In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites
We tested a series of sulfur-containing linear bisphosphonates against Toxoplasma gondii, the etiologic agent of toxoplasmosis. The most potent compound (compound 22; 1-[(n-decylsulfonyl)ethyl]-1,1-bisphosphonic acid) is a sulfonecontaining compound, which had a 50% effective concentration (EC50) of...
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paper:paper_00664804_v61_n2_p_Szajnman2023-06-08T15:06:12Z In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista Bisphosphonates Cryptosporidium parvum Farnesyl diphosphate synthase Isoprenoids Plasmodium falciparum Toxoplasma gondii (2,2 diphosphonoethyl)(methyl)(hexyl)sulfonium tetrafluoroborate (2,2 diphosphonoethyl)(methyl)(pentyl)sulfonium tetrafluoroborate 1 [(n decylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n heptylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n hexylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n nonylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n octylsulfonyl)ethyl] 1,1 biphosphonic acid atorvastatin bisphosphonic acid derivative geranyltransferase hydroxymethylglutaryl coenzyme A reductase inhibitor pamidronic acid risedronic acid sulfone sulfur unclassified drug zoledronic acid antiprotozoal agent bisphosphonic acid derivative enzyme inhibitor sulfur animal cell animal experiment animal model Apicomplexa Article controlled study cryptosporidiosis Cryptosporidium parvum EC50 enzyme activity experimental model IC50 in vitro study in vivo study malaria mouse nonhuman Plasmodium falciparum priority journal selectivity index tachyzoite tissue culture toxicity Toxoplasma toxoplasmosis animal antagonists and inhibitors chemistry dose response drug effects enzymology growth, development and aging human inbred mouse strain preclinical study procedures synthesis toxoplasmosis Animals Antiprotozoal Agents Chemistry Techniques, Synthetic Cryptosporidium parvum Diphosphonates Dose-Response Relationship, Drug Drug Evaluation, Preclinical Enzyme Inhibitors Geranyltranstransferase Humans Mice, Inbred Strains Plasmodium falciparum Sulfur Toxoplasma Toxoplasmosis We tested a series of sulfur-containing linear bisphosphonates against Toxoplasma gondii, the etiologic agent of toxoplasmosis. The most potent compound (compound 22; 1-[(n-decylsulfonyl)ethyl]-1,1-bisphosphonic acid) is a sulfonecontaining compound, which had a 50% effective concentration (EC50) of 0.11 ± 0.02 μM against intracellular tachyzoites. The compound showed low toxicity when tested in tissue culture with a selectivity index of >2,000. Compound 22 also showed high activity in vivo in a toxoplasmosis mouse model. The compound inhibited the Toxoplasma farnesyl diphosphate synthase (TgFPPS), but the concentration needed to inhibit 50% of the enzymatic activity (IC50) was higher than the concentration that inhibited 50% of growth. We tested compound 22 against two other apicomplexan parasites, Plasmodium falciparum (EC50 of 0.6 ± 0.01 μM), the agent of malaria, and Cryptosporidium parvum (EC50 of ∼65 μM), the agent of cryptosporidiosis. Our results suggest that compound 22 is an excellent novel compound that could lead to the development of potent agents against apicomplexan parasites. © 2017 American Society for Microbiology. All Rights Reserved. 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. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v61_n2_p_Szajnman http://hdl.handle.net/20.500.12110/paper_00664804_v61_n2_p_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 |
Bisphosphonates Cryptosporidium parvum Farnesyl diphosphate synthase Isoprenoids Plasmodium falciparum Toxoplasma gondii (2,2 diphosphonoethyl)(methyl)(hexyl)sulfonium tetrafluoroborate (2,2 diphosphonoethyl)(methyl)(pentyl)sulfonium tetrafluoroborate 1 [(n decylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n heptylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n hexylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n nonylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n octylsulfonyl)ethyl] 1,1 biphosphonic acid atorvastatin bisphosphonic acid derivative geranyltransferase hydroxymethylglutaryl coenzyme A reductase inhibitor pamidronic acid risedronic acid sulfone sulfur unclassified drug zoledronic acid antiprotozoal agent bisphosphonic acid derivative enzyme inhibitor sulfur animal cell animal experiment animal model Apicomplexa Article controlled study cryptosporidiosis Cryptosporidium parvum EC50 enzyme activity experimental model IC50 in vitro study in vivo study malaria mouse nonhuman Plasmodium falciparum priority journal selectivity index tachyzoite tissue culture toxicity Toxoplasma toxoplasmosis animal antagonists and inhibitors chemistry dose response drug effects enzymology growth, development and aging human inbred mouse strain preclinical study procedures synthesis toxoplasmosis Animals Antiprotozoal Agents Chemistry Techniques, Synthetic Cryptosporidium parvum Diphosphonates Dose-Response Relationship, Drug Drug Evaluation, Preclinical Enzyme Inhibitors Geranyltranstransferase Humans Mice, Inbred Strains Plasmodium falciparum Sulfur Toxoplasma Toxoplasmosis |
| spellingShingle |
Bisphosphonates Cryptosporidium parvum Farnesyl diphosphate synthase Isoprenoids Plasmodium falciparum Toxoplasma gondii (2,2 diphosphonoethyl)(methyl)(hexyl)sulfonium tetrafluoroborate (2,2 diphosphonoethyl)(methyl)(pentyl)sulfonium tetrafluoroborate 1 [(n decylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n heptylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n hexylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n nonylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n octylsulfonyl)ethyl] 1,1 biphosphonic acid atorvastatin bisphosphonic acid derivative geranyltransferase hydroxymethylglutaryl coenzyme A reductase inhibitor pamidronic acid risedronic acid sulfone sulfur unclassified drug zoledronic acid antiprotozoal agent bisphosphonic acid derivative enzyme inhibitor sulfur animal cell animal experiment animal model Apicomplexa Article controlled study cryptosporidiosis Cryptosporidium parvum EC50 enzyme activity experimental model IC50 in vitro study in vivo study malaria mouse nonhuman Plasmodium falciparum priority journal selectivity index tachyzoite tissue culture toxicity Toxoplasma toxoplasmosis animal antagonists and inhibitors chemistry dose response drug effects enzymology growth, development and aging human inbred mouse strain preclinical study procedures synthesis toxoplasmosis Animals Antiprotozoal Agents Chemistry Techniques, Synthetic Cryptosporidium parvum Diphosphonates Dose-Response Relationship, Drug Drug Evaluation, Preclinical Enzyme Inhibitors Geranyltranstransferase Humans Mice, Inbred Strains Plasmodium falciparum Sulfur Toxoplasma Toxoplasmosis Szajnman, Sergio Hernán Moreno, Silvia N. J. Rodríguez, Juan Bautista In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| topic_facet |
Bisphosphonates Cryptosporidium parvum Farnesyl diphosphate synthase Isoprenoids Plasmodium falciparum Toxoplasma gondii (2,2 diphosphonoethyl)(methyl)(hexyl)sulfonium tetrafluoroborate (2,2 diphosphonoethyl)(methyl)(pentyl)sulfonium tetrafluoroborate 1 [(n decylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n heptylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n hexylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n nonylsulfonyl)ethyl] 1,1 biphosphonic acid 1 [(n octylsulfonyl)ethyl] 1,1 biphosphonic acid atorvastatin bisphosphonic acid derivative geranyltransferase hydroxymethylglutaryl coenzyme A reductase inhibitor pamidronic acid risedronic acid sulfone sulfur unclassified drug zoledronic acid antiprotozoal agent bisphosphonic acid derivative enzyme inhibitor sulfur animal cell animal experiment animal model Apicomplexa Article controlled study cryptosporidiosis Cryptosporidium parvum EC50 enzyme activity experimental model IC50 in vitro study in vivo study malaria mouse nonhuman Plasmodium falciparum priority journal selectivity index tachyzoite tissue culture toxicity Toxoplasma toxoplasmosis animal antagonists and inhibitors chemistry dose response drug effects enzymology growth, development and aging human inbred mouse strain preclinical study procedures synthesis toxoplasmosis Animals Antiprotozoal Agents Chemistry Techniques, Synthetic Cryptosporidium parvum Diphosphonates Dose-Response Relationship, Drug Drug Evaluation, Preclinical Enzyme Inhibitors Geranyltranstransferase Humans Mice, Inbred Strains Plasmodium falciparum Sulfur Toxoplasma Toxoplasmosis |
| description |
We tested a series of sulfur-containing linear bisphosphonates against Toxoplasma gondii, the etiologic agent of toxoplasmosis. The most potent compound (compound 22; 1-[(n-decylsulfonyl)ethyl]-1,1-bisphosphonic acid) is a sulfonecontaining compound, which had a 50% effective concentration (EC50) of 0.11 ± 0.02 μM against intracellular tachyzoites. The compound showed low toxicity when tested in tissue culture with a selectivity index of >2,000. Compound 22 also showed high activity in vivo in a toxoplasmosis mouse model. The compound inhibited the Toxoplasma farnesyl diphosphate synthase (TgFPPS), but the concentration needed to inhibit 50% of the enzymatic activity (IC50) was higher than the concentration that inhibited 50% of growth. We tested compound 22 against two other apicomplexan parasites, Plasmodium falciparum (EC50 of 0.6 ± 0.01 μM), the agent of malaria, and Cryptosporidium parvum (EC50 of ∼65 μM), the agent of cryptosporidiosis. Our results suggest that compound 22 is an excellent novel compound that could lead to the development of potent agents against apicomplexan parasites. © 2017 American Society for Microbiology. All Rights Reserved. |
| 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 |
In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| title_short |
In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| title_full |
In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| title_fullStr |
In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| title_full_unstemmed |
In Vitro and in Vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| title_sort |
in vitro and in vivo activities of sulfur-containing linear bisphosphonates against apicomplexan parasites |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v61_n2_p_Szajnman http://hdl.handle.net/20.500.12110/paper_00664804_v61_n2_p_Szajnman |
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