Chromen-based TNF-α converting enzyme (TACE) inhibitors: Design, synthesis, and biological evaluation

A series of coumarin types MMP inhibitors were designed based on gelastatin hydroxamates (1) and evaluated for TACE, cellular TNF-α, and NO inhibitory activities. Among them, compounds 9b had potent inhibitory activities in enzymatic and cellular assays and good selectivity to MMP-2 and MMP-9. Further investigation of 9b will be carried out for its efficacy in RA animal model system.

Novel coumarin derivatives exhibited potent inhibitory activity profiles against TACE, MMP-2, and MMp-9 with good selectivity.Figure optionsDownload as PowerPoint slide