Proteasome as a New Target for Bio-Inspired Benzo[k,l]xanthene Lignans

Mass spectrometry-based chemical proteomics is apowerful tool in the target discovery of small molecules. Here wepresent the application of this approach to define the target profile ofbio-inspired synthetic benzo[k,l]xanthene lignans, endowed withinteresting biological properties. Proteasome has been identified asa new main interactor for this class of compounds. A combination ofmolecular docking and in vitro and in cell fluorescence assays gaveinsights on the molecular mechanism of interaction, highlighting thethe attitude of these lignans to inhibit the proteasome.