Gibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum

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dc.citation.issue4
dc.citation.volume26
dc.contributor.authorVarela, Marina T. [UNIFESP]
dc.contributor.authorDias, Roberto Z. [UNIFESP]
dc.contributor.authorMartins, Ligia F.
dc.contributor.authorFerreira, Daiane D.
dc.contributor.authorTempone, Andre G.
dc.contributor.authorUeno, Anderson K. [UNIFESP]
dc.contributor.authorLago, Joao Henrique G. [UNIFESP]
dc.contributor.authorFernandes, Joao Paulo S. [UNIFESP]
dc.coverageOxford
dc.date.accessioned2020-08-21T17:00:23Z
dc.date.available2020-08-21T17:00:23Z
dc.date.issued2016
dc.description.abstractThe essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 mu M against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI = 13.1) and T. cruzi (SI = 4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites. (C) 2016 Elsevier Ltd. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, Brazil
dc.description.affiliationAdolfo Lutz Inst, Ctr Parasitol & Micol, Ave Dr Arnaldo 355, BR-01246902 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCNPq
dc.description.sponsorshipFAPESP
dc.description.sponsorshipIDCNPq: 455411/2014-0
dc.description.sponsorshipIDCNPq: 470853/2012-3
dc.description.sponsorshipIDCNPq: 471458/2012-0
dc.description.sponsorshipIDFAPESP: 2015/11936-2
dc.description.sponsorshipIDFAPESP: 2013/20479-9
dc.description.sponsorshipIDFAPESP: 2012/18756-1
dc.description.sponsorshipIDFAPESP: 2014/16564-3
dc.format.extent1180-1183
dc.identifierhttp://dx.doi.org/10.1016/j.bmcl.2016.01.040
dc.identifier.citationBioorganic & Medicinal Chemistry Letters. Oxford, v. 26, n. 4, p. 1180-1183, 2016.
dc.identifier.doi10.1016/j.bmcl.2016.01.040
dc.identifier.issn0960-894X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57974
dc.identifier.wosWOS:000369377700015
dc.language.isoeng
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofBioorganic & Medicinal Chemistry Letters
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectGibbilimbol Aen
dc.subjectGibbilimbol Ben
dc.subjectNatural product derivativesen
dc.subjectSARen
dc.subjectLeishmanicidalen
dc.subjectTrypanocidalen
dc.titleGibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantumen
dc.typeinfo:eu-repo/semantics/article
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