title: 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 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.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Osaka, Japan.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Kashima
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000975:Antioxidants; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000502:physiology; D019817:Benzoic Acid / Q000737:chemistry; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000009:adverse effects; D031995:Saxifragaceae / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D011480:Protease Inhibitors; D017382:Reactive Oxygen Species; D019817:Benzoic Acid; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C006741:bergenin