(-)-tarchonanthuslactone: Design Of New Analogues, Evaluation Of Their Antiproliferative Activity On Cancer Cell Lines, And Preliminary Mechanistic Studies.

dc.creatorToneto Novaes, Luiz Fernando
dc.creatorMartins Avila, Carolina
dc.creatorPelizzaro-Rocha, Karin Juliane
dc.creatorVendramini-Costa, Débora Barbosa
dc.creatorPereira Dias, Marina
dc.creatorBarbosa Trivella, Daniela Barreto
dc.creatorErnesto de Carvalho, João
dc.creatorFerreira-Halder, Carmen Veríssima
dc.creatorPilli, Ronaldo Aloise
dc.date2015-Oct
dc.date2016-05-23T19:41:13Z
dc.date2016-05-23T19:41:13Z
dc.date.accessioned2018-03-29T01:28:44Z
dc.date.available2018-03-29T01:28:44Z
dc.identifierChemmedchem. v. 10, n. 10, p. 1687-1699, 2015-Oct.
dc.identifier1860-7187
dc.identifier10.1002/cmdc.201500246
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/?term=26305900
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/235485
dc.identifier26305900
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1303728
dc.descriptionNatural products containing the α,β-unsaturated δ-lactone skeleton have been shown to possess a variety of biological activities. The natural product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total syntheses of dihydropyran-2-ones modeled on the structure of 1 were undertaken. These compounds were obtained in overall yields of 17-21 % based on the Keck asymmetric allylation reaction and were evaluated in vitro against eight different cultured human tumor cell lines. We further conducted initial investigation into the mechanism of action of selected analogues. Dihydropyran-2-one 8 [(S,E)-(6-oxo-3,6-dihydro-2H-pyran-2-yl)methyl 3-(3,4-dihydroxyphenyl)acrylate], a simplified analogue of (-)-tarchonanthuslactone (1) bearing an additional electrophilic site and a catechol system, was the most cytotoxic and selective compound against six of the eight cancer cell lines analyzed, including the pancreatic cancer cell line. Preliminary studies on the mechanism of action of compound 8 on pancreatic cancer demonstrated that apoptotic cell death takes place mediated by an increase in the level of reactive oxygen species. It appears as though compound 8, possessing two Michael acceptors and a catechol system, may be a promising scaffold for the selective killing of cancer cells, and thus, it deserves further investigation to determine its potential for cancer therapy.
dc.description10
dc.description1687-1699
dc.languageeng
dc.relationChemmedchem
dc.relationChemMedChem
dc.rightsfechado
dc.sourcePubMed
dc.subjectAntitumor Agents
dc.subjectCancer
dc.subjectNatural Products
dc.subjectReactive Oxygen Species
dc.subjectTarchonanthuslactone
dc.title(-)-tarchonanthuslactone: Design Of New Analogues, Evaluation Of Their Antiproliferative Activity On Cancer Cell Lines, And Preliminary Mechanistic Studies.
dc.typeArtículos de revistas


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