Disassembly of preformed amyloid beta fibrils by small organofluorine molecules

被引：28

作者：

Sood, Abha ^{[1
]}

Abid, Mohammed ^{[1
]}

Sauer, Catharine ^{[1
]}

Hailemichael, Samson ^{[1
]}

Foster, Michelle ^{[1
]}

Toeroek, Bela ^{[1
]}

Toeroek, Marianna ^{[1
]}

机构：

[1] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 07期

关键词：

Alzheimer's disease; Amyloid-beta; Fibrils; Disassembly; Organofluorine compounds; ATOMIC-FORCE MICROSCOPY; ALZHEIMERS-DISEASE; THIOFLAVINE-T; AGGREGATION; INHIBITORS; HYDROXYALKYLATION; FIBRILLOGENESIS; ASSEMBLIES; MECHANISM; OLIGOMERS;

D O I：

10.1016/j.bmcl.2011.02.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2044 / 2047

页数：4

共 26 条

[1] Synthesis of N-heteroaryl(trifluoromethyl)hydroxyalkanoic acid esters by highly efficient solid acid-catalyzed hydroxyalkylation of indoles and pyrroles with activated trifluoromethyl ketones [J].