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Title

Diterpenoid alkaloid derivatives as potential chemotherapeutic agents in American trypanosomiasis

AuthorsGonzález, Patricia; Marín, Clotilde; Rodríguez-González, Isabel; Illana, Antonio; Mateo, Héctor; Longoni, Silvia Stefánia; Rosales, María José; González-Coloma, Azucena ; Reina, Matías ; Sánchez Moreno, Manuel
KeywordsTrypanosoma cruzi
Chemotherapy
Diterpenoid alkaloids
Issue Date2-Jan-2006
PublisherS. Karger AG
CitationPharmacology 76(3): 123-128 (2006)
AbstractThe use of natural products for the treatment of protozoal infections (Leishmania and Trypanosoma spp.) is well known and has been documented since ancient times. We have already established an in vitro culture system using mammalian host cells (Vero) infected with Trypanosoma cruzi in which the time course of parasite growth is determined quantitatively. This system was used to screen anti-T. cruzi agents using two experimental models: simultaneous cell infection and compound addition or preincubation of the parasite with the test compound prior to cell infection. Among 64 diterpenoid alkaloids tested, including C19 and C20 skeletons, five C20 compounds were active on T. cruzi epimastigotes: azitine, isoazitine and 15,22-O-diacetyl-19-oxodihydroatisine had moderate effects on the parasite, while atisinium chloride and 13-oxocardiopetamine were potent T. cruzi epimastigote growth inhibitors with activity levels similar to that of benznidazole, used as the reference drug. Additionally, these compounds decreased the ability of metacyclic forms to invade mammalian cells, their intracellular replications and their transformation into trypomastigotes, with no toxicity to the host cell. These results suggest that these alkaloids are structural leads of clinically active compounds against T. cruzi and probably other members of the Trypanosomatidae.
Description6 pages, 2 figures, 1 table.-- PMID: 16391494 [PubMed].
Publisher version (URL)http://dx.doi.org/10.1159/000090600
URIhttp://hdl.handle.net/10261/14316
DOI10.1159/000090600
ISSN0031-7012
Appears in Collections:(ICA) Artículos
(IPNA) Artículos
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