Design, Synthesis, and Preliminary Activity Evaluation of Novel Peptidomimetics as Aminopeptidase N/CD13 Inhibitors

Abstract

The synthesis of a series of novel N-α-galloylated isoglutamic acid γ-amide peptidomimetics is described. Their enzymatic inhibition against aminopeptidase N (APN/CD13) and matrix metalloproteinase-2 (MMP-2) was tested. The preliminary activity assay revealed that most of the compounds displayed selective inhibition against APN as compared with MMP-2, with IC(50) values in a micromolar range. Within this series, compound 4 (IC(50) = 10.2 ± 0.9 µM) demonstrated comparable APN inhibition as compared with the positive control bestatin (IC(50) = 13.1 ± 0.7 µM), which might be a promising lead for further molecular optimizations.