1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase

α-Fluorinated-1,1-bisphosphonic acids derived from fatty acids were designed, synthesized and biologically evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and against Toxoplasma gondii, the agent responsible for toxoplasmosis, and also towards the target parasitic enzymes...

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Detalles Bibliográficos
Autores principales: Szajnman, S.H., Rosso, V.S., Malayil, L., Smith, A., Moreno, S.N.J., Docampo, R., Rodriguez, J.B.
Formato: JOUR
Materias:
Chagas disease
Enzymatic activities
Etiologic agents
Farnesyl pyrophosphates
Growth inhibition
Nanomolar range
Potent inhibitor
Risedronate
Selective inhibitors
Synthases
Toxoplasma gondii
Trypanosoma cruzi
Chemistry
Positive ions
Enzyme activity
1 fluorononylidene 1,1 bisphosphonic acid
1-fluorononylidene-1,1-bisphosphonic acid
antiprotozoal agent
bisphosphonic acid derivative
enzyme inhibitor
geranyltransferase
article
chemistry
drug antagonism
enzymology
metabolism
Toxoplasma
Antiprotozoal Agents
Diphosphonates
Enzyme Inhibitors
Geranyltranstransferase
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_14770520_v10_n7_p1424_Szajnman
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:α-Fluorinated-1,1-bisphosphonic acids derived from fatty acids were designed, synthesized and biologically evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and against Toxoplasma gondii, the agent responsible for toxoplasmosis, and also towards the target parasitic enzymes farnesyl pyrophosphate synthase of T. cruzi (TcFPPS) and T. gondii (TgFPPS). Interestingly, 1-fluorononylidene-1,1-bisphosphonic acid (compound 43) proved to be an extremely potent inhibitor of the enzymatic activity of TgFPPS at the low nanomolar range, exhibiting an IC 50 of 30 nM. This compound was two-fold more potent than risedronate (IC 50 = 74 nM) that was taken as a positive control. This enzymatic activity was associated with a strong cell growth inhibition against tachyzoites of T. gondii, with an IC 50 value of 2.7 μM. © 2012 The Royal Society of Chemistry.

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