New PPARγ ligands based on 2-hydroxy-1,4-naphthoquinone: Computer-aided design, synthesis, and receptor-binding studies

FlexX-based molecular docking study was employed to identify 2-hydroxy-1,4-naphthoquinone as a new ‘acidic head group’ for the design of a novel series of PPARγ ligands. To provide the proof of concept, designed molecules were synthesized and evaluated in a standard radioligand-binding assay. Out of eight molecules, four were found to bind to the murine PPARγ with IC50 ranging from 0.2 to 56.2 μM as compared to standard pioglitazone, with IC50 of 0.7 μM.

Graphical abstract2-Hydroxy-1,4-naphthoquinone was identified as a novel ‘acidic head group’ for the design of new series PPARγ ligands using docking studies. Synthesis and receptor-binding studies were used to validate the concept.Figure optionsDownload full-size imageDownload as PowerPoint slide