Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides

Several gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to prot...

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Detalles Bibliográficos
Autores: Gutiérrez, Alejandro, Marzo, Isabel, Cativiela, Carlos, Laguna, Antonio, Gimeno, M. Concepción
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/123038
Acceso en línea:http://hdl.handle.net/10261/123038
Access Level:acceso abierto
Palabra clave:Bioconjugation
Cytotoxic activity
Dipeptides
Gold
Medicinal chemistry
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spelling Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptidesGutiérrez, AlejandroMarzo, IsabelCativiela, CarlosLaguna, AntonioGimeno, M. ConcepciónBioconjugationCytotoxic activityDipeptidesGoldMedicinal chemistrySeveral gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh3)] gives the gold-dipeptide-phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR3)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non-proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC50 values in the very low micromolar range. Structure–activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents.The authors thank the Ministerio de Economía y Competitividad (MINECO, FEDER CTQ2013-48635-C2-1-P, CTQ2013-40855-R) and DGA-FSE (E40 and E77) for financial support. A.G. thanks the CSIC for a Jae-Predoc fellowship.Peer reviewedWiley-VCHMinisterio de Economía y Competitividad (España)European CommissionDiputación General de AragónConsejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201520152015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/123038reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2013-48635-C2-1-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2013-40855-Rhttp://dx.doi.org/10.1002/chem.201501458Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1230382026-05-22T06:33:51Z
dc.title.none.fl_str_mv Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
title Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
spellingShingle Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
Gutiérrez, Alejandro
Bioconjugation
Cytotoxic activity
Dipeptides
Gold
Medicinal chemistry
title_short Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
title_full Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
title_fullStr Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
title_full_unstemmed Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
title_sort Highly cytotoxic bioconjugated gold(I) complexes with cysteine-containing dipeptides
dc.creator.none.fl_str_mv Gutiérrez, Alejandro
Marzo, Isabel
Cativiela, Carlos
Laguna, Antonio
Gimeno, M. Concepción
author Gutiérrez, Alejandro
author_facet Gutiérrez, Alejandro
Marzo, Isabel
Cativiela, Carlos
Laguna, Antonio
Gimeno, M. Concepción
author_role author
author2 Marzo, Isabel
Cativiela, Carlos
Laguna, Antonio
Gimeno, M. Concepción
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Diputación General de Aragón
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Bioconjugation
Cytotoxic activity
Dipeptides
Gold
Medicinal chemistry
topic Bioconjugation
Cytotoxic activity
Dipeptides
Gold
Medicinal chemistry
description Several gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh3)] gives the gold-dipeptide-phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR3)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non-proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC50 values in the very low micromolar range. Structure–activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/123038
url http://hdl.handle.net/10261/123038
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#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2013-48635-C2-1-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2013-40855-R
http://dx.doi.org/10.1002/chem.201501458
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-VCH
publisher.none.fl_str_mv Wiley-VCH
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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score 15,811543

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