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Abstract:

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.

Registro:

Documento: Artículo
Título:1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
Autor:Szajnman, S.H.; Rosso, V.S.; Malayil, L.; Smith, A.; Moreno, S.N.J.; Docampo, R.; Rodriguez, J.B.
Filiación:Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EHA, Buenos Aires, Argentina
Center for Tropical and Emerging Global Diseases, Department of Cellular Biology, University of Georgia, Athens, GA 30602, United States
Palabras clave: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
Año:2012
Volumen:10
Número:7
Página de inicio:1424
Página de fin:1433
DOI: http://dx.doi.org/10.1039/c1ob06602a
Título revista:Organic and Biomolecular Chemistry
Título revista abreviado:Org. Biomol. Chem.
ISSN:14770520
CAS:geranyltransferase, 37277-79-5, 50812-36-7; 1-fluorononylidene-1,1-bisphosphonic acid; Antiprotozoal Agents; Diphosphonates; Enzyme Inhibitors; Geranyltranstransferase, 2.5.1.10
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v10_n7_p1424_Szajnman

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Citas:

---------- APA ----------
Szajnman, S.H., Rosso, V.S., Malayil, L., Smith, A., Moreno, S.N.J., Docampo, R. & Rodriguez, J.B. (2012) . 1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase. Organic and Biomolecular Chemistry, 10(7), 1424-1433.
http://dx.doi.org/10.1039/c1ob06602a
---------- CHICAGO ----------
Szajnman, S.H., Rosso, V.S., Malayil, L., Smith, A., Moreno, S.N.J., Docampo, R., et al. "1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase" . Organic and Biomolecular Chemistry 10, no. 7 (2012) : 1424-1433.
http://dx.doi.org/10.1039/c1ob06602a
---------- MLA ----------
Szajnman, S.H., Rosso, V.S., Malayil, L., Smith, A., Moreno, S.N.J., Docampo, R., et al. "1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase" . Organic and Biomolecular Chemistry, vol. 10, no. 7, 2012, pp. 1424-1433.
http://dx.doi.org/10.1039/c1ob06602a
---------- VANCOUVER ----------
Szajnman, S.H., Rosso, V.S., Malayil, L., Smith, A., Moreno, S.N.J., Docampo, R., et al. 1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase. Org. Biomol. Chem. 2012;10(7):1424-1433.
http://dx.doi.org/10.1039/c1ob06602a