title: Antiparasitic Activity of Sulfur- and Fluorine-Containing Bisphosphonates against Trypanosomatids and Apicomplexan Parasites.
abstract: Based on crystallographic data of the complexes 2-alkyl(amino)ethyl-1,1-bisphosphonates-Trypanosoma cruzifarnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated againstT. cruzi, the responsible agent of Chagas disease and againstToxoplasma gondii, the etiologic agent of toxoplasmosis and also towards the target enzymes farnesyl pyrophosphate synthase ofT. cruzi(TcFPPS) andT gondii(TgFPPS), respectively. The isoprenoid-containing 1,1-bisphosphonates exhibited modest antiparasitic activity, whereas the linear α-fluoro-2-alkyl(amino)ethyl-1,1-bisphosphonates were unexpectedly devoid of antiparasitic activity. In spite of not presenting efficient antiparasitic activity, these data turned out to be very important to establish a structural activity relationship.
authors.affiliation: Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina. galakatamila@qo.fcen.uba.ar.
authors.forename: Tamila
authors.initials: T
authors.lastname: Galaka
authors.affiliation: Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina. mferrer@qo.fcen.uba.ar.
authors.forename: Mariana
authors.initials: M
authors.lastname: Ferrer Casal
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. mtayl04@uga.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Storey
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. catli@uga.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Li
authors.affiliation: Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina. nchao@qo.fcen.uba.ar.
authors.forename: María N
authors.initials: MN
authors.lastname: Chao
authors.affiliation: Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina. shs@qo.fcen.uba.ar.
authors.forename: Sergio H
authors.initials: SH
authors.lastname: Szajnman
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. rdocampo@uga.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. smoreno@uga.edu.
authors.forename: Silvia N J
authors.initials: SN
authors.lastname: Moreno
authors.affiliation: Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina. jbr@qo.fcen.uba.ar.
authors.forename: Juan B
authors.initials: JB
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015870:Gene Expression; D051228:Geranyltranstransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054879:Halogenation; D006801:Humans; D021261:Parasitic Sensitivity Tests; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014122:Toxoplasma / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D004164:Diphosphonates; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D051228:Geranyltranstransferase
keywords: Chagas disease; Toxoplasma gondii; Trypanosoma cruzi; antiparasitic agents; bisphosphonates; farnesyl diphosphate synthase; toxoplasmosis