Design, synthesis and evaluation of novel metalloproteinase inhibitors based on l-tyrosine scaffold

Abstract

A series of novel L-tyrosine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and histone deacetylase 8 (HDAC-8). The results showed that these L-tyrosine derivatives exhibited inhibitory profiles against MMP-2 and HDAC-8. The compounds 6h (IC(50)=0.013 ± 0.001 μM) and 6j (IC(50)=0.017 ± 0.001 μM) were equal potent MMP-2 inhibitors to the positive control NNGH (IC(50)=0.014 ± 0.001 μM). As for HDAC-8 inhibition, some of the hydroxamate compounds, such as 6d (IC(50)=3.6 ± 0.2 μM) and 6c (IC(50)=5.8 ± 0.5 μM), were equal potent to the positive control SAHA (IC(50)=1.6 ± 0.1 μM). Structure-activity relationships were also briefly discussed.