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

Authors

  • Xun Li,

    1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong Province, P.R. China
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  • Junli Wang,

    1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong Province, P.R. China
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  • Lei Zhang,

    1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong Province, P.R. China
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  • Wenfang Xu

    Corresponding author
    1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong Province, P.R. China
    • School of Pharmaceutical Sciences, Shandong University, No 44 Wenhua Xi Road, Ji'nan, 250012, Shandong Province, P.R. China. Fax: +86-531-88382264.
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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 IC50 values in a micromolar range. Within this series, compound 4 (IC50 = 10.2 ± 0.9 µM) demonstrated comparable APN inhibition as compared with the positive control bestatin (IC50 = 13.1 ± 0.7 µM), which might be a promising lead for further molecular optimizations.

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