Polymethoxyflavones: Novel β-Secretase (BACE1) Inhibitors from Citrus Peels.

ABSTRACT: Beta-site amyloid precursor protein (APP) cleaving enzyme1 (BACE1) catalyzes the rate-limiting step of amyloid-β protein (Aβ) generation, and is considered as a prime target for Alzheimer's disease (AD). In search of a candidate for AD prevention, our efforts exploring the natural BACE1 inhibitor have led to the finding of nobiletin, tangeretin, and sinensetin-representative compounds of polymethoxyflavones (PMFs). Tangeretin exhibited the strongest BACE1 inhibition (IC50, 4.9 × 10-5 M), followed by nobiletin and sinensetin with IC50 values of 5.9 × 10-5 M and 6.3 × 10-5 M, respectively. In addition, all compounds reacted in a non-competitive manner with the substrate. Docking analysis results for complexes with BACE1 indicated that SER10 and THR232 residues of BACE1 hydrogen bonded with t

SUBMITTER: Youn K 

PROVIDER: S-EPMC5622733 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature