Abstract
BackgroundChagas 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.MethodsThe 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.ResultsWe 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).ConclusionsResults reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.
Highlights
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide
Regarding the two cytotoxicity assays used in this study, we retrieved Z’ = 0.76 (0.067) for the assay based on Vero cells, and a Z’ = 0.73 (0.054) for the assay based on HepG2 cells (Fig. 2c–e)
Results obtained from the phenotypic T. cruzi growth inhibition assay revealed that lycorine, hippeastrine, haemanthamine, narciclasine and montanine were active, while crinine, tazettine, sanguinine and 1-O-acetylcaranine were inactive against the parasite (Fig. 3)
Summary
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide. Since the 1970s only two drugs have been available to treat T. cruzi infections: benznidazole (BNZ) and nifurtimox (NFX) [1] Both have good efficacy and tolerability when administered to infected new-borns [4]. Their efficacy diminishes at the chronic stage, which is usually diagnosed at adulthood with serological tests that detect specific anti-T. cruzi type G immunoglobulins [1]. Both drugs have long regimens of administration that entail the advent of frequent adverse events which often drive to treatment discontinuation [5,6,7].
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