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Updated: May 10, 2026

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Published on: January 25, 2018
Structure-activity relationships for bergenin analogues as β-secretase (BACE1) inhibitors
Yusei Kashima1, Mitsuo Miyazawa
1Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Osaka, Japan.
Abstract:
Here we evaluated the inhibitory effects of bergenin analogues (2-10), prepared from naturally occurring bergenin, (1) on β-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 μM. 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 μM. 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.
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