Département de chimie moléculaire

The formation of tau aggregates is strongly linked to the neurodegenerative process in tauopathies such as Alzheimer's disease (AD). Yet only a few mols. have shown to efficiently prevent the in vitro formation of those aggregates, and the identification of such mols. is still an ongoing interest in a therapeutic context. Herein, we report the in vitro evaluation of a series of aurones against the fibrillation of the tau-derived hexapeptide AcPHF6 model. Using thioflavin T-based fluorescence assays, CD and at. force microscopy, we showed that aurones are capable of efficiently interacting with the tau-derived hexapeptide. Importantly, this work reveals a significant activity obsd. for polyhydroxylated aurones. In particular, aurone 23 displayed an almost complete inhibition of fibers formation as shown by AFM at a peptide/inhibitor 1:1 ratio. It is similar to that obsd. for myricetin, a polyphenolic compd., well-known to prevent the in vitro elongation of tau fibers. Moreover, a tetrahydroxylated isomer, compd. 24, was shown as a chem. probe of fibers rather than an inhibitor. Consequently, these results highlight aurones as a new promising scaffold to interfere with tau aggregation for both treatment and diagnosis of AD. [on SciFinder(R)]