A SAR study on a series of synthetic lipophilic chalcones as Inhibitor of transcription factor NF-κB

► SAR of novel 2,4-dihydroxy-6-isopentyloxychalcone as NF-κB inhibitor was explored. ► Replacement of isopentyl chain with C8-C14 linear alkyls increases the activity. ► Hydroxyl group and its location at 4-position on ring B are important. ► The α,β-unsaturated ketone moiety appears as a crucial motif.