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A novel hybrid of chloroquine and primaquine linked by Gold(I) : multitarget and multiphase antiplasmodial agent

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dc.contributor.authorSouza Pereira, Caroline
dc.contributor.authorCosta Quadros, Helenita
dc.contributor.authorMagalhães Moreira, Diogo Rodrigo
dc.contributor.authorCastro, William
dc.contributor.authorSantos de Deus da Silva, Romulo Ivisson
dc.contributor.authorBotelho Pereira Soares, Milena
dc.contributor.authorFontinha, Diana
dc.contributor.authorPrudêncio, Miguel
dc.contributor.authorSchmitz, Vinicius
dc.contributor.authorDos Santos, Hélio F.
dc.contributor.authorGendrot, Mathieu
dc.contributor.authorFonta, Isabelle
dc.contributor.authorMosnier, Joel
dc.contributor.authorPradines, Bruno
dc.contributor.authorNavarro, Maribel
dc.date.accessioned2021-04-06T12:42:01Z
dc.date.available2021-04-06T12:42:01Z
dc.date.issued2020
dc.description© 2020 Wiley‐VCH GmbHpt_PT
dc.description.abstractPlasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmodial candidates. In this work, we present a novel strategy to develop a multitarget metallic hybrid antimalarial agent with possible dual efficacy in both sexual and asexual erythrocytic stages. A hybrid of antimalarial drugs (chloroquine and primaquine) linked by gold(I) was synthesized and characterized by spectroscopic and analytical techniques. The CQPQ-gold(I) hybrid molecule affects essential parasite targets, it inhibits β-hematin formation and interacts moderately with the DNA minor groove. Its interaction with PfTrxR was also examined in computational modeling studies. The CQPQ-gold(I) hybrid displayed an excellent in vitro antimalarial activity against the blood-stage of Plasmodium falciparum and liver-stage of Plasmodium berghei and efficacy in vivo against P. berghei, thereby demonstrating its multiple-stage antiplasmodial activity. This metallic hybrid is a promising chemotherapeutic agent that could act in the treatment, prevention, and transmission of malaria.pt_PT
dc.description.sponsorshipThis work was supported by the Brazilian funding agencies: CAPES(grant no. 23038.006713/2013-88), CNPq (grant no. 305732/2019-6), FAPES grant number APP0088/2016) and Fiocruz/Inova (grant no.1642178247). MP was supported by grant PTDC-SAU-INF-29550-2017 (FCT,Portugal).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationChemMedChem. 2021 Feb 17;16(4):662-678pt_PT
dc.identifier.doi10.1002/cmdc.202000653pt_PT
dc.identifier.eissn1860-7187
dc.identifier.issn1860-7179
dc.identifier.urihttp://hdl.handle.net/10451/47253
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationPTDC-SAU-INF-29550-2017pt_PT
dc.relation.publisherversionhttps://chemistry-europe.onlinelibrary.wiley.com/journal/18607187pt_PT
dc.subjectDNApt_PT
dc.subjectChloroquinept_PT
dc.subjectGoldpt_PT
dc.subjectHemept_PT
dc.subjectMalariapt_PT
dc.subjectPrimaquinept_PT
dc.titleA novel hybrid of chloroquine and primaquine linked by Gold(I) : multitarget and multiphase antiplasmodial agentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage678pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage662pt_PT
oaire.citation.titleChemMedChempt_PT
oaire.citation.volume16pt_PT
person.familyNameFontinha
person.familyNamePrudêncio
person.givenNameDiana
person.givenNameMiguel
person.identifierhttps://scholar.google.pt/citations?user=zduN6wsAAAAJ&hl=pt-PT&oi=ao
person.identifier.ciencia-id6A17-C404-F33B
person.identifier.ciencia-id5511-16ED-48E0
person.identifier.orcid0000-0002-0046-648X
person.identifier.orcid0000-0003-1746-6029
person.identifier.scopus-author-id6603561872
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication4fa5980c-148c-4e44-a818-9e8d09245891
relation.isAuthorOfPublication80e4e74d-bf34-4a71-8530-cc3280543b65
relation.isAuthorOfPublication.latestForDiscovery80e4e74d-bf34-4a71-8530-cc3280543b65

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