Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure

Autores
Turk, Gabriela Julia Ana; Fernández Moroni, Guillermo; Pampuro, Sandra Esther; Brión, Margarita C.; Salomon, Horacio Eduardo
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3′-azido-3′-deoxy-5′-O-oxalyl-N-valinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-leucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-isoleucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-phenylalaninethymidine, 3′-azido-3′-deoxy-5′-O-oxalylthymidine acid, 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3′-azido-3′-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.
Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fernández Moroni, Guillermo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pampuro, Sandra Esther. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Brión, Margarita C.. Universidad Nacional de Córdoba; Argentina
Fil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
ANTIRETROVIRAL ACTIVITY
CYTOTOXICITY
HIV
ZIDOVUDINE ANALOGUES
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:11336/162824
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162824
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structureTurk, Gabriela Julia AnaFernández Moroni, GuillermoPampuro, Sandra EstherBrión, Margarita C.Salomon, Horacio EduardoANTIRETROVIRAL ACTIVITYCYTOTOXICITYHIVZIDOVUDINE ANALOGUEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3′-azido-3′-deoxy-5′-O-oxalyl-N-valinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-leucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-isoleucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-phenylalaninethymidine, 3′-azido-3′-deoxy-5′-O-oxalylthymidine acid, 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3′-azido-3′-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Fernández Moroni, Guillermo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pampuro, Sandra Esther. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Brión, Margarita C.. Universidad Nacional de Córdoba; ArgentinaFil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaElsevier Science2002-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162824Turk, Gabriela Julia Ana; Fernández Moroni, Guillermo; Pampuro, Sandra Esther; Brión, Margarita C.; Salomon, Horacio Eduardo; Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure; Elsevier Science; International Journal of Antimicrobial Agents; 20; 4; 10-2002; 282-2880924-8579CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0924857902001917?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0924-8579(02)00191-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:21Zoai:ri.conicet.gov.ar:11336/162824instacron: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 09:44:21.896CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
title Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
spellingShingle Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
Turk, Gabriela Julia Ana
ANTIRETROVIRAL ACTIVITY
CYTOTOXICITY
HIV
ZIDOVUDINE ANALOGUES
title_short Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
title_full Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
title_fullStr Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
title_full_unstemmed Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
title_sort Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
dc.creator.none.fl_str_mv Turk, Gabriela Julia Ana
Fernández Moroni, Guillermo
Pampuro, Sandra Esther
Brión, Margarita C.
Salomon, Horacio Eduardo
author Turk, Gabriela Julia Ana
author_facet Turk, Gabriela Julia Ana
Fernández Moroni, Guillermo
Pampuro, Sandra Esther
Brión, Margarita C.
Salomon, Horacio Eduardo
author_role author
author2 Fernández Moroni, Guillermo
Pampuro, Sandra Esther
Brión, Margarita C.
Salomon, Horacio Eduardo
author2_role author
author
author
author
dc.subject.none.fl_str_mv ANTIRETROVIRAL ACTIVITY
CYTOTOXICITY
HIV
ZIDOVUDINE ANALOGUES
topic ANTIRETROVIRAL ACTIVITY
CYTOTOXICITY
HIV
ZIDOVUDINE ANALOGUES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3′-azido-3′-deoxy-5′-O-oxalyl-N-valinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-leucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-isoleucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-phenylalaninethymidine, 3′-azido-3′-deoxy-5′-O-oxalylthymidine acid, 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3′-azido-3′-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.
Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fernández Moroni, Guillermo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pampuro, Sandra Esther. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Brión, Margarita C.. Universidad Nacional de Córdoba; Argentina
Fil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3′-azido-3′-deoxy-5′-O-oxalyl-N-valinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-leucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-isoleucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-phenylalaninethymidine, 3′-azido-3′-deoxy-5′-O-oxalylthymidine acid, 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3′-azido-3′-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.
publishDate 2002
dc.date.none.fl_str_mv 2002-10
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/11336/162824
Turk, Gabriela Julia Ana; Fernández Moroni, Guillermo; Pampuro, Sandra Esther; Brión, Margarita C.; Salomon, Horacio Eduardo; Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure; Elsevier Science; International Journal of Antimicrobial Agents; 20; 4; 10-2002; 282-288
0924-8579
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162824
identifier_str_mv Turk, Gabriela Julia Ana; Fernández Moroni, Guillermo; Pampuro, Sandra Esther; Brión, Margarita C.; Salomon, Horacio Eduardo; Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure; Elsevier Science; International Journal of Antimicrobial Agents; 20; 4; 10-2002; 282-288
0924-8579
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/abs/pii/S0924857902001917?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/S0924-8579(02)00191-7
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
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv 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
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score 13.070432

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