Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata

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dc.citation.volume174
dc.contributor.authorde Sousa, Carolina Bruno
dc.contributor.authorGangadhar, Katkam N.
dc.contributor.authorMorais, Thiago R. [UNIFESP]
dc.contributor.authorConserva, Geanne A. A. [UNIFESP]
dc.contributor.authorVizetto-Duarte, Catarina
dc.contributor.authorPereira, Hugo
dc.contributor.authorLaurenti, Marcia D.
dc.contributor.authorCampino, Lenea
dc.contributor.authorLevy, Debora
dc.contributor.authorUemi, Miriam [UNIFESP]
dc.contributor.authorBarreira, Luisa
dc.contributor.authorCustodio, Luisa
dc.contributor.authorPassero, Luiz Felipe D.
dc.contributor.authorLago, Joao Henrique G. [UNIFESP]
dc.contributor.authorVarela, Joao
dc.coverageSan Diego
dc.date.accessioned2020-07-17T14:02:46Z
dc.date.available2020-07-17T14:02:46Z
dc.date.issued2017
dc.description.abstractThe development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.en
dc.description.affiliationUniv Algarve, Ctr Ciencias Mar, Campus Gambelas, P-8005139 Faro, Portugal
dc.description.affiliationUniv Nova Lisboa, Inst Tecnol Quim & Biol, Oeiras, Portugal
dc.description.affiliationUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, BR-09972270 Diadema, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Dept Patol, Lab Patol Molestias Infecciosas LIM 50, Sao Paulo, Brazil
dc.description.affiliationUniv Nova Lisboa, Global Hlth & Trop Med Ctr, Inst Higiene & Med Trop, Lisbon, Portugal
dc.description.affiliationUniv Algarve, Dept Ciencias Biomed & Med, Campus Gambelas, Faro, Portugal
dc.description.affiliationUniv Sao Paulo, Fac Med, Dept Clin Med, Lab Genet & Hematol Mol LIM 31, Sao Paulo, Brazil
dc.description.affiliationSao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, BR-09972270 Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipPortuguese FCT
dc.description.sponsorshipFAPESP
dc.description.sponsorshipCNPq
dc.description.sponsorshipFCT doctoral grants
dc.description.sponsorshipFCT Investigator Programme
dc.description.sponsorshipIDPortuguese FCT: PTDC/MAR/103957/2008
dc.description.sponsorshipIDPortuguese FCT: CCMAR/Multi/04326/2013
dc.description.sponsorshipIDFAPESP: 2013/16297-2
dc.description.sponsorshipIDFAPESP: 2015/11936-2
dc.description.sponsorshipIDCNPq: 470853/2012-3
dc.description.sponsorshipIDFCT doctoral grants: SFRH/BD/78062/2011
dc.description.sponsorshipIDFCT doctoral grants: SFRH/BD/81425/2011
dc.description.sponsorshipIDFCT doctoral grants: SFRH/BD/105541/2014
dc.description.sponsorshipIDFCT doctoral grants: SFRH/BPD/81882/2011
dc.description.sponsorshipIDFCT Investigator Programme: IF/00049/2012
dc.format.extent1-9
dc.identifierhttp://dx.doi.org/10.1016/j.exppara.2017.01.002
dc.identifier.citationExperimental Parasitology. San Diego, v. 174, p. 1-9, 2017.
dc.identifier.doi10.1016/j.exppara.2017.01.002
dc.identifier.issn0014-4894
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55008
dc.identifier.wosWOS:000396381600001
dc.language.isoeng
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofExperimental Parasitology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectLeishmania infantumen
dc.subjectMacroalgaeen
dc.subjectCystoseira baccataen
dc.subjectMeroterpenoidsen
dc.subjectTetraprenyltoluquinolen
dc.subjectTetraprenyltoluquinoneen
dc.titleAntileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccataen
dc.typeinfo:eu-repo/semantics/article
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