Novel aminopeptidase N (APN/CD13) inhibitors derived from 3-phenylalanyl-N'-substituted-2,6-piperidinedione

Bioorg Med Chem. 2010 Aug 15;18(16):5981-7. doi: 10.1016/j.bmc.2010.06.078. Epub 2010 Jun 26.

Abstract

Aminopeptidase N (APN/CD13) over expressed on tumor cells, plays a critical role in tumor invasion, metastasis, and tumor angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel APN inhibitors with 3-phenylalanyl-N'-substituted-2,6-piperidinedione scaffold. The results showed that compound 7c had the most potent inhibitory activity against APN with the IC(50) value to 5.00 +/-3.17 microM, which could be used as the lead compound in the future for anticancer agent research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / metabolism
  • Cell Proliferation / drug effects
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neoplasms / drug therapy
  • Phenylalanine / chemical synthesis
  • Phenylalanine / chemistry
  • Piperidones / chemical synthesis
  • Piperidones / chemistry*
  • Piperidones / pharmacology*
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Swine

Substances

  • Antineoplastic Agents
  • Piperidones
  • Protease Inhibitors
  • Phenylalanine
  • CD13 Antigens