Effect of chirality of small molecule organofluorine inhibitors of amyloid self-assembly on inhibitor potency

Bioorg Med Chem Lett. 2009 Dec 15;19(24):6931-4. doi: 10.1016/j.bmcl.2009.10.066. Epub 2009 Oct 21.

Abstract

The effect of enantiomeric trifluoromethyl-indolyl-acetic acid ethyl esters on the fibrillogenesis of Alzheimer's amyloid beta (Abeta) peptide is described. These compounds have been previously identified as effective inhibitors of the Abeta self-assembly in their racemic form. Thioflavin-T Fluorescence Spectroscopy and Atomic Force Microscopy were applied to assess the potency of the chiral target compounds. Both enantiomers showed significant inhibition in the in vitro assays. The potency of the enantiomeric inhibitors appeared to be very similar to each other suggesting the lack of the stereospecific binding interactions between these small molecule inhibitors and the Abeta peptide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Fluorine / chemistry
  • Fluorine / pharmacology*
  • Humans
  • Microscopy, Atomic Force
  • Propionates / chemistry
  • Propionates / pharmacology*
  • Spectrometry, Fluorescence
  • Stereoisomerism

Substances

  • Amyloid beta-Peptides
  • Propionates
  • Fluorine