Sun Yedi, Zhang Guohua, Hawkes Cheryl A, Shaw James E, McLaurin JoAnne, Nitz Mark
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ont., Canada M5S 3H6.
Bioorg Med Chem. 2008 Aug 1;16(15):7177-84. doi: 10.1016/j.bmc.2008.06.045. Epub 2008 Jun 26.
scyllo-Inositol has shown promise as a potential therapeutic for Alzheimer's disease, by directly interacting with the amyloid beta (Abeta) peptide to inhibit Abeta42 fiber formation. To explore the molecular details of the inositol-Abeta42 interaction, a series of scyllo-inositol derivatives have been synthesized which contain deoxy, fluoro, chloro, and methoxy substitutions. The effects of these compounds on the aggregation cascade of Abeta42 have been investigated using electron microscopy (EM). EM analyses revealed that the 1-deoxy-1-fluoro- and 1,4-dimethyl-scyllo-inositols significantly inhibit the formation of Abeta42 fibers. The other derivatives showed some alterations in the morphology of the Abeta42 fibers produced. These findings indicate the importance of all of the hydroxyl groups of scyllo-inositol for complete inhibition of Abeta aggregation.
scyllo-肌醇已显示出作为阿尔茨海默病潜在治疗药物的前景，它通过与淀粉样β（Aβ）肽直接相互作用来抑制Aβ42纤维的形成。为了探究肌醇与Aβ42相互作用的分子细节，已合成了一系列含有脱氧、氟、氯和甲氧基取代基的scyllo-肌醇衍生物。使用电子显微镜（EM）研究了这些化合物对Aβ42聚集级联反应的影响。EM分析表明，1-脱氧-1-氟-和1,4-二甲基-scyllo-肌醇显著抑制Aβ42纤维的形成。其他衍生物使产生的Aβ42纤维的形态发生了一些改变。这些发现表明scyllo-肌醇的所有羟基对于完全抑制Aβ聚集的重要性。
