RESUMO
An efficient and divergent methodology for the synthesis of new anthracenone-pyranones and anthracenone-furans is described. Key reactions discussed in these syntheses include an aldehyde promoted annulation with a ß-keto-sulfoxide, a domino alkyne insertion/carbonylation/Nu-acylation and a DMEDA promoted Castro-Stephens reaction. We also report the in vitro growth inhibition of these compounds in a range of human cancer cells. The natural product BE-26554A displayed good cell growth activity on BE2-C neuroblastoma and SMA glioblastoma cell lines at 0.17 and 0.16µM (GI50), respectively. Of note, were a CF3 functionalised anthracenone 4-pyranone (chromone) derivative 22, and an anthracenone-furan derivative 54 which displayed 0.20µM and 0.38µM growth inhibition, respectively, in the BE2-C neuroblastoma cell line.
Assuntos
Antracenos/síntese química , Antineoplásicos/síntese química , Cromonas/síntese química , Furanos/síntese química , Antracenos/farmacologia , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
A domino alkyne addition/CO insertion/Nu acylation reaction to a series of novel anthrapyran-2-ones in good to excellent yields is described. In addition, an efficient synthetic sequence involving carbonylation, formation of a ß-keto-sulfoxide, and cyclization is presented en route to the antibiotic and antitumor compound (±)-BE-26554A.
