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.

中文翻译：

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Chlorocyclinones AD，来自链霉菌属（Streptomyces sp。）的氯化古环霉素。强烈拮抗罗格列酮诱导的PPAR-γ激活。

在我们的筛选过程中，鉴定出可潜在治疗2型糖尿病的新型PPAR-γ调节剂，从链霉菌属菌丝体中分离出了四个新的氯化古环素，氯环素AD（1-4）。菌株DSM17045。其结构通过光谱法确定。氯霉素在体外使用AlphaScreen测定法拮抗罗格列酮诱导的过氧化物酶体增殖物激活受体γ（PPAR-γ）活化，IC 50≤0.4 microM，并且能够在闪烁时将罗格列酮从PPAR-γ配体结合域（LBD）中置换出来邻近分析（SPA）。该化合物还被证明在基于细胞的报告基因分析中也具有活性，可拮抗罗格列酮诱导的PPAR-γ活性，其IC 50值为0.60至7.0 microM。