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Probing the aurone scaffold against Plasmodium falciparum: design, synthesis and antimalarial activity

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dc.contributor.authorCarrasco, Marta
dc.contributor.authorNewton, Ana
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorGóis, Ana
dc.contributor.authorMachado, Marta
dc.contributor.authorGut, Jiri
dc.contributor.authorNogueira, Fátima
dc.contributor.authorHanscheid, Thomas
dc.contributor.authorGuedes, Rita C.
dc.contributor.authordos Santos, Daniel J.V.A.
dc.contributor.authorRosenthal, Philip J.
dc.contributor.authorMoreira, Rui
dc.date.accessioned2022-02-10T16:52:59Z
dc.date.available2022-02-10T16:52:59Z
dc.date.issued2014
dc.description© 2014 Elsevier Masson SAS. All rights reserved.pt_PT
dc.description.abstractA library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold. Additionally, Mannich-base derivatives, containing a 7-aminomethyl-6-hydroxy substitution pattern at ring A, were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2, two validated targets expressed during the blood stage of P. falciparum infection and functional in digestive vacuole of the parasite. Overall, this study highlight (i) the usefulness of aurones as platforms for synthetic procedures using palladium catalyzed protocols to rapidly deliver lead compounds for further optimization and (ii) the potential of novel aurone derivatives as promising antimalarial compounds.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal) through projects PTDC/SAU-FAR/118459/2010 and Pest-OE/SAL/UI4013/2011. A.S.N. and M.P.C. acknowledge FCT for grants SFRH/BD/41276/2007 and SFRH/BD/61611/2009, respectively. P.J.R. is a Doris Duke Charitable Foundation Distinguished Clinical Scientist.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEuropean Journal of Medicinal Chemistry 80 : 523-534pt_PT
dc.identifier.doi10.1016/j.ejmech.2014.04.076pt_PT
dc.identifier.eissn1768-3254
dc.identifier.issn0223-5234
dc.identifier.urihttp://hdl.handle.net/10451/51215
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationPest-OE/SAL/UI4013/2011pt_PT
dc.relationTowards malaria eradication. A novel approach for multi-targeting the parasite´s life cycle
dc.relationSYNTHESIS AND COMPUTER-ASSISTED DESIGN OF MITOCHONDRIAL ELECTRON TRANSPORT-CHAIN INHIBITORS AS ANTIMALARIAL AGENTS
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/european-journal-of-medicinal-chemistrypt_PT
dc.subjectAuronespt_PT
dc.subjectCross-coupling reactionspt_PT
dc.subjectMalariapt_PT
dc.subjectPlasmodium falciparumpt_PT
dc.titleProbing the aurone scaffold against Plasmodium falciparum: design, synthesis and antimalarial activitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/SAU-FAR/118459/2010
oaire.awardNumberSFRH/BD/41276/2007
oaire.awardNumberSFRH/BD/61611/2009
oaire.awardTitleTowards malaria eradication. A novel approach for multi-targeting the parasite´s life cycle
oaire.awardTitleSYNTHESIS AND COMPUTER-ASSISTED DESIGN OF MITOCHONDRIAL ELECTRON TRANSPORT-CHAIN INHIBITORS AS ANTIMALARIAL AGENTS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-FAR%2F118459%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F41276%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F61611%2F2009/PT
oaire.citation.endPage534pt_PT
oaire.citation.startPage523pt_PT
oaire.citation.titleEuropean Journal of Medicinal Chemistrypt_PT
oaire.citation.volume80pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamSFRH
person.familyNameCarrasco
person.familyNameDiogo Gonçalves
person.familyNameHanscheid
person.familyNameMoreira
person.givenNameMarta
person.givenNameLídia Maria
person.givenNameThomas
person.givenNameRui
person.identifier913375
person.identifierG-7485-2011
person.identifier.ciencia-id5115-5F8B-11F3
person.identifier.ciencia-id7211-22BA-86AD
person.identifier.ciencia-id8B11-E8C0-DFD0
person.identifier.orcid0000-0002-7775-2919
person.identifier.orcid0000-0002-6799-2740
person.identifier.orcid0000-0001-6353-9132
person.identifier.orcid0000-0003-0727-9852
person.identifier.ridE-2971-2016
person.identifier.scopus-author-id35555220500
person.identifier.scopus-author-id7004266513
person.identifier.scopus-author-id7102554088
project.funder.identifierhttp://doi.org/10.13039/501100001871
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
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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