Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla

Autores
Salas Sarduy, Emir; Cabrera Muñoz, Aymara; Cauerff, Ana Albina; González González, Yamile; Trejo, Sebastian Alejandro; Chidichimo, Agustina; Chávez Planes, Maria de Los Angeles; Cazzulo, Juan Jose
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Malaria and American Trypanosomiasis constitute major global health problems. The continued emergence and spreading of resistant strains and the limited efficacy and/or safety of currently available therapeutic agents require a constant search for new sources of antiparasitic compounds. In the present study, a fraction enriched in tight-binding protease inhibitors was isolated from the Caribbean coral Plexaura homomalla (Esper, 1792), functionally characterized and tested for their antiparasitic activity against Trypanosoma cruzi and Plasmodium falciparum. The resultant fraction was chromatographically enriched in tight-binding inhibitors active against Papain-like cysteine peptidases (92%) and Pepsin-like aspartyl peptidases (8%). Globally, the inhibitors present in the enriched fraction showed no competition with substrates and apparent Ki values of 1.99 and 4.81 nM for Falcipain 2 and Cruzipain, the major cysteine peptidases from P. falciparum and T. cruzi, respectively. The inhibitor-enriched fraction showed promising antiparasitic activity in cultures. It reduced the growth of the chloroquine-resistant P. falciparum strain Dd2 (IC50 = 0.46 μM) and promoted the apparent accumulation of trophozoites, both consistent with a blockade in the hemoglobin degradation pathway. At sub-micromolar concentrations, the inhibitor-enriched fraction reduced the infection of VERO cells by T. cruzi (CL Brener clone) trypomastigotes and interfered with intracellular differentiation and/or replication of the parasites. This study provides new scientific evidence that confirms P. homomalla as an excellent source of tight-biding protease inhibitors for different proteases with biomedical relevance, and suggests that either the individual inhibitors or the enriched fraction itself could be valuable as antiparasitic compounds.
Fil: Salas Sarduy, Emir. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Cabrera Muñoz, Aymara. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba
Fil: Cauerff, Ana Albina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales (i); Argentina
Fil: González González, Yamile . Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Trejo, Sebastian Alejandro. Universitat Autònoma de Barcelona. Servei de Proteomica i Biologia Estructural; España. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Chidichimo, Agustina. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina
Fil: Chávez Planes, Maria de Los Angeles. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Cazzulo, Juan Jose. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (san Martin); Argentina. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Materia
Trypanosoma Cruzi
Plasmodium Falciparum
Plexaura Homomalla
Cysteine Peptidases
Tight-Binding Inhibitor
Antiparasitic Agents
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4318
Acceder
id CONICETDig_b7fd871358c64417fd165291853aad2e
oai_identifier_str oai:ri.conicet.gov.ar:11336/4318
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomallaSalas Sarduy, EmirCabrera Muñoz, AymaraCauerff, Ana AlbinaGonzález González, Yamile Trejo, Sebastian AlejandroChidichimo, AgustinaChávez Planes, Maria de Los AngelesCazzulo, Juan JoseTrypanosoma CruziPlasmodium FalciparumPlexaura HomomallaCysteine PeptidasesTight-Binding InhibitorAntiparasitic Agentshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Malaria and American Trypanosomiasis constitute major global health problems. The continued emergence and spreading of resistant strains and the limited efficacy and/or safety of currently available therapeutic agents require a constant search for new sources of antiparasitic compounds. In the present study, a fraction enriched in tight-binding protease inhibitors was isolated from the Caribbean coral Plexaura homomalla (Esper, 1792), functionally characterized and tested for their antiparasitic activity against Trypanosoma cruzi and Plasmodium falciparum. The resultant fraction was chromatographically enriched in tight-binding inhibitors active against Papain-like cysteine peptidases (92%) and Pepsin-like aspartyl peptidases (8%). Globally, the inhibitors present in the enriched fraction showed no competition with substrates and apparent Ki values of 1.99 and 4.81 nM for Falcipain 2 and Cruzipain, the major cysteine peptidases from P. falciparum and T. cruzi, respectively. The inhibitor-enriched fraction showed promising antiparasitic activity in cultures. It reduced the growth of the chloroquine-resistant P. falciparum strain Dd2 (IC50 = 0.46 μM) and promoted the apparent accumulation of trophozoites, both consistent with a blockade in the hemoglobin degradation pathway. At sub-micromolar concentrations, the inhibitor-enriched fraction reduced the infection of VERO cells by T. cruzi (CL Brener clone) trypomastigotes and interfered with intracellular differentiation and/or replication of the parasites. This study provides new scientific evidence that confirms P. homomalla as an excellent source of tight-biding protease inhibitors for different proteases with biomedical relevance, and suggests that either the individual inhibitors or the enriched fraction itself could be valuable as antiparasitic compounds.Fil: Salas Sarduy, Emir. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; ArgentinaFil: Cabrera Muñoz, Aymara. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; CubaFil: Cauerff, Ana Albina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales (i); ArgentinaFil: González González, Yamile . Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; ArgentinaFil: Trejo, Sebastian Alejandro. Universitat Autònoma de Barcelona. Servei de Proteomica i Biologia Estructural; España. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; ArgentinaFil: Chidichimo, Agustina. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); ArgentinaFil: Chávez Planes, Maria de Los Angeles. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; ArgentinaFil: Cazzulo, Juan Jose. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (san Martin); Argentina. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; ArgentinaElsevier2013-09-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4318Salas Sarduy, Emir; Cabrera Muñoz, Aymara; Cauerff, Ana Albina; González González, Yamile ; Trejo, Sebastian Alejandro; et al.; Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla; Elsevier; Experimental Parasitology; 135; 3; 30-9-2013; 611-6220014-4894enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014489413002580info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2013.09.013info:eu-repo/semantics/altIdentifier/issn/0014-4894info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:30Zoai:ri.conicet.gov.ar:11336/4318instacron: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:34982025-09-29 09:34:30.747CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
title Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
spellingShingle Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
Salas Sarduy, Emir
Trypanosoma Cruzi
Plasmodium Falciparum
Plexaura Homomalla
Cysteine Peptidases
Tight-Binding Inhibitor
Antiparasitic Agents
title_short Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
title_full Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
title_fullStr Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
title_full_unstemmed Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
title_sort Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
dc.creator.none.fl_str_mv Salas Sarduy, Emir
Cabrera Muñoz, Aymara
Cauerff, Ana Albina
González González, Yamile
Trejo, Sebastian Alejandro
Chidichimo, Agustina
Chávez Planes, Maria de Los Angeles
Cazzulo, Juan Jose
author Salas Sarduy, Emir
author_facet Salas Sarduy, Emir
Cabrera Muñoz, Aymara
Cauerff, Ana Albina
González González, Yamile
Trejo, Sebastian Alejandro
Chidichimo, Agustina
Chávez Planes, Maria de Los Angeles
Cazzulo, Juan Jose
author_role author
author2 Cabrera Muñoz, Aymara
Cauerff, Ana Albina
González González, Yamile
Trejo, Sebastian Alejandro
Chidichimo, Agustina
Chávez Planes, Maria de Los Angeles
Cazzulo, Juan Jose
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trypanosoma Cruzi
Plasmodium Falciparum
Plexaura Homomalla
Cysteine Peptidases
Tight-Binding Inhibitor
Antiparasitic Agents
topic Trypanosoma Cruzi
Plasmodium Falciparum
Plexaura Homomalla
Cysteine Peptidases
Tight-Binding Inhibitor
Antiparasitic Agents
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Malaria and American Trypanosomiasis constitute major global health problems. The continued emergence and spreading of resistant strains and the limited efficacy and/or safety of currently available therapeutic agents require a constant search for new sources of antiparasitic compounds. In the present study, a fraction enriched in tight-binding protease inhibitors was isolated from the Caribbean coral Plexaura homomalla (Esper, 1792), functionally characterized and tested for their antiparasitic activity against Trypanosoma cruzi and Plasmodium falciparum. The resultant fraction was chromatographically enriched in tight-binding inhibitors active against Papain-like cysteine peptidases (92%) and Pepsin-like aspartyl peptidases (8%). Globally, the inhibitors present in the enriched fraction showed no competition with substrates and apparent Ki values of 1.99 and 4.81 nM for Falcipain 2 and Cruzipain, the major cysteine peptidases from P. falciparum and T. cruzi, respectively. The inhibitor-enriched fraction showed promising antiparasitic activity in cultures. It reduced the growth of the chloroquine-resistant P. falciparum strain Dd2 (IC50 = 0.46 μM) and promoted the apparent accumulation of trophozoites, both consistent with a blockade in the hemoglobin degradation pathway. At sub-micromolar concentrations, the inhibitor-enriched fraction reduced the infection of VERO cells by T. cruzi (CL Brener clone) trypomastigotes and interfered with intracellular differentiation and/or replication of the parasites. This study provides new scientific evidence that confirms P. homomalla as an excellent source of tight-biding protease inhibitors for different proteases with biomedical relevance, and suggests that either the individual inhibitors or the enriched fraction itself could be valuable as antiparasitic compounds.
Fil: Salas Sarduy, Emir. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Cabrera Muñoz, Aymara. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba
Fil: Cauerff, Ana Albina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales (i); Argentina
Fil: González González, Yamile . Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Trejo, Sebastian Alejandro. Universitat Autònoma de Barcelona. Servei de Proteomica i Biologia Estructural; España. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Chidichimo, Agustina. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina
Fil: Chávez Planes, Maria de Los Angeles. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
Fil: Cazzulo, Juan Jose. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (san Martin); Argentina. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina
description Malaria and American Trypanosomiasis constitute major global health problems. The continued emergence and spreading of resistant strains and the limited efficacy and/or safety of currently available therapeutic agents require a constant search for new sources of antiparasitic compounds. In the present study, a fraction enriched in tight-binding protease inhibitors was isolated from the Caribbean coral Plexaura homomalla (Esper, 1792), functionally characterized and tested for their antiparasitic activity against Trypanosoma cruzi and Plasmodium falciparum. The resultant fraction was chromatographically enriched in tight-binding inhibitors active against Papain-like cysteine peptidases (92%) and Pepsin-like aspartyl peptidases (8%). Globally, the inhibitors present in the enriched fraction showed no competition with substrates and apparent Ki values of 1.99 and 4.81 nM for Falcipain 2 and Cruzipain, the major cysteine peptidases from P. falciparum and T. cruzi, respectively. The inhibitor-enriched fraction showed promising antiparasitic activity in cultures. It reduced the growth of the chloroquine-resistant P. falciparum strain Dd2 (IC50 = 0.46 μM) and promoted the apparent accumulation of trophozoites, both consistent with a blockade in the hemoglobin degradation pathway. At sub-micromolar concentrations, the inhibitor-enriched fraction reduced the infection of VERO cells by T. cruzi (CL Brener clone) trypomastigotes and interfered with intracellular differentiation and/or replication of the parasites. This study provides new scientific evidence that confirms P. homomalla as an excellent source of tight-biding protease inhibitors for different proteases with biomedical relevance, and suggests that either the individual inhibitors or the enriched fraction itself could be valuable as antiparasitic compounds.
publishDate 2013
dc.date.none.fl_str_mv 2013-09-30
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/11336/4318
Salas Sarduy, Emir; Cabrera Muñoz, Aymara; Cauerff, Ana Albina; González González, Yamile ; Trejo, Sebastian Alejandro; et al.; Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla; Elsevier; Experimental Parasitology; 135; 3; 30-9-2013; 611-622
0014-4894
url http://hdl.handle.net/11336/4318
identifier_str_mv Salas Sarduy, Emir; Cabrera Muñoz, Aymara; Cauerff, Ana Albina; González González, Yamile ; Trejo, Sebastian Alejandro; et al.; Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla; Elsevier; Experimental Parasitology; 135; 3; 30-9-2013; 611-622
0014-4894
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014489413002580
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2013.09.013
info:eu-repo/semantics/altIdentifier/issn/0014-4894
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
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