RESUMEN
A new angucyclinone antibiotic, frigocyclinone, was isolated from Streptomyces griseus strain NTK 97, consisting of a tetrangomycin moiety attached through a C-glycosidic linkage with the aminodeoxysugar ossamine. Frigocyclinone showed antibacterial activities against Gram-positive bacteria.
Asunto(s)
Antraquinonas/farmacología , Antibacterianos/farmacología , Streptomyces griseus/metabolismo , Regiones Antárticas , Antraquinonas/aislamiento & purificación , Antraquinonas/metabolismo , Antibacterianos/biosíntesis , Antibacterianos/aislamiento & purificación , Fenómenos Químicos , Química Física , Cromatografía Líquida de Alta Presión , Fermentación , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Espectrofotometría UltravioletaRESUMEN
In the course of our screening to identify novel PPAR-gamma modulators for the potential treatment of type 2 diabetes, four new chlorinated angucyclinones, chlorocyclinones A-D ( 1- 4), were isolated from the mycelium of Streptomyces sp. strain DSM 17045. Their structures were established by spectroscopic methods. Chlorocyclinones antagonize rosiglitazone-induced peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation with IC 50's < 0.4 microM in vitro using an AlphaScreen assay and are able to displace rosiglitazone from the PPAR-gamma ligand-binding domain (LBD) in a scintillation proximity assay (SPA). The compounds proved to be active in a cell-based reporter gene assay as well, antagonizing rosiglitazone-induced PPAR-gamma activity with IC 50 values between 0.60 and 7.0 microM. Chlorocyclinone C ( 3) exhibited the most potent activity in all assays.