Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that afects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side efects and limited efcacy at the chronic stage. Natural products provide a pool of diver sity 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 evalu ated 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 identifed 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 specifc 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: Chagas disease, Trypanosoma cruzi, Alkaloids, Amaryllidaceae, Hippeastrine, Phenotypic assays, Cytotoxicit

Amaryllidaceae plants: a potential natural resource for the treatment of Chagas disease

Background Chagas disease is a neglected zoonosis caused by the parasite Trypanosoma cruzi. It affects over six million people, mostly in Latin America. Drugs available to treat T. cruzi infection have associated toxicity and questionable efficacy at the chronic stage. Hence, the discovery of more effective and safer drugs is an unmet medical need. For this, natural products represent a pool of unique chemical diversity that can serve as excellent templates for the synthesis of active molecules. Methods A collection of 79 extracts of Amaryllidaceae plants were screened against T. cruzi. Active extracts against the parasite were progressed through two cell toxicity assays based on Vero and HepG2 cells to determine their selectivity profile and discard those toxic to host cells. Anti-T. cruzi-specific extracts were further qualified by an anti-amastigote stage assay. Results Two extracts, respectively from Crinum erubescens and Rhodophiala andicola, were identified as highly active and specific against T. cruzi and its mammalian replicative form. Conclusions The results retrieved in this study encourage further exploration of the chemical content of these extracts in search of new anti-T. cruzi drug development starting points

Perspectives en l'estudi de nous productes naturals amb activitat farmacològica, biològica i/o terapèutica

The research of new natural compounds can be considered in many cases as a feasible alternative to the organic synthesis of either more active and specific pharmaceutical products, or ones without secondary effects. The phytochemical and pharmacological screenings, by means of which plant and animal extracts are tested for different kinds of biological activity, have been responsible for the discovery of these compounds. However, some of these substances have been finally discarded because of their toxicity, and others have not been isolated, purified or chemically identified yet. A careful methodology is certainly needed to attain reliable results. In this article an updated review of the knowledge in the natural products field is given. At the same time, a work program that can be used as a pattern to carry out a research for new compounds with pharmacological, biological and/or therapeutical activity from our flora is suggested

Presència d'alcaloides en plantes de la flora de Catalunya

523 species of higher plants from Catalonia (Spain), belonging to 308 genera from 94 families, were screened for alkaloids, one of the most structurally diverse group of secondary metabolites, in order to find new pharmacologically active substances. 101 species (19,3 °-o of those analyzed) were found to contain alkaloids; 42 of them are reported as alkaloid-bearing for the first time

Presència d'alcaloides en plantes de la flora de Catalunya

523 species of higher plants from Catalonia (Spain), belonging to 308 genera from 94 families, were screened for alkaloids, one of the most structurally diverse group of secondary metabolites, in order to find new pharmacologically active substances. 101 species (19,3 °-o of those analyzed) were found to contain alkaloids; 42 of them are reported as alkaloid-bearing for the first time