Artículos de revistas
(-)-tarchonanthuslactone: Design Of New Analogues, Evaluation Of Their Antiproliferative Activity On Cancer Cell Lines, And Preliminary Mechanistic Studies
Registro en:
(-)-tarchonanthuslactone: Design Of New Analogues, Evaluation Of Their Antiproliferative Activity On Cancer Cell Lines, And Preliminary Mechanistic Studies. Wiley-v C H Verlag Gmbh, v. 10, p. 1687-1699 OCT-2015.
1860-7179
WOS:000362295400009
10.1002/cmdc.201500246
Autor
Toneto Novaes
Luiz Fernando; Avila
Carolina Martins; Pelizzaro-Rocha
Karin Juliane; Vendramini-Costa
Debora Barbosa; Dias
Marina Pereira; Barbosa Trivella
Daniela Barreto; de Carvalho
Joao Ernesto; Ferreira-Halder
Carmen Verissima; Pilli
Ronaldo Aloise
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Natural products containing the alpha,beta-unsaturated delta-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. 10 10
1687 1699 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Institute of Chemistry/UNICAMP Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP [2009/51602-5, 2010/17544-5, 2010/08673-6, 2012/09254-2, 2012/24385-6, 2013/08896-3]