Nitrocatechols versus nitrocatecholamines as novel competitive inhibitors of neuronal nitric oxide synthase: lack of the aminoethyl side chain determines loss of tetrahydrobiopterin-antagonizing properties

Bioorg Med Chem Lett. 2002 Jan 7;12(1):13-6. doi: 10.1016/s0960-894x(01)00680-1.

Abstract

6-Nitrocatecholamines were recently described as novel neuronal nitric oxide synthase inhibitors competing with both L-arginine and tetrahydrobiopterin (BH(4)). We report now that simple nitrocatechols are also competitive inhibitors, lacking however BH(4)-antagonizing properties. It is argued that 6-nitrocatecholamines interact with the L-arginine- and BH(4)-binding sites through the nitrocatechol and aminoethyl moieties, respectively.

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Arginine / pharmacology
  • Binding Sites
  • Biopterins / analogs & derivatives*
  • Biopterins / chemistry
  • Catecholamines / chemistry*
  • Catecholamines / pharmacology
  • Catechols / chemistry*
  • Catechols / pharmacology
  • Drug Evaluation, Preclinical
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type I
  • Nitro Compounds / chemistry*
  • Nitro Compounds / pharmacology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Catecholamines
  • Catechols
  • Nitro Compounds
  • Protein Isoforms
  • Biopterins
  • Arginine
  • NOS1 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • sapropterin