Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA 02125-3393, USA.
Bioorg Med Chem Lett. 2011 Apr 1;21(7):2044-7. doi: 10.1016/j.bmcl.2011.02.012. Epub 2011 Feb 25.
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.
阿尔茨海默病的一种潜在治疗方法是减少有毒淀粉样β寡聚体和纤维状淀粉样斑块的数量。为了为此方法做出贡献，研究了先前报道的成功抑制纤维形成的小分子有机氟化合物破坏淀粉样β肽原纤维的能力。这些有机氟分子，包括手性化合物，使用基于 Thioflavin-T（THT）荧光光谱法、原子力显微镜（AFM）和傅里叶变换红外光谱（FTIR）的标准方法在体外进行了测试。观察到 5'-卤素取代的 3,3,3-三氟甲基-2-羟基-（吲哚-3-基）-丙酸酯显示出在解聚原纤维方面的显著活性。由于相同的化合物也被鉴定为强纤维形成抑制剂，这种双重作用使它们成为进一步药物开发的有前途的候选物。
