Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors

Autores: Laiolo, Jerónimo; Tomasič, Tihomir; Vera, Domingo Mariano Adolfo; González, María L.; Lanza Castronuovo, Priscila Ailin; Gancedo, Samanta Nerea; Hodnik, Žiga; Peterlin Masic, Lucija; Kikelj, Danijel; Carpinella, Maria Cecilia
Año de publicación: 2018
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol (1) used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with 1, eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds 7, 8, and 9 successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.5, and 6.25 μM, respectively. Among a series of analogues of 9, compounds 26–30 were shown to be active, with 26 and 27 causing a significant increase in DOX accumulation from 1.56 μM and rendering Lucena 1 sensitive to DOX from 1.56 and 0.78 μM, respectively. Molecular modeling studies showed that both compounds bind to the P-gp at transmembrane helices (TMH) 4, 5, and 6, with 27 also showing contacts with TMH 3.
Fil: Laiolo, Jerónimo. 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: Tomasič, Tihomir. University of Ljubljana; Eslovenia
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: González, María L.. 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: 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: Gancedo, Samanta Nerea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Hodnik, Žiga. University of Ljubljana; Eslovenia
Fil: Peterlin Masic, Lucija. University of Ljubljana; Eslovenia
Fil: Kikelj, Danijel. University of Ljubljana; Eslovenia
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
Materia: DIETHYLSTILBESTROL DERIVATIVES
MDR REVERSING AGENTS
MOLECULAR DOCKING
P-GLYCOPROTEIN
PINORESINOL
STRUCTURE-ACTIVITY RELATIONSHIP
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/95224

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spelling	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) InhibitorsLaiolo, JerónimoTomasič, TihomirVera, Domingo Mariano AdolfoGonzález, María L.Lanza Castronuovo, Priscila AilinGancedo, Samanta NereaHodnik, ŽigaPeterlin Masic, LucijaKikelj, DanijelCarpinella, Maria CeciliaDIETHYLSTILBESTROL DERIVATIVESMDR REVERSING AGENTSMOLECULAR DOCKINGP-GLYCOPROTEINPINORESINOLSTRUCTURE-ACTIVITY RELATIONSHIPhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol (1) used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with 1, eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds 7, 8, and 9 successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.5, and 6.25 μM, respectively. Among a series of analogues of 9, compounds 26–30 were shown to be active, with 26 and 27 causing a significant increase in DOX accumulation from 1.56 μM and rendering Lucena 1 sensitive to DOX from 1.56 and 0.78 μM, respectively. Molecular modeling studies showed that both compounds bind to the P-gp at transmembrane helices (TMH) 4, 5, and 6, with 27 also showing contacts with TMH 3.Fil: Laiolo, Jerónimo. 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: Tomasič, Tihomir. University of Ljubljana; EsloveniaFil: 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: González, María L.. 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: 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: Gancedo, Samanta Nerea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Hodnik, Žiga. University of Ljubljana; EsloveniaFil: Peterlin Masic, Lucija. University of Ljubljana; EsloveniaFil: Kikelj, Danijel. University of Ljubljana; EsloveniaFil: 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.; ArgentinaAmerican Chemical Society2018-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95224Laiolo, Jerónimo; Tomasič, Tihomir; Vera, Domingo Mariano Adolfo; González, María L.; Lanza Castronuovo, Priscila Ailin; et al.; Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors; American Chemical Society; ACS Medicinal Chemistry Letters; 9; 12; 11-2018; 1186-11921948-5875CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsmedchemlett.8b00324info:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.8b00324info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:45:11Zoai:ri.conicet.gov.ar:11336/95224instacron: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 09:45:12.092CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
title	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
spellingShingle	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors Laiolo, Jerónimo DIETHYLSTILBESTROL DERIVATIVES MDR REVERSING AGENTS MOLECULAR DOCKING P-GLYCOPROTEIN PINORESINOL STRUCTURE-ACTIVITY RELATIONSHIP
title_short	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
title_full	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
title_fullStr	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
title_full_unstemmed	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
title_sort	Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors
dc.creator.none.fl_str_mv	Laiolo, Jerónimo Tomasič, Tihomir Vera, Domingo Mariano Adolfo González, María L. Lanza Castronuovo, Priscila Ailin Gancedo, Samanta Nerea Hodnik, Žiga Peterlin Masic, Lucija Kikelj, Danijel Carpinella, Maria Cecilia
author	Laiolo, Jerónimo
author_facet	Laiolo, Jerónimo Tomasič, Tihomir Vera, Domingo Mariano Adolfo González, María L. Lanza Castronuovo, Priscila Ailin Gancedo, Samanta Nerea Hodnik, Žiga Peterlin Masic, Lucija Kikelj, Danijel Carpinella, Maria Cecilia
author_role	author
author2	Tomasič, Tihomir Vera, Domingo Mariano Adolfo González, María L. Lanza Castronuovo, Priscila Ailin Gancedo, Samanta Nerea Hodnik, Žiga Peterlin Masic, Lucija Kikelj, Danijel Carpinella, Maria Cecilia
author2_role	author author author author author author author author author
dc.subject.none.fl_str_mv	DIETHYLSTILBESTROL DERIVATIVES MDR REVERSING AGENTS MOLECULAR DOCKING P-GLYCOPROTEIN PINORESINOL STRUCTURE-ACTIVITY RELATIONSHIP
topic	DIETHYLSTILBESTROL DERIVATIVES MDR REVERSING AGENTS MOLECULAR DOCKING P-GLYCOPROTEIN PINORESINOL STRUCTURE-ACTIVITY RELATIONSHIP
purl_subject.fl_str_mv	https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv	To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol (1) used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with 1, eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds 7, 8, and 9 successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.5, and 6.25 μM, respectively. Among a series of analogues of 9, compounds 26–30 were shown to be active, with 26 and 27 causing a significant increase in DOX accumulation from 1.56 μM and rendering Lucena 1 sensitive to DOX from 1.56 and 0.78 μM, respectively. Molecular modeling studies showed that both compounds bind to the P-gp at transmembrane helices (TMH) 4, 5, and 6, with 27 also showing contacts with TMH 3. Fil: Laiolo, Jerónimo. 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: Tomasič, Tihomir. University of Ljubljana; Eslovenia 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: González, María L.. 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: 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: Gancedo, Samanta Nerea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: Hodnik, Žiga. University of Ljubljana; Eslovenia Fil: Peterlin Masic, Lucija. University of Ljubljana; Eslovenia Fil: Kikelj, Danijel. University of Ljubljana; Eslovenia 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
description	To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol (1) used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with 1, eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds 7, 8, and 9 successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.5, and 6.25 μM, respectively. Among a series of analogues of 9, compounds 26–30 were shown to be active, with 26 and 27 causing a significant increase in DOX accumulation from 1.56 μM and rendering Lucena 1 sensitive to DOX from 1.56 and 0.78 μM, respectively. Molecular modeling studies showed that both compounds bind to the P-gp at transmembrane helices (TMH) 4, 5, and 6, with 27 also showing contacts with TMH 3.
publishDate	2018
dc.date.none.fl_str_mv	2018-11
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/11336/95224 Laiolo, Jerónimo; Tomasič, Tihomir; Vera, Domingo Mariano Adolfo; González, María L.; Lanza Castronuovo, Priscila Ailin; et al.; Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors; American Chemical Society; ACS Medicinal Chemistry Letters; 9; 12; 11-2018; 1186-1192 1948-5875 CONICET Digital CONICET
url	http://hdl.handle.net/11336/95224
identifier_str_mv	Laiolo, Jerónimo; Tomasič, Tihomir; Vera, Domingo Mariano Adolfo; González, María L.; Lanza Castronuovo, Priscila Ailin; et al.; Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors; American Chemical Society; ACS Medicinal Chemistry Letters; 9; 12; 11-2018; 1186-1192 1948-5875 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://pubs.acs.org/doi/10.1021/acsmedchemlett.8b00324 info:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.8b00324
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
dc.publisher.none.fl_str_mv	American Chemical Society
publisher.none.fl_str_mv	American Chemical Society
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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score	13.070432

Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors

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