Novel inhibitors of neuronal nitric oxide synthase with potent antioxidant properties

Bioorg Med Chem Lett. 2003 Jan 20;13(2):209-12. doi: 10.1016/s0960-894x(02)00883-1.

Abstract

A series of hybrid compounds possessing an nNOS pharmacophore linked to an antioxidant fragment has been synthesized. Among them, compound 8d, a propofol derivative, displayed the greatest dual potencies against nNOS (IC(50)=0.12 microM) and lipid peroxidation (IC(50)=0.4 microM) accompanied with e/nNOS selectivity (67.5). This shows that nNOS was able to accommodate very bulky groups such as di-tert-butyl or di-iso-propyl phenol in its active site.

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Lipid Peroxidation / drug effects
  • Lipoxygenase Inhibitors / chemical synthesis
  • Lipoxygenase Inhibitors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type III
  • Propofol / analogs & derivatives
  • Propofol / chemical synthesis
  • Propofol / pharmacology
  • Substrate Specificity

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Lipoxygenase Inhibitors
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type III
  • Propofol