Design, synthesis and biological evaluation of novel L-isoserine tripeptide derivatives as aminopeptidase N inhibitors.

Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, one compound 16l (IC₅₀ = 2.51 ± 0.2 µM) showed similar inhibitory effect compared with control compound Bestatin (IC₅₀ = 6.25 ± 0.4 µM) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.