3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi.
Bioorg Chem
; 38(5): 190-5, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20638707
ABSTRACT
We have synthesized the Morita-Baylis-Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile (3) in quantitative yield and evaluated on Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Compound 3 strongly inhibited epimastigote growth, with IC(50)/72hof 28.5 microM and also caused intense trypomastigotes lysis, with an IC(50)/24h of 25.5 microM. Ultrastructural analysis showed significant morphological changes on both parasite forms treated with 3, including increase of cell volume and rounding of cell body as well as intense intracellular disorganization. Morphological changes indicative of apoptosis, autophagy or necrosis were observed in most affected cells. Docking calculations of 1, 2 and 3 pointed out the possibility of T. cruzi Farnesyl Pyrophosphate Synthase (TcFPPS) enzyme inhibition in 3 mechanism of action.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tripanossomicidas
/
Trypanosoma cruzi
/
Álcoois Benzílicos
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Acrilonitrila
/
Doença de Chagas
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article