Synthesis and biological evaluation of 1-amino-1,1-bisphosphonates derived from fatty acids against Trypanosoma cruzi targeting farnesyl pyrophosphate synthase

We have investigated the effect of a series of 1-amino-1,1-bisphosphonates derived from fatty acids against proliferation of the clinically more relevant form of Trypanosoma cruzi, the causative agent of American trypanosomiasis (Chagas' disease). Some of these drugs were potent inhibitors agai...

ver descrição completa

Detalhes bibliográficos
Autores: Szajnman, Sergio Hernan, Ravaschino, Esteban L., Docampo, Roberto, Rodriguez, Juan Bautista
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2005
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/85347
Acesso em linha:http://hdl.handle.net/11336/85347
Access Level:acceso abierto
Palavra-chave:BISPHOSPHONATES
CHAGAS' DISEASE
FARNESYL PYROPHOSPHATE SYNTHASE
TRYPANOSOMA CRUZI
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descrição
Resumo:We have investigated the effect of a series of 1-amino-1,1-bisphosphonates derived from fatty acids against proliferation of the clinically more relevant form of Trypanosoma cruzi, the causative agent of American trypanosomiasis (Chagas' disease). Some of these drugs were potent inhibitors against the intracellular form of the parasite, exhibiting IC50 values at low micromolar level. Cellular activity was associated with the inhibition of enzymatic activity of T. cruzi farnesyl pyrophosphate synthase. As bisphosphonate-containing drugs are FDA-approved for the treatment of bone resorption disorders, their potential innocuousness makes them good candidates to control tropical diseases.