| Abstract
| - In the course of our screening to identify novel PPAR-γ 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-γ) activation with IC50ʼs < 0.4 µM in vitro using an AlphaScreen assay and are able to displace rosiglitazone from the PPAR-γ 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-γ activity with IC50 values between 0.60 and 7.0 µM. Chlorocyclinone C (3) exhibited the most potent activity in all assays.
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