Novel aminopeptidase N inhibitors derived from antineoplaston AS2–5 (Part I)

Overexpression of zinc-dependent metalloproteinase, aminopeptidase N (APN/CD13), is considered to be involved in the process of tumor invasion and metastasis. Herein we describe the synthesis and in vitro enzymatic inhibition assay of antineoplaston AS2–5 scaffold peptidomimetic compounds. The results demonstrated that most of these l-iso-glutamine derivatives displayed selective inhibitory activity against APN as compared with MMP-2, with IC50 values in the micromole range. The structure–activity relationships were also briefly discussed.

A series of novel l-iso-glutamine derivatives (6a–u) based on the antineoplaston AS2-5 scaffold were synthesized and evaluated for their in vitro enzymatic inhibitory activities against aminopeptidase N (APN) and MMP-2.Figure optionsDownload as PowerPoint slide