Structure-activity relationships for bergenin analogues as β-secretase (BACE1) inhibitors

Abstract

Here we evaluated the inhibitory effects of bergenin analogues (2-10), prepared from naturally occurring bergenin, (1) on b-secretase (BACE1) activity. All the bergenin analogues that were analyzed inhibited BACE1 in a dose-dependent manner. 11-O-protocatechuoylbergenin (5) was the most potent inhibitor, with an IC50 value of 0.6 ± 0.07 mM. The other bergenin analogues, in particular, 11-O-3′,4′- dimethoxybenzoyl)-bergenin (6), 11-O-vanilloylbergenin (7), and 11-O-isovanilloylbergenin (8), inhibited BACE1 activity with IC50 values of <10.0 mM. BACE1 inhibitory activity was influenced by the substituents of the benzoic acid moiety. To the best of our knowledge, this is the first report on the structure-activity relationships (SAR) in the BACE1 inhibitory activities of bergenin analogues. These bergenin analogues may be useful in studying the mechanisms of Alzheimer's disease. ©2013 by Japan Oil Chemists' Society.