Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?

Autores
Riafrecha, Leonardo Ezequiel; Le Pors, Macarena Soledad; Lavecchia, Martín José; Bua, Silvia; Supuran, Claudiu T.; Colinas, Pedro Alfonso
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
New C-glycosides and a,b-unsaturated ketones incorporating the 4-hydroxy-3-methoxyphenyl (vanillin) moiety as inhibitors of carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated. The inhibition profile of these compounds is presented against four human CA (hCA) isozymes, comprising hCAs I and II (cytosolic, ubiquitous enzymes) and hCAs IX and XII (tumour associated isozymes). Docking analysis of the inhibitors within the active sites of these enzymes has been performed and is discussed, showing that the observed selectivity could be explained in terms of an alternative pocket out of the CA active site where some of these compounds may bind. Several derivatives were identified as selective inhibitors of the tumour-associated hCA IX and XII. Their discovery might be a step in the strategy for finding an effective non-sulfonamide CA inhibitor useful in therapy/diagnosis of hypoxic tumours or other pathologies in which CA isoforms are involved.
Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Le Pors, Macarena Soledad. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Bua, Silvia. Università degli Studi di Firenze; Italia
Fil: Supuran, Claudiu T.. Università degli Studi di Firenze; Italia
Fil: Colinas, Pedro Alfonso. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Materia
VANILLIN
CARBONIC ANHYDRASE
MOLECULAR DOCKING
ENONES
ENZYME INHIBITORS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/155128
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/155128
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?Riafrecha, Leonardo EzequielLe Pors, Macarena SoledadLavecchia, Martín JoséBua, SilviaSupuran, Claudiu T.Colinas, Pedro AlfonsoVANILLINCARBONIC ANHYDRASEMOLECULAR DOCKINGENONESENZYME INHIBITORShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1New C-glycosides and a,b-unsaturated ketones incorporating the 4-hydroxy-3-methoxyphenyl (vanillin) moiety as inhibitors of carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated. The inhibition profile of these compounds is presented against four human CA (hCA) isozymes, comprising hCAs I and II (cytosolic, ubiquitous enzymes) and hCAs IX and XII (tumour associated isozymes). Docking analysis of the inhibitors within the active sites of these enzymes has been performed and is discussed, showing that the observed selectivity could be explained in terms of an alternative pocket out of the CA active site where some of these compounds may bind. Several derivatives were identified as selective inhibitors of the tumour-associated hCA IX and XII. Their discovery might be a step in the strategy for finding an effective non-sulfonamide CA inhibitor useful in therapy/diagnosis of hypoxic tumours or other pathologies in which CA isoforms are involved.Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Le Pors, Macarena Soledad. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Bua, Silvia. Università degli Studi di Firenze; ItaliaFil: Supuran, Claudiu T.. Università degli Studi di Firenze; ItaliaFil: Colinas, Pedro Alfonso. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaTaylor & Francis Ltd2021-10-04info: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/11336/155128Riafrecha, Leonardo Ezequiel; Le Pors, Macarena Soledad; Lavecchia, Martín José; Bua, Silvia; Supuran, Claudiu T.; et al.; Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 36; 1; 4-10-2021; 2118-21271475-6366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/14756366.2021.1982933info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/14756366.2021.1982933info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:45:24Zoai:ri.conicet.gov.ar:11336/155128instacron: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 10:45:25.273CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
title Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
spellingShingle Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
Riafrecha, Leonardo Ezequiel
VANILLIN
CARBONIC ANHYDRASE
MOLECULAR DOCKING
ENONES
ENZYME INHIBITORS
title_short Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
title_full Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
title_fullStr Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
title_full_unstemmed Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
title_sort Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?
dc.creator.none.fl_str_mv Riafrecha, Leonardo Ezequiel
Le Pors, Macarena Soledad
Lavecchia, Martín José
Bua, Silvia
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author Riafrecha, Leonardo Ezequiel
author_facet Riafrecha, Leonardo Ezequiel
Le Pors, Macarena Soledad
Lavecchia, Martín José
Bua, Silvia
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author_role author
author2 Le Pors, Macarena Soledad
Lavecchia, Martín José
Bua, Silvia
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv VANILLIN
CARBONIC ANHYDRASE
MOLECULAR DOCKING
ENONES
ENZYME INHIBITORS
topic VANILLIN
CARBONIC ANHYDRASE
MOLECULAR DOCKING
ENONES
ENZYME INHIBITORS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv New C-glycosides and a,b-unsaturated ketones incorporating the 4-hydroxy-3-methoxyphenyl (vanillin) moiety as inhibitors of carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated. The inhibition profile of these compounds is presented against four human CA (hCA) isozymes, comprising hCAs I and II (cytosolic, ubiquitous enzymes) and hCAs IX and XII (tumour associated isozymes). Docking analysis of the inhibitors within the active sites of these enzymes has been performed and is discussed, showing that the observed selectivity could be explained in terms of an alternative pocket out of the CA active site where some of these compounds may bind. Several derivatives were identified as selective inhibitors of the tumour-associated hCA IX and XII. Their discovery might be a step in the strategy for finding an effective non-sulfonamide CA inhibitor useful in therapy/diagnosis of hypoxic tumours or other pathologies in which CA isoforms are involved.
Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Le Pors, Macarena Soledad. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Bua, Silvia. Università degli Studi di Firenze; Italia
Fil: Supuran, Claudiu T.. Università degli Studi di Firenze; Italia
Fil: Colinas, Pedro Alfonso. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
description New C-glycosides and a,b-unsaturated ketones incorporating the 4-hydroxy-3-methoxyphenyl (vanillin) moiety as inhibitors of carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated. The inhibition profile of these compounds is presented against four human CA (hCA) isozymes, comprising hCAs I and II (cytosolic, ubiquitous enzymes) and hCAs IX and XII (tumour associated isozymes). Docking analysis of the inhibitors within the active sites of these enzymes has been performed and is discussed, showing that the observed selectivity could be explained in terms of an alternative pocket out of the CA active site where some of these compounds may bind. Several derivatives were identified as selective inhibitors of the tumour-associated hCA IX and XII. Their discovery might be a step in the strategy for finding an effective non-sulfonamide CA inhibitor useful in therapy/diagnosis of hypoxic tumours or other pathologies in which CA isoforms are involved.
publishDate 2021
dc.date.none.fl_str_mv 2021-10-04
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/11336/155128
Riafrecha, Leonardo Ezequiel; Le Pors, Macarena Soledad; Lavecchia, Martín José; Bua, Silvia; Supuran, Claudiu T.; et al.; Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 36; 1; 4-10-2021; 2118-2127
1475-6366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/155128
identifier_str_mv Riafrecha, Leonardo Ezequiel; Le Pors, Macarena Soledad; Lavecchia, Martín José; Bua, Silvia; Supuran, Claudiu T.; et al.; Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII: The out of the active site pocket for the design of selective inhibitors?; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 36; 1; 4-10-2021; 2118-2127
1475-6366
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/14756366.2021.1982933
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/14756366.2021.1982933
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis Ltd
publisher.none.fl_str_mv Taylor & Francis Ltd
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

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