Separation and peroxisome proliferator-activated receptor-γ agonist activity evaluation of synthetic racemic bavachinin enantiomers.

Abstract

Bavachinin, isolated from Psoralea corylifolia seeds, has been reported to demonstrate peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist activity. However, isolated bavachinin is actually a mixture of S and R configurations, with an enantiomeric excess value of approximately 24.3%. For further study on the structure-activity relationships of bavachinin, investigating the PPAR-γ agonist activity of the two enantiomers is crucial. Considering the limited availability, racemic bavachinin was prepared in this study using chemical synthesis. The enantiomers of racemic bavachinin were then separated using supercritical fluid chromatography. This concise strategy yielded (S)- and (R)-bavachinin in optical purity as high as ⩾97.5%. The PPAR-γ agonist activity of the two enantiomers was evaluated using a time-resolved fluorescence resonance energy transfer-based competitive binding assay method; IC50 values of (S)- and (R)-bavachinin were 616.7 and 471.2 nM, respectively. The interaction between the compounds and PPAR-γ was further explored using a molecular docking method. This study suggests that (S)- and (R)-bavachinin demonstrate similar PPAR-γ agonist activities.