Design, synthesis and preliminary evaluation of α-sulfonyl γ-(glycinyl-amino)proline peptidomimetics as matrix metalloproteinase inhibitors

A series of novel α-sulfonyl γ-(glycinyl-amino)proline peptidomimetic derivatives were designed, synthesized and assayed for their activities against matrix metalloproteinase-2 (MMP-2), aminopeptidase N (APN)/CD13 and HDACs. The results indicated that all the compounds exhibited highly selective inhibition against MMP-2 as compared with APN and HDACs. The antiproliferative activities of some compounds against SKOV3, HL60 and A549 cells were also investigated. Comparing with the control LY52, compound 12u, with excellent activity both in the enzymatic inhibition assay and cell-based assay, could be used as lead compound for the further development of MMP inhibitors.

A series of novel α-sulfonyl γ-(glycinyl-amino)proline peptidomimetic derivatives were synthesized and evaluated for their in vitro enzymatic inhibitory activities against MMP-2. Compound 12u had the most potent inhibitory activity against MMP-2 with the IC50 of 0.27 ± 0.02 μM.Figure optionsDownload as PowerPoint slide