RESUMO
Southern belles! Simplified analogues of tedanolide, a natural product with picomolar activity against a range of tumor cell lines, were synthesized and evaluated for potency in mammalian cancer cells. The truncated analogues were found to retain significant activity in vitro (23 µmol mL(-1) for the example shown) compared with the parent compound tedanolide (0.33 nmol mL(-1)), and represent potential leads for the development of novel anticancer agents.
Assuntos
Alcenos/síntese química , Compostos de Epóxi/síntese química , Macrolídeos/síntese química , Alcenos/química , Alcenos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Ácidos Graxos Monoinsaturados/síntese química , Ácidos Graxos Monoinsaturados/química , Ácidos Graxos Monoinsaturados/farmacologia , Humanos , Concentração Inibidora 50 , Macrolídeos/química , Macrolídeos/farmacologia , Camundongos , Estrutura Molecular , Neoplasias/tratamento farmacológicoRESUMO
The improved synthesis of the antitumor compound (+)-tedanolide is described through an aldol coupling of bis-ketone 7. This modification shortens the synthetic steps in the endgame and provides rapid access to this biologically important natural product. Additionally, it serves as a probe in order to unravel the conformational effects that impede or enable its successful synthesis. Having this way access to des-epoxy-tedanolide, its biological characterization surprisingly unravelled the mode of action to resemble candidaspongiolide rather than deoxytedanolide.