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New anionic poly(alkylideneamine) dendrimers as microbicide agents against HIV-1 infection

2019-05-16Journal article Restricted access
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dc.contributor.authorMaciel, Dina
dc.contributor.authorGuerrero-Beltrán, Carlos
dc.contributor.authorCeña-Diez, Rafael
dc.contributor.authorTomás, Helena
dc.contributor.authorMuñoz-Fernández, M. Ángeles
dc.contributor.authorRodrigues, João
dc.date.accessioned2019-06-28T14:06:30Z
dc.date.available2019-06-28T14:06:30Z
dc.date.issued2019-05-16
dc.description.abstractAcquired immune deficiency syndrome (AIDS) due to human immunodeficiency virus type-1 (HIV-1) represents one of the most important sexually transmitted infections (STI) worldwide. Great international efforts have been made to stop new infections but, to date, several compounds failed as microbicides at different stages of clinical trials. The quest to design new molecules that could prevent these infections is essential. In this work, we synthesized the first, second and third generations of anionic dendrimers having carboxylate and sulfonate terminal groups, respectively named G1C, G2C, G3C and G1S, G2S, and G3S, starting from a family of poly(alkylideneamine) dendrimers with nitrile termini. The anionic terminal groups of these dendrimers were expected to prompt them to act against HIV-1 infection. All dendrimers were fully characterized by 1H- and 13C-NMR, FTIR, MS and zeta potential techniques. Importantly, they were able to remain stable in the solid state and aqueous solutions at least for one and a half years. Screening of these six new dendrimers was then performed to shed light on their potential anti-HIV-1 activity and their mechanism of action. Results showed that the dendrimers were cytocompatible and that G1C and G1S dendrimers had important activity against R5-HIV-1NLAD8 and X4-HIV-1NL4.3 isolates by acting directly on viral particles and blocking their entry in host cells. Additionally, G1C and G1S dendrimers maintained their inhibitory effect at different pH values. Through a vaginal irritation assay carried out in BALB/c mice, the safety of these new dendrimers for topical application was also shown. Taken together, our results clearly show that G1C and G1S dendrimers are strong candidates for developing an effective microbicide to prevent HIV-1 new infections.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMaciel, D., Guerrero-Beltrán, C., Ceña-Diez, R., Tomás, H., Muñoz-Fernández, M. Á., & Rodrigues, J. (2019). New anionic poly (alkylideneamine) dendrimers as microbicide agents against HIV-1 infection. Nanoscale.pt_PT
dc.identifier.doi10.1039/c9nr00303gpt_PT
dc.identifier.issn2040-3364
dc.identifier.urihttp://hdl.handle.net/10400.13/2445
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherRoyal Society of Chemistrypt_PT
dc.relationMetallodendrimers as HIV antiviral and anticancer agents.
dc.subjectAnionic poly(alkylideneamine) dendrimerspt_PT
dc.subjectDendrimerspt_PT
dc.subjectMicrobicide agentspt_PT
dc.subjectHIV-1 infectionpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.subjectCentro de Química da Madeira
dc.titleNew anionic poly(alkylideneamine) dendrimers as microbicide agents against HIV-1 infectionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMetallodendrimers as HIV antiviral and anticancer agents.
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F00674%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F102123%2F2014/PT
oaire.citation.endPage9690pt_PT
oaire.citation.startPage9679pt_PT
oaire.citation.titleNanoscalept_PT
oaire.citation.volume11(19)pt_PT
oaire.fundingStream5876
oaire.fundingStreamOE
person.familyNameMaciel
person.familyNameTomás
person.familyNameMuñoz-Fernández
person.familyNameRodrigues
person.givenNameDina
person.givenNameHelena
person.givenNameMª Ángeles
person.givenNameJoão
person.identifier556975
person.identifier548431
person.identifier.ciencia-id211C-6048-FB1A
person.identifier.ciencia-id4D14-D31E-A8BE
person.identifier.ciencia-id361C-ABDD-87F4
person.identifier.ciencia-idA81C-620E-DD6A
person.identifier.orcid0000-0001-8684-6100
person.identifier.orcid0000-0002-7856-2041
person.identifier.orcid0000-0002-0813-4500
person.identifier.orcid0000-0003-4552-1953
person.identifier.ridE-5991-2010
person.identifier.ridB-6816-2008
person.identifier.scopus-author-id54781586200
person.identifier.scopus-author-id6508104177
person.identifier.scopus-author-id25931106800
person.identifier.scopus-author-id9233278800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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