1. In Vitro and In Vivo Activity 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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Autores: Szajnman, Sergio Hernan, Galaka, Tamila Pavlivna, Li, Zhu-Hong, Li, Catherine, Howell, Nathan M., Chao, Maria Noelia, Striepen, Boris, Muralidharan, Vasant, Moreno, Silvia N. J., Rodriguez, Juan Bautista
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/60235
Acceso en línea:http://hdl.handle.net/11336/60235
Access Level:acceso abierto
Palabra clave:BISPHOSPHONATES
CRYPTOSPORIDIUM PARVUM
FARNESYL DIPHOSPHATE SYNTHASE
ISOPRENOIDS
PLASMODIUM FALCIPARUM
TOXOPLASMA GONDII
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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repository_id_str
dc.title.none.fl_str_mv 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
title 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
spellingShingle 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
Szajnman, Sergio Hernan
BISPHOSPHONATES
CRYPTOSPORIDIUM PARVUM
FARNESYL DIPHOSPHATE SYNTHASE
ISOPRENOIDS
PLASMODIUM FALCIPARUM
TOXOPLASMA GONDII
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
title_short 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
title_full 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
title_fullStr 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
title_full_unstemmed 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
title_sort 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites
dc.creator.none.fl_str_mv Szajnman, Sergio Hernan
Galaka, Tamila Pavlivna
Li, Zhu-Hong
Li, Catherine
Howell, Nathan M.
Chao, Maria Noelia
Striepen, Boris
Muralidharan, Vasant
Moreno, Silvia N. J.
Rodriguez, Juan Bautista
author Szajnman, Sergio Hernan
author_facet Szajnman, Sergio Hernan
Galaka, Tamila Pavlivna
Li, Zhu-Hong
Li, Catherine
Howell, Nathan M.
Chao, Maria Noelia
Striepen, Boris
Muralidharan, Vasant
Moreno, Silvia N. J.
Rodriguez, Juan Bautista
author_role author
author2 Galaka, Tamila Pavlivna
Li, Zhu-Hong
Li, Catherine
Howell, Nathan M.
Chao, Maria Noelia
Striepen, Boris
Muralidharan, Vasant
Moreno, Silvia N. J.
Rodriguez, Juan Bautista
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BISPHOSPHONATES
CRYPTOSPORIDIUM PARVUM
FARNESYL DIPHOSPHATE SYNTHASE
ISOPRENOIDS
PLASMODIUM FALCIPARUM
TOXOPLASMA GONDII
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
topic BISPHOSPHONATES
CRYPTOSPORIDIUM PARVUM
FARNESYL DIPHOSPHATE SYNTHASE
ISOPRENOIDS
PLASMODIUM FALCIPARUM
TOXOPLASMA GONDII
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/60235
Szajnman, Sergio Hernan; Galaka, Tamila Pavlivna; Li, Zhu-Hong; Li, Catherine; Howell, Nathan M.; et al.; 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 61; 2; 11-2016; 1590-1600
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/60235
identifier_str_mv Szajnman, Sergio Hernan; Galaka, Tamila Pavlivna; Li, Zhu-Hong; Li, Catherine; Howell, Nathan M.; et al.; 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 61; 2; 11-2016; 1590-1600
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01590-16
info:eu-repo/semantics/altIdentifier/url/https://aac.asm.org/content/61/2/e01590-16
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195634726600704
spelling 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan ParasitesSzajnman, Sergio HernanGalaka, Tamila PavlivnaLi, Zhu-HongLi, CatherineHowell, Nathan M.Chao, Maria NoeliaStriepen, BorisMuralidharan, VasantMoreno, Silvia N. J.Rodriguez, Juan BautistaBISPHOSPHONATESCRYPTOSPORIDIUM PARVUMFARNESYL DIPHOSPHATE SYNTHASEISOPRENOIDSPLASMODIUM FALCIPARUMTOXOPLASMA GONDIIhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1We 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.Fil: Szajnman, Sergio Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Galaka, Tamila Pavlivna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Li, Zhu-Hong. University of Georgia; Estados UnidosFil: Li, Catherine. University of Georgia; Estados UnidosFil: Howell, Nathan M.. University of Georgia; Estados UnidosFil: Chao, Maria Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Striepen, Boris. University of Georgia; Estados UnidosFil: Muralidharan, Vasant. University of Georgia; Estados UnidosFil: Moreno, Silvia N. J.. University of Georgia; Estados UnidosFil: Rodriguez, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaAmerican Society for Microbiology2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/60235Szajnman, Sergio Hernan; Galaka, Tamila Pavlivna; Li, Zhu-Hong; Li, Catherine; Howell, Nathan M.; et al.; 1. In Vitro and In Vivo Activity of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 61; 2; 11-2016; 1590-16000066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01590-16info:eu-repo/semantics/altIdentifier/url/https://aac.asm.org/content/61/2/e01590-16info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:58:42Zoai:ri.conicet.gov.ar:11336/60235instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:58:42.718CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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