Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new...

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Autores: Mazzotta, Sarah, Berastegui-Cabrera, Judith, Vega-Holm, Margarita, García-Lozano, María del Rosario, Carretero-Ledesma, Marta, Aiello, Francesca, Vega-Pérez, José Manuel, Pachón, Jerónimo, Iglesias-Guerra, Fernando, Sánchez-Céspedes, Javier
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/265548
Acesso em linha:http://hdl.handle.net/10261/265548
Access Level:acceso abierto
Palavra-chave:Adenovirus
Antiviral drugs
Aminoalcohol
Ester
Carbamate
Triazole
Urea
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spelling Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediolMazzotta, SarahBerastegui-Cabrera, JudithVega-Holm, MargaritaGarcía-Lozano, María del RosarioCarretero-Ledesma, MartaAiello, FrancescaVega-Pérez, José ManuelPachón, JerónimoIglesias-Guerra, FernandoSánchez-Céspedes, JavierAdenovirusAntiviral drugsAminoalcoholEsterCarbamateTriazoleUreaNowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication.This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos - Proyectos I + D + i (PID2019-104767RB-I00); Ministerio de Economía y Competitividad, Plan Nacional I + D + i 2013-2016, Retos-Proyectos (CTQ2016-78580-C2-2-R); Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía.ElsevierMinisterio de Ciencia, Innovación y Universidades (España)Ministerio de Economía y Competitividad (España)Instituto de Salud Carlos IIIMinisterio de Economía, Industria y Competitividad (España)Red Española de Investigación en Patología InfecciosaEuropean CommissionSpanish Adenovirus NetworkJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/265548reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104767RB-I00info:eu-repo/grantAgreement/MINECO//CTQ2016-78580-C2-2-Rinfo:eu-repo/grantAgreement/MINECO//BIO2015-68990-REDThttp://dx.doi.org/10.1016/j.bioorg.2021.105095Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2655482026-05-22T06:33:51Z
dc.title.none.fl_str_mv Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
title Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
spellingShingle Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
Mazzotta, Sarah
Adenovirus
Antiviral drugs
Aminoalcohol
Ester
Carbamate
Triazole
Urea
title_short Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
title_full Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
title_fullStr Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
title_full_unstemmed Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
title_sort Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
dc.creator.none.fl_str_mv Mazzotta, Sarah
Berastegui-Cabrera, Judith
Vega-Holm, Margarita
García-Lozano, María del Rosario
Carretero-Ledesma, Marta
Aiello, Francesca
Vega-Pérez, José Manuel
Pachón, Jerónimo
Iglesias-Guerra, Fernando
Sánchez-Céspedes, Javier
author Mazzotta, Sarah
author_facet Mazzotta, Sarah
Berastegui-Cabrera, Judith
Vega-Holm, Margarita
García-Lozano, María del Rosario
Carretero-Ledesma, Marta
Aiello, Francesca
Vega-Pérez, José Manuel
Pachón, Jerónimo
Iglesias-Guerra, Fernando
Sánchez-Céspedes, Javier
author_role author
author2 Berastegui-Cabrera, Judith
Vega-Holm, Margarita
García-Lozano, María del Rosario
Carretero-Ledesma, Marta
Aiello, Francesca
Vega-Pérez, José Manuel
Pachón, Jerónimo
Iglesias-Guerra, Fernando
Sánchez-Céspedes, Javier
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
Ministerio de Economía, Industria y Competitividad (España)
Red Española de Investigación en Patología Infecciosa
European Commission
Spanish Adenovirus Network
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Adenovirus
Antiviral drugs
Aminoalcohol
Ester
Carbamate
Triazole
Urea
topic Adenovirus
Antiviral drugs
Aminoalcohol
Ester
Carbamate
Triazole
Urea
description Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/265548
url http://hdl.handle.net/10261/265548
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104767RB-I00
info:eu-repo/grantAgreement/MINECO//CTQ2016-78580-C2-2-R
info:eu-repo/grantAgreement/MINECO//BIO2015-68990-REDT
http://dx.doi.org/10.1016/j.bioorg.2021.105095
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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