Chlorocyclinones A−D, Chlorinated Angucyclinones from Streptomyces sp. Strongly Antagonizing Rosiglitazone-Induced PPAR-γ Activation
| Autor: | Olivier Potterat, Stefan Kauschke, Klaus Wagner, Walter Bolek, Regine Vettermann, Carsten H. Puder |
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| Rok vydání: | 2007 |
| Předmět: |
Pharmaceutical Science
Peroxisome proliferator-activated receptor Anthraquinones Streptomyces Analytical Chemistry Rosiglitazone Inhibitory Concentration 50 Drug Discovery Hydrocarbons Chlorinated medicine Humans Luciferases Pharmacology chemistry.chemical_classification Reporter gene Molecular Structure biology Chemistry Organic Chemistry Biological activity biology.organism_classification In vitro PPAR gamma Scintillation proximity assay Diabetes Mellitus Type 2 Complementary and alternative medicine Nuclear receptor Biochemistry Molecular Medicine Thiazolidinediones medicine.drug |
| Zdroj: | Journal of Natural Products. 70:1934-1938 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | 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's0.4 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. |
| Databáze: | OpenAIRE |
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