Inhibition of β-Amyloid Aggregation in Alzheimer's Disease: The Key Role of (Pro)electrophilic Warheads.

ABSTRACT: Catechols have been largely investigated as antiaggregating agents toward β-amyloid peptide. Herein, as a follow up of a previous series of hydroxycinnamic derivatives, we synthesized a small set of dihydroxy isomers for exploring the role of the reciprocal position of the two hydroxyl functions at a molecular level. Para- and ortho-derivatives effectively reduced amyloid fibrillization, while the meta-analogue was devoid of any activity in this respect. Electrochemical analyses showed that the antiaggregating potency correlates with the oxidation potential, hence indicating the proelectrophilic character as a prerequisite for activity. Interestingly, mass spectrometry studies and quantum mechanical calculations revealed different modes of action for active para

SUBMITTER: Basagni F 

PROVIDER: S-EPMC9661696 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature