A series of aminopeptidase N (APN) inhibitors were designed and synthesized. Enzyme inhibitory,
docking and antiproliferative studies were performed to evaluate the derived molecules.
Molecule D15, with IC50 values of 10.9 μM, showed the best performance in the APN enzymatic inhibition
assay. The binding pattern of molecule D9 and D15 in the active site of APN was predicted by
docking studies. Hydrophobic and H-bond interactions were discovered to make key roles in the ligand-receptor bindings.
Compared with the previous C7, several molecules such as D9, D14 and D15, exhibited significantly improved activities
in inhibiting the growth of HL-60, ES-2, A549 and PLC cell lines.