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Article
Disassembly of Preformed Amyloid ß Fibrils by Small Organofluorine Molecules
Bioorganic and Medicinal Chemistry Letters (2011)
  • Abha Sood, University of Massachusetts
  • Abid Shaikh, Georgia Southern University
  • Catharine Sauer, University of Massachusetts
  • Samson Hailemichael, University of Massachusetts
  • Michelle Foster, University of Massachusetts
  • Béla Török
  • Marianna Török
Abstract
A potential therapeutic approach for Alzheimer’s disease is to reduce the amount of toxic amyloid-beta oligomers and fibrillar amyloid plaques. In order to contribute to this approach the ability of small organofluorine compounds that were previously reported as successful inhibitors of fibrillogenesis to destabilize preformed fibrils of the amyloid-beta peptide was studied. These organofluorine molecules including chiral compounds were tested in vitro using standard methods based on Thioflavin-T (THT) fluorescence spectroscopy, atomic force microscopy (AFM) and Fourier-transform infrared spectroscopy (FTIR). It was observed that 5′-halogen substituted 3,3,3-trifluoromethyl-2-hydroxyl-(indol-3-yl)-propionic acid esters showed significant activity in the disassembly of the preformed fibrils. Since the same compounds were identified as strong fibrillogenesis inhibitors as well, this dual action makes them promising candidates for further drug development.
Keywords
  • Alzheimer’s disease,
  • Amyloid-beta,
  • Fibrils,
  • Disassembly,
  • Organofluorine compounds
Disciplines
Publication Date
2011
Publisher Statement
This is an Accepted Author Manuscript obtained from PMC. The publisher's final edited version of this article is available at Bioorganic and Medicinal Chemistry Letters.
Citation Information
Abha Sood, Abid Shaikh, Catharine Sauer, Samson Hailemichael, Michelle Foster, Béla Török, and Marianna Török. "Disassembly of Preformed Amyloid ß Fibrils by Small Organofluorine Molecules" Bioorganic and Medicinal Chemistry Letters 21.7 (2011): 2044-2047.
doi:10.1016/j.bmcl.2011.02.012
source:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056901/
Available at: http://works.bepress.com/abid_shaikh/3