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.
一系列
氨肽酶N(A
PN)
抑制剂的设计与合成得以完成。通过酶抑制、对接和抗增殖研究来评估所得到的分子。分子D15在A
PN酶抑制试验中表现最佳,其IC50值为10.9微摩尔。对接研究发现,分子D9与D15在A
PN活性位点的结合模式得以预测,发现疏
水性和氢键相互作用在
配体与受体结合中发挥了关键作用。与先前的C7相比,多个分子如D9、D14和D15在抑制HL-60、ES-2、A549和PLC
细胞系的生长方面表现出显著提升的活性。