کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1393193 | 1501193 | 2010 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Identification of (β-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor γ activity Identification of (β-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor γ activity](/preview/png/1393193.png)
We applied an improved virtual screening scheme combining ligand-centric and receptor-centric methods for the identification of a new series of PPARγ agonists known as (β-carboxyethyl)-rhodanine derivatives which include a thiazolidin-based core structure, 2-thioxo-thiazolidine-4-one. An in vitro assay confirmed the nanomolar binding affinity in one of the (β-carboxyethyl)-rhodanine derivatives, SP1818. It showed a PPARγ agonistic activity similar to that of a known PPARγ drug, pioglitazone, in a cell-based transactivation assay. Furthermore, the structure–activity relationships of the rhodanine derivatives were investigated through comparative molecular field analysis. We also characterized the inconsistency between the in vitro binding affinity and cell-based transactivation ability by using a set of property-based molecular descriptors. The binding mode analysis provided new insight concerning their agonistic effect on PPARγ.
This rhodanine study presents new findings of derivatives as PPAR agonists and significantly improves the understanding of their SARs.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 45, Issue 1, January 2010, Pages 193–202