Anti-inflammatory effects of an optimized PPAR-γ agonist via NF-κB pathway inhibition.

•New PPAR-γ ligands were designed based on (+)-(R,E)-6a1.•Synthetic analogs were evaluated for PPAR-γ activation by luciferase reporter assay.•Synthetic analogs were evaluated for stability to enzymatic hydrolysis using porcine liver esterase.•Compound (+)-(R,E)-5f showed potent in vitro anti-inflammatory activity via inhibition of the NF-κB pathway.