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...
Guardado en:
| Autores principales: | , , |
|---|---|
| Publicado: |
2012
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v10_n7_p1424_Szajnman http://hdl.handle.net/20.500.12110/paper_14770520_v10_n7_p1424_Szajnman |
| Aporte de: |
| id |
paper:paper_14770520_v10_n7_p1424_Szajnman |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_14770520_v10_n7_p1424_Szajnman2023-06-08T16:18:02Z 1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista 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. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v10_n7_p1424_Szajnman 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, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista 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. |
| author |
Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista |
| author_facet |
Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista |
| author_sort |
Szajnman, Sergio Hernán |
| 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 |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v10_n7_p1424_Szajnman http://hdl.handle.net/20.500.12110/paper_14770520_v10_n7_p1424_Szajnman |
| work_keys_str_mv |
AT szajnmansergiohernan 1fluoroalkylidene11bisphosphonicacidsarepotentandselectiveinhibitorsoftheenzymaticactivityoftoxoplasmagondiifarnesylpyrophosphatesynthase AT morenosilvianj 1fluoroalkylidene11bisphosphonicacidsarepotentandselectiveinhibitorsoftheenzymaticactivityoftoxoplasmagondiifarnesylpyrophosphatesynthase AT rodriguezjuanbautista 1fluoroalkylidene11bisphosphonicacidsarepotentandselectiveinhibitorsoftheenzymaticactivityoftoxoplasmagondiifarnesylpyrophosphatesynthase |
| _version_ |
1768545343967854592 |