RESUMO
Rocaglamides are bioactive natural compounds which have a cyclopenta[b]benzofuran core structure. The total synthesis of a reported natural product, 3'-hydroxymethylrocaglate (5), was achieved using [3 + 2] cycloaddition between 3-hydroxyflavone and methyl cinnamate. We also describe the synthesis of rocaglamide heterocycle derivatives and evaluate their Wnt signal inhibitory activities. Compounds 4, 5, 22a, 22b, 22c and 23c showed potent Wnt signal inhibitory activity.
Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos , Benzofuranos/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cinamatos/síntese química , Cinamatos/química , Cristalografia por Raios X , Reação de Cicloadição , Flavonoides/síntese química , Flavonoides/química , Células HEK293 , Humanos , Modelos Moleculares , Proteínas Wnt/metabolismoRESUMO
Two new phenazine derivatives, aotaphenazine (1) and 5,10-dihydrophencomycin (2), were isolated from the ethyl acetate extract of Streptomyces sp. IFM 11694. In addition, the known 1-phenazinecarboxylic acid (3), phencomycin (4) and 1,6-phenazinedicarboxylic acid (5) were identified. The structures of the isolated compounds (1-5) were characterized by spectroscopic methods including NMR and mass spectrometry data. Compound 1 showed the ability to overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance at concentration of 12.5 µM. Aotaphenazine (1) enhanced the levels of apoptosis inducing proteins DR4, DR5, p53 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant human gastric adenocarcinoma (AGS) cells in a dose-dependent manner.
