Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII

Autores
Riafrecha, Leonardo Ezequiel; Rodríguez, Oscar Mariano; Vullo, Daniela; Supuran, Claudiu T.; Colinas, Pedro Alfonso
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.
Fil: Riafrecha, Leonardo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina
Fil: Rodríguez, Oscar Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina
Fil: Vullo, Daniela. Universita Degli Studi Di Firenze; Italia
Fil: Supuran, Claudiu T.. Universita Degli Studi Di Firenze; Italia
Fil: Colinas, Pedro Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina
Materia
Glycomimetics
Enzyme Inhibitors
Cancer
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:11336/32829
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XIIRiafrecha, Leonardo EzequielRodríguez, Oscar MarianoVullo, DanielaSupuran, Claudiu T.Colinas, Pedro AlfonsoGlycomimeticsEnzyme InhibitorsCancerhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.Fil: Riafrecha, Leonardo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; ArgentinaFil: Rodríguez, Oscar Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; ArgentinaFil: Vullo, Daniela. Universita Degli Studi Di Firenze; ItaliaFil: Supuran, Claudiu T.. Universita Degli Studi Di Firenze; ItaliaFil: Colinas, Pedro Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; ArgentinaPergamon-Elsevier Science Ltd.2014-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32829Rodríguez, Oscar Mariano; Colinas, Pedro Alfonso; Supuran, Claudiu T.; Vullo, Daniela; Riafrecha, Leonardo Ezequiel; Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII; Pergamon-Elsevier Science Ltd.; Bioorganic & Medicinal Chemistry; 22; 19; 8-2014; 5308-53140968-0896CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2014.07.052info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0968089614005768info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:07Zoai:ri.conicet.gov.ar:11336/32829instacron: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 10:02:07.632CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
title Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
spellingShingle Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
Riafrecha, Leonardo Ezequiel
Glycomimetics
Enzyme Inhibitors
Cancer
title_short Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
title_full Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
title_fullStr Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
title_full_unstemmed Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
title_sort Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
dc.creator.none.fl_str_mv Riafrecha, Leonardo Ezequiel
Rodríguez, Oscar Mariano
Vullo, Daniela
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author Riafrecha, Leonardo Ezequiel
author_facet Riafrecha, Leonardo Ezequiel
Rodríguez, Oscar Mariano
Vullo, Daniela
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author_role author
author2 Rodríguez, Oscar Mariano
Vullo, Daniela
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author2_role author
author
author
author
dc.subject.none.fl_str_mv Glycomimetics
Enzyme Inhibitors
Cancer
topic Glycomimetics
Enzyme Inhibitors
Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.
Fil: Riafrecha, Leonardo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina
Fil: Rodríguez, Oscar Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina
Fil: Vullo, Daniela. Universita Degli Studi Di Firenze; Italia
Fil: Supuran, Claudiu T.. Universita Degli Studi Di Firenze; Italia
Fil: Colinas, Pedro Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina
description The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
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/11336/32829
Rodríguez, Oscar Mariano; Colinas, Pedro Alfonso; Supuran, Claudiu T.; Vullo, Daniela; Riafrecha, Leonardo Ezequiel; Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII; Pergamon-Elsevier Science Ltd.; Bioorganic & Medicinal Chemistry; 22; 19; 8-2014; 5308-5314
0968-0896
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32829
identifier_str_mv Rodríguez, Oscar Mariano; Colinas, Pedro Alfonso; Supuran, Claudiu T.; Vullo, Daniela; Riafrecha, Leonardo Ezequiel; Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII; Pergamon-Elsevier Science Ltd.; Bioorganic & Medicinal Chemistry; 22; 19; 8-2014; 5308-5314
0968-0896
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2014.07.052
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0968089614005768
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.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd.
publisher.none.fl_str_mv Pergamon-Elsevier Science 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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