Design, synthesis, and evaluation of new type of L-amino acids containing pyridine moiety as nitric oxide synthase inhibitor

Bioorg Med Chem. 2006 May 15;14(10):3563-70. doi: 10.1016/j.bmc.2006.01.020. Epub 2006 Feb 8.

Abstract

New amino acids 7-12 were designed and synthesized as candidate inhibitors of human nitric oxide synthase (NOS). The 2-aminopyridine-containing l-amino acids 8 had potent inhibitory activity toward all of the human NOS isozymes. However, the regioisomers 9 and 10, and 2-methylpyridine-containing compound 11 had much lower inhibitory activity. Human NOS isozymes were also inhibited by 7, which lacks an amino group on the pyridine moiety. A computational docking study was carried out to investigate the mechanism of the inhibitory effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis
  • Amino Acids / chemistry*
  • Amino Acids / pharmacology*
  • Animals
  • Cell Line
  • Computer Simulation
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Models, Molecular
  • Molecular Structure
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Protein Conformation
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Enzyme Inhibitors
  • Isoenzymes
  • Pyridines
  • Recombinant Proteins
  • Nitric Oxide Synthase