Synthesis and activity of a new series of (Z)-3-phenyl-2-benzoylpropenoic acid derivatives as aldose reductase inhibitors

Molecules. 2007 Apr 30;12(4):885-95. doi: 10.3390/12040885.

Abstract

During the course of studies directed towards the discovery of novel aldose reductase inhibitors for the treatment of diabetic complications, we synthesized a series of new (Z)-3-phenyl-2-benzoylpropenoic acid derivatives and tested their in vitro inhibitory activities on rat lens aldose reductase. Of these compounds, (Z)-3-(3,4-dihydroxyphenyl)-2-(4-methylbenzoyl)propenoicacid (3k) was identified as the most potent inhibitor, with an IC50 of 0.49 microM. The theoretical binding mode of 3k was obtained by simulation of its docking into the active site of the human aldose reductase crystal structure.

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Aldehyde Reductase / chemistry
  • Amino Acids / chemistry
  • Benzoates / chemistry*
  • Binding Sites
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Inhibitory Concentration 50
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Propionates / chemistry*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Benzoates
  • Enzyme Inhibitors
  • Propionates
  • benzoylpropionic acid
  • AKR1B1 protein, human
  • Aldehyde Reductase