Inhibitors of human bitter taste receptors from the five-flavour berry

The human bitter taste 2 receptor member 16 (TAS2R16) is one of 25 class A G-protein-coupled receptors (GPCRs) and responds to a variety of molecules responsible for the bitter taste sensation perceived in humans. TAS2R16 can be activated by β-glucopyranosides, and its activation can be inhibited by probenecid, a synthetic drug compound used to treat gout. In this study we describe naturally derived compounds which can inhibit the activation of TAS2R16 by salicin in vitro . These compounds belong to the lignan class derived from the fruit of Schisandra chinensis , which is commonly known as the five-flavour berry. We further tested other analogs with this lignan scaffold, found their differential inhibitory activities towards TAS2R16 in vitro , and sought to rationalize the activity using molecular docking of these lignans on a computationally modelled structure of TAS2R16. Selected lignans with inhibitory activity against other TAS2Rs reveal sub-millimolar inhibitory activity towards TAS2R10, TAS2R14, and TAS2R43 in cell-based assays. These compounds with demonstrated in vitro inhibition of bitter taste receptors may serve as tool compounds to investigate the molecular mechanisms of hTAS2Rs biology in gustatory and non-gustatory tissues. Dibenzocyclooctadiene lignans inhibit several bitter taste receptors and may be useful compounds in bitterness reduction of functional foods.