Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta

Autores
Llorens de Los Ríos, María Candelaria; Barbieri, Cecilia Luján; Lanza Castronuovo, Priscila Ailin; Funes Chabán, Macarena; Vera, Domingo Mariano Adolfo; Soria, Gastón; Carpinella, Maria Cecilia; Joray, Mariana Belén
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Angiogenesis is an essential mechanism involved in biological processes such as reproduction, development and wound healing. Imbalances between the factors that regulate angiogenesis have been linked to different diseases that affect human health. Despite the great progress achieved in antiangiogenic therapy, its limited efficacy, severe adverse effects and the development of resistance demands the continuous development of novel therapeutic agents to overcome these obstacles. In this context plant-derived metabolites continue to play a highly significant role in drug discovery. From a screening performed in our laboratory, the ethanol extract of Tagetes minuta arose as a potent antiangiogenic agent. This effect was evaluated by the tube formation assay using bovine aortic endothelial cells (BAEC). Through bio-guided chemical fractionation three compounds identified as: 5´-methyl-5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (1), 5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (2) and alfa-terthienylmethanol (3) were obtained. Among these, compound 3 showed a potent antiangiogenic activity (IC50 = 2.69 μM). The influence of 3 over cell proliferation and cell invasion induced by the vascular endothelial growth factor (VEGF) was evaluated. While no effect was observed in the MTT proliferation assays, 3D transwell experiments demonstrated that compound 3 efficiently blocked cell invasion. Additionally, molecular docking experiments showed that 3 overlaps with the tyrosine kinase inhibitor sorafenib (a potent antioangiogenic agent) at the catalytic cleft of VEGF receptor 2 interacting with key aminoacids such as Glu885, Phe1047 and Cys919, extending over Val916 into the adjacent allosteric hydrophobic back pocket resembling a type II inhibition. These studies contribute to position 3 as a potential candidate to be used in antiangiogenic therapy itself or as a lead compound for the development of analogues with improved activity.
Fil: Llorens de Los Ríos, María Candelaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Barbieri, Cecilia Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Lanza Castronuovo, Priscila Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Funes Chabán, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Soria, Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: Joray, Mariana Belén. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Tecnología de Animales de Laboratorio
Materia
ANTIANGIOGENIC-THERAPY
MOLECULAR-DOCKING
PLANT-DERIVED-METABOLITES
VEGF
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:11336/153591
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/153591
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minutaLlorens de Los Ríos, María CandelariaBarbieri, Cecilia LujánLanza Castronuovo, Priscila AilinFunes Chabán, MacarenaVera, Domingo Mariano AdolfoSoria, GastónCarpinella, Maria CeciliaJoray, Mariana BelénANTIANGIOGENIC-THERAPYMOLECULAR-DOCKINGPLANT-DERIVED-METABOLITESVEGFhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Angiogenesis is an essential mechanism involved in biological processes such as reproduction, development and wound healing. Imbalances between the factors that regulate angiogenesis have been linked to different diseases that affect human health. Despite the great progress achieved in antiangiogenic therapy, its limited efficacy, severe adverse effects and the development of resistance demands the continuous development of novel therapeutic agents to overcome these obstacles. In this context plant-derived metabolites continue to play a highly significant role in drug discovery. From a screening performed in our laboratory, the ethanol extract of Tagetes minuta arose as a potent antiangiogenic agent. This effect was evaluated by the tube formation assay using bovine aortic endothelial cells (BAEC). Through bio-guided chemical fractionation three compounds identified as: 5´-methyl-5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (1), 5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (2) and alfa-terthienylmethanol (3) were obtained. Among these, compound 3 showed a potent antiangiogenic activity (IC50 = 2.69 μM). The influence of 3 over cell proliferation and cell invasion induced by the vascular endothelial growth factor (VEGF) was evaluated. While no effect was observed in the MTT proliferation assays, 3D transwell experiments demonstrated that compound 3 efficiently blocked cell invasion. Additionally, molecular docking experiments showed that 3 overlaps with the tyrosine kinase inhibitor sorafenib (a potent antioangiogenic agent) at the catalytic cleft of VEGF receptor 2 interacting with key aminoacids such as Glu885, Phe1047 and Cys919, extending over Val916 into the adjacent allosteric hydrophobic back pocket resembling a type II inhibition. These studies contribute to position 3 as a potential candidate to be used in antiangiogenic therapy itself or as a lead compound for the development of analogues with improved activity.Fil: Llorens de Los Ríos, María Candelaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Barbieri, Cecilia Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Lanza Castronuovo, Priscila Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Funes Chabán, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Soria, Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Joray, Mariana Belén. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaReunión Anual de Sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasTecnología de Animales de LaboratorioFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153591Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 251-2520025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:22:29Zoai:ri.conicet.gov.ar:11336/153591instacron: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:34982025-11-05 10:22:29.444CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
title Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
spellingShingle Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
Llorens de Los Ríos, María Candelaria
ANTIANGIOGENIC-THERAPY
MOLECULAR-DOCKING
PLANT-DERIVED-METABOLITES
VEGF
title_short Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
title_full Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
title_fullStr Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
title_full_unstemmed Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
title_sort Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta
dc.creator.none.fl_str_mv Llorens de Los Ríos, María Candelaria
Barbieri, Cecilia Luján
Lanza Castronuovo, Priscila Ailin
Funes Chabán, Macarena
Vera, Domingo Mariano Adolfo
Soria, Gastón
Carpinella, Maria Cecilia
Joray, Mariana Belén
author Llorens de Los Ríos, María Candelaria
author_facet Llorens de Los Ríos, María Candelaria
Barbieri, Cecilia Luján
Lanza Castronuovo, Priscila Ailin
Funes Chabán, Macarena
Vera, Domingo Mariano Adolfo
Soria, Gastón
Carpinella, Maria Cecilia
Joray, Mariana Belén
author_role author
author2 Barbieri, Cecilia Luján
Lanza Castronuovo, Priscila Ailin
Funes Chabán, Macarena
Vera, Domingo Mariano Adolfo
Soria, Gastón
Carpinella, Maria Cecilia
Joray, Mariana Belén
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTIANGIOGENIC-THERAPY
MOLECULAR-DOCKING
PLANT-DERIVED-METABOLITES
VEGF
topic ANTIANGIOGENIC-THERAPY
MOLECULAR-DOCKING
PLANT-DERIVED-METABOLITES
VEGF
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Angiogenesis is an essential mechanism involved in biological processes such as reproduction, development and wound healing. Imbalances between the factors that regulate angiogenesis have been linked to different diseases that affect human health. Despite the great progress achieved in antiangiogenic therapy, its limited efficacy, severe adverse effects and the development of resistance demands the continuous development of novel therapeutic agents to overcome these obstacles. In this context plant-derived metabolites continue to play a highly significant role in drug discovery. From a screening performed in our laboratory, the ethanol extract of Tagetes minuta arose as a potent antiangiogenic agent. This effect was evaluated by the tube formation assay using bovine aortic endothelial cells (BAEC). Through bio-guided chemical fractionation three compounds identified as: 5´-methyl-5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (1), 5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (2) and alfa-terthienylmethanol (3) were obtained. Among these, compound 3 showed a potent antiangiogenic activity (IC50 = 2.69 μM). The influence of 3 over cell proliferation and cell invasion induced by the vascular endothelial growth factor (VEGF) was evaluated. While no effect was observed in the MTT proliferation assays, 3D transwell experiments demonstrated that compound 3 efficiently blocked cell invasion. Additionally, molecular docking experiments showed that 3 overlaps with the tyrosine kinase inhibitor sorafenib (a potent antioangiogenic agent) at the catalytic cleft of VEGF receptor 2 interacting with key aminoacids such as Glu885, Phe1047 and Cys919, extending over Val916 into the adjacent allosteric hydrophobic back pocket resembling a type II inhibition. These studies contribute to position 3 as a potential candidate to be used in antiangiogenic therapy itself or as a lead compound for the development of analogues with improved activity.
Fil: Llorens de Los Ríos, María Candelaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Barbieri, Cecilia Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Lanza Castronuovo, Priscila Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Funes Chabán, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Soria, Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: Joray, Mariana Belén. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Tecnología de Animales de Laboratorio
description Angiogenesis is an essential mechanism involved in biological processes such as reproduction, development and wound healing. Imbalances between the factors that regulate angiogenesis have been linked to different diseases that affect human health. Despite the great progress achieved in antiangiogenic therapy, its limited efficacy, severe adverse effects and the development of resistance demands the continuous development of novel therapeutic agents to overcome these obstacles. In this context plant-derived metabolites continue to play a highly significant role in drug discovery. From a screening performed in our laboratory, the ethanol extract of Tagetes minuta arose as a potent antiangiogenic agent. This effect was evaluated by the tube formation assay using bovine aortic endothelial cells (BAEC). Through bio-guided chemical fractionation three compounds identified as: 5´-methyl-5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (1), 5-(4-hydroxybut-1-ynyl)-2,2´-bithiophene (2) and alfa-terthienylmethanol (3) were obtained. Among these, compound 3 showed a potent antiangiogenic activity (IC50 = 2.69 μM). The influence of 3 over cell proliferation and cell invasion induced by the vascular endothelial growth factor (VEGF) was evaluated. While no effect was observed in the MTT proliferation assays, 3D transwell experiments demonstrated that compound 3 efficiently blocked cell invasion. Additionally, molecular docking experiments showed that 3 overlaps with the tyrosine kinase inhibitor sorafenib (a potent antioangiogenic agent) at the catalytic cleft of VEGF receptor 2 interacting with key aminoacids such as Glu885, Phe1047 and Cys919, extending over Val916 into the adjacent allosteric hydrophobic back pocket resembling a type II inhibition. These studies contribute to position 3 as a potential candidate to be used in antiangiogenic therapy itself or as a lead compound for the development of analogues with improved activity.
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/11336/153591
Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 251-252
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153591
identifier_str_mv Study of the antiangiogenic effect of a terthiophene isolated from Tagetes minuta; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 251-252
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://www.medicinabuenosaires.com/indices-de-2010-a-2019/
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.coverage.none.fl_str_mv Internacional
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)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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