Fine-tuning the amphiphilicity: a crucial parameter in the design of potent alpha-phenyl-N-tert-butylnitrone analogues

J Med Chem. 2007 Aug 23;50(17):3976-9. doi: 10.1021/jm0706968. Epub 2007 Jul 25.

Abstract

A new series of hydrophilic, lipophilic, and amphiphilic alpha-phenyl-N-tert-butylnitrone (PBN) derivatives were synthesized to explore the relationship between their hydrophilic-lipophilic properties and antioxidant potency. Very potent protective effects of amphiphilic lactobionamide and tris(hydroxymethyl)aminomethane PBN derivatives were observed in mitochondrial preparations, in cell cultures, and in rotifers exposed to unspecific and mitochondria targeted oxidotoxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cells, Cultured
  • Cyclic N-Oxides / chemistry*
  • Disaccharides / chemical synthesis
  • Disaccharides / chemistry
  • Disaccharides / pharmacology
  • Drug Design
  • Electron Transport Complex I / metabolism
  • In Vitro Techniques
  • Nitrogen Oxides / chemical synthesis*
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / pharmacology
  • Rats
  • Rotifera / drug effects
  • Structure-Activity Relationship
  • Submitochondrial Particles / drug effects
  • Submitochondrial Particles / metabolism
  • Tromethamine / analogs & derivatives
  • Tromethamine / chemical synthesis
  • Tromethamine / chemistry
  • Tromethamine / pharmacology

Substances

  • Antioxidants
  • Cyclic N-Oxides
  • Disaccharides
  • Nitrogen Oxides
  • lactobionamide
  • nitrones
  • Tromethamine
  • phenyl-N-tert-butylnitrone
  • Electron Transport Complex I