Article

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

Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
Bioorganic & Medicinal Chemistry Letters (impact factor: 2.55). 12/2005; 15(21):4685-90. DOI:10.1016/j.bmcl.2005.07.060 pp.4685-90
Source: PubMed

ABSTRACT 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.

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Keywords

American trypanosomiasis
 
bisphosphonate-containing drugs
 
bone resorption disorders
 
causative agent
 
Chagas' disease
 
control tropical diseases
 
enzymatic activity
 
fatty acids
 
parasite
 
relevant form
 
T. cruzi farnesyl pyrophosphate synthase
 
Trypanosoma cruzi