title: Synthesis and biological evaluation of 1-amino-1,1-bisphosphonates derived from fatty acids against Trypanosoma cruzi targeting farnesyl pyrophosphate synthase.
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.
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
authors.forename: Sergio H
authors.initials: SH
authors.lastname: Szajnman
authors.forename: Esteban L
authors.initials: EL
authors.lastname: Ravaschino
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
authors.forename: Juan B
authors.initials: JB
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D004164:Diphosphonates; D005227:Fatty Acids; D011755:Pyrophosphatases; C108148:farnesyl pyrophosphatase