Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I)

J Comput Aided Mol Des. 1996 Apr;10(2):100-6. doi: 10.1007/BF00402818.

Abstract

The structural and electronic properties of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters were studied and related to the inhibitory effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential surfaces, dipole moments and molecular geometries were analysed. Based on the conformational analysis and the electronic parameters, a simple model for the active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters was developed, explaining the inhibitory power. The strongest inhibition effects were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic acid diethyl ester 1bab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cattle
  • Computer Simulation
  • Electrochemistry
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Mitochondria, Heart / enzymology
  • Mitochondria, Heart / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure*
  • NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors*
  • NAD(P)H Dehydrogenase (Quinone) / chemistry*
  • Organophosphorus Compounds / chemistry*
  • Organophosphorus Compounds / pharmacology
  • Oxygen Consumption
  • Protein Conformation
  • Software
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Organophosphorus Compounds
  • NAD(P)H Dehydrogenase (Quinone)