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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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

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spelling	todo:paper_14770520_v10_n7_p1424_Szajnman2023-10-03T16:19:02Z 1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase Szajnman, S.H. Rosso, V.S. Malayil, L. Smith, A. Moreno, S.N.J. Docampo, R. Rodriguez, J.B. 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 Toxoplasma Toxoplasma gondii Trypanosoma cruzi 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. Fil:Szajnman, S.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Moreno, S.N.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rodriguez, J.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_14770520_v10_n7_p1424_Szajnman
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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 Toxoplasma Toxoplasma gondii Trypanosoma cruzi
spellingShingle	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 Toxoplasma Toxoplasma gondii Trypanosoma cruzi Szajnman, S.H. Rosso, V.S. Malayil, L. Smith, A. Moreno, S.N.J. Docampo, R. Rodriguez, J.B. 1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
topic_facet	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 Toxoplasma Toxoplasma gondii Trypanosoma cruzi
description	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.
format	JOUR
author	Szajnman, S.H. Rosso, V.S. Malayil, L. Smith, A. Moreno, S.N.J. Docampo, R. Rodriguez, J.B.
author_facet	Szajnman, S.H. Rosso, V.S. Malayil, L. Smith, A. Moreno, S.N.J. Docampo, R. Rodriguez, J.B.
author_sort	Szajnman, S.H.
title	1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
title_short	1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
title_full	1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
title_fullStr	1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
title_full_unstemmed	1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
title_sort	1-(fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of toxoplasma gondii farnesyl pyrophosphate synthase
url	http://hdl.handle.net/20.500.12110/paper_14770520_v10_n7_p1424_Szajnman
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1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase

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