Synthesis and Biological Evaluation of 1-Amino-1,1-Bisphosphonates Derived from Fatty Acids against Trypanosoma cruzi targeting Farnesyl Pyrophosphate Synthase

SZAJNMAN, SERGIO HERNÁN; RAVASCHINO, ESTEBAN LUIS; DOCAMPO, ROBERTO; RODRIGUEZ, JUAN BAUTISTA

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Elsevier

Lugar: Hilversum; Año: 2005 vol. 15 p. 4685 - 4690

0960-894X

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 the low micromolar level. The cellular activity was associated with the inhibition of the 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.