Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach

Autores
Ganuza, Agustina; Alberca, Lucas Nicolás; Dietrich, Roque Carlos; Gavernet, Luciana; Talevi, Alan; Corvi, Maria Martha
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Although healthy individuals present few symptoms, the disease could have a high impact in immunocompromised individuals and in congenital infection, leading to serious health problems. Although the combination of pyrimethamine with a sulfonamide is still very effective for treatment of toxoplasmosis, the use of these two drugs in immunocompromised individuals for long periods of time frequently leads to adverse reactions. As such, there is a need for alternative therapeutic options. Recently, by application of in silico drug repurposing it was reported that cisapride (gastroprokinetic agent), cinnarizine (antihistamine used to treat travel sickness), clofazimine (antimycobacterial compound), triclabendazole (antihelminthic drug) and paroxetine (antidepressant) inhibit putrescine uptake in Trypanosoma cruzi. Given that T. gondii is auxotroph for polyamines, here we evaluated these compounds on T. gondii growth in vitro. All the tested compounds presented anti-toxoplasmic effect. The calculated IC50 for paroxetine, cinnarizine and cisapride were 2.42, 3.12 and 4.72 μM, respectively. However, triclabendazole and clofazimine presented a higher selectivity towards T. gondii inhibition growth: selectivity index of 15.67 and 10.3, respectively (IC50 0.61 μM for triclabendazole and 0.3 μM for clofazimine) without showing a cytotoxic effect on host-cells. Our results suggest that target and drug repurposing are valid approaches for the study of putative antiparasitic compounds, especially for neglected diseases.
Fil: Ganuza, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Dietrich, Roque Carlos. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gavernet, Luciana. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Corvi, Maria Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Reunión anual de sociedades de Biociencia 2019
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Materia
TOXOPLASMA GONDII
TOXOPLASMOSIS
DRUG REPOSITIONING
PUTRESCINE UPTAKE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/153615
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/153615
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approachGanuza, AgustinaAlberca, Lucas NicolásDietrich, Roque CarlosGavernet, LucianaTalevi, AlanCorvi, Maria MarthaTOXOPLASMA GONDIITOXOPLASMOSISDRUG REPOSITIONINGPUTRESCINE UPTAKEhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Although healthy individuals present few symptoms, the disease could have a high impact in immunocompromised individuals and in congenital infection, leading to serious health problems. Although the combination of pyrimethamine with a sulfonamide is still very effective for treatment of toxoplasmosis, the use of these two drugs in immunocompromised individuals for long periods of time frequently leads to adverse reactions. As such, there is a need for alternative therapeutic options. Recently, by application of in silico drug repurposing it was reported that cisapride (gastroprokinetic agent), cinnarizine (antihistamine used to treat travel sickness), clofazimine (antimycobacterial compound), triclabendazole (antihelminthic drug) and paroxetine (antidepressant) inhibit putrescine uptake in Trypanosoma cruzi. Given that T. gondii is auxotroph for polyamines, here we evaluated these compounds on T. gondii growth in vitro. All the tested compounds presented anti-toxoplasmic effect. The calculated IC50 for paroxetine, cinnarizine and cisapride were 2.42, 3.12 and 4.72 μM, respectively. However, triclabendazole and clofazimine presented a higher selectivity towards T. gondii inhibition growth: selectivity index of 15.67 and 10.3, respectively (IC50 0.61 μM for triclabendazole and 0.3 μM for clofazimine) without showing a cytotoxic effect on host-cells. Our results suggest that target and drug repurposing are valid approaches for the study of putative antiparasitic compounds, especially for neglected diseases.Fil: Ganuza, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Dietrich, Roque Carlos. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gavernet, Luciana. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Corvi, Maria Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaReunión anual de sociedades de Biociencia 2019Mar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153615Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach; Reunión anual de sociedades de Biociencia 2019; Mar del Plata; Argentina; 2019; 1-50025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:33Zoai:ri.conicet.gov.ar:11336/153615instacron: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:34982025-09-03 10:06:33.793CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
title Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
spellingShingle Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
Ganuza, Agustina
TOXOPLASMA GONDII
TOXOPLASMOSIS
DRUG REPOSITIONING
PUTRESCINE UPTAKE
title_short Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
title_full Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
title_fullStr Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
title_full_unstemmed Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
title_sort Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach
dc.creator.none.fl_str_mv Ganuza, Agustina
Alberca, Lucas Nicolás
Dietrich, Roque Carlos
Gavernet, Luciana
Talevi, Alan
Corvi, Maria Martha
author Ganuza, Agustina
author_facet Ganuza, Agustina
Alberca, Lucas Nicolás
Dietrich, Roque Carlos
Gavernet, Luciana
Talevi, Alan
Corvi, Maria Martha
author_role author
author2 Alberca, Lucas Nicolás
Dietrich, Roque Carlos
Gavernet, Luciana
Talevi, Alan
Corvi, Maria Martha
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv TOXOPLASMA GONDII
TOXOPLASMOSIS
DRUG REPOSITIONING
PUTRESCINE UPTAKE
topic TOXOPLASMA GONDII
TOXOPLASMOSIS
DRUG REPOSITIONING
PUTRESCINE UPTAKE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Although healthy individuals present few symptoms, the disease could have a high impact in immunocompromised individuals and in congenital infection, leading to serious health problems. Although the combination of pyrimethamine with a sulfonamide is still very effective for treatment of toxoplasmosis, the use of these two drugs in immunocompromised individuals for long periods of time frequently leads to adverse reactions. As such, there is a need for alternative therapeutic options. Recently, by application of in silico drug repurposing it was reported that cisapride (gastroprokinetic agent), cinnarizine (antihistamine used to treat travel sickness), clofazimine (antimycobacterial compound), triclabendazole (antihelminthic drug) and paroxetine (antidepressant) inhibit putrescine uptake in Trypanosoma cruzi. Given that T. gondii is auxotroph for polyamines, here we evaluated these compounds on T. gondii growth in vitro. All the tested compounds presented anti-toxoplasmic effect. The calculated IC50 for paroxetine, cinnarizine and cisapride were 2.42, 3.12 and 4.72 μM, respectively. However, triclabendazole and clofazimine presented a higher selectivity towards T. gondii inhibition growth: selectivity index of 15.67 and 10.3, respectively (IC50 0.61 μM for triclabendazole and 0.3 μM for clofazimine) without showing a cytotoxic effect on host-cells. Our results suggest that target and drug repurposing are valid approaches for the study of putative antiparasitic compounds, especially for neglected diseases.
Fil: Ganuza, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Alberca, Lucas Nicolás. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Dietrich, Roque Carlos. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gavernet, Luciana. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Corvi, Maria Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Reunión anual de sociedades de Biociencia 2019
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
description Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Although healthy individuals present few symptoms, the disease could have a high impact in immunocompromised individuals and in congenital infection, leading to serious health problems. Although the combination of pyrimethamine with a sulfonamide is still very effective for treatment of toxoplasmosis, the use of these two drugs in immunocompromised individuals for long periods of time frequently leads to adverse reactions. As such, there is a need for alternative therapeutic options. Recently, by application of in silico drug repurposing it was reported that cisapride (gastroprokinetic agent), cinnarizine (antihistamine used to treat travel sickness), clofazimine (antimycobacterial compound), triclabendazole (antihelminthic drug) and paroxetine (antidepressant) inhibit putrescine uptake in Trypanosoma cruzi. Given that T. gondii is auxotroph for polyamines, here we evaluated these compounds on T. gondii growth in vitro. All the tested compounds presented anti-toxoplasmic effect. The calculated IC50 for paroxetine, cinnarizine and cisapride were 2.42, 3.12 and 4.72 μM, respectively. However, triclabendazole and clofazimine presented a higher selectivity towards T. gondii inhibition growth: selectivity index of 15.67 and 10.3, respectively (IC50 0.61 μM for triclabendazole and 0.3 μM for clofazimine) without showing a cytotoxic effect on host-cells. Our results suggest that target and drug repurposing are valid approaches for the study of putative antiparasitic compounds, especially for neglected diseases.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/153615
Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach; Reunión anual de sociedades de Biociencia 2019; Mar del Plata; Argentina; 2019; 1-5
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153615
identifier_str_mv Antiproliferative effect of triclabendazole and clofazimine on Toxoplasma gondii growth, a repurposing approach; Reunión anual de sociedades de Biociencia 2019; Mar del Plata; Argentina; 2019; 1-5
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdf
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rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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