Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies

Autores
Salomón, Débora Gisele; Mascaro, Evangelina; Grioli, Silvina Mariela; Ferronato, María Julia; Vitale, Cristian Alejandro; Radivoy, Gabriel Eduardo; Curino, Alejandro Carlos; Facchinetti, Maria Marta
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The active metabolite of vitamin D, 1α, 25 dihydroxyvitamin D3 (calcitriol) is classically known to regulate calcium and phosphate homeostasis and bone mineralization. In addition, calcitriol has also been documented to act as a potent anticancer agent in multiple cell culture and animal models of cancer. However, major side effects, such as hypercalcemia, hinder broad-spectrum therapeutic uses of calcitriol in cancer chemotherapy. Synthesis of calcitriol analogues with the same or increased antiproliferative and pro-differentiating activities, and with reduced undesired effects on calcium and bone metabolism, is getting significant attention towards rational therapeutics to treat cancer. In this regard, phosphonate analogues have been shown to display a certain degree of dissociation between the vitamin D activity in vitro and undesired hypercalcemia in vivo. However, few phosphonates have been described in the literature and fewer of them tested for antitumoral effects. Our group has synthesized a novel vitamin D analogue (EM1) bearing an alkynylphosphonate moiety that combines the low calcemic properties of phosphonates with the decreased metabolic inactivation due to the presence of a triple bond between C-23 and C-24. Biological assays demonstrated that this analogue has potent antiproliferative effects in a wide panel of tumour cell lines, even in those resistant to calcitriol treatment. Importantly, EM1 does not show toxic effects in animals, even administered at high doses and for extended periods of time. In the current review we discuss the effects and the potential application in cancer of vitamin D and its derivatives, with an emphasis on phosphonate analogues.
Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Fil: Mascaro, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina
Fil: Grioli, Silvina Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Fil: Vitale, Cristian Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina
Fil: Radivoy, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Materia
Calcitriol
Analogos
Fosfonatos
Antitumoral
Hypercalcemia
Therapy
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:11336/7621
Acceder
id CONICETDig_40e3fd148d7381786019ab898f5f5ae7
oai_identifier_str oai:ri.conicet.gov.ar:11336/7621
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapiesSalomón, Débora GiseleMascaro, EvangelinaGrioli, Silvina MarielaFerronato, María JuliaVitale, Cristian AlejandroRadivoy, Gabriel EduardoCurino, Alejandro CarlosFacchinetti, Maria MartaCalcitriolAnalogosFosfonatosAntitumoralHypercalcemiaTherapyCancerhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The active metabolite of vitamin D, 1α, 25 dihydroxyvitamin D3 (calcitriol) is classically known to regulate calcium and phosphate homeostasis and bone mineralization. In addition, calcitriol has also been documented to act as a potent anticancer agent in multiple cell culture and animal models of cancer. However, major side effects, such as hypercalcemia, hinder broad-spectrum therapeutic uses of calcitriol in cancer chemotherapy. Synthesis of calcitriol analogues with the same or increased antiproliferative and pro-differentiating activities, and with reduced undesired effects on calcium and bone metabolism, is getting significant attention towards rational therapeutics to treat cancer. In this regard, phosphonate analogues have been shown to display a certain degree of dissociation between the vitamin D activity in vitro and undesired hypercalcemia in vivo. However, few phosphonates have been described in the literature and fewer of them tested for antitumoral effects. Our group has synthesized a novel vitamin D analogue (EM1) bearing an alkynylphosphonate moiety that combines the low calcemic properties of phosphonates with the decreased metabolic inactivation due to the presence of a triple bond between C-23 and C-24. Biological assays demonstrated that this analogue has potent antiproliferative effects in a wide panel of tumour cell lines, even in those resistant to calcitriol treatment. Importantly, EM1 does not show toxic effects in animals, even administered at high doses and for extended periods of time. In the current review we discuss the effects and the potential application in cancer of vitamin D and its derivatives, with an emphasis on phosphonate analogues.Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); ArgentinaFil: Mascaro, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Grioli, Silvina Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); ArgentinaFil: Ferronato, María Julia. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); ArgentinaFil: Vitale, Cristian Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Radivoy, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); ArgentinaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); ArgentinaBentham Science Publishers2014-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7621Salomón, Débora Gisele; Mascaro, Evangelina; Grioli, Silvina Mariela; Ferronato, María Julia; Vitale, Cristian Alejandro; et al.; Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies; Bentham Science Publishers; Current Topics In Medicinal Chemistry; 14; 1-11-2014; 2408-24231568-0266enginfo:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/126788/articleinfo:eu-repo/semantics/altIdentifier/url/http://www.ingentaconnect.com/content/ben/ctmc/2014/00000014/00000021/art00007info:eu-repo/semantics/altIdentifier/doi/10.2174/1568026615666141208101418info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:34:11Zoai:ri.conicet.gov.ar:11336/7621instacron: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:34982025-10-15 15:34:11.705CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
title Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
spellingShingle Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
Salomón, Débora Gisele
Calcitriol
Analogos
Fosfonatos
Antitumoral
Hypercalcemia
Therapy
Cancer
title_short Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
title_full Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
title_fullStr Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
title_full_unstemmed Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
title_sort Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies
dc.creator.none.fl_str_mv Salomón, Débora Gisele
Mascaro, Evangelina
Grioli, Silvina Mariela
Ferronato, María Julia
Vitale, Cristian Alejandro
Radivoy, Gabriel Eduardo
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author Salomón, Débora Gisele
author_facet Salomón, Débora Gisele
Mascaro, Evangelina
Grioli, Silvina Mariela
Ferronato, María Julia
Vitale, Cristian Alejandro
Radivoy, Gabriel Eduardo
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author_role author
author2 Mascaro, Evangelina
Grioli, Silvina Mariela
Ferronato, María Julia
Vitale, Cristian Alejandro
Radivoy, Gabriel Eduardo
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Calcitriol
Analogos
Fosfonatos
Antitumoral
Hypercalcemia
Therapy
Cancer
topic Calcitriol
Analogos
Fosfonatos
Antitumoral
Hypercalcemia
Therapy
Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The active metabolite of vitamin D, 1α, 25 dihydroxyvitamin D3 (calcitriol) is classically known to regulate calcium and phosphate homeostasis and bone mineralization. In addition, calcitriol has also been documented to act as a potent anticancer agent in multiple cell culture and animal models of cancer. However, major side effects, such as hypercalcemia, hinder broad-spectrum therapeutic uses of calcitriol in cancer chemotherapy. Synthesis of calcitriol analogues with the same or increased antiproliferative and pro-differentiating activities, and with reduced undesired effects on calcium and bone metabolism, is getting significant attention towards rational therapeutics to treat cancer. In this regard, phosphonate analogues have been shown to display a certain degree of dissociation between the vitamin D activity in vitro and undesired hypercalcemia in vivo. However, few phosphonates have been described in the literature and fewer of them tested for antitumoral effects. Our group has synthesized a novel vitamin D analogue (EM1) bearing an alkynylphosphonate moiety that combines the low calcemic properties of phosphonates with the decreased metabolic inactivation due to the presence of a triple bond between C-23 and C-24. Biological assays demonstrated that this analogue has potent antiproliferative effects in a wide panel of tumour cell lines, even in those resistant to calcitriol treatment. Importantly, EM1 does not show toxic effects in animals, even administered at high doses and for extended periods of time. In the current review we discuss the effects and the potential application in cancer of vitamin D and its derivatives, with an emphasis on phosphonate analogues.
Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Fil: Mascaro, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina
Fil: Grioli, Silvina Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Fil: Vitale, Cristian Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina
Fil: Radivoy, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cientificas y T__etilde__cnicas. Centro Cient__itilde__fico Tecnol__otilde__gico Bahia Blanca. Instituto de Investigaciones Bioqu__itilde__micas Bahia Blanca (i); Argentina
description The active metabolite of vitamin D, 1α, 25 dihydroxyvitamin D3 (calcitriol) is classically known to regulate calcium and phosphate homeostasis and bone mineralization. In addition, calcitriol has also been documented to act as a potent anticancer agent in multiple cell culture and animal models of cancer. However, major side effects, such as hypercalcemia, hinder broad-spectrum therapeutic uses of calcitriol in cancer chemotherapy. Synthesis of calcitriol analogues with the same or increased antiproliferative and pro-differentiating activities, and with reduced undesired effects on calcium and bone metabolism, is getting significant attention towards rational therapeutics to treat cancer. In this regard, phosphonate analogues have been shown to display a certain degree of dissociation between the vitamin D activity in vitro and undesired hypercalcemia in vivo. However, few phosphonates have been described in the literature and fewer of them tested for antitumoral effects. Our group has synthesized a novel vitamin D analogue (EM1) bearing an alkynylphosphonate moiety that combines the low calcemic properties of phosphonates with the decreased metabolic inactivation due to the presence of a triple bond between C-23 and C-24. Biological assays demonstrated that this analogue has potent antiproliferative effects in a wide panel of tumour cell lines, even in those resistant to calcitriol treatment. Importantly, EM1 does not show toxic effects in animals, even administered at high doses and for extended periods of time. In the current review we discuss the effects and the potential application in cancer of vitamin D and its derivatives, with an emphasis on phosphonate analogues.
publishDate 2014
dc.date.none.fl_str_mv 2014-11-01
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/11336/7621
Salomón, Débora Gisele; Mascaro, Evangelina; Grioli, Silvina Mariela; Ferronato, María Julia; Vitale, Cristian Alejandro; et al.; Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies; Bentham Science Publishers; Current Topics In Medicinal Chemistry; 14; 1-11-2014; 2408-2423
1568-0266
url http://hdl.handle.net/11336/7621
identifier_str_mv Salomón, Débora Gisele; Mascaro, Evangelina; Grioli, Silvina Mariela; Ferronato, María Julia; Vitale, Cristian Alejandro; et al.; Phosphonate analogues of 1, 25 dihydroxyvitamin D3 are promising candidates for antitumoural therapies; Bentham Science Publishers; Current Topics In Medicinal Chemistry; 14; 1-11-2014; 2408-2423
1568-0266
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/126788/article
info:eu-repo/semantics/altIdentifier/url/http://www.ingentaconnect.com/content/ben/ctmc/2014/00000014/00000021/art00007
info:eu-repo/semantics/altIdentifier/doi/10.2174/1568026615666141208101418
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
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 13.22299

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