Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties

Autores
Riafrecha, Leonardo Ezequiel; Bua, Silvia; Supuran, Claudiu T.; Colinas, Pedro Alfonso
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
One of the most successful approaches for designing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was denominated ‘the sugar approach’. The sugar approach consists in attaching different carbohydrates to CA inhibiting pharmacophores for modulating the physicochemical properties of these pharmacological agents. In line with this approach, in this paper, we present a new class of C-glycosides incorporating the sulfamoylphenyl moiety. These compounds have been prepared by sulfamoylation of C-glycosyl phenols, which have been synthetized by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. The inhibition profile of the new glycomimetics was determined against four human (h) CA isozymes, comprising hCAs I and II (cytosolic, ubiquitous isozymes), hCA IV and hCA IX (tumor associated isozyme). Peracetylated and deprotected C-glycosyl sulfamates showed better inhibition selectivity compared to structurally related phenylsulfamates. In this study, deprotected compound 12 was identified as selective inhibitor of hCA IX. These results confirm that attaching carbohydrate moieties to CA sulfamoylphenyl pharmacophore improves its inhibitory activity.
Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
CARBONIC aNHYDRASES
C-GLYCOSYL SULFAMATES
CARBOHYDRATE
PHARMACOPHORE
PHARMACOPHORE
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:11336/99690
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moietiesRiafrecha, Leonardo EzequielBua, SilviaSupuran, Claudiu T.Colinas, Pedro AlfonsoCARBONIC aNHYDRASESC-GLYCOSYL SULFAMATESCARBOHYDRATEPHARMACOPHOREPHARMACOPHOREhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1One of the most successful approaches for designing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was denominated ‘the sugar approach’. The sugar approach consists in attaching different carbohydrates to CA inhibiting pharmacophores for modulating the physicochemical properties of these pharmacological agents. In line with this approach, in this paper, we present a new class of C-glycosides incorporating the sulfamoylphenyl moiety. These compounds have been prepared by sulfamoylation of C-glycosyl phenols, which have been synthetized by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. The inhibition profile of the new glycomimetics was determined against four human (h) CA isozymes, comprising hCAs I and II (cytosolic, ubiquitous isozymes), hCA IV and hCA IX (tumor associated isozyme). Peracetylated and deprotected C-glycosyl sulfamates showed better inhibition selectivity compared to structurally related phenylsulfamates. In this study, deprotected compound 12 was identified as selective inhibitor of hCA IX. These results confirm that attaching carbohydrate moieties to CA sulfamoylphenyl pharmacophore improves its inhibitory activity.Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAcademic Press Inc Elsevier Science2018-02info: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/11336/99690Riafrecha, Leonardo Ezequiel; Bua, Silvia; Supuran, Claudiu T.; Colinas, Pedro Alfonso; Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 76; 2-2018; 61-660045-2068CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0045206817306387info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioorg.2017.10.020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:02:38Zoai:ri.conicet.gov.ar:11336/99690instacron: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:34982025-09-10 13:02:39.219CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
title Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
spellingShingle Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
Riafrecha, Leonardo Ezequiel
CARBONIC aNHYDRASES
C-GLYCOSYL SULFAMATES
CARBOHYDRATE
PHARMACOPHORE
PHARMACOPHORE
title_short Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
title_full Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
title_fullStr Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
title_full_unstemmed Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
title_sort Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties
dc.creator.none.fl_str_mv Riafrecha, Leonardo Ezequiel
Bua, Silvia
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author Riafrecha, Leonardo Ezequiel
author_facet Riafrecha, Leonardo Ezequiel
Bua, Silvia
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author_role author
author2 Bua, Silvia
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author2_role author
author
author
dc.subject.none.fl_str_mv CARBONIC aNHYDRASES
C-GLYCOSYL SULFAMATES
CARBOHYDRATE
PHARMACOPHORE
PHARMACOPHORE
topic CARBONIC aNHYDRASES
C-GLYCOSYL SULFAMATES
CARBOHYDRATE
PHARMACOPHORE
PHARMACOPHORE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv One of the most successful approaches for designing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was denominated ‘the sugar approach’. The sugar approach consists in attaching different carbohydrates to CA inhibiting pharmacophores for modulating the physicochemical properties of these pharmacological agents. In line with this approach, in this paper, we present a new class of C-glycosides incorporating the sulfamoylphenyl moiety. These compounds have been prepared by sulfamoylation of C-glycosyl phenols, which have been synthetized by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. The inhibition profile of the new glycomimetics was determined against four human (h) CA isozymes, comprising hCAs I and II (cytosolic, ubiquitous isozymes), hCA IV and hCA IX (tumor associated isozyme). Peracetylated and deprotected C-glycosyl sulfamates showed better inhibition selectivity compared to structurally related phenylsulfamates. In this study, deprotected compound 12 was identified as selective inhibitor of hCA IX. These results confirm that attaching carbohydrate moieties to CA sulfamoylphenyl pharmacophore improves its inhibitory activity.
Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description One of the most successful approaches for designing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was denominated ‘the sugar approach’. The sugar approach consists in attaching different carbohydrates to CA inhibiting pharmacophores for modulating the physicochemical properties of these pharmacological agents. In line with this approach, in this paper, we present a new class of C-glycosides incorporating the sulfamoylphenyl moiety. These compounds have been prepared by sulfamoylation of C-glycosyl phenols, which have been synthetized by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. The inhibition profile of the new glycomimetics was determined against four human (h) CA isozymes, comprising hCAs I and II (cytosolic, ubiquitous isozymes), hCA IV and hCA IX (tumor associated isozyme). Peracetylated and deprotected C-glycosyl sulfamates showed better inhibition selectivity compared to structurally related phenylsulfamates. In this study, deprotected compound 12 was identified as selective inhibitor of hCA IX. These results confirm that attaching carbohydrate moieties to CA sulfamoylphenyl pharmacophore improves its inhibitory activity.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
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/11336/99690
Riafrecha, Leonardo Ezequiel; Bua, Silvia; Supuran, Claudiu T.; Colinas, Pedro Alfonso; Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 76; 2-2018; 61-66
0045-2068
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99690
identifier_str_mv Riafrecha, Leonardo Ezequiel; Bua, Silvia; Supuran, Claudiu T.; Colinas, Pedro Alfonso; Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl pharmacophore by attachment of carbohydrate moieties; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 76; 2-2018; 61-66
0045-2068
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.sciencedirect.com/science/article/pii/S0045206817306387
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioorg.2017.10.020
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 Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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
_version_ 1842980031123423232
score 12.993085

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