Design, synthesis and evaluation of PPAR gamma binding activity of 2-thioxo-4-thiazolidinone derivatives

We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ (PPARγ) binding activities. Through the biological assays, compounds 18 and 38 were highlighted with Ki values of 12.15 nmol/L and 14.46 nmol/L, respectively. Then structure–activity relationship (SAR) was analyzed to screen privileged structural modifications. Moreover, molecular fitting of these compounds onto the approved drug Rosiglitazone in the PPARγ ligand binding domain was performed to elucidate the SAR and explore potential receptor–ligand interactions. These results demonstrate that the 2-thioxo-4-thiazolidinones can be considered as new promising molecular probes with excellent binding activities to PPARγ.

Graphical abstractA series of 2-thioxo-4-thiazolidinone derivatives was designed, synthesized and biologically evaluated for their PPARγ binding activities. We established a molecular docking based SAR model for PPARγ ligand binding domain.Figure optionsDownload full-size imageDownload as PowerPoint slide