2-Phenylbenzofuran derivatives alleviate mitochondrial damage via the inhibition of β-amyloid aggregation

Bioorg Med Chem Lett. 2013 Nov 1;23(21):5882-6. doi: 10.1016/j.bmcl.2013.08.087. Epub 2013 Sep 3.

Abstract

To obtain modulators for reducing mitochondrial damage by the inhibition of Aβ oligomer formation, 2-phenylbenzofuran derivatives were designed and prepared. Their inhibitory activity against Aβ fibril formation was screened using ThT fluorescence assay, and the effect of derivatives on mitochondrial function was evaluated using JC-1 and MTT assay. 2-Phenylbenzofuran derivatives with dimethylamino group at p-position had an excellent inhibitory activity against Aβ fibril formation. Particularly, compound 19m alleviated mitochondrial damage remarkably and possessed protective effects against Aβ-induced cytotoxicity.

Keywords: 2-Phenylbenzofuran; Alzheimer’s disease; Aβ aggregation inhibitor; Mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Benzimidazoles / pharmacology
  • Benzofurans / chemistry*
  • Benzofurans / pharmacology*
  • Carbocyanines / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / pathology

Substances

  • Amyloid beta-Peptides
  • Benzimidazoles
  • Benzofurans
  • Carbocyanines
  • 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine