemical synthesis of novel molecules for this purpose. Herein we analyzed the anti-T. cruzi activity of nine alkaloids derived from plants of the family Amaryllidaceae.

Methods: The activity of each alkaloid was assessed by means of an anti-T. cruzi phenotypic assay. We further evaluated the compounds that inhibited parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity.

Results: We identified a single compound (hippeastrine) that was selectively active against the parasite yielding selectivity indexes of 12.7 and 35.2 against Vero and HepG2 cells, respectively. Moreover, it showed specific activity against the amastigote stage (IC₅₀ = 3.31 μM).

Conclusions: Results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.

Keywords: Alkaloids; Amaryllidaceae; Chagas disease; Cytotoxicity; Hippeastrine; Phenotypic assays; Trypanosoma cruzi.