The Effect of Halogen-to-Hydrogen Bond Substitution on Human Aldose Reductase Inhibition

ACS Chem Biol. 2015 Jul 17;10(7):1637-42. doi: 10.1021/acschembio.5b00151. Epub 2015 May 6.


The effect of halogen-to-hydrogen bond substitution on the binding energetics and biological activity of a human aldose reductase inhibitor has been studied using X-ray crystallography, IC50 measurements, advanced binding free energy calculations, and simulations. The replacement of Br or I atoms by an amine (NH2) group has not induced changes in the original geometry of the complex, which made it possible to study the isolated features of selected noncovalent interactions in a biomolecular complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Aldehyde Reductase / chemistry
  • Aldehyde Reductase / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Halogenation
  • Humans
  • Hydrogen Bonding
  • Models, Molecular


  • Enzyme Inhibitors
  • Aldehyde Reductase