Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation

scyllo-Inositol has shown promise as a potential therapeutic for Alzheimer’s disease, by directly interacting with the amyloid β (Aβ) peptide to inhibit Aβ42 fiber formation. To explore the molecular details of the inositol-Aβ42 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 Aβ42 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 Aβ42 fibers. The other derivatives showed some alterations in the morphology of the Aβ42 fibers produced. These findings indicate the importance of all of the hydroxyl groups of scyllo-inositol for complete inhibition of Aβ aggregation.