Novel imaging agents for β-amyloid plaque based on the N-benzoylindole core

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5594-7. doi: 10.1016/j.bmcl.2011.06.077. Epub 2011 Jul 7.

Abstract

We report the synthesis and evaluation of a series of N-benzoylindole derivatives as novel potential imaging agents for β-amyloid plaques. In vitro binding studies using Aβ(1-40) aggregates versus [(125)I]TZDM showed that all these derivatives demonstrated high binding affinities (K(i) values ranged from 8.4 to 121.6 nM). Moreover, two radioiodinated compounds [(125)I]7 and [(125)I]14 were prepared. Autoradiography for [(125)I]14 displayed intense and specific labeling of Aβ plaques in the brain sections of AD model mice (C57, APP/PS1) with low background. In vivo biodistribution in normal mice exhibited sufficient initial brain uptake for imaging (2.19% and 2.00%ID/g at 2 min postinjection for [(125)I]7 and [(125)I]14, respectively). Although additional modifications are necessary to improve brain uptake and clearance from the brain, the N-benzoylindole may be served as a backbone structure to develop novel β-amyloid imaging probes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Indoles / chemistry
  • Indoles / metabolism
  • Indoles / pharmacokinetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Probes / chemistry
  • Molecular Probes / metabolism
  • Molecular Probes / pharmacokinetics*
  • Molecular Structure
  • Plaque, Amyloid / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Amyloid beta-Peptides
  • Indoles
  • Molecular Probes