4.6 Article

Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Journal

PARASITES & VECTORS
Volume 13, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13071-020-04171-6

Keywords

Chagas disease; Trypanosoma cruzi; Alkaloids; Amaryllidaceae; Hippeastrine; Phenotypic assays; Cytotoxicity

Funding

  1. Departament d'Universitats i Recerca de la Generalitat de Catalunya, Spain (AGAUR) [2017SGR00924]
  2. Instituto de Salud Carlos III RICET Network for Cooperative Research in Tropical Diseases (ISCIII) [RD12/0018/0010]
  3. FEDER
  4. CYTED [2017SGR604, 416RT0511]
  5. Ministry of Health, Government of Catalunya [PERIS 2016-2010 SLT008/18/00132]
  6. Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019-2023 Program [CEX2018-000806-S]
  7. Generalitat de Catalunya through the CERCA Program
  8. Juan de la Cierva -Incorporacion contract from the Spanish Science Ministry

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BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects similar to 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 mu M).ConclusionsResults reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.

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